Scientific American-January 2008

TECHNOLOGY LEADERS: THE SCIAM 50 Trends Shaping Tomorrow’s Computers, Medicine, Materials and More

New Concerns about FLUORIDE page 74

January 2008 $4.99 www.SciAm.com A GRAND PLAN FOR

By 2050 it could free the U.S. from foreign oil and slash greenhouse emissions. Here’s how...

Nanotech Power Tiny Devices Reclaim Wasted Energy Cancer Drug Paradox It Kills Tumors by Repairing Them Sing Out! The Physics of the Voice

BIG IDEAS A Solar Grand Plan By Ken Zweibel, James Mason 64 and Vasilis Fthenakis An ambitious scheme would enable solar power to end U.S. dependence on foreign oil and slash greenhouse gas emissions by 2050. IMAGE BY KENN BROWN KENN BY IMAGE

TECHNOLOGY LEADERSHIP 41 The SciAm 50 Which researchers, companies and architects of 56 industrial and government policy are leading the most important trends shaping tomorrow’s technologies? Our annual roundup of world shakers gives credit where it is due.

MEDICINE 56 Taming Vessels to Treat Cancer By Rakesh K. Jain Drugs that restore order to the chaotic blood vessels inside a tumor open a window of opportunity 74 82 for attacking it.

PUBLIC HEALTH 74 Second Thoughts about Fluoride By Dan Fagin New research indicates that a cavity-ﬁ ghting treatment could be risky if overused. ON THE COVER ENGINEERING Solar power is sometimes dismissed as too expensive 82 Self-Powered Nanotech or impractical. Yet with sufficient commitment and By Zhong Lin Wang investment, it could become the major source of Tiny systems that draw waste energy from their electricity in the U.S. Image by Jean-Francois Podevin. surroundings could power nanosize machines. Photograph of toothbrush by Smitha Alampur.

EARTH SCIENCE 88 Hotspots Unplugged 88 94 By John A. Tarduno Long considered ﬁ xed founts of molten material from deep within the planet, the hotspots that raise islands now join the list of the earth’s moving parts.

PHYSIOLOGY 94 The Human Instrument By Ingo R. Titze When judged by its size, our vocal system fails to impress as a musical instrument. How, then, can it produce all those remarkable sounds?

GO TO .COM RECORD-SETTING STELLAR BLACK HOLE Ç Scientists uncovered the newly crowned champ, 8 In Focus Hospitals and Superbugs: Go in Sick ... Get Sicker shown here stealing gas from its neighboring blue star. Nearly 100,000 people die every year More at www.SciAm.com/ontheweb from preventable infections they pick up in health care facilities. 8 News Can a Lack of Sleep Cause Psychiatric Disorders? Study shows that sleep deprivation leads to a rewiring of the brain’s emotional circuitry. 8 Podcast Mom’s Baby Talk Crucial for Baby Adults have to engage in baby talk, regardless of the language they speak, so that babies can learn to talk like adults. 8 Blog Video of a Sphere Turning Inside Out without Creasing Check out Outside In, an animation that shows how to “evert” a sphere. 8 Strange but True Snake Oil Salesmen Were On to Something Sonoma State University/NASASonoma State Snake oil really is a cure for what ails you, if that happens to be arthritis, heart disease or maybe even depression. AURORE SIMONNET

Scientifi c American (ISSN 0036-8733), published monthly by Scientifi c American, Inc., 415 Madison Avenue, New York, N.Y. 10017-1111. Copyright © 2007 by Scientifi c American, Inc. All rights reserved. No part of this issue may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying and recording for public or private use, or by any information storage or retrieval system, without the prior written permission of the publisher. Periodicals postage paid at New York, N.Y., and at additional mailing offi ces. Canada Post International Publications Mail (Canadian Distribution) Sales Agreement No. 40012504. Canadian BN No. 127387652RT; QST No. Q1015332537. Publication Mail Agreement #40012504. Return undeliverable mail to Scientifi c American, P.O. Box 819, Stn Main, Markham, ON L3P 8A2. Subscription rates: one year $34.97, Canada $49 USD, International $55 USD. Postmaster: Send address changes to Scientifi c American, Box 3187, Harlan, Iowa 51537. Reprints available: write Reprint Department, Scientifi c American, Inc., 415 Madison Avenue, New York, N.Y. 10017-1111; (212) 451-8877; fax: (212) 355-0408. Subscription inquiries: U.S. and Canada (800) 333-1199; other (515) 248-7684. Send e-mail to [email protected] Printed in U.S.A.

8 From the Editor 10 Letters 16 14 50, 100 and 150 Years Ago 16 Updates 24 18 NEWS SCAN ■ Gene therapy: Moving past a wretched history. ■ Putting major nutrients in microcapsules. ■ Oddball neutron star. 102 ■ Neandertal language puzzle. ■ Time for a new physics of time. ■ Hyena relations and genetic paradox. ■ Signs of early symbolic thought. ■ Data Points: The MRSA threat.

OPINION 33 ■ SciAm Perspectives What has Congress done for science?

34 ■ Sustainable Developments By Jeffrey D. Sachs KATHLEEN DOOHER Ten resolutions could universally improve primary Featured Q & A health standards at an almost unnoticeable cost. Read an interview with Richard Wrangham at www.SciAm.com/ontheweb 36 ■ Forum By Eva Kaplan Bed nets can beat malaria—but not these bed nets. 102 Insights Our hominid ancestors could never have eaten 38 ■ Skeptic enough raw food to create our large, calorie-hungry By Michael Shermer brains, Richard Wrangham claims. The secret to our Evolution and economics are both examples evolution, this anthropologist says, is cooking. of a larger mysterious phenomenon. 106 Working Knowledge 40 ■ Anti Gravity The striking mechanics of bowling pinsetters. By Steve Mirsky What’s in a (Latin) name? 108 Reviews Conservation and politics in Nepal. Embracing (or questioning) future design. 110 Ask the Experts 33 How do we remember smells for so long? Why do migratory birds ﬂ y in a V formation? 112 Fact or Fiction? Does inﬁ nity come in different sizes? 110 112

Big and Small Solutions Meeting U.S. energy challenges requires more than one kind of ambition

With oil nearing $100 a barrel pendent of overseas oil and to drop carbon and atmospheric greenhouse dioxide emissions to a bit more than a third gas concentrations steadily of what they are now. The authors do not rising, the U.S. must commit invoke hypothetical breakthroughs in so- seriously to a long-term plan lar technologies; they rely on existing tech- that will improve the nation’s energy secu- nology and incremental improvements to rity and address climate change threats. it. By their estimate the scheme would re- To date, national leaders have expended quire $420 billion in subsidies over 40 a lot of rhetoric on the importance of years. But that sum could be a bargain in those goals, but relative to the country’s terms of energy and environmental secu- magnitude as both a consumer of energy rity—as they point out, it is in line with and a producer of carbon dioxide, they other major expenditures, such as farm have taken few meaningful steps to reach supports (and, we might point out, fund- them. The U.S. needs to ing for the Iraq War). get off the sidelines and Whether their analyses put some skin into the are correct and whether game. such a solar plan is real- A business-as-usual ly the best choice avail- approach will not work. able are open to debate, Over time, economies but that is rather the Among Our and policies may spon- point: it behooves all of taneously migrate to us to think boldly about Contributors more effi cient, more en- what should be done DAN FAGIN vironmentally benign and not to be intimidat- is director of the Science, Health and energy technologies, ed by the problem’s Environmental Reporting Program at New York University and was but those responses large scope. an award-winning writer for the will almost certainly Zhong Lin Wang de- newspaper Newsday. HOW BRIGHT are solar power’s be too slow to stave off scribes a very different prospects? RAKESH K. JAIN massive climate disrup- approach to obtaining is a tumor biologist at Massachusetts tions, which require that greenhouse gas and conserving energy in “Self-Powered General Hospital and Harvard Medical School. He is a distinguished member of emissions be capped within 50 years. This Nanotech,” starting on page 82. The sys- both the National Academy of Engineering magazine has long taken the position that tems of tiny piezoelectric elements he and and the Institute of Medicine. the best strategy will probably require his colleagues are developing could be ide- JOHN A. TARDUNO calling on every available option: not only al for powering microscale devices. They is founder of the paleomagnetism solar, wind, nuclear and other sources of can tap into the ambient energy in their laboratory at the University of Rochester power but also cleaner coal and more ex- surroundings—for instance, future medi- and is one of Scientifi c American‘s few authors who can claim to have tensive conservation. Still, if only as an ex- cal appliances might draw power from the ) survived a sandstorm. ercise in showing what might be possible, rush of blood through veins. Expect such solar panels INGO R. TITZE it is sometimes worth contemplating how self-powered systems to play a pervasive ( was originally trained as a physicist but much a single brace of related technolo- role in tomorrow’s technology. Wang’s ar- Corbis has become one of the world’s leading gies can do. ticle is a good counterpoint to that of scientifi c authorities on the human voice. He directs the National Center for Voice In “A Solar Grand Plan,” beginning on Zweibel, Mason and Fthenakis: to deal and Speech in Denver. page 64, Ken Zweibel, James Mason and with our energy and environmental chal- ); MIKE ROESSLER ROESSLER MIKE ); ZHONG LIN WANG Vasilis Fthenakis sketch out how the U.S. lenges, we can’t be afraid to think big, but g directs the Center for Nanostructure could build a solar energy infrastructure we also should not overlook the small. Rennie Characterization at the Georgia Institute that might provide two thirds of its elec- of Technology and has received multiple awards for his accomplishments tricity and one third of its total energy by JOHN RENNIE in constructing nanoscale devices. 2050—enough to make the nation inde- editor in chief LARSEN ( FLYNN

® Obesity ■ Weight and Mortality ■ Caloric Beverages Established 1845

EDITOR IN CHIEF: John Rennie EXECUTIVE EDITOR: Mariette DiChristina MANAGING EDITOR: Ricki L. Rusting CHIEF NEWS EDITOR: Philip M. Yam “Our 2005 paper on the excess SENIOR WRITER: Gary Stix EDITORS: Mark Alpert, Steven Ashley, Peter Brown, mortality associated with levels Graham P. Collins, Mark Fischetti, Steve Mirsky, George Musser, Christine Soares of BMI in the U.S. did not state CONTRIBUTING EDITORS: W. Wayt Gibbs, Marguerite Holloway, Michelle Press, Michael Shermer, or imply that excess fat Sarah Simpson carries no health risks.”

EDITORIAL DIRECTOR, ONLINE: Kate Wong —Katherine M. Flegal et al. NEWS EDITOR, ONLINE: Lisa Stein ASSOCIATE EDITORS, ONLINE: David Biello, SEPTEMBER 2007 Larry Greenemeier SPECIAL PROJECTS EDITOR, ONLINE: Christopher Mims ■ NEWS REPORTERS, ONLINE: JR Minkel, Feast and Famine macological interventions and food choic- Nikhil Swaminathan The special issue on obesity [“Feast es and ignored the interrelation between COMMUNITY EDITOR, ONLINE: Christie Nicholson and Famine”] did not adequately address emotions and food. All addictions, in- ART DIRECTOR, ONLINE: Ryan Reid the skepticism that has developed con- cluding food obsessions, have the same ART DIRECTOR: Edward Bell cerning health research. Too often we roots: low self-esteem, a feeling of an in- ASSOCIATE ART DIRECTOR: Mark Clemens have been encouraged to, say, increase our explicable void, the inability to process ASSISTANT ART DIRECTOR: Johnny Johnson ASSISTANT ART DIRECTOR: Jen Christiansen consumption of broccoli or oatmeal, only emotions or responses to stress, and a PHOTOGRAPHY EDITOR: Emily Harrison to then be told that the initial claims were sense of being out of control, which man- PRODUCTION EDITOR: Richard Hunt faulty or exaggerated. These inconsisten- ifests as a variety of self-destructive and COPY DIRECTOR: Maria-Christina Keller cies often arise from the misapplication of compulsive tendencies. COPY CHIEF: Daniel C. Schlenoff the basic principles of scientiﬁ c methodol- Jennifer Delaney COPY AND RESEARCH: Michael Battaglia, John Matson, Aaron Shattuck, Rachel Dvoskin, ogy. There is a chronic failure to select un- via e-mail Smitha Alampur, Michelle Wright biased samples, to identify appropriate control groups, to employ reliable statisti- ■ The Consequences of Corpulence EDITORIAL ADMINISTRATOR: Jacob Lasky SENIOR SECRETARY: Maya Harty cal techniques and to recognize that cor- Paul Raeburn should have consulted us relation does not necessarily imply cause. before addressing our 2005 paper on the ASSOCIATE PUBLISHER, PRODUCTION: Christopher Bruce excess mortality associated with levels of William Sherman MANUFACTURING MANAGER: Janet Cermak Calgary, Alberta BMI in the U.S. in “Can Fat Be Fit?” We ADVERTISING PRODUCTION MANAGER: Carl Cherebin did not state or imply that excess fat car- PREPRESS AND QUALITY MANAGER: Silvia De Santis PRODUCTION MANAGER: Christina Hippeli I am a little surprised that you permit- ries no health risks. On the contrary, we CUSTOM PUBLISHING MANAGER: ted the use of such a fuzzy measurement as found that death from all causes was more Madelyn Keyes-Milch body mass index (BMI). Like a number of likely among the obese (BMI 30 and over) BOARD OF ADVISERS other people at my gym, I am well into the than among those of normal weight. “overweight” zone, not because of fat but We found no excess mortality among RITA R. COLWELL Distinguished Professor, University of Maryland because once a person carries a substantial the overweight (BMI between 25 and College Park and Johns Hopkins University amount of muscle, that person rates as 30)—a ﬁ nding that has been reported by Bloomberg School of Public Health overweight on a BMI scale. BMI is not other large prospective studies such as the DANNY HILLIS Co-chairman, Applied Minds only widely used in both popular works Seven Countries Study and the Cardiovas- VINOD KHOSLA and professional analyses but is cited in cular Health Study. Our study carefully Founder, Khosla Ventures public policy making, which makes the controlled for smoking and other possible M. GRANGER MORGAN notion that it applies to only some part of confounding factors. Nevertheless, we Professor and Head of Engineering and Public the population a bit dreadful. checked whether the results could have Policy, Carnegie Mellon University David Seaver been affected by smoking or preexisting LISA RANDALL Professor of Physics, Harvard University via e-mail GEORGE M. WHITESIDES Read an expanded version of the Professor of Chemistry, Harvard University I was disappointed that your solutions letter by Flegal et al. at for obesity and overeating explored phar- www.SciAm.com/ontheweb

PASSE NEMO DABS TAHOE ANSWERS to the AGENT I TON EGOS I NERT December 2007 crossword. Ir Ra Ti O N Al C Ho I Ce Co N S Ta N Tl Y Mo V Es ® APES DECREE isfaction is because of the salt or ATLASES DUDES ASSIST fat in soup, the way it is consumed, Established 1845 LOAM TENNI S AFT CaNCEr our perception of it as a filling food, U Ni V Er Se S W A I L T W O D R E A M or other reasons. Similarly, many MCA CAPE SUBMERSE STS CHAIRMAN: Brian Napack studies have demonstrated that PYRO PrOTeInS ECTO PRESIDENT: Steven Yee ALVA ASCENDS RaBIEsVIrUS beverages containing sugar, high- VICE PRESIDENT AND MANAGING DIRECTOR, INTERNATIONAL: Dean Sanderson TEETH TOP BIO TAILS fructose corn syrup or alcohol are VICE PRESIDENT: Frances Newburg FErAlHoUSeCAt LEGENDS LSTS handled differently by the body CHAIRMAN EMERITUS: John J. Hanley SAGA VOYAgEr ETDS than when sugar or high-fructose AAA NORTHSEA I SEE HEF corn syrup is incorporated in solid ASSOCIATE PUBLISHER, CIRCULATION: Simon Aronin UNR I G DAS L RON PErSONAl CIRCULATION DIRECTOR: Christian Dorbandt foods; as a result, the overall calor- Ge Ne Ti C A S P R E I N I N O B I S RENEWALS MANAGER: Karen Singer RESEAL AETNA IMPLODE ic intake from solid food does not FULFILLMENT AND DISTRIBUTION MANAGER: Rosa Davis MA S ADA B E AU adjust to account for the calories in Ti Ta N S At Mo S P He Re Co Sm I C In F La Ti O N these beverages. The mechanism VICE PRESIDENT AND PUBLISHER: Bruce Brandfon PLUTO TORN MOLE FIRMA responsible for that weaker com- SALES DEVELOPMENT MANAGER: David Tirpack SKI LL SPED AGES STEAM pensatory response to fluids is SALES REPRESENTATIVES: Jeffrey Crennan, Stephen Dudley, Stan Schmidt unknown. I posited the hypothesis illnesses by running numerous additional that humans may lack a physiological basis for pro- ASSOCIATE PUBLISHER, STRATEGIC PLANNING: Laura Salant cessing carbohydrate or alcoholic calories in bever- analyses. These analyses, published on- PROMOTION MANAGER: Diane Schube line by the American Journal of Epidemi- ages because only breast milk and water were avail- RESEARCH MANAGER: Aida Dadurian ology in August 2007 and on the Centers able for the majority of our evolutionary history. PROMOTION DESIGN MANAGER: Nancy Mongelli for Disease Control and Prevention Web Another possibility is that carbohydrate- and alcohol- GENERAL MANAGER: Michael Florek site, found no confounding in our results. containing beverages may produce an incomplete BUSINESS MANAGER: Marie Maher It is important to remember that nutri- satiation sequence that prevents us from becoming MANAGER, ADVERTISING ACCOUNTING AND COORDINATION: Constance Holmes tional reserves may offer a survival advan- satiated on them. George Bray of Louisiana State

tage in some illnesses. That may be par- University, my co-author for a study that will ampli- DIRECTOR, SPECIAL PROJECTS: Barth David Schwartz ticularly true for the elderly, among whom fy these theories, suggests that one possible mecha- MANAGING DIRECTOR AND VICE PRESIDENT, most deaths occur. nism is the way the gastrointestinal tract responds ONLINE: Mina C. Lux Katherine M. Flegal Barry I. Graubard to the form in which it is exposed to nutrients. ASSOCIATE PUBLISHER, ONLINE: Paul Rothkopf David F. Williamson Mitchell H. Gail DIRECTOR, WEB TECHNOLOGIES, ONLINE: Vincent Ma SALES REPRESENTATIVE, ONLINE: Gary Bronson Centers for Disease National Cancer Institute ERRATUM “Developmental Disorder in Mice

Control and Prevention Reversed,” by Nikhil Swaminathan [News Scan], DIRECTOR, ANCILLARY PRODUCTS: Diane McGarvey incorrectly states that Fragile X syndrome causes PERMISSIONS MANAGER: Linda Hertz ■ Soup Is Good Filling? cognitive dissonance. The text should have read In “The World Is Fat,” Barry M. Pop- “cognitive deficits.” kin states that humans did not evolve to How to Contact Us become satiated by beverages because wa- CLARIFICATION The box “A Champion for Bio- SUBSCRIPTIONS For new subscriptions, renewals, gifts, payments, and ter lacks calories. Calories in drinks such tech,” by Graham P. Collins, on page 108, should have changes of address: U.S. and Canada, 800-333-1199; as soda contribute to obesity, he explains, clarified that research at the University of Cape Town outside North America, 515-248-7684 or www.SciAm.com because people tend to consume them in in South Africa into developing maize genetically REPRINTS conjunction with more calories from food. modified to be resistant to the maize streak virus is a To order reprints of articles: Reprint Department, Scientiﬁ c American, 415 Madison Ave., But many people lose weight by going on joint effort between Edward P. Rybicki’s group (Dionne New York, NY 10017-1111; soup diets, and he notes that we did evolve N. Shepherd in particular) and Jennifer Thomson’s. 212-451-8877, fax: 212-355-0408; [email protected] to consume breast milk (a breast-feeding

baby will get full). Why is it that soup and PERMISSIONS breast milk can satiate humans if bever- Letters to the Editor For permission to copy or reuse material: Permissions Scientifi c American Department, Scientifi c American, 415 Madison Ave., ages cannot? New York, NY 10017-1111; www.SciAm.com/permissions 415 Madison Ave. Forest Ray or 212-451-8546 for procedures. Please allow three to six New York, NY 10017-1111 weeks for processing. New York City or [email protected] ADVERTISING Letters may be edited for length and clarity. POPKIN REPLIES: Many studies have shown that soup www.SciAm.com has electronic contact information for We regret that we cannot answer sales representatives of Scientifi c American in all regions does make us feel full, whereas caloric and noncaloric all correspondence. of the U.S. and in other countries. beverages do not. We are unsure if this appetite sat-

Uncertainty ■ Limited Flight ■ Forbidden Territory Compiled by Daniel C. Schlenoff

JANUARY 1958 fl ight by a heavier-than-air machine of one itive indeed, being only two blades and a UNCERTAINTY—“It may seem a paradox kilometer in a closed circuit. By Farman’s spring back; and with this simple implement that one of the cornerstones of modern recent successful fl ight in a circle, the rec- sheep have been sheared for thousands of physics is something called the principle ord of the Wright brothers made in this years past; it is but lately that a new imple- of uncertainty. The idea of indeterminacy country over two years ago has in this re- ment has been introduced which can be as a rule of science does, in fact, disturb spect been duplicated; however, Farman worked by power, thus leaving the operator many 20th-century philosophers. But the has found that his machine in its present all his strength to manage the sheep and uncertainty principle has proved a power- condition is incapable of long-distance guide the shears. Our engraving represents ful answer—so far the most fruitful—to fl ight, because of its inability to lift any per- a sheep being sheared by one of these ma- important questions in present-day phys- ceptible quantity of fuel. Also, he has not chines, which is suspended from a beam.” ics. During the past decade the validity of demonstrated its capability of fl ying with the uncertainty principle has been argued safety against a wind having a velocity of NIGHT INTO DAY—“Whale oils are in com- voluminously, both by writers who under- 20 miles an hour—a feat which the Wright paratively limited use for illumination, stand the problems at issue and by writers brothers accomplished with their fi rst mo- and are becoming more limited every year. who do not. Up to the present this so- tor-driven machine in 1903.” Sperm oil has no superior among all the called ‘Copenhagen interpretation of the burning fl uids, but it has become so dear quantum theory’ has stood its ground. In The entire article from 1908 is available at that cheaper substitutes have been sought my opinion and in the opinion of many www.SciAm.com/ontheweb and obtained. The most common of these other theoretical physicists, the uncertain- is a compound of alcohol and turpentine, ty principle will stand its ground indefi - commonly known by the name of burning nitely. —George Gamow” JANUARY 1858 fluid, which is very cheap and cleanly. SHAGGY SHEEP—“One of the oldest materi- This fl uid was fi rst brought into public use KRILL—“The whale’s example shows that als used in the manufacture of fabric is the in 1830. Were it not so volatile, no burn- we can reap vastly increased returns from wool and hair of animals. The scissors or ing fl uid could be more desirable. Horrible the biological economy of the oceans. The shears used for this purpose were very prim- accidents, causing death in many instanc- 270 million tons of krill on which the es, have occurred from the explosion Antarctic whales fed in their heyday of lamps, hence a safer substitute would be more than enough to supply is desirable.” the annual requirements of the entire U.S. population. There are growing BLACK HILLS—“The St. Louis (Mo.) indications that krill may be a timely Republican states that a party has just subject. Some 250 ships and 16,000 recently returned to that city from an men—the largest whaling fl eet in his- exploring expedition in a wild region tory—are now operating in the Ant- known as The Black Hills. It is a vast arctic Ocean. They depend mainly on country of movable sands, sterile, the fi n whale. If and when this species bleak and inhospitable. There are follows the blue and humpback small streams at remote distances in it, whales into near-extinction, whalers upon which there is spare vegetation; may fi nd it worthwhile to turn their suffi cient, however, for the subsistence attention to krill.” of the Indians’ horses and some buf- falo. The party consisted of sixty men, and the Sioux, who are numerous JANUARY 1908 there, forbid the return of any more FARMAN’S FLIGHT—“M. Henri Far- white men. They said that this party VOL. XIII, NO. JANUARY 17; 2, 1858 man, on Monday, January 13, before might pass, because it was the fi rst, the officials of the Aero Club of but no others may come, as they scared France, won the Deutsch-Archdeacon away their game, and would discover

prize of 50,000 francs for the ﬁ rst SHEAR POWER: Mechanizing agriculture, 1858 their strongholds and hiding-places.” SCIENTIFIC AMERICAN,

Dimmed Hopes ■ Vioxx Settlement ■ Prion Holes ■ Nukes and No Nukes Edited by Philip Yam

■ ■ Vioxx Payout settlement, which repre- prion [see “Shoot This Deer”; The Not New Thing Merck appears to sents a bit less than SciAm, June 2003, and “De- Physicist Sidney Drell and have closed the Merck’s expected 2007 tecting Mad Cow Disease”; former secretaries of state chapter on Vioxx, earnings, is much SciAm, July 2004]. But look- Henry Kissinger and George P. as the pharmaceuti- smaller than the $25 ing for that version may miss Shultz have all endorsed a cal giant agreed to billion some analysts some cases. In a study pub- “world free of nuclear weap- pay $4.85 billion to had expected Merck lished online October 8 by ons” and urged governments plaintiffs. Clinical would have to pay. the Journal of Biological to work “energetically on the trials had revealed Chemistry, researchers found actions required to achieve ■ that the painkiller Prion Disease that mice that died of a “mad that goal” [see “A Need for raised the risk of without Prions? cow” infection failed to show New Warheads?”; SciAm, heart attack and stroke [see Abnormal proteins known as any of the enzyme-resistant, November 2007]. In a recent “Avoiding Another Vioxx”; prions play an essential role misfolded prions. The results letter to senators, however, SciAm, February 2005]. But in the development of brain- hint that other states of the they wrote that development Merck won most of the trials destroying diseases that af- prion may be the cause of in- of the Reliable Replacement to reach juries, because plain- fect cows, deer and humans, fection or that prions are a by- Warhead (RRW) “should cer- tiffs’ lawyers had a hard time among other mammals. Tests product of an infection trig- tainly go ahead.” linking any particular prob- for these illnesses look for an gered by some other, as yet The two points evidently lem with the drug itself. The enzyme-resistant form of the unidentifi ed pathogen. do not contradict each other. “I never said kill RRW,” Drell ■ Here Doesn’t Come the Sun says. In the A town that gets no sun sounds like Gothic horror, but that is the case in winter for Ratten- course of chang- berg, an Austrian village nestled among huge mountains. Two years ago the residents hoped ing the world to by now to have installed 15 large mirrors, or heliostats, which would refl ect the sun’s rays what we want it onto streets [see “Lifting the Winter Dark”; SciAm, April 2006]. Budget problems, however, to be, “we have to have dimmed Rattenberg’s hopes. The town had lined up Bartenbach Light Laboratory—an maintain the [nucle- innovator in lighting design—and Bomin Solar, and the European Union kicked in money. ar warhead] stockpile as safe But additional funding sources fell through, and Bomin dropped out. Bartenbach research and reliable.” The stockpile director Wilfried Pohl says the lab recently met with town offi cials to fi nd alternative fi nanc- includes the warheads ing. Most likely, residents will not see the light for at least another winter. —Michael Dumiak (above) on the MX missile. Drell’s endorsement rests on several assumptions, he notes: that RRW is not a

weapon for new applications, ); that it does not drain funds from the successful mainte- MX warheads MX nance of existing weapons and that it would not violate nonproliferation treaties. Although experts wonder ) whether the RRW can be cer- ); Vioxx Rattenberg ( tiﬁ ed as reliable without test- (

ing, Drell insists that “no new Corbis testing is absolutely critical” Photo AP to help ensure U.S. integrity concerning test bans and non- DAVID KADLUBOWSKIDAVID NUKEPHOTO.COM/PAUL SHAMBROOM/AURORA PHOTOS ( PHOTOS SHAMBROOM/AURORA NUKEPHOTO.COM/PAUL proliferation. —David Biello PARIGGER ROBERT

MEDICINE Regaining Lost Luster New developments and clinical trials breathe life back into gene therapy BY MELINDA WENNER

he past 15 years have been a roller tary disorders such as cystic fi brosis, in Presbyterian Hospital announced promis- coaster for gene therapy. After be- which normal gene products are defi cient, ing results from a phase I trial for Parkin- T ing touted in the early 1990s as “the by delivering functional copies of missing son’s disease; a therapy that has restored medicine of the future,” gene therapy left genes to cells that need them. Since then, sight to 70 congenitally blind dogs is being an 18-year-old dead and three others with scientists have expanded gene therapy’s tested in humans at the University of Penn- leukemia; in July it was tied to the death possible applications to include “training” sylvania; and eight research groups are of a 36-year-old Illinois woman undergo- immune cells to hunt down cancer, build- gearing up to test new HIV treatments. Al- ing treatment for rheumatoid arthritis, al- ing new blood vessels and making the im- though no gene therapies have yet been ap- though further investigation cleared her mune system resistant to infection. proved by the U.S. Food and Drug Admin- therapy of the blame. Gene therapy scien- “We really don’t know the full dimen- istration, more than 800 trials are ongoing; tists, however, believe they can put the sion of what it can do,” says Arthur Nien- China has approved two cancer treatments, bad news behind them, thanks to a hand- huis, a hematologist at St. Jude Children’s but their effi cacy remains unclear. ful of recent developments and others just Research Hospital in Memphis and presi- What makes gene therapy so promising over the horizon. dent of the American Society of Gene Ther- also makes it extremely challenging. It can Gene therapy describes any treatment in apy (ASGT). In addition to 12 cancer treat- target only those tissues that need it, which doctors insert new or modifi ed genes ments and a heart treatment currently in “which is a major contrast with traditional into a person’s cells to treat or prevent dis- large phase III clinical trials, there have pharmacotherapy, where you take a pill or ease. Researchers initially been a handful of early-stage develop- receive an injection, and a very, very small planned to treat heredi- ments: in June doctors at New York– portion of the injected or ingested drug actually arrives at the [correct] site,” says David Dichek, a cardiologist at the Uni- versity of Washington. But ensuring that the gene reaches its target is no small feat. ) Trials can skirt this problem when target-

ed cells can be injected directly or easily tubestest ( removed—with the latter method, doctors can manipulate isolated cells in the lab Corbis and replace them in the patient later. But getting genes to inaccessible targets has been one of the ﬁ eld’s biggest hurdles. ); PHILIPPE ERANIAN); PHILIPPE Most scientists use modiﬁ ed viruses as “vectors” to deliver gene therapy. Viruses are good at delivering genetic payloads to cells; after all, that is what they do. If scientists strip viruses of their genetic mate- scanning electron micrographscanning rial and replace it with therapeutic genes, ( viruses will deliver this payload to the cells instead. Different viruses do differ- SPECIAL DELIVERY: Viruses carrying human genes accumulate in the blue layer of liquid ent things—some attack the liver, others

after centrifugation. So modiﬁ ed, the virus can deliver its payload to treat or prevent nerves; some insert their DNA into the Researchers,Photo Inc.

diseases. The inset shows ordinary adenoviruses (yellow) on a red blood cell. host genome, others do not—so physicians CNRI

can choose those that best suit their pur- these challenges, will it ever overcome its dence that gene therapy is any more dan- poses and further engineer them if need negative reputation? Some scientists main- gerous,” says Savio Woo, an oncologist at be. “There’s been a lot of effort to steer vi- tain that it has never been that unsafe, rel- Mount Sinai Hospital in New York City. ruses to go specifi c places,” says Donald atively speaking. “If you compare the Thousands of patients have been treated, Kohn, an immunologist at the Keck School safety profi le of gene drugs in develop- and only a few adverse events have been of Medicine of the University of Southern ment versus the traditional small-mole- reported, he states; the leukemia that de- California and Childrens Hospital Los cule pharmaceutical drugs, there’s no evi- veloped in three “bubble boy” patients Angeles. may have been a side effect specifi c But viruses come with a catch: to the therapeutic gene, which stimu- “Our immune system developed to lates immune cell growth. “Any time reject them,” Kohn explains. What a few cells divide a lot, you always killed 18-year-old Jesse Gelsinger in worry about secondary genetic 1999 was a powerful immune re- changes, which is how cancers form,” sponse to his therapy, not the therapy notes Mark Kay, a geneticist at Stan- itself. So even if a vector reaches its ford University. target, scientists must ensure that the As the fi eld continues to evolve body does not attack the “infected” and improve, scientists hope that the cells. Recently scientists have identi- public’s perceptions of it will, too. fi ed a number of ways of achieving “We clearly have had clinical suc- this, by using lower therapy doses, cesses, and now we’re on the thresh- pretreating patients with immuno- old of achieving many more,” says suppressive drugs and masking vec- ASGT president Nienhuis. “I think tors so immune cells do not notice we’re going to hear a lot about them them. Some scientists also use vec- in the next several years.” torless “naked” DNA and genes TRIALS AND TRIBULATIONS: The death of Jesse

packaged in other ways. Gelsinger during a gene therapy trial in 1999 gave Melinda Wenner is a freelance Newscom

Even if gene therapy conquers the ﬁ eld a shock from which it is slowly recovering. writer based in New York City. MBR

FOOD SCIENCE A Dash of Nutrition Iron- and vitamin-fortifi ed salt gets set to fi ght defi ciency diseases BY DIANE MARTINDALE

he fortifi cation of salt with iodine is a ple-fortify salt, which might also be more mixed together, iodine vaporizes and iron T global success story: with two out of acceptable to people than genetically mod- degrades. After more than a decade, Lev- three households in the developing world ifi ed foods in tackling malnutrition. ente Diosady, a chemical engineer at the now consuming iodized salt, an estimated Adding iron to iodized salt is a simple University of Toronto, fi nally solved the 82 million children are protected from idea that has proved diffi cult to execute. problem by borrowing a technique from thyroid disease and resultant learning dis- The chemicals are incompatible: when the food industry referred to as microen- abilities every year. Still, people suffer from a lack of other micronutrients. Nourishing Soft Drinks? For years, food scientists have looked for a way to fortify iodized salt to combat Besides fortifying salt, Levente Diosady of the University of Toronto has also developed a iron-deficiency anemia, which affects method to purify rapeseed protein, a by-product of canola oil manufacture. “The protein some two billion people, as well as vita- meal is highly nutritious, but it comes out as black sludge,” Diosady explains. His process min A defi ciency, which affl icts at least separates the protein from bitter compounds and then concentrates it into a neutral-tasting 100 million children in poor countries and powder that contains all the essential amino acids. Similar to soy, the canola protein has the additional quality of being soluble in acidic liquids and hence could supplement soft is the leading cause of blindness among drinks, which in developing countries are often consumed in lieu of water because of safety them. Canadian researchers have now de- concerns. Diosady plans to develop a protein-enriched soft drink called LiveADE. veloped a practical way to double- and tri-

capsulation. The process involves spray- sady notes, because almost everyone con- tene, a precursor to vitamin A. The rice ing iron particles with stearine, a vegeta- sumes it and it is relatively inexpensive to has yet to be introduced into developing ble fat, which creates a protective coat and fortify—about 1.7 cents per kilogram of countries amid fears about its safety and prevents the iron from reacting with the salt for double-fortifi ed salt. “Even the concerns that the crops may not have high iodine. poorest of the poor have to barter or buy enough concentrations of micronutrients. Encapsulating the iron, however, was salt. There’s no person in the world so But fortifi ed salt cannot supply all the only part of the solution. Diosady’s team poor that they have to make their own critical nutrients. For instance, vitamin C also had to change the appearance of the salt,” he says. Also, the amount of salt eat- is needed in such large quantities that it iron particles—which are dark brown and en in a given population is about the same, would end up carrying the salt, not the much smaller than salt grains. “The iron making dosage easier to control. People other way around. And because, on aver- can’t look like mice droppings in the salt,” might also accept fortifi ed salt more read- age, the daily intake of salt is 10 grams, Diosady says. “This is important in devel- ily than genetically modifi ed foods such as the fortifi ed version could only supple- oping countries where food contamina- Golden Rice, which contains beta-caro- ment a person’s nutritional requirements, tion is a problem.” not supply all of them. So to make the iron resem- Howarth Bouis, director of ble salt, Diosady fi rst sprays HarvestPlus, an international the microscopic iron granules research program that seeks with maltodextrin, a modifi ed to reduce micronutrient mal- food starch that acts like a glue nutrition with enriched staple to bind the iron particles to- foods, believes that fortifying gether until they form spheres commercial products such as about the size of salt crystals. salt can work in urban re- He then spray-coats the iron gions, but such efforts may clusters with hot vegetable fat not be able to reach all those containing food-grade titani- in need, especially the poor um dioxide, a whitening pig- living in remote rural areas. ment. When mixed with io- Instead HarvestPlus promotes dized salt, the modifi ed iron the use of biofortifi ed crops, capsules are nearly impercep- produced through either con- tible. Vitamin A can also be ventional plant breeding or added using a similar method genetic modification. With to create triple-fortifi ed salt. this strategy, Bouis says, peo- Field tests in Nigeria and ple can grow for themselves Kenya showed that the double- the nutrient-rich foods that and triple-fortifi ed salts are they need: “It is the plants that stable in humid and hot cli- are doing the work and not mates and acceptable to the manufacturers.” But the pro- locals. The Micronutrient Ini- cess of biofortification can tiative, an Ottawa-based non- cause color changes to the governmental organization, foods, so convincing consum- tested iron-enriched salt in ers to accept them could be a Ghana, where in eight months challenge. the number of anemic chil- Everyone agrees that a bal- dren dropped by 23 percent anced diet is the best way to without any other iron supple- combat micronutrient defi- mentation. The technology ciencies. But for people in the has been scaled up in two developing world without ac- large plants in India, and the cess to such a diet, they might initiative is currently leading a NOW WITH IRON: A key to making fortifi ed salt acceptable to take their nourishment with a University of Toronto of University study with 3.6 million school- people is to ensure that the iron looks like salt. In the vials few grains of fortifi ed salt. children. (clockwise from top left): iron particles; iron coated with titanium Salt is an ideal vehicle for dioxide; iodized salt; and iodized salt mixed with the coated iron. Diane Martindale is a science

providing micronutrients, Dio- writer based in Toronto. DIOSADY ANDREW

ASTRONOMY Neutron Oddball A newly discovered neutron star doesn’t behave like it’s supposed to BY MARK ALPERT

ur galaxy is littered with the corpses from the sun) and relatively young (prob- the disk of the Milky Way. If one assumes O of dead stars. At the end of their use- ably less than a million years old). that Calvera has the same characteristics ful lives, the vast majority of the stars in In an effort to fi nd additional INS ob- as the other INS objects, then the neutron the Milky Way shed their outer layers and jects, a team composed of Robert Rut- star must lie 25,000 light-years from shrink to white dwarfs, dense spheres ledge of McGill University and Derek Fox Earth and 15,000 light-years above the about the size of Earth. But very massive and Andrew Shevchuk, both at Pennsylva- galactic plane. stars explode in supernovae and leave be- nia State University, identifi ed another That position would put Calvera hind even denser relics, called neutron ROSAT x-ray source in a patch of sky squarely in the galactic halo, the diffuse stars, which are only 20 to 40 kilometers where there were no ordinary stars. Clos- spherical region surrounding the Milky across but weigh more than our sun. (The Way. Because it is unlikely that a neutron most massive stars of all become black star would form in the halo, the research holes.) Since the 1960s astronomers have team speculated that Calvera might have observed a wide variety of neutron been fl ung out of the galactic disk by stars, including madly rotating pul- the force of its violent birth. But if sars that sweep radio beams across Calvera formed less than a million the galaxy and x-ray binaries years ago, as the models predict, that devour material pulled it would have had to fl y out of from their companion stars. the Milky Way at a blistering But last August researchers speed of more than 5,000 ki- announced the discovery of lometers per second, which is perhaps the oddest neutron far faster than any other neu- star yet, a lone x-ray emitter tron star. in the Ursa Minor constella- This conundrum led the re- tion that does not seem to fi t searchers to reconsider Calve- into any observed category. ra’s classification in the INS Scientists have long been fas- category. They postulated that cinated by neutron stars because the object might instead be a mil- their physics is so extreme. Their lisecond pulsar, a neutron star crushing gravity fuses electrons and whose rotation has been wildly accel- protons into neutrons, and at the core the erated by the accretion of material from a neutrons may break down to their constit- companion star (which, in Calvera’s case, uent quarks. To better understand the for- would have been fully devoured or dis- ON ITS OWN: Artist’s rendition of an isolated mation and evolution of these bodies, neutron star shows the magnetic fi eld lines persed long ago). If this hypothesis were some researchers have focused on isolated surrounding the ultradense stellar remnant. true, Calvera would be a lot closer to neutron stars (INS) that have moved away Earth: between 250 and 1,000 light-years from the nebulous remnants of the super- er observations with space- and ground- away, making it one of the nearest neutron novae that created them. Over the past de- based telescopes revealed an object whose stars. But when the investigators pointed cade astronomers have detected seven spectrum was roughly similar to those of a radio telescope at Calvera, they did not such objects that emitted x-rays observed the Magnifi cent Seven. But the new object detect the ultrafast pulses expected of a by the German space telescope ROSAT was different enough from the other INS millisecond pulsar. “That defi nitely deep- but produced no radio beams like the ones sources that the researchers eventually ened the mystery,” Fox says. The research- generated by the rotation-powered pul- named it Calvera, after the villain who ers are planning more observations of sars. Dubbed “The Magnifi cent Seven” fought the seven hired gunmen in the fi lm. Calvera to clarify its status. And in the after the classic 1960 movie, the neutron Calvera is located at an unusually high ga- meantime, they are beginning to study 10 Courtesy Pennsylvania of University State stars were deemed to be relatively nearby lactic latitude; from Earth’s perspective, other isolated x-ray sources that may turn

(most of them less than 2,000 light-years the neutron star is about 30 degrees above out to be equally bafﬂ ing. CASEY REED

EVOLUTION Paging Dr. Doolittle The “language” gene FOXP2 proves critical for animal vocalizations BY JOHN WHITFIELD

othing shows that Neandertals didn’t have language in many of the most sophisticated sounds in the animal kingdom, “N abilities,” says Johannes Krause of the Max Planck In- suggesting that these behaviors are the foundation on which hu- stitute for Evolutionary Anthropology in Leipzig, Germany. In- man language is built. deed, the recent fi nding by Krause and his colleagues that Nean- An English family known as “KE” revealed the link between dertals and humans have the same version of the gene FOXP2— FOXP2 and language. Many members of this family have severe the only gene linked to language so far—might be thought of as diffi culties with language. They struggle to control their facial evidence that they did. movements and have diffi culty with reading, writing, grammar But although studies of modern humans suggest that FOXP2 and understanding others. is necessary for speech, no one believes that it is suffi cient. The In 2001 Fisher and his colleagues found that the gene at gene is “just one piece of a complicated the root of the family’s trouble is FOXP2, located on chromo- puzzle,” says geneticist Simon Fisher of some 7. The gene makes a protein that binds to DNA, switching the University of Oxford, part of the other genes on or off. Last month Fisher’s group published a team that discovered it. As such, the study identifying the 100 genes whose activity is most strong- Neandertal sequence is interesting ly infl uenced by FOXP2. Many of the genes turn out to be but provides little information about involved in the development and organization of the ner- their linguistic skills. “No single ge- vous system. netic factor can tell us whether or But most speech disorders—which affect not an extinct species was capable of about 5 percent of all children and have a speech,” Fisher says. strong hereditary component—do not in- Despite several years of intense volve mutations in FOXP2. They more study, researchers are still unsure commonly involve interactions between what FOXP2 does or how it might many genes and environmental factors, have contributed to the evolution of says Barbara Lewis, who studies

) language. Studies of extinct humans communication disorders at bat ( have yet to uncover much about SHRIEKS, SONGS Case Western Reserve Uni- these things, but studies of living AND SENTENCES all versity. “It’s a very impor- animals are starting to provide some seem to depend on tant gene, but it’s not the

Minden Pictures Pictures Minden hints. The gene has been implicated a gene called FOXP2. only speech gene out there,” she says. The idea that changes in FOXP2 Doing the FOXP2 Trot might have driven the evolution of lan-

); MICHAEL DURHAM DURHAM MICHAEL ); guage got a boost from the ﬁ nding that bird Johannes Krause was surprised when Neandertals turned out to the chimpanzee and human versions of have the same version of FOXP2 as humans. His previous stud- the protein differ by two amino acids. ies of the genetic variation in modern populations had suggest- This disparity might not sound like ed that the human form of the gene arose within the past 200,000 years—150,000 years after Neandertals and modern much, but FOXP2 is one of the least human lineages diverged. It shows, he says, that our under- variable vertebrate proteins. There is standing of how current genetics reflects our evolutionary past only one amino acid difference be- may need revising. tween the mouse and chimpanzee ); ALTRENDO NATURE/GETTY IMAGES ( IMAGES NATURE/GETTY ALTRENDO ); But Krause still thinks that FOXP2 has been under recent selec- forms, which diverged 60 million years

woman tion pressure in the human lineage. It may have changed just ago, compared with the six-million- ( before Neandertals and humans split, he speculates, or it might year date for the human-chimp split. have helped make our common ancestor more intelligent. “In On the other hand, more recent ev-

Getty Images the fossil record 500,000 years ago, there’s a huge increase in brain size,” Krause notes. “It’s hard to say if it was anything idence has muddied the link between to do with FOXP2, but something was going on.” FOXP2 and language evolution. For

PAUL BURNS instance, the mutations that cause

speech defects in humans do not affect larly important in the physical control of tist Stephanie White of the University of those parts of FOXP2 unique to us. And speech. Like talking, which engages more California, Los Angeles, has found. “Birds “some of the changes in humans previous- than 100 muscles, making the sounds may have the same circuitry that formed ly thought unique are seen in other mam- needed for sonar requires “massively com- the foundations for human language,” mals,” such as cats, says Stephen Rossiter plex coordination of the face and mouth,” White explains. The evidence points to of Queen Mary, University of London. Rossiter says. FOXP2 being a switch, she says, that dif- “As we’re looking at more species, we’re Bats are one of the few animals that ferent species put to varying uses in their seeing more differences. The picture is show vocal learning, along with humans, neural machinery. getting complicated.” some songbirds, whales and dolphins. The gene’s story hints at how evolution In September, Rossiter and his col- That is, the sounds they make are not inputs old materials to new uses, points out leagues revealed that bats, which use echo- nate but require practice and imitation. psychologist Gary Marcus of New York location are an exception to the rule of Studies in songbirds support the link be- University. “It’s a very good entrée into FOXP2’s unchanging nature: the gene tween FOXP2 and vocal learning, sug- language and how it relates to whatever varies widely within the group. “There’s gesting that as well as controlling how our preadaptations for language we inherited double the number of changes within bats brain forms, the gene might also infl uence from our ancestors.” as compared with all the other vertebrates how we use it. The gene changes its activ- surveyed,” he says. The fi nding supports ity in the brains of adult birds when they John Whitfi eld is a freelance science the idea that human FOXP2 is particu- learn and practice their songs, neuroscien- writer based in London.

PHYSICS Making Space for Time Physicists meet to puzzle out why time ﬂ ows one way BY SCOTT DODD

moclew dna olleh,” Columbia Uni- affected by the direction of time. “Eversity string theorist Brian Greene From the point of view of physics, said as he opened a conference at the New the past, present and future exist York Academy of Sciences last October. simultaneously. “If you understood that as ‘Hello and wel- For more than a century, come’ in time reverse,” he clarifi ed, “you physicists have proposed any probably don’t need to be here.” number of explanations for this No one left. Many of the world’s top apparent contradiction, from the theoretical physicists and cosmologists psychological (the fl ow of time is an gathered at the conference to grapple with illusion) to the physical (some un- the mystery of how time works. New tele- known property of quantum mechanics scope observations and novel thinking reconciles the contradiction). None has about quantum gravity have convinced proved satisfactory. In 1927 astrophysicist them that it is time to reexamine time. Sir Arthur Eddington coined the term insisting on being identifi ed as “Mr. X.” “We’ve answered classic questions about “time’s arrow” for the phenomenon and “The problem is at the borderline be- time by replacing them with other hard linked it to entropy: as the universe gets tween science and philosophy, and a lot of questions,” says cosmologist Max Teg- older, it becomes more disordered, follow- people don’t feel comfortable in that area,” mark of the Massachusetts Institute of ing the second law of thermodynamics. says Laura Mersini-Houghton, a physicist Technology. But scientists cannot explain why order at the University of North Carolina at On the face of it, time seems pretty sim- lies in the past and disorder in the future. Chapel Hill and co-organizer of the con- ple, like a one-way street: eggs don’t un- A solution has appeared so elusive that ference. “It’s been very diffi cult to make scramble, laugh lines don’t vanish (not at times it has been regarded as a distrac- progress over the past 20 years, because

without Botox, anyway), and your grand- tion from more “respectable” research. there hasn’t been much new to say.” Getty Images parents will never be younger than you. Physicist Richard Feynman even refused That is all changing thanks to stronger But the universe’s basic laws appear to be to have comments about time’s arrow at- instruments for probing the heavens. The

time-symmetrical, meaning they are un- tributed to him at a conference in 1963, cosmic microwave background radiation, FREDRIK SKOLD

a remnant of the big bang, shows that 380,000 years after its birth, the universe was fi lled with hot gas, all evenly distributed and highly ordered. Eventu- ally the early cosmos underwent infl a- tion and began to coalesce into the disordered universe of stars and atoms we know today. What remains puzzling, though, is why the early universe was so orderly—a condition that physicists consider highly improbable—and what caused it to swell so rapidly. “The arrow-of-time problem, once you get down to the nitty-gritty of it, is, Why was the early universe the way it was?” says Sean Carroll, a cosmologist at the California Institute of Tech- nology. What is more, the cosmos is now going through another period of expansion, with galaxies fl ying apart at an increasing rate because of a mysterious dark energy. “The fact that it appears that the universe is just going to expand forever and get colder and colder makes [the different conditions] even more striking,” Carroll adds. Mersini-Houghton and her colleagues brought together some of the best minds in the fi eld for the conference because, as she puts it, “we can’t just brush this problem under the rug any- more and hope it will be solved by something else.” Prominent physicists such as Greene, Tegmark, Lee Smolin of the Perimeter Institute for Theoretical Phys- ics in Ontario, Paul Davies of Arizona State University and Andreas Albrecht of the University of California, Davis, invoked string theory, black hole equa- tions and the idea that we live in one of many parallel universes as possible explanations. The multiverse concept emerged as one of the more favored—or at least fre- quently talked about—theories for the strange tidiness of the early cosmos. “If you accept the idea that this might be only one of many possible universes, then that makes it more plausible,” Mersini- Houghton says. Universes that started out more chaotic might not have survived or evolved to support intelligent life. So one- way time—and our entire existence, for

that matter—could be just a happenstance. predictions about the nature of time and Several attendees said that under- the early universe that could soon be test- standing time is vital to helping them an- ed through new observations. “We can swer other fundamental questions, in- see a lot more than we could before, and cluding what happens at the center of a that means we can be a bit more daring,” singularity and whether cosmic inﬂ ation Mersini-Houghton says. It’s about time. could one day reverse, causing the universe to collapse. And the growing cos- Scott Dodd is a freelance writer based mological data allow physicists to make in New York City.

ECOLOGY Relative Distance Hyena “wingmen” sacriﬁ ce sex for an unrelated male BY DAN EATHERLEY

n many animals, relatives tend to stay behavior. One would expect relatives to I close, either sharing the same territory share the same territory or to inhabit ter- or living in neighboring ones. By stick- ritories close together. This is not always ing together, individuals can defend so, however, claims Aaron P. Wagner, food, mates and other resources, thereby now at Michigan State University. working to perpetuate the family genes, Wagner and his colleagues trapped an even if not all manage to breed or raise entire population of striped hyenas in young. Kenya’s Laikipia District, about 135 One particular mammal, however, miles north of Nairobi, and collected its turns this general observation on its members’ DNA. The scientists also ra- head, and experts in behavioral ecology dio-tracked the animals to understand do not quite understand why. Striped hy- their movements. “As far as we are aware, enas (Hyaena hyaena), which live in Af- the patterns of relatedness and space use rica and parts of Asia, demonstrate so- we found in these hyenas are unseen in called protosocial tendencies. Although any other carnivore,” says Wagner, who little direct interaction occurs among in- published some of the results of the four- dividual hyenas, a closer look reveals year study in the October 2007 Molecu- that they actually form spatial groups lar Ecology. living on exclusive and stable ranges just Wagner’s team found that the spatial like species that display obvious social groups formed by this species always consist of just a single female de- fended by up to three males. Similar coalitions occur in other carnivores, but in those cases the males usually guard several females so that each male has a chance to mate. With only one female available, however, some male striped hyenas are unlikely to breed at all. Such sacriﬁ ce and cooperation could be under- standable if all males were relat- RANGE ROVERS: Tracking collars revealed that, ed, but genetic analysis showed unlike other mammals that display social behavior, that the hyena coalitions often

A. P. WAGNER WAGNER P. A. neighboring striped hyenas are often not related. include unrelated males.

Even more remarkable, for both sexes, competition and costly fi ghts with one an- urated-environment scenario, arguing hyenas living in neighboring territories other. In the spotted hyena (Crocuta cro- that it could explain why some relatives are less closely related than nonneighbors. cuta), male and female group members end up far away but does not explain why Wagner found this arrangement puzzling sometimes engage in aggressive disputes almost none ever live close by. because individuals that disperse and with neighbors over food or mates—even Calling the results “tantalizing,” biolo- cross territorial boundaries are at great battling with their own kin. Zoologist gist Gus Mills of South Africa’s Tony and risk of being attacked and killed by others Kay E. Holekamp, also at Michigan State, Lisette Lewis Foundation, which funds na- of their species. “Therefore, you would questions the evidence that striped hyenas ture conservation, appeals for longer-term expect to fi nd relatives living near one an- actually engage in these boundary con- studies. “Large carnivores are long-lived other and for relatedness to decline with fl icts at all and instead suggests that in- and reproduce quite slowly. Getting large distance,” Wagner says. breeding avoidance might account for samples over extended periods is very dif- No single theory can explain the over- their odd patterns of dispersal. According fi cult and so is interpretation of results.” all patterns recorded. Wagner speculates to Wagner, however, the need to prevent Wagner agrees and argues that research that for males, any form of coalition— inbreeding would not explain why low has been too skewed toward species with even with nonrelatives—might provide a levels of relatedness were found among well-developed social behavior, such as li- temporary safe haven when the alterna- neighbors of the same sex. ons or spotted hyenas. “Up to 90 percent tive of roaming alone is too hazardous or Maybe, at the time of the study, there of carnivores are, like striped hyenas, be- the chance of single-handedly defending a was nowhere else to go, suggests ecologist haviorally solitary. We must learn more female is too low. Hans Kruuk of the University of Aberdeen about the solitary majority before claim- But given the dangers, why would in Scotland. “Dispersing animals might ing we know why and how groups form striped hyenas leave their kin, risking not have found an empty space in a neigh- and how sociality evolved.” death to travel to distant nonneighboring boring territory,” meaning that individu- territories? Perhaps relatives settle in non- als would have had to venture farther into Dan Eatherley is an environmental con- adjacent territories to avoid cross-border several territories. Wagner doubts this sat- sultant and writer based near London.

PALEOANTHROPOLOGY Food for Symbolic Thought Besides the ﬁ rst seafood dinner, signs of the earliest symbolic thought BY JR MINKEL

cave on the southern coast of South South Africa’s Pinnacle Point. In addition rock with fl attened sides bearing parallel A Africa contains a bowl’s worth of ed- to discovering the first known seafood grooves, indicating that the shellfi sh eaters ible shellfi sh dating back to about 165,000 dinner—mostly brown mussels—they scraped the rocks to make powder. Mixing years ago. Besides pushing back the earli- found small stone blades and reddish rocks that powder with sap or another binder est known seafood meal by 40,000 years, tossed in with the shells. They identifi ed a yields a reddish or pinkish paint, possibly the discovery also marks the earliest time dozen or so pieces of iron-rich hematite to adorn the body or the face. when people might have engaged in That people were working symbolic thought. with pigments back then “is a Anatomically modern humans pretty good indicator of sym- probably emerged between 150,000 bolic thought,” says Marean, and 200,000 years ago in eastern who published the fi ndings in Africa. When those humans fi rst the October 18 Nature. A pop- developed the potential for symbol- ulation living on shellfi sh would ic thought, including language, has have stayed in one place and remained a puzzle. grown in number, he notes, in- Looking for early human re- 1 centimeter creasing the need for negotia- mains, Curtis W. Marean of the In- tions between individuals or stitute of Human Origins at Arizo- WHAT, NO LOBSTER FORK? Iron-rich blades of 165,000 years social groups, which might na State University and his col- ago show grooves, suggesting that the shellfi sh eaters have led to a system of decora-

leagues homed in on the caves at scraped them to obtain a red powder for painting. tive markings. PROJECT ARCHAEOLOGY BAY MOSSEL OF COURTESY

PESTICIDES Data Points Bt -Beating Bugs

Researchers have long worried that crop- specifi c receptors in pest midguts. They munching insects could become resistant to found three insect species that had evolved Bt, a toxin naturally produced by the mi- altered toxin receptors, which appar- crobe Bacillus thuringiensis that is ently grant Bt resistance. But the good harmless to most other organisms. news is that the researchers also Bt use is common; crops with the constructed modified toxins pesticide cover more than 32 mil- that can kill Bt-resistant pink lion hectares of land worldwide— bollworms. These new toxins are an area slightly larger than Italy. slightly less potent than the original Mario Soberón of the National versions against vulnerable insects, Autonomous University of Mex- but further research might improve ico and his colleagues investigat- them. Chew on the fi ndings re- No Mercy ed the most commonly used Bt BOLLWORM munches ported online November 1 by toxins, which work by binding to on a cotton fl ower. Science. —Charles Q. Choi from MRSA New estimates of infections by an OBESITY antibiotic-resistant bacterium, methi- cillin-resistant Staphylococcus aureus (MRSA), have astounded experts, who Weight Loss on Shaky Ground had not considered it a major public health threat. Researchers conducted Exercise takes energy, and presumably platforms. They also had signifi cantly re- population-based surveillance at nine that is what combats obesity, but provoca- duced levels of fatty compounds linked sites and extrapolated the 2005 data tive experiments now suggest that jiggling with type 2 diabetes. for the entire U.S. Recent fatal cases of invasive MRSA in children have might be enough. For 15 minutes almost The researchers speculate that the vibra- also raised some concerns, although every day for 15 weeks, scientists at Stony tions inhibited the formation of fat cells most deaths happened to people old- Brook University had mice sit on a buzzing from stem cells. The work could lead to a er than 65, and infections tended to platform that almost imperceptibly vibrat- nonstrenuous, drug-free method for con- occur at hospitals, rather than at ed at 90 times per second, accelerating up trol of obesity, but the investigators caution schools and playgrounds. and down at 20 percent the strength of the that exercise remains key to weight control Number of earth’s gravitational pull. After this treat- and loss. The results appear in the Novem- MRSA cases in 2005: 8,987 ment, the mice had 27 percent less fat in ber 6 Proceedings of the National Acade- their torso than mice kept on stationary my of Sciences USA. —Charles Q. Choi Number of in-hospital deaths: 1,598

BIOLOGY Estimated number of U.S. cases: 94,360 Bone Sweet Bone Estimated number ); ILLUSTRATION BY MATT COLLINS MATT BY ); ILLUSTRATION of deaths: Although sweets can help weaken teeth, sugars are apparently key to making bone 18,650 bollworm ( strong. The extraordinary strength of bone depends on the complex, precise way Number of in which its organic and inorganic components are ordered. Scientists had long AIDS deaths in 2005: 17,011 thought that collagen and other proteins directly control the structure of bone. MRSA infections Now it turns out that sugary compounds are responsible instead—speciﬁ cally, per 100,000 people: polysaccharides known as glycosaminoglycans and proteoglycans. Based on nu- 31.8 clear magnetic resonance imaging of horse bones, researchers conclude that poly- In those 65 years saccharides help to guide the proper crystallization of bone minerals. Better un- and older: 127.7 derstanding of how bone forms should alter the way osteoporosis and osteoarthri- tis are treated and perhaps lead to new ways of creating synthetic bone. This work In those between five and 17 years: 1.4 Holt Studios International/Photo Researchers, Inc. may also strengthen the rationale for over-the-counter joint and bone pain rem- edies such as chondroitin, a glycosaminoglycan. Bone up on the research in the SOURCES: Journal of the American Medical Association, October 17, 2007; Centers for Disease Control and Prevention October 16 Chemistry of Materials. —Charles Q. Choi NIGEL CATTLIN

In Brief NEUROSCIENCE

FASTBALLS FROM BLACK HOLES Psychiatric Disorders from No Sleep? A network of 1,400 ground-based particle detectors and two dozen telescopes Psychiatric problems can trigger sleep is- amok,” Walker says of that forebrain has located the possible origin of the sues, and now research suggests the reverse structure that decodes emotion. The highest-energy cosmic rays. Traveling is true—that is, a lack of shut-eye can cause boosted activity leads to a pendulum of at near light speed, these rays—most psychological disturbances. Matthew emotions, from upset and annoyed to gid- 20 likely protons—pack 10 electron volts, Walker of the University of California, dy, in moments. Among its many other 100 million times the energy produced by the largest particle accelerators and Berkeley, and his collaborators studied 26 functions, sleep may serve to prepare “our roughly equivalent to that of a fast-pitch volunteers, 14 of whom spent 35 hours emotional brains for the next day’s social baseball. The source appears to be near- without getting a wink. All the subjects and emotional interactions,” says Walker, by active galactic nuclei: bright galactic then saw photographs that went whose work appears in the October 23 cores probably powered by supermas- from benign (wicker baskets) to Current Biology. sive black holes. Scientists say they would never have guessed that black increasingly disturbing (tarantu- —Nikhil Swaminathan holes might have such powers if not for las and burn victims). Brain high-energy cosmic rays. —JR Minkel scans revealed that when the sleep-deprived participants MOTHER’S MILK AND IQ viewed more gruesome images, The fatty acids in human milk may boost their amygdala showed 60 IQ. Breast-fed infants with at least one percent more activity relative copy of a common variant of the gene to the normal population’s FADS2 had IQ scores that were six to seven points higher than those of non- response. “The amygdala nursed kids with similar genetics. But seems to be able to run breast-feeding did not appear to affect those children (10 percent of the study population) with only a less common version of FADS2. The gene variants may AGRICULTURE affect the conversion of dietary precur- sors to long-chain polyunsaturated fatty Signs of a Green Revolution acids, which aggregate in the brain after birth. Alternatively, the fatty acids may Per capita food production in sub-Saharan Africa is at last rising. According to the World act on the gene itself, causing it to affect the metabolic processing of the Bank’s World Development Report 2008, agricultural growth there “has accelerated

acids. —Nikhil Swaminathan from 2.3 percent per year in the 1980s to 3.3 percent in the 1990s and to 3.8 percent per ) year between 2000 and 2005.” That growth has cut poverty rates in 10 of 13 countries ROBO BUDDY analyzed. In addition to lack of drought, these results arose from an African “green bottom right bottom ( For robots to be accepted as human revolution” that experts and United Nations ofﬁ cials called for in 2004. It entails peers (as Bender is on Futurama), it relatively simple strategies, such as government subsidies for fertilizers and better Photo AP might just take a light touch. Scien- crop varieties, so that tists introduced a classroom of tod- farmers pay only 25 dlers—who naturally had no preconceived notions regarding percent of the actual ZILWA OBED ); droids—to a two-foot-tall human- costs. Moreover, food

oid robot, QRIO, which giggled production has been left bottom when its head was touched. Over increasing more than time, the children bonded with QRIO, touching it as they did other population growth. humans. After five months, the children Problems still persist, treated QRIO as a near equal, even cov- though, such as a lack of ac- ering it with a blanket and telling it cess to agricultural markets “night night” when its batteries ran out.

in the developed world. CORP., FILM FOX CENTURY 20TH © COPYRIGHT AND TM ); But when the robot was reprogrammed top ( just to dance, the toddlers lost interest. And global pressure to pro- The findings appear in the November 13 duce biofuels rather than Proceedings of the National Academy food may mean that hunger Getty Images of Sciences USA. —Charles Q. Choi will not be erased anytime GROWING SUCCESS: Simple measures, such as irrigation ALL RIGHTS RESERVED, COURTESY OF EVERETT ( OF COLLECTION COURTESY RESERVED, RIGHTS ALL soon. —David Biello with manual pumps, boosted Malawi’s food production. TIM HALL

SciAm Perspectives Congress Fails Science The Democratic majority continues a legacy of inaction

BY THE EDITORS

he U.S. Congress has long been a slow and irresolute insti- lative mill and may also face opposition from the White House. tution, especially when it comes to science issues. Unfor- Drug safety reform. One of the modest victories of the 2007 ses- T tunately, the Democratic majority that came to power in sion was a law giving the U.S. Food and Drug Administration the 2006 midterm election has so far done little to change that more power to monitor the safety of newly introduced pharma- reputation. Nearly a year after the Democrats took over the leg- ceuticals. Spurred by the Vioxx debacle of 2004, the reform legislative branch, America continues to escalate its emissions of islation enables the FDA to force drugmakers to conduct long-term carbon dioxide and other greenhouse gases that are slowly roast- studies of drugs whose side effects may not become apparent until ing the globe. Furthermore, although Congress has proposed they are in widespread use. The law also orders the pharmaceuti- funding increases for many scientifi c agencies and national labo- cal industry to pony up $225 million over the next fi ve years to ratories, researchers still have no reassurance that Uncle Sam will pay for the new safety monitoring. actually deliver its promised grants and budgets. Here are some Science funding. In his State of the Union address last January, highlights of how the 110th Congress has handled science mea- President Bush announced the American Competitiveness Initia- sures over the past year. tive, an ambitious plan to beef up federal funding for the physi- Energy. Promoting energy effi ciency and renewable sources is cal sciences. Congress responded by signifi cantly boosting the vital to curbing greenhouse gases, but as of early November proposed budgets for the National Science Foundation, the Congress’s much anticipated energy bill was stuck in legislative National Oceanic and Atmospheric Administration, the Nation- limbo. In June the Senate passed a promising measure that al Institute of Standards and Technology, and the U.S. Depart- would raise the fuel economy of cars and light trucks from the ment of Energy’s Offi ce of Science. The extra money would be a current average of 26 miles per gallon to 35 mpg by 2020; in particularly great boon for researchers investigating climate August the House approved a bill that would repeal subsidies for change, but because Congress approved the budget increases the oil and gas industry and require utilities to produce 15 per- without cutting funding in other areas, President Bush is now cent of their electricity from renewable sources such as wind threatening to veto the appropriations bills. Many of the pro- power. Unfortunately, the House and Senate bills were wildly different, and the usual process for reconciling the measures— negotiations in a House-Senate conference committee—broke down. Claiming that Senate Republicans had blocked efforts to appoint committee members, House Speaker Nancy Pelosi of California announced in October that Democratic leaders in the House and Senate would ham- mer out a compromise. In the face of veto threats from President George W. Bush, will the tough effi ciency propos- als survive? The chances look dim. Global warming. As the energy bill falters, Congress has launched a parallel effort to fi ght global warming by proposing a “cap and trade” system for industrial polluters. Sponsored by Senators John Warner of Virginia and Joseph Lieberman of Connecticut, America’s Climate Security Act is aimed at reducing greenhouse gas emissions to 60 percent of current levels by 2050. Although the

MATT COLLINS MATT bill has bipartisan support, it has only just entered the legis-

posed increases may vanish before the ic stem cell research. But some Demo- bills become law, and in the meantime cratic lawmakers have also obstructed THE EDITORS’ BL8G federal agencies have to operate at last progress. Representative John Dingell of For more posts from SciAm Observa- year’s funding levels. Michigan, chairman of the House Ener- tions, see www.SciAm.com/blog Who’s to blame? Our government’s gy and Commerce Committee, fought dismal science record for 2007 is partly the increase in fuel economy standards Won a Nobel? Go Nuts! the result of the political gridlock that proposed in the Senate’s energy bill, say- Posted by Philip Yam, October 19, 2007 occurs whenever one party controls ing it would devastate U.S. automakers. As a long-time science journalist, I have Congress and the other rules the White Internal divisions among Democrats led learned to take what James Watson says House. Last June, for example, President to the current logjam on the energy issue, with a grain of salt. Even so, I was caught Bush vetoed legislation that would have which must be untangled for the sake of off guard by the outrageousness of his expanded federal funding for embryon- our planet. g latest words. Watson gets all the kudos for his genetics work, and his discovery with Francis Crick of the double-helical structure of DNA unquestionably Sustainable Developments deserved the Nobel Prize. But maybe that’s what’s wrong. For most research scientists, winning the Nobel Prize stands as the pinnacle of Primary Health for All success, the ultimate goal that takes intelligence, dedication, luck and Ten resolutions could globally ensure a basic human right ambition (and don’t be fat, Watson would at almost unnoticeable cost say, because fat folks are not ambitious). BY JEFFREY D. SACHS Once the king of Sweden drapes that medal around your neck, life is good— Sixty years ago at the Second, half the increase should be people want to hear you speak, offer you launch of the World channeled through the Global Fund to prestigious positions and are more Health Organization, Fight AIDS, Tuberculosis and Malaria. inclined to give you what you want. the world’s govern- The Global Fund has proved to be a To their credit, some scientists take ments declared health highly effective institution, with mini- the opportunity to tackle very “out there” to be a fundamental mal bureaucracy and maximum impact. research. Soon after he won his 1995 Nobel in Physics, Martin Perl launched a human right “without It has supported the distribution of project to fi nd “free quarks.” distinction of race, religion, political approximately 30 million antimalaria Conventional thinking says there can be belief, economic or social condition.” bed nets, helped to get nearly one million no such things—quarks must remain Thirty years ago in Alma Ata, the world’s Africans on antiretroviral treatment and bound in the particles in which they governments called for health for all helped to cure more than two million build—but some scientists speculate that by the year 2000, mainly through the people of TB. some quarks might have been left over expansion of access to primary health Third, low-income countries should during the big bang. Perl recognized the facilities and services. While the world devote 15 percent of their own national long-shot odds of fi nding these quarks, missed that target by a budgets to health. but it was a project he could do because long shot, we can still Consider a poor coun- of his Nobel. A graduate student would be achieve it, at remark- These simple steps try where the average committing career suicide. ably low cost. Ten key income is $300 a year. Other researchers run from the glory. could save the lives steps can bring us to The total national Brian Josephson, who discovered the of nearly 10 million quantum effect in which superconducting health for all in the budget might be electrons could jump across a narrow next few years. adults and children. around 15 percent of barrier, went off to study mysticism and First, affl uent coun- GDP, or roughly $45 psychic phenomena. (His problems, tries should devote 0.1 percent of their per capita. Fifteen percent of that fi gure though, may run deeper; not many people gross domestic product to health care for devoted to health would come to just would choose Taco Bell for a [free] lunch low-income countries. With a rich world $6.75 per person per year: not enough to meeting.) GDP of $35 trillion, that would create a provide adequate basic health care on its After the wacky things James Watson fund of roughly $35 billion a year— own, but combined with $35 per capita has uttered over the past decades—on enough for $35 per capita in added health from donor aid, it would do the job. continued on page 37 services for the roughly one billion peo- Fourth, the world should adopt a plan

ple who need them. for comprehensive malaria control, aim- INSTITUTE GILBERT/EARTH BRUCE

ing to bring malaria mortality nearly to zero by 2012 through nurses and community health comprehensive access to antimalaria bed workers. nets, indoor spraying where appro- Tenth, using recent break- priate, and effective medicines throughs in medicine and when malarial illness arises. public health, the expanded Fifth, the rich countries health systems in the poorest should follow through on their countries should be equipped long-standing and achievable to handle noncommunicable commitment to ensure access diseases that have long been to antiretrovirals for all HIV- neglected but are treatable at low cost: infected individuals by 2010. hypertension, cataracts and depression. Sixth, the world should fi ll the These simple steps could save the lives of nearly 10 million fi nancing gap of roughly $3 billion adults and children a year, at a cost that would be nearly unno- a year for comprehensive TB control— ticeable to the world’s wealthiest nations. These measures would another area where known and long-proved interventions are also slow, rather than accelerate, population growth in impover- highly effective but chronically underfunded. ished regions, thereby easing the economic and environmental Seventh, the world should honor, for just a few billion dollars strains that bulging populations are imposing on them. Health a year, the access of the poorest of the poor to sexual and repro- for all is not only the moral imperative it was at the launch of the ductive health services, including family planning, contraception World Health Organization 60 years ago, it is also the best prac- and emergency obstetrical care. tical bargain on the planet. g Eighth, the Global Fund should offer roughly $400 million a year for comprehensive control of several tropical diseases (main- Jeffrey D. Sachs is director of the Earth Institute ly worm infections), which occur in virtually the same regions at Columbia University (www.earth.columbia.edu). where malaria is rampant. Ninth, the Global Fund should open a new fi nancing mecha- An expanded version of this essay is available at nism to bolster primary health care, including—most impor- www.SciAm.com/ontheweb tant—the construction of clinics and the hiring and training of

Forum A Better Mosquito Net Fighting malaria will require more innovative defenses BY EVA KAPLAN

Malaria remains one of To combat the disease, many develop- there is anecdotal evidence that some the world’s great scourges, ment agencies have focused on distribut- people have employed the nets as wedding striking more than 500 ing mosquito nets that would protect Afri- veils or fishing aids. Some economists million people every year. cans from being bitten while they sleep. argue that charging a small fee for the The groups most at risk This strategy has resulted in a huge upsurge nets would increase the likelihood that are pregnant women and in the number of bed nets supplied to the they would be used appropriately. Others children younger than population as a whole and particularly to claim such a fee would prevent a large ﬁ ve years old. In sub-Saharan Africa, 20 pregnant women and young children. The part of the population from receiving percent of all childhood deaths are from widespread distribution, however, has nets. These are valuable debates. Before malaria. Pregnant women who contract not resulted in a signiﬁ cant decrease in delving into behavioral economics, the mosquito-borne disease can develop malaria. Many doctors in sub-Saharan though, it might be useful to consider a severe anemia and give birth to under- Africa attribute the failure to an overreli- more basic problem: the mosquito nets weight babies. The World Health Organi- ance on nets in lieu of other interventions, are poorly designed. zation estimates that 10,000 pregnant such as the indoor spraying of dwellings The bed nets distributed by govern- woman and 200,000 infants in Africa die with insecticide. Other experts say the ments and international organizations

from malarial infections every year. problem is the misuse of mosquito nets; have one of two basic designs: circular or COLLINS MATT BY ILLUSTRATION BORLAND; JAMES BY PHOTOGRAPH

THE EDITORS’ BL8G For more posts from SciAm Observa- tions, see www.SciAm.com/blog

continued from page 34

women, homosexuals and the obese, to name a few—now comes his decision to join hands with the transistor-developing, eugenics-advocating, sperm-donating William Shockley, who, I recall, blamed his wife’s genes for his kids being less than genius. As a geneticist, Watson arguably has better credentials to rant about race and IQ than Shockley. But that still doesn’t make him an expert on IQ studies. It’s true that blacks have historically scored 15 points lower than whites on IQs. What’s been debated endlessly is how much is tied to heredity and how much to environment. Intelligence researchers such as James Flynn have found that IQ can change over rectangular. The circular design hangs young children would be a net that does time, suggesting a strong environmental from the ceiling by one string, with the not hang at all. One possibility would be infl uence. Others, such as Philippe Rushton net fanning out from a ring at the top a collapsible, tentlike structure, very and Linda Gottfredson, say the data are at and tucked tightly under the mattress on similar to the crawl-through children’s least as consistent with hereditarian arguments as they are with environmental all sides. The rectangular design ties to toys that clutter so many playrooms in ones. I don’t want to get into a whole the ceiling with four strings and hangs the U.S. The challenge would be to make discussion about IQ again—we’ve covered straight down on all sides of the bed, the structure both affordable to produce it a lot in this magazine (see, for instance, with the fringes again tucked under the and durable enough to be used daily for “Unsettled Scores” [February 2007] and our mattress. Both designs work well for years. In addition to being user-friendly, Intelligence special issue [Scientifi c middle-class homes with flat ceilings this free-standing mosquito net would American Presents, Winter 1999]). But and a bed for every member of the fam- have to be sized for children to ensure while I’m at it, one question I have for the ily. But most of the poor in sub-Saharan that it is used by the intended recipients hereditarians: How do you separate genetic Africa, especially in rural areas, live in rather than older, hardier members of explanations from womb conditions—a mud huts, often with thatched roofs. the family. crucial environmental factor? Hanging mosquito nets is very diffi - Mosquito nets have been changed Without having mucked around in the cult in these homes, and most people before to meet user needs. Several com- morass that is IQ research, Watson can at prefer the circular nets because they are panies have recently introduced nets that best be only a casual observer. He’s reportedly dim about the prospects of easier to hang. Although the rectangular are impregnated with long-lasting insec- Africa because of that continent’s lower nets can be used without a bed, the cir- ticide, eliminating the need for people to intelligence test scores. What—cultural cular nets cannot, because they have to continually apply fresh coatings of confl icts, religious attitudes and greed are be tucked under the mattress to fan out. chemicals to the nets. Companies must less important? That’s hard to justify when In many African communities, most continue to improve mosquito nets if you look at what’s going on in different children younger than fi ve sleep on the progress is to be made in combating parts of the world right now. fl oor, so only the rectangular nets would malaria. And once better nets are avail- Yet because of his Nobel and past be effective. But the rectangular nets able, researchers will be able to objec- accomplishments as a geneticist, Watson’s take up quite a bit of room in a mud hut tively judge the effectiveness of the dis- words take on added meaning and weight and have to be taken down and rehung tribution programs. g beyond what they deserve. Winning the every night for the hut to be of use dur- Nobel grants a great deal of power. Too bad ing the day. Given the diffi culty of hang- Eva Kaplan is a writer and consultant Watson didn’t channel Stan Lee and ing the nets, it is unreasonable to expect who has managed research projects recognize that with great power comes people to follow this routine. focused on disease prevention in great responsibility.

MATT COLLINS MATT A design more suited to the needs of sub-Saharan Africa.

Skeptic Evonomics Evolution and economics are both examples of a larger mysterious phenomenon BY MICHAEL SHERMER

Living along the Orinoco River that borders Brazil and Venezuela are the Yanomamö people, hunter-gatherers every aspect of whose average annual income has the economy. But just been estimated at the equivalent of $90 as living organisms are per person per year. Living along the shaped from the bottom up by Hudson River that borders New York natural selection, the economy is mold- State and New Jersey are the Manhattan people, con- ed from the bottom up by the invisible hand. sumer-traders whose average annual income has been The correspondence between evolution and eco- estimated at $36,000 per person per year. That dramatic dif- nomics is not perfect, because some top-down institution- ference of 400 times, however, pales in comparison to the differ- al rules and laws are needed to provide a structure within which ences in Stock Keeping Units (SKUs, a measure of the number of free and fair trade can occur. But too much top-down interference types of retail products available), which has been estimated at into the marketplace makes trade neither free nor fair. When such 300 for the Yanomamö and 10 billion for the Manhattans, a dif- attempts have been made in the past, they have failed—because ference of 33 million times! markets are far too complex, interactive and autocatalytic to be How did this happen? According to economist Eric D. Bein- designed from the top down. In his 1922 book, Socialism, Lud- hocker, who published these calculations in his revelatory work wig von Mises spelled out the reasons why, most notably the prob- The Origin of Wealth (Harvard Business School Press, 2006), lem of “economic calculation” in a planned socialist economy. In the explanation is to be found in complexity theory. Evolution capitalism, prices are in constant and rapid fl ux and are deter- and economics are not just analogous to each other, but they are mined from below by individuals freely exchanging in the mar- actually two forms of a larger phenomenon called complex adap- ketplace. Money is a means of exchange, and prices are the infor- tive systems, in which individual elements, parts or agents inter- mation people use to guide their choices. Von Mises demonstrat- act, then process information and adapt their behavior to changed that socialist economies depend on capitalist economies to ing conditions. Immune systems, ecosystems, language, the law determine what prices should be assigned to goods and services. and the Internet are all examples of complex adaptive systems. And they do so cumbersomely and ineffi ciently. Relatively free In biological evolution, nature selects from the variation pro- markets are, ultimately, the only way to fi nd out what buyers are duced by random genetic mutations and the mixing of parental willing to pay and what sellers are willing to accept. genes. Out of that process of cumulative selection emerges com- Evonomics helps to explain how Yanomamö-like hunter-gath- plexity and diversity. In economic evolution, our material econ- erers evolved into Manhattan-like consumer-traders. Nine- omy proceeds through the production and selection of numerous teenth-century French economist Frédéric Bastiat well captured permutations of countless products. Those 10 billion products the principle: “Where goods do not cross frontiers, armies will.” in the Manhattan village represent only those variations that In addition to being fi erce warriors, the Yanomamö are also made it to market, after which there is a cumulative selection by sophisticated traders, and the more they trade the less they fi ght. consumers in the marketplace for those deemed most useful: The reason is that trade is a powerful social adhesive that creates VHS over Betamax, DVDs over VHS, CDs over vinyl records, political alliances. One village cannot go to another village and flip phones over brick phones, computers over typewriters, announce that they are worried about being conquered by a third, Google over Altavista, SUVs over station wagons, paper books more powerful village—that would reveal weakness. Instead over e-books (still), and Internet news over network news (soon). they mask the real motives for alliance through trade and recip- Those that are purchased “survive” and “reproduce” into the rocal feasting. And, as a result, not only gain military protection future through repetitive use and remanufacturing. but also initiate a system of trade that—in the long run—leads to As with living organisms and ecosystems, the economy looks an increase in both wealth and SKUs. g designed—so just as humans naturally deduce the existence of a top-down intelligent designer, humans also (understandably) Michael Shermer is publisher of Skeptic (www.skeptic.com).

PHOTOGRAPH BY BRAD SWONETZ; ILLUSTRATION BY MATT COLLINS infer that a top-down government designer is needed in nearly His latest book is The Mind of the Market (Times Books).

Anti Gravity What’s in a (Latin) Name? The special genius behind the species and genus BY STEVE MIRSKY

The greater roadrunner is offi cially classifi ed as with Brassica oleracea (Capitata Group) is even nuttier (Berthol- Geococcyx californianus. The lesser roadrun- letia excelsa) in Latin. Preventing mix-ups is one reason why ner is Geococcyx velox. And the more familiar Linnaeus’s system comes in so handy: French president Nicolas cartoon Road Runner (beep beep) has been Sarkozy might call it a moineau, Spain’s King Juan Carlos might designated on different occasions as Accelerati call it a gorrión, and Vice President Dick Cheney might (or might incredibilus, Velocitus tremenjus, Birdibus zip- not) call out “fi re in the hole” before trying to blow it out of the pibus, Speedipus rex and Morselus babyfatious sky, but the bird in question would be recognizable to all their tastius. Consistently unsuccessful in his attempts to catch Fasti- science advisers as Passer domesticus. Which is also known in us tasty-us is Wile E. Coyote, himself variously classifi ed as a English as the house sparrow. And because common species representative of the species Carnivorous slobbius, Eatius bird- names, even within a single language, lack the authority of the ius, Overconfi dentii vulgaris, Poor schinookius or Caninus ner- offi cial Linnaean designations, the house sparrow is also known vous rex. (Real coyotes are Canis latrans, which sounds like a in English as the English sparrow. Help, is there a taxonomist in bathroom used by Roman legionnaires.) the house? So who do we, and the Looney Tunes folks, have to Linnaeus’s twin great works were the 1753 Species thank for setting the ground rules that led to all this Planterum, in which he classifi ed all the known highfalutin Latinate humor? None other than Swedish species of vegetation, and the naturalist Carl Linnaeus, who was so in love with 1758 Systema Naturae, which naming things that he gave himself a few more: Carl celebrates its 250th anniversary Linné, Carl von Linné, Carolus Linnaeus and Car- this year and which was the fi rst oli Linnaei, the name by which he proposed the major effort at organizing the standard genus-species system of taxonomic animal world. The Wikipedia binomial nomenclature still used to keep track entry on Linnaeus notes that because of all that life out there. The year 2007 was of his habit of naming all the living the tricentennial of Linnaeus’s birth, which things he encountered, “he thought shows that some people’s contributions of himself as a second Adam.” The give them a postmortem vita that’s not at cover of Systema Naturae shows a all brevis. man, presumably Linnaeus, toss- American journalist and wag H. L. ing Latin titles to “new creatures Mencken paid unwitting tribute to Linnae- as they are created in the Gar- us’s classifi cation scheme when he dubbed a den of Eden.” No shrink- large percentage of the U.S. population ing member of the genus Boobus americanus. (Don’t worry, he Viola was he. meant the other guys, not you.) Mencken Linnaeus appears to described the perpetually bamboozled have occasionally abused B. americanus as “a bird that knows no closed his absolute appellative power. season,” which coincidentally describes the Road The New York Botanical Gar- Runner, also known as Disappearialis quickius. Mencken, by the den, which hosted a rare public display of Linnaeus’s own anno- way, covered the famous Scopes trial, in which some Homo sapi- tated copy of the Systema Naturae last November, notes on its ens treated the notion that they were related to Gorilla gorilla and Web site that “he got revenge on his critics by naming unpleasant Pan troglodytes like it was a Yersinia pestis infection. plants and animals after them. For example, he named Sieges- Among Mencken’s many pithy comments about H. sapiens is, beckia, an unattractive Asian weed that exudes foul-smelling liq- “An idealist is one who, on noticing that a rose smells better than uid, for German botanist Johan Siegesbeck.” So Linnaeus was a cabbage, concludes that it will also make better soup.” And in probably a pain in the Equus asinus. But without him, biology

fact, mixing up any of the numerous species of the genus Rosa could not have become big-name science. g COLLINS MATT BY ILLUSTRATION LARSEN; FLYNN BY PHOTOGRAPH

40 SCIENTIFIC AMERICAN January 2008 © 2007 SCIENTIFIC AMERICAN, INC. Technological overoptimism lurks as a persistent risk to both profes- TRENDS sional and amateur watchers of advances, from artiﬁ cial intelligence to the ﬂ ying car. But sometimes new technologies actually live up to ■ Wireless Power some of the wildest expectations for them.

■ Drug Delivery This year’s SciAm 50 awards are replete with instances of new ■ Sustainable Fuels machines or chemicals that come close to the true meaning of innova- tion as something entirely new. One winner has created an instrument ■ Toxic Housewares that measures ﬂ uids in zeptoliters, or sextillionths of a liter. (You know, ■ Ultrameasurement the zeptoliter, the measurement unit that is 1,000th of an attoliter?) ■ Malaria-Free Mosquitoes Another innovator has devised a method that could recharge a phone ■ Bioinspired Materials without plugging it in. All you would have to do is sit at the dining ■ Diagnosing Alzheimer’s room table, phone in pocket, a few feet away from a recharging coil ■ Optical Chips hidden in the ceiling. Still another visionary is paving the way for treat- ■ Prion Disease Treatments ing mysterious and deadly prion diseases such as mad cow and kuru. ■ Sun Power Award winners highlighted here have the potential to contribute ■ Understanding Stem Cells much more to human health, consumer electronics and numerous other ﬁ elds than if they were simply offering another antidepressant that ■ Chip Printers tweaked serotonin levels or ratcheting up the speed of a microproces- ■ Prosthetics sor. What they have done is decidedly new. ■ Intelligent Route Finders —The Editors

www.SciAm.com SCIENTIFIC AMERICAN 41 © 2007 SCIENTIFIC AMERICAN, INC. SCIAM 50 RESEARCH LEADER OF THE YEAR The Wellcome Trust Case Control Consortium U.K. A massive genetic study turns up the complex roots of major diseases

ith genetic scientifi c advances reported almost daily, it anomalies. Some of the signals were in coding regions of genes; W sometimes seems as if we are merely waiting for research- some were in noncoding regions that might regulate other ers to discover the gene at fault for every human disease. The genes; and some were in “gene deserts”—noncoding regions complex genetic basis of many common diseases, however, with no identifi ed function. The variants themselves may not complicates prediction, diagnosis and treatment. actually be responsible for the diseases. But they serve as sign- The Wellcome Trust Case Control Consortium (WTCCC), posts for other researchers to investigate DNA at a fi ne scale. a constellation of more than 50 British research groups, took on Every person possesses a certain pattern of “polymorphisms” the mammoth challenge of ferreting out the causes of diseases in the six billion nucleotides of their genomic DNA—three bil- in which multiple genes are implicated. Last June they reported lion for each of the two sets of chromosomes. The statistical the fi ndings of a study that scanned for specifi c gene variations pattern of how these variations occur, provided by studies such among 17,000 British citizens: 2,000 each from patient groups as the one conducted by the WTCCC, will help physicians cal- diagnosed with bipolar disorder, coronary heart disease, Crohn’s culate the chances that a patient could develop symptoms of a disease, rheumatoid arthritis, hypertension and diabetes types hereditary disorder. The ultimate goal of this research is per- 1 and 2, as well as 3,000 unaffl icted who served as a control sonalized medicine in which patients submit a blood sample group. The large scale of the study was unprecedented and so and have their entire set of genes analyzed to determine predis- was the payoff: 24 locations in the genome were found to be position to chronic diseases, the best food and exercise regi- associated with six of the seven diseases. mens to stay healthy, and which drugs and dosages will be most The WTCCC compared the genomes of each affected group effective when illness does strike. —Kaspar Mossman with those of the controls and zeroed in on locations where

GENOME-WIDE SCANS turned up gene variants associated with dis- ) DNA bases differed between the two groups. The size of the ease, such as those for type 1 diabetes, shown as green highlights bottom study was essential in enabling the researchers to spot rare on a representation of chromosomes. ( CASE CONTROL CONSORTIUM,

TYPE 1 DIABETES NCMIR/Photo Researchers, Inc. Inc. Researchers, NCMIR/Photo

BUSINESS LEADER OF THE YEAR

SCIAM 50 ); THOMAS DEERINCK top Amyris Biotechnologies Emeryville, Calif. The emerging ﬁ eld of synthetic biology provides candidates for a new generation of biofuels

thanol is not the most energy-dense burned in modern engines and would be E of fuels nor the cheapest. Consequent- compatible with the existing petroleum ly, Amyris Biotechnologies in Emeryville, infrastructure. Then the company used Calif., has come up with a potentially custom-designed microbes to produce better solution. It did so by starting with the new fuels by fermentation from a a long roster of organic compounds from conventional ethanol feedstock.

which it chose potential replacements for To create the novel strains was no YEAST microbes, once genetically engin eered, VOL. 447; JUNE REPRINTED 2007. 7, BY PERMISSION OF MACMILLAN PUBLISHERS LTD. ( gasoline, diesel and jet fuel that could be small genetic feat. The task required sub- can boost biofuel yields dramatically. NATURE, NATURE, FROM “GENOME-WIDE ASSOCIATION STUDY OF 14,000 CASES OF SEVEN COMMON DISEASES AND 3,000 SHARED CONTROLS,” BY THE WELLCOME TRUST IN IN

42 SCIENTIFIC AMERICAN January 2008 © 2007 SCIENTIFIC AMERICAN, INC. stantial alterations to the yeast genome. Economic Forum as a Technology Pio- more valuable: a fuel end product has to Genes from the original plant source and neer, is now close to its goal of supplying be cheap enough to burn. Amyris will two other organisms were inserted, and cheap industrial quantities of artemis- have to optimize each microbial strain so a preexisting biochemical pathway was inin to developing countries. that it cranks out fuel without poisoning carefully adjusted. The engineered yeast Amyris decided that its expertise itself and produces enough fuel molecules boasted a millionfold increase in yield. could prove equally profitable when so that it is economically worthwhile to A leader in the emerging ﬁ eld of syn- applied to biofuels. It initiated a search grow. In the history of the large-scale thetic biology, Amyris is well known for for fuels that could be produced in the chemical industry, the subtlety of techni- developing a strain of yeast for large-scale lab and that met criteria on energy con- cal expertise involved in this project is manufacture of a precursor to the antima- tent, volatility and water solubility. without precedent. Yet Amyris, which larial drug artemisinin, for which the The difference between engineering last June added several oil industry veter- Asian plant source is in short supply. The microbes to produce drugs versus fuel is ans to its management, has shown that it company, chosen in 2006 by the World that, ounce for ounce, drugs are much means business. —Kaspar Mossman

SCIAM 50 POLICY LEADER OF THE YEAR

X Prize Foundation Santa Monica, Calif. The lure of multimillion-dollar prizes prompts inventors to pursue breakthroughs in space travel, DNA sequencing, automotive fuel efﬁ ciency, and robotics

n 1927 the aviation world marveled at Charles A. Lindbergh’s Archon X Prize is Stephen Hawking, the renowned theoretical I nonstop fl ight from New York to Paris. Lindbergh was in it for physicist who suffers from amyotrophic lateral sclerosis. more than thrills: he was after the $25,000 Orteig Prize. In a 21st- Last April the foundation also offered the Automotive X century encore, the 12-year-old nonprofi t X Prize Foundation Prize, for the fi rst 100-mile-per-gallon production car. And in conceives and manages competitions for daring innovators. September the group announced the $30-million Google Lunar The foundation’s game plan is to defi ne an exciting target X Prize purse for the fi rst private groups to land spacecraft on that benefi ts humanity, bait it with a large stack of cash, and the moon. Money may be an object for some, but there is no draw out the best in design and invention from private, nongov- doubt that the challenges set by the X Prize Foundation light a ernmental teams. The competitors, the thinking goes, will fi re under innovators worldwide. —Kaspar Mossman invest much more in technology chasing the prestige of the prize than the foundation will hand out at the awards ceremony. Events have borne out this prediction. The foundation set a goal in 1995 “to make space travel safe, affordable and accessible to everyone through the creation of a personal spacefl ight industry.” In 2004 Mojave Aerospace Ventures won the Ansa- ri X Prize as the fi rst team to build a space plane that could reach low-Earth orbit, return to Earth and repeat the fl ight within two weeks. Twenty-six teams entered the contest and collectively spent more than $100 million on research. The second prize, which the foundation offered in late 2006, is the $10-million Archon X Prize, for the fi rst private team to sequence 100 human genomes in 10 days at a cost of less than $1 million. At least four teams have already signed up for the challenge of inventing an instrument that will correctly sequence 98 percent of each genome with no more than 60,000 errors. The winning technology would accelerate deployment of new discoveries such as genome-wide association studies, which analyze large patient groups to identify genes responsible for AMBITIOUS GOALS that benefi t humanity, such as a private robotic complex hereditary diseases. A prominent supporter of the moon mission, serve as the rationale for the X Prize Foundation. COURTESY OF X PRIZE FOUNDATION

www.SciAm.com SCIENTIFIC AMERICAN 43 © 2007 SCIENTIFIC AMERICAN, INC. SCIAM 50 TRENDS IN BUSINESS, POLICY AND RESEARCH Connections to an Untethered Future Delivering electric power through the air cuts the ﬁ nal cord

lthough laptops, cell phones and other gadgets give us up to pay $600 for it. The handheld device combines all the A remarkable mobility, we can roam untethered only for as functions of an advanced mobile phone with those of the latest long as our batteries hold out. Photonics researcher Marin Soljaˇcić iPod, thereby allowing users to wander freely while making of the Massachusetts Institute of Technology wants to eliminate phone calls, accessing the Web, sending text messages and e- that shackle by delivering wireless electricity, or WiTricity. mail, taking photographs, listening to music and watching vid- Soljaˇcic ´ hung a copper coil 0.6 meter (two feet) in diameter eos. Although some earlier phones had offered many of these from a ceiling, then hung another coil about 2.1 meters (seven functions, the iPhone’s full-size “multi-touch” screen gave cus- feet) away, with a 60-watt lightbulb dangling from it. When he tomers far more fl exibility, including use of a standard keyboard for messaging, streaming of YouTube video and a visual list of voice mails—not to mention access to iTunes, by far the dominant online music source. Wireless sensors also gained fl exibility. Reduced to the size of rice grains or dust, they can mount a vigil for chemical and biological weapons or check for moisture content in the soil. Already they are changing how people monitor the world. A major barrier, however, has been how to know if such networks of randomly distributed sensors leave gaps in coverage or if the sensors’ ranges overlap, thus wasting the precious bits of power they may carry. Robert Ghrist, a mathematician at the University of Illinois at The iPhone’s “multi-touch” screen gives the user access to a stan- Urbana-Champaign, and mathematics professor Vin de Silva of dard keyboard, streaming video, music and a list of voice mails. Pomona College harnessed the science of mathematical homology to answer both questions. Homology analyzes the points, plugged the fi rst coil into a power source, the lightbulb on the lines and geometric arrangements within shapes. By treating sen- second coil lit up. Electric current in the fi rst coil established a sors as points, pairs of sensors as edges, and collections of edges magnetic fi eld that induced current in the second one. as shapes, Ghrist and de Silva devised algorithms that can tell Many motors exploit this effect, but normally induction works whether a sprinkled network of sensors overlap or leave gaps. only across gaps of a few millimeters, dying off rapidly with The advantage of Ghrist’s and de Silva’s algorithms is that they greater distance. Soljaˇcic ´ tuned his coils to resonate, allowing effi - only need to know which sensors are within range of one anoth- cient energy exchange over a distance. Future implementations er, not where each sensor actually is; they eliminate the need for of his system might enable laptops and cell phones to recharge expensive global-positioning circuits or the manual mapping of when they are in a room equipped with a resonance emitter. circuits. Knowing the locations of gaps and overlaps, network The human impulse to cut the cord runs deep. Apple released operators could turn up the power of certain sensors or strategi- the iPhone as an ultimate wireless interface, and people lined cally add new ones to fi ll in blank spots. —Mark Fischetti

Getting from Here to There A protein borrowed from the rabies virus gets a drug to where it is needed

s hard as it is for scientists to develop new drugs, some- es, but Manjunath N. Swamy and his team at Harvard Medical A times just getting the drug to where it needs to act is equal- School’s Immune Disease Institute devised a clever way to ly challenging. Nowhere is this more true than in the brain, sneak a drug through and insert it directly into brain cells. where blood vessel walls are tightly knit, keeping most large Some viruses that specialize in infecting the nervous sys- molecules from seeping out of the bloodstream and into brain tem, such as rabies and herpes, are adept at penetrating the tissue. This blood-brain barrier is a formidable obstacle to blood-brain barrier. Swamy’s group exploited that capability delivering certain types of treatments for neurological diseas- by disguising a drug with a small protein normally found © 2007 APPLE, INC. APPLE, INC. 2007 ©

on the surface of the rabies virus. The protein is believed to of a biopolymer cage that can protect or conceal a variety of unlock a passageway through the blood vessel walls, and a substances until their release is desirable. Both the cage mate- drug molecule hitched to the viral protein was able to pene- rial and the trigger to discharge its contents can be tailored to trate the barrier. Once inside the brain, the protein also specifi c situations. allowed the drug to enter individual nerve cells, much as a For instance, Boumans’s group created a germ-killing plas- virus would infect them. The therapeutic molecule used in tic wrap for meat by encapsulating a bactericidal enzyme Swamy’s experiments was a small nucleic acid chain, known inside woven cages of cross-linked starch molecules, then coat- as a short-interfering RNA (siRNA), which can be customized ing the plastic with them. The starch cages remain inert unless to target specifi c genes and suppress their effects, making bacteria are present and start eating the starch, thus degrad- siRNA delivered straight to the brain a versatile tool for a wide ing the cage until—surprise—the killer enzyme is released. A range of uses. similar system could allow unstable food-fl avoring molecules The same can be said of another tiny Trojan horse built by to remain encased until they contact enzymes on the tongue Hans Boumans and his colleagues at the Netherlands Organi- or foul-tasting nutrients to stay sealed in their cages until they zation for Applied Research. The team’s “BioSwitch” consists reach digestive enzymes in the gut. —Christine Soares

Fueling Alternatives Engineers make progress toward new green fuels and energy storage devices

espite efforts to brew ethanol as a sus- So when James A. Dumesic and his fel- on the electrode’s surface from oxidiz- D tainable automotive fuel substitute for low chemical engineers at the University ing, which slows down power-generating gasoline, the plant-derived alcohol has its of Wisconsin–Madison developed a chemical reactions and also often causes drawbacks. A gallon (3.8 liters) of etha- straightforward way to extract a syn- its membrane to degrade, rendering the nol, for one, contains almost a third less thetic fuel from sugar that in many ways cell useless. By spraying the electrode energy than the same volume of gasoline. surpasses ethanol, the scientifi c commu- with nanoparticles of gold, Adzic’s team nity took notice. Called 2,5-dimethylfu- made the platinum layer resistant to dis- ran, or simply DMF, the fuel possesses solving and helped it retain most of its an energy density equivalent to that of original catalytic effi cacy. gasoline. It is also insoluble in water and To produce electricity, most PEM fuel stable in storage. Although chemists have cells must be supplied either with hydro- long known about the compound, vol- gen or with hydrocarbon compounds ume production has been tricky. The that can be catalytically decomposed new two-step process makes improve- into hydrogen. Some prototype fuel cells, ments in an intermediate manufacturing however, resemble biological cells in that 2 nanometers step that was a barrier to mass produc- they use chemical enzymes to break tion of DMF. down sugars—a special class of hydro- Beyond fi nding new alternative fuels carbon molecules—to generate electrons. for internal-combustion engines, re- Unlike living cells, they typically soon searchers are working on fuel cells that run out of the enzymes necessary to sus- offer another path toward environmen- tain the reaction. tally acceptable power. The key to an Electrochemist Shelley D. Minteer and

VOL. 315; 2007. REPRINTED WITH PERMISSION OF AAAS OF PERMISSION WITH REPRINTED 2007. 315; VOL. effective hydrogen, or proton-exchange her colleague Tamara Klotzbach, both at membrane (PEM), fuel cell is the micro- Saint Louis University, have developed a SCIENCE, thin coating of platinum particles on method to replenish the enzymes in a the positively charged electrode, where sugar-powered fuel cell as they degrade oxygen molecules split into individual with use. The researchers have come up charged atoms. with a polymer wrapping for an enzyme, 3 nanometers Chemist Radoslav R. Adzic and his which keeps the catalytic molecule active Gold clusters (circles) retard the oxidation team at Brookhaven National Laborato- for months instead of days. of a platinum catalyst in a fuel cell. ry have found a way to stop the platinum —Steven Ashley FROM “STABILIZATION OF PLATINUM OXYGEN REDUCTION ELECTROCATALYSTS USING GOLD CLUSTERS,” BY J. ZHANG, ZHANG, J. BY CLUSTERS,” GOLD USING ELECTROCATALYSTS REDUCTION OXYGEN PLATINUM OF “STABILIZATION FROM IN ADZIC, R. R. AND SUTTER SASAKI, E. K.

www.SciAm.com SCIENTIFIC AMERICAN 45 © 2007 SCIENTIFIC AMERICAN, INC. SCIAM 50 TRENDS IN BUSINESS, POLICY AND RESEARCH Fighting Toxins in the Home Everyday materials may pose health and environmental threats

esearchers are continually fi nding new evidence that com- Unused pharmaceuti- R mon items in our kitchens, bathrooms and toy chests can cals are a particularly make us sick. One of the most insidious substances is bisphenol serious threat because A, a component of the light plastics used in baby bottles and consumers often fl ush Ordinary plastic items may many other consumer products. Over the past several years, sci- them down the toilet, send- cause sickness. entists have reported that low levels of bisphenol A can disrupt ing the potent molecules cell division, leading to spontaneous miscarriages and birth into rivers and lakes. Discarded birth-control pills can trigger defects such as Down syndrome. reproductive problems in fi sh, and surplus antibiotics can In early 2007 a team led by Patricia A. Hunt of Washington enhance the spread of bacteria that are resistant to the drugs. State University found that small amounts of bisphenol A inter- In an attempt to tackle this problem, the American Pharmacists fered with the growth of egg cells in developing female mouse Association and the U.S. Fish and Wildlife Service signed an embryos. As many as 40 percent of the eggs from fetuses agreement last year to launch a public-awareness campaign to exposed to bisphenol A had an abnormal number of chromo- change consumer habits. When people pick up their prescrip- somes. This stunning fi nding showed that the chemical’s effects tions, they will be advised to dispose of their unused pharma- can run through three generations: the pregnant mother’s expo- ceuticals through hazardous-waste collection programs. If sure damages the daughter’s reproductive cells, which in turn such programs are not locally available, the next best option is disrupts the development of the daughter’s own children. crushing and diluting the medicines, then sealing them in plas- The National Toxicology Program, which is part of the tic bags and dumping them in the trash. (Some narcotic drugs National Institutes of Health, is currently reviewing the safety of will be exempt from the recommendations because of the risk bisphenol A. In the meantime, some physicians advise pregnant that addicts will retrieve the pills from garbage cans.) women to avoid drinking water from plastic bottles, especially An even better solution would be the establishment of incen- once the containers become visibly scratched or scuffed, which tives to encourage consumers to return their unused drugs to may indicate that they are leaching the hazardous chemical. pharmacies. Pilot programs of this type are now operating in Toxic household items also pose a danger to the environment. California, Washington State and Maine. —Mark Alpert

Advances in Ultrameasurement )

Zeptoliter pipettes and quantum rulers give new meaning to the word “small” bottom

cientists use pipettes when they need S to dispense well-deﬁ ned volumes of liquid. Existing pipettes can deliver ﬂ uid volumes as small as an attoliter—a quin- tillionth, or a billionth of a billionth, of a liter. Physicists Peter W. Sutter and Eli A. Sutter of Brookhaven National Lab- oratory have broken that lower limit by

constructing a pipette that metes out a ( LABORATORY NATIONAL BROOKHAVEN OF COURTESY ); top droplet measured in a unit that is a thou- ( sandth as small—a zeptoliter (a sextil- lionth of a liter). Such a minute volume Design Pics/Corbis Pics/Corbis Design Eli A. Sutter and Peter W. Sutter built the world’s smallest pipette, which helped to show that droplets of liquid metal freeze differently than scientists expected. KRISTY-ANNE GLUBISH GLUBISH KRISTY-ANNE

can contain as little as 10,000 to as much ments—has allowed physicists at Hokkai- as a million atoms of metal. do University in Japan and the University The researchers used a germanium of Bristol in England to almost double the nanowire with a solid reservoir of gold- precision of measurement when using germanium alloy at one end. They encap- photons to gauge distances. sulated the two-micron-long assembly in The scientists have built on previous a carbon shell, which constituted the work that uses photons “entangled” in pipette. Inside a vacuum chamber, they the same quantum superposition of heated and melted the alloy and then states. The team directed two photonic aimed an electron beam at the shell’s tip. pairs into an interferometer—an instru- The beam bored an escape hole for the ment that creates a circular beam path molten metal, which formed a minuscule with mirrors in which light waves inter- droplet up to 40 nanometers in diameter fere with one another. Each photon Entangled photons in an interferometer and 35 zeptoliters in volume. splits, taking separate paths simultane- make ultraprecise measurements. If measuring things in zeptoliters is ously. Four photons in an entangled state difficult, consider doing so at a scale circulate around the interferometer in how far each quadruplet has traveled. where the rules of classical physics cease one direction, and another quadruplet The precision measurements could, to prevail. Quantum metrology—the traverses the loop in the other. The inter- for example, be useful when using lasers field in which quantum mechanics is ference produced by the countercirculat- to etch ultrathin circuits on computer

); ); used to obtain highly precise measure- ing photons reveals tiny differences in chips. —Steven Ashley top

Mosquitoes Enlisted to Beat Malaria Bugs engineered to avoid transmitting the disease could outcompete bugs that do transmit it

alaria still kills more than a million Anopheles that directs production of a ogy presented evidence that engineered M people a year. Even though low-tech peptide called SM1, which manifests in genes can indeed spread throughout a measures such as spraying insecticides the mosquito’s gut and prevents malaria bug population. Working with fruit ﬂ ies,

VOL. 316; 2007. REPRINTED WITH PERMISSION OF AAAS OF ( PERMISSION WITH REPRINTED 2007. 316; VOL. and distributing treated bed netting to parasites in rodents from reproducing. Hay’s team combined a segment of non- residents can reduce infection rates, poor The Johns Hopkins team put the trans- coding RNA, known as a microRNA, SCIENCE, countries, where most victims live, cannot genic and natural with a gene that was afford them. mosquitoes in cages critical to the develop- As an alternative strategy, researchers with malaria-infect- ment of fruit fl y embry- have tried for years to genetically engi- ed mice, on which the os; the researchers then neer mosquitoes so they will not transmit mosquitoes fed. Over altered that gene so that the disease. Malaria is caused by proto- time the mosquitoes it was unaffected by the zoan parasites that reproduce inside reproduced. After RNA. Next they re- human liver and red blood cells and are nine generations, leased the fruit fl ies into passed from person to person by female transgenic bugs made cages with three times Anopheles mosquitoes. Although several up 70 percent of the Mosquitoes can be genetically as many normal flies. engineered to avoid passing malaria research teams managed to insert genes overall population. to humans. As generations mixed, ) into lab-bred mosquitoes that made the The disease-resistant wild fl ies that incorpo- bottom ( bugs less hospitable to the parasites, the strains not only competed with the wild rated the microRNA died because it altered strains did not reproduce or sur- ones but survived better. destroyed their unprotected version of the vive as well as wild strains did. The test did not prove that infection- critical developmental gene, whereas fl ies But last March microbiologist Marcelo resistance genes would spread in the wild, that bore the altered version of that gene Jacobs-Lorena of Johns Hopkins Univer- but it raised hope that mosquitoes doped were able to survive. After nine to 11 gen- Photo Researchers,Photo Inc. sity announced results indicating that with those genes would survive. Hardly a erations, all the offspring in the cage car- engineered insects could outsurvive wild month later, however, biologist Bruce A. ried the human-made gene combination. ones. Jacobs-Lorena inserted a gene into Hay of the California Institute of Technol- —Mark Fischetti FROM “BEATING THE STANDARD QUANTUM LIMIT WITH FOUR-ENTANGLED PHOTONS,” BY T. NAGATA ET AL., IN IN AL., ET NAGATA T. BY PHOTONS,” FOUR-ENTANGLED WITH LIMIT QUANTUM STANDARD THE “BEATING FROM SINCLAIR STAMMERS

www.SciAm.com SCIENTIFIC AMERICAN 47 © 2007 SCIENTIFIC AMERICAN, INC. SCIAM 50 TRENDS IN BUSINESS, POLICY AND RESEARCH Material World Scientists take inspiration from nature and instill novel magnetic properties

ut your fi nger, and your body starts measuring about a millimeter across cut Ontario and their co-workers have pro- C mending the wound even before you out of a rubbery polymer a mere 40 to 80 duced a new class of magnets that com- have had time to go and fi nd a Band-Aid. microns thick. Thanks to the way that bine nickel with a variety of organic Synthetic materials are not so forgiving, surface tension scales with size, the tech- compounds. The dark, powdery sub- but Nancy R. Sottos, Scott R. White and nique may be effective for self-assem- stances remain magnetized up to 200 their colleagues at the University of Illi- bling micron- or nanometer-scale objects degrees Celsius. The researchers’ ulti- nois at Urbana-Champaign are looking made of thinner sheets of polymer. mate goal is to produce magnetic organ- to change all that. They developed a self- Electronic components based on plas- ic compounds that can be easily molded healing plastic that contains a three- tic or organic materials have become into thin fi lms or other useful shapes for dimensional network of microscopic electronics. capillaries fi lled with a liquid healing It was thought that the only way to agent. When the material is cracked, the see the exotic state of matter known as a released fl uid is hardened by particles of Bose-Einstein condensate—in which a a catalyst that are also sprinkled through- collection of particles essentially behaves out. The new material can repair minor as one superparticle—involved forbid- cracks up to seven times at each location, ding, near-absolute-zero cold. Sergej improving on the group’s previous sys- Demokritov of the University of Muen- tem (in which the fl uid was located in ster in Germany and his colleagues were individual pockets) that could repair the fi rst to create such condensates at only one injury at each place. room temperature. Demokritov used Another feature of natural organisms small, ephemeral packets of magnetic that scientists have been seeking to emu- When cracked, the plastic cube releases a energy known as magnons, which he self-healing agent from its microvascular late is self-assembly. Benoît Roman and network—up to seven times at one location. generated in yttrium-iron-garnet fi lms José Bico of the City of Paris Industrial by exposing them to microwaves. Mag- Physics and Chemistry Higher Educa- increasingly common in recent years, nons are far less massive than atoms and tion Institution used the surface tension but the same cannot be said for magnets. thus can form condensates at much high- of evaporating water droplets to fold Now Robin G. Hicks of the University of er temperatures. fl ea-size origami cubes, pyramids and Victoria in British Columbia, Rajsapan —Graham P. Collins and other structures. Their work used shapes Jain of the University of Windsor in Charles Q. Choi

Neurological Insights Biologists devise a memory on a chip and new ways to tackle Alzheimer’s

ow does a memory form? To demon- After some time, the neurons began to fi re proteins that combines advanced instru- H strate how this process occurs at the in the same way without chemical activa- mentation with sophisticated image pro- most basic level, biophysicists at Tel Aviv tion—the point at which they claim a cessing to inspect one-millimeter cubes University replicated that event with neu- memory becomes imprinted. of brain tissue from a pair of normal rons attached to a computer chip. Itay Understanding differences between mice. The investigators determined the Baruchi and Eshel Ben-Jacob placed neu- the proteins made by normal and dis- abundance of 1,028 proteins in the tis- rons from rat embryos on a chip surface eased brain tissues may provide a new sues. Future experiments will use this and connected 64 electrodes to record approach to diagnostics. Richard D. Smith methodology to compare normal brain activity. The researchers witnessed an of the Pacifi c Northwest National Labo- tissue with that affl icted by a neurode- identical pattern of nerve fi rings when ratory and Desmond J. Smith of the Uni- generative disease. University of Illinois at Urbana-Champaign at Illinois of University chemical stimulants were dropped repeat- versity of California, Los Angeles, have Better diagnostic techniques are need- edly at the same location on the chip. created a complex system for analyzing ed, in particular, for Alzheimer’s disease. ROB SHEPHERDROB

Stina M. Tucker, Esther Oh and Juan C. Troncoso of the Johns Hopkins University School of Medicine demonstrated a test using antibodies that bind to the amyloid-beta proteins that form damaging plaques in the brains of Alzhei mer’s patients. The antibodies adhered to proteins in an early stage of a disease that mimics Alzheimer’s in genetically engineered mice. That ﬁ nding might eventually lead to a test for humans that could be used along with drugs under development to avert the disease through preventive treatment. Conceivably, that test could be combined with a treatment that uses phages—viruses that infect bacteria—to break up nox- ious plaque. Beka Solomon of Tel Aviv University showed preliminary proof of this idea by administering phages via a nasal spray to 100 mice genetically engineered to develop Alzhei- 200 microns mer’s-like plaques. After a year of treatment, the mice had 80 percent fewer plaques than untreated mice. — Gary Stix Electrodes record when neurons ﬁ re so that a memory forms.

Light Manipulation New technologies exercise extraordinary control over light

s computer chips become ever more Another way of delaying light in micro- fi laments about 25 nanometers in diameter A prodigious in their data-processing scopic devices is to use photonic crystal and up to 300 nanometers long—stacked capacities, the task of shuttling all those components, which contain carefully on a transparent semiconductor wafer. gigabits around inside a chip becomes an designed arrays of holes whose size and Each layer had a lower refractive index increasing challenge. Help spacing exclude light in a than the one below it. The uncoated semi- may be on the way in the certain frequency band (a conductor refl ected about 12 percent of form of photonic compo- so-called photonic band light incident on it; when coated, it refl ect- nents, which deal in pulses of gap). A photonic crystal ed as little as 0.1 percent. The coating could light instead of slower pack- wave guide can consist of a have applications in photonic components, ets of electric charge. For sev- path without holes running light-emitting diodes and solar cells. eral years researchers have through such an array in a Other investigators are pursuing the been making so-called sili- thin slab of silicon. The far more speculative goal of building con optical waveguides, in band gap generated by the quantum computers, which would exploit Microscopic loops which light speeds along control light pulses. holes on each side of the weird features of quantum mechanics to inside the ridge between two path confines the light to achieve unprecedented processing capa- channels as if along an optical fi ber. travel that route. Takasumi Tanabe and his bilities. One approach involves storing But such optical interconnects must colleagues at the NTT Basic Research quantum data as long-lived states of deliver their data at precise times, which Laboratories in Japan took this scheme atoms and transmitting the information requires delaying the light pulses by con- several steps forward by temporarily with light waves. But combining those

) trolled amounts. One method is to send storing photons in a photonic crystal two media requires the transfer of delicate

bottom the light pulses into microscopic loops nano cavity—in this case, a small region quantum states between matter and light. made of waveguides where they circulate where the waveguide is slightly wider. In 2006 a group of researchers led by ex- ); IBM ( IBM );

top dozens of times before continuing on Whereas some researchers want to perimentalist Eugene S. Polzik of the Niels their journey. Yurii A. Vlasov and his co- delay light, others at the Rensselaer Poly- Bohr Institute at the University of Copen- workers at the IBM Thomas J. Watson technic Institute led by E. Fred Schubert hagen and theorist Ignacio Cirac of the Research Center in Yorktown Heights, have created a coating that reﬂ ects almost Max Planck Institute for Quantum Optics N.Y., sent pulses of light through strings none of it. The coating, about 600 nano- in Garching, Germany, teleported quan- of as many as 100 such loops without meters thick, consisted of ﬁ ve layers of tum information from a light pulse to a suffering prohibitive losses of data. nanorods—titanium dioxide and silica cloud of atoms. —Graham P. Collins ITAY BARUCHIITAY AND ESHEL BEN-JACOB (

www.SciAm.com SCIENTIFIC AMERICAN 49 © 2007 SCIENTIFIC AMERICAN, INC. SCIAM 50 TRENDS IN BUSINESS, POLICY AND RESEARCH Progress against Prions Ideas for treating the human form of mad cow disease begin to emerge

ore than 200 cases of variant Creutz- mal behav ior patterns. The absence of M feldt-Jakob disease, the human form the natural protein did not appear to of mad cow, have occurred worldwide have an adverse effect on the restored ro- since the 1990s. No accepted treatment dents. If this approach proves itself fur- exists for the devastatingly fatal disease ther, it might lead to drugs or gene thera- or any of the others caused by infection pies that diminish PrP. with the malformed, malignant protein Until that happens, the possibility of particles called prions. Giovanna R. prions infecting people through the Mallucci and her co-workers at the Insti- blood supply remains an ever present tute of Neurology in London have per- fear. Robert Rohwer of the Veterans formed an experiment in mice that could Affairs Medical Center in Baltimore and lay the groundwork for an eventual cure. his colleagues invented a fi lter that might Researchers genetically engineered mice be able to purge red blood cells of prions. to produce the protein PrP for only the The team members began by searching fi rst nine weeks after birth. PrP misfolds through a library of millions of chemi- in the presence of prions, which causes it cals until they discovered a compound, to produce more prions. L13, that readily sticks to prions. Scra- When both the altered mice and a nor- Blood fi lters through beads coated with pie-containing blood filtered through a compound that readily sticks to prions. mal group were injected with prions beads coated with L13 and then injected causing the illness called scrapie, both deteriorate. But by 12 weeks, the engi- into hamsters did not cause disease in the groups experienced a cognitive decline at neered group, without an ongoing supply animals, unlike tainted, unfi ltered blood. fi rst. The normal subjects continued to of PrP, had recovered memory and nor- — Gary Stix

Sun Power Gets a Boost A stolen idea from the plant world could improve prospects for solar power

hotovoltaic cells can generate electricity with- The researchers found that by using this P out adding greenhouse gases to the atmo- spectroscopy technique, they could explain sphere, but solar power is signifi cantly more how plants effi ciently transfer solar energy expensive than the electricity produced by coal- to molecular reaction centers for conver- and gas-fi red plants. To boost the competitive- sion into chemical energy. The previous ness of solar energy, researchers have striven to view of photosynthesis postulated that make solar cells convert sunlight into electricity light-harvesting molecules called chromo- more effi ciently. phores absorbed energy from the sun and Inspiration may come from the most basic sci- then transferred it from one such molecule entifi c research. Investigators are starting to delve to another along one of various possible into the intricacies of photosynthesis, which con- routes until reaching a reaction center. verts sunlight into chemical energy with almost The study found that in contrast to the ) 100 percent effi ciency. A group led by Gregory S. prevailing notion, energy moves in a wave- Engel, formerly at the University of California, like motion along all the pathways in the bottom Berkeley, and now at the University of Chicago, Insights into the photosynthesis sys- system at once, a quantum effect that tem for bacteria (above) and other orga- cooled a green sulfur bacterium to 77 kelvins nisms may improve solar technology. ensures that the energy takes the most effi - ); GREG ENGEL ( ENGEL GREG );

(–321 degrees Fahrenheit) and then zapped it cient route, arriving at its destination almost top with ultrashort pulses from a laser, enabling the tracking of the instantaneously. Eventually this new understanding may become energy ﬂ ow through the bacterium’s photosynthetic apparatus. the basis for an artiﬁ cial photosynthesis process that can be incor- MACOPHARMA ( MACOPHARMA

porated into the design of more efficient photovoltaic cells. cool the building’s interior, depending on the direction of the Other scientists are devising better ways to use sunlight to fl ow of the current. The research group is now investigating the heat and cool buildings. Steven Van Dessel of the Rensselaer Poly- possibility of creating a transparent ABE system using thin-fi lm technic Institute and his colleagues have developed a prototype photovoltaic cells and thermoelectric materials instead of bulky system called the Active Building Envelope (ABE), which couples components. The transparent fi lms could be applied like a glaze solar panels to thermoelectric heat pumps. Electricity produced to the windows of buildings and to the windshields and sunroofs by the solar cells goes to the heat pumps, which can either heat or of cars. —Mark Alpert

Stem Cell Control The essential character of the mother of all cells reveals itself in a set of breakthrough ﬁ ndings

he all-powerful potential of stem trolling the differentiation of ESCs, oth- recycling unhealthy fertilized embryos, T cells to become any kind of cell is ers were focused on fi nding out what which have no other viable use, has what makes them so promising for keeps adult stem cells in an undifferenti- promise as a source of ESCs for research. restoring diseased or damaged tissues ated state. Frank D. McKeon of Harvard Kevin Eggan of the Harvard Stem Cell throughout the body—and also what Medical School showed last year that the Institute and his team used aberrant makes them so diffi cult for scientists to activity of a single gene, known as p63, embryos with extra chromosome sets— control. But several breakthroughs rep- is the key to a cell staying a stem, at least which can occur naturally during in resent major strides toward understand- in epithelial cell types, which include a vitro embryo creation when two sperm ing and harnessing the cells’ elusive prop- variety of tissues such as skin, prostate, fertilize an egg—as stand-ins for the pre- erty of inherent “stemness.” breast and thymus. cious eggs. They found that when the Shinya Yamanaka of Kyoto University, There is no shortage of adult stem chromosomes were removed and new who transformed a regular mouse skin cells for investigators who want to probe genetic material introduced, the result- cell into a cell with most of the charac- their relation to health and disease, but ing embryo developed successfully about teristics of embryonic stem cells (ESCs) that is not true for ESC scientists who as often as embryos made from eggs and by turning up the activity of just four typically must fi rst create embryos from yielded stem cells that were apparently genes, demonstrated recently a more hard-to-procure eggs. A technique for normal. —Christine Soares precise way of isolating cells “reprogrammed” to an ESC-like state—and several other laboratories have replicated his results. Coaxing cultured ESCs to go in the opposite direction—to become skin cells or some other type of tissue—is a tricky process involving the cells’ own gene activity and signals from their surrounding environment. Peidong Yang of the University of California, Berkeley, and Bruce R. Conklin of the Gladstone Insti- tute of Cardiovascular Disease in San Francisco showed a new way to deliver those external signals by growing ESCs embedded with nanoscale silicon wires. Yang and Conklin envision the technique being used to guide the differentiation of stem cells into specifi c tissue types through electrical pulses or chem- University of California, Berkeley California, of University icals transmitted via nanowires. As some researchers worked on con- Nanowires could deliver signals to prompt a stem cell to differentiate into another cell type. PEIDONG YANG YANG PEIDONG

www.SciAm.com SCIENTIFIC AMERICAN 51 © 2007 SCIENTIFIC AMERICAN, INC. SCIAM 50 TRENDS IN BUSINESS, POLICY AND RESEARCH Squirt and Spin Printers squirt out silicon chips, and the spin of electrons is used in computer logic

e now look back with pity on old cent of the original silicon is thrown trons, ignoring the particles’ spin (the W computer printers, with their glacial away. The silicon printer is still fussy and quantum analogue of rotation). The bizz-buzz and annoying perforated-edge does not produce chips with as fi ne a lev- emerging technology of spin-based elec- paper. A decade from now people will el of detail. Nevertheless, it might lower tronics, or “spintronics,” seeks to make surely look back in pity on the things we use of this wasted information. So far its call printers today. Three-dimensional only application has been in hard disks. printers, capable of producing entire Researchers have also sought to exploit objects, are already coming down in price, it in logic gates for computational pro- and new types of printers can output elec- cessing, not least because it takes less tronic circuit boards or even entire func- energy to fl ip an electron’s spin than to tional circuits. Now researchers have a change its direction of motion. The hang- printer that outputs silicon chips. up is that detecting and manipulating The device, created by materials sci- spin requires magnets, which are tricky entist Masahiro Furusawa of Seiko Epson to integrate into silicon circuits. Corporation in Japan and his colleagues, Physicist Hanan Dery of the University squirts out polysilane, a polymer of sili- of California, San Diego, and his col- con and hydrogen. Once laid down, it can leagues have now come up with a work- Transistor made from polysilicon was be baked at kitchen-oven-cleaning tem- literally printed onto a surface. able logic-gate design. A combination of peratures to drive out the hydrogen and fi xed magnets and voltage levels steers leave behind crystalline silicon. The tech- the cost of low-resolution silicon devices electrons based on their spin and the nique provides an alternative to the con- such as display circuitry and solar cells. desired gate function. The team outlined ventional process for producing micro- Gizmo users of the future will also a proposal for a spintronics computer chips, which requires refi ning, stenciling look back in pity on what fl ows through based on the gate, but it remains to be and etching the silicon—a sequence that those circuits. Right now circuits convey seen whether it will work in practice. is both complicated and wasteful: 99 per- signals by the presence or absence of elec- —George Musser )

Making Them Whole bottom Artiﬁ cial limbs and a prosthetic arm create a path to better bionics

esearch on prosthetics takes its greatest strides during or R just after wartime, and the past several years have sadly been no exception. Todd A. Kuiken of the Rehabilitation Insti- tute of Chicago and his team have pioneered “targeted rein- nervation,” which jacks an artiﬁ cial arm into the nervous system. They transplant nerves from the shoulder of a lost arm to a patch on the chest. In trying to move the arm, the person ); COURTESY OF REHABILITATION INSTITUTE OF CHICAGO ( CHICAGO OF INSTITUTE REHABILITATION OF ); COURTESY

causes chest muscles to ﬂ ex, which electrodes pick up and top transmit to the prosthesis. The researchers have begun to experiment with two-way connections, relaying signals from sensors on the arm to sensory nerves. Details about the prosthetic arm by Segway inventor Dean Kamen of DEKA Research & Development Corporation are limited to a YouTube video (www.youtube.com/watch?v=1hz Rja9eunY), but it is jaw-dropping. In a demonstration that Patient at the Rehabilitation Institute of Chicago demonstrates the looks like a scene from Bionic Woman, an engineer wearing manual control that can be achieved with one of his protheses. COPYRIGHT © 2007 SEIKO EPSON CORPORATION (

a prototype arm grasps a water bottle, picks up a pen and scratches his nose. One can only hope that, unlike the Seg- way, it will be priced at a level affordable to all. Every year more than 200,000 Americans tear their knee ligaments, which, as the Mafi a knows, is a painful and hard-to-treat injury. Cato T. Laurencin of the Univer- sity of Virginia and his team have developed polymers that serve as tissue scaffolding, promoting the growth of brand-new ligaments. In tests on rabbits’ knees, the regen- erated ligament supported a third as much tension as a fresh one. To be sure, half the bunnies suffered new rup- tures, but Laurencin attributed this to the diffi culty of convincing them to go through physical therapy. —George Musser Polymer fi bers (shown in cross section) encourage growth of new ligaments. ); ); top The Fastest Way to Get There Novel ways of calculating routes and predicting traffi c jams promise less time in the car

roviding directions instantly online that are sparsely interconnected. Figur- navigational view. With a system of suc- P has until recently meant that naviga- ing the best route occurs by precomput- cessive panoramic snapshots of the sug- tional mapping programs, such as Map- ing the connections between a starting gested route, Google Street View allows Quest and Google Maps, often simplify point (or destination) and its nearest travelers to verify the landmarks they

2007. © 2007 NATIONAL ACADEMY OF SCIENCES USA ( USA SCIENCES OF ACADEMY NATIONAL 2007 © 2007. the problem by not considering every pos- major intersections and between all loca- will encounter from the driver’s seat. sible route to a destination. Scientists at tions where major routes cross each oth- Even with the best directions in hand, the University of Karlsruhe in Germany er’s paths—so-called transit nodes. When unforeseeable traffic can ruin a trip. have designed a computer application that this parsimonious algorithm was tested IntelliOne, a company that explores ways can quickly calculate the most expedient on densely routed maps of western to combine transportation and commu- of all possible driving routes without the Europe and the U.S., the route calcula- nications networks, has recently unveiled need for excessive computation. tions improved by a factor of 100. the Traffi cAid, which translates anony- ) Dominik Schultes, one of the project’s To actually ensure that drivers do not mous cell phone signals into an accurate, scientists, designed the program around go astray on their road excursion, Google real-time traffi c map. bottom right bottom a simple premise: driving somewhere usu- has begun installing an option to its map- By harnessing ubiquitous cellular net- ally requires crossing major intersections ping program that provides a street-level works, the system avoids having to install separate sensors along traffi c routes. Spe- cifi c servers, instead, can detect a phone’s specifi c location and speed. IntelliOne transfers these signaling data to its data- ); INTELLIONE TECHNOLOGIES ( TECHNOLOGIES INTELLIONE ); base, where detected phones are associated with a certain road, thereby produc- bottom left bottom ing accurate and timely information about traffi c conditions. Freed of dependence on traffi c information from video cameras, roadside radars and in-pavement monitors, the Traffi cAid updates its map of bunched signals more quickly and makes a calculation to within fi ve to eight kilometers Street View (left) adds imagery of U.S. cities to Google’s mapping program, whereas (three to fi ve miles) per hour of actual Traffi cAid (right) transforms signals received from cell phones into a real-time traffi c map. speed. —Peter Sergo FROM “BIOMIMETIC TISSUE-ENGINEERED ANTERIOR CRUCIATE LIGAMENT REPLACEMENT,” BY A. COOPER ET AL., PUBLISHED ONLINE FEBRUARY 20, © 2007 GOOGLE IMAGERY/BLUESKY/IMMERSIVE ( MEDIA2 GOOGLE 2007 ©

See-Through Technology and Better Sleep A mix of technology accompanies the doings of a maverick researcher

T-ray Vision down with 3.7 kilograms (eight pounds) n principle, terahertz radiation—which of force when walking and as much as I lies between the microwave and infra- 6.9 kilograms (15 pounds) when run- red segments of the electromagnetic spec- ning. Using pulleys and bungee cords, trum— could help people safely peer the new backpack damps this motion by through fl esh, plastic, fabrics and ceram- half or more. In effect, the pack feels ics to detect anomalies, from tumors to about a fi fth lighter. bombs, for medical or security applica- One version even generates electrici- tions. But for decades, so-called t-ray ty—more than seven watts, enough to devices were impractical outside the lab recharge phones. Rome has set up a com- because they were fragile and because they pany, Lightning Packs, to develop the weighed 45 kilograms (100 pounds) or idea. — George Musser more. Yet after just a few months of work, A new drug may fi ght the parasites that cause schistosomiasis. Brian Schulkin of the Rensselaer Polytech- Better Sleep Aid nic Institute created a rugged t-ray imager bout nine years ago researchers dis- dubbed the “Mini-Z” that is less than 2.3 A covered that the sudden spells of ty of California, San Francisco, and his kilograms (fi ve pounds) in weight and can sleepiness called narcolepsy were caused colleagues have found a new drug that fi t in a briefcase. A prototype detected by a defi cit of a brain peptide called orex- can kill the blood fl ukes that cause the fl aws purposely embedded in samples of in. Actelion Pharmaceuticals in Allschwil, ailment. They investigated the drug foam used to insulate the space shuttle. Switzerland, used this knowledge to cre- K11777, which interferes with the fl ukes’ Schulkin next plans to develop a handheld ate a type of sleeping pill that works by digestive enzymes, and discovered that it t-ray device. —Charles Q. Choi blocking two orexin receptors. Drug tests could eliminate the parasites in lab mice. have shown that the compound known as If effective in humans, K11777 could Load-Lightening Backpack ACT-078573 induces sleep in both ani- work in tandem with praziquantel, with few hardcover textbooks in a school mals and humans. —Gary Stix the former taking care of early-stage ill- A backpack are enough to cause mus- nesses and the latter killing later-stage cle strain. Lawrence C. Rome of the Uni- Antiparasite Weapon infections. —Charles Q. Choi versity of Pennsylvania and of the he debilitating parasitic illness known Marine Biological Laboratory in Woods T as schistosomiasis infects roughly Bird Flu Research for All Hole, Mass., and his colleagues have 200 million people worldwide, making it ntil recently, laboratories doing bird developed a backpack suspension system second only to malaria in importance for U fl u research often kept their fi ndings that minimizes stress on its wearer. As public health. Currently just one drug, private, with access to many avian infl u-

people walk, they typically bob up and praziquantel, commonly treats the enza gene sequences conﬁ ned to just 15 )

down by several centimeters, which chronic disease, raising fears that the facilities globally, potentially hindering right causes a pack to swing up and down. A parasite could evolve resistance against them from doing research that could pro- 2.3-kilogram (fi ve-pound) laptop slams it. Now Conor R. Caffrey of the Universi- vide new insight into the virus. Instead of entering her avian infl uenza fi ndings into Peer-through technology has gone mobile. this database, Ilaria Capua of Vialle Uni- versity in Padua, Italy, disclosed the results of her studies in the publicly accessible GenBank and boldly rallied her colleagues to follow. Her efforts helped to pave the way for the Global Initiative on Sharing Avian

Inﬂ uenza Data, a consortium through ( INC. RESEARCHERS, INSTITUTE/PHOTO CANCER NATIONAL );

which ﬁ ndings can be freely shared while left giving credit to researchers involved. —Charles Q. Choi BRIAN SCHULKIN ( SCHULKIN BRIAN

Research Leader of the Year Material World Stem Cell Control 1. The Wellcome Trust Case Control Consortium 18. Nancy R. Sottos and Scott R. White, 34. Shinya Yamanaka, Kyoto University (research) University of Illinois at 35. Peidong Yang, University of California, Business Leader of the Year Urbana-Champaign (research) Berkeley, and Bruce R. Conklin, 2. Amyris Biotechnologies 19. Benoît Roman and José Bico, Gladstone Institute of Cardiovascular Disease, City of Paris Industrial Physics and Chemistry San Francisco (research) Policy Leader of the Year Higher Education Institution (research) 36. Frank D. McKeon, 3. X Prize Foundation 20. Robin G. Hicks, Harvard Medical School (research) University of Victoria, British Columbia, 37. Kevin Eggan, Other Research, Business and Rajsapan Jain, Harvard Stem Cell Institute (research) and Policy Leaders University of Windsor, Ontario (research) Connections to 21. Sergej Demokritov, Squirt and Spin an Untethered Future University of Muenster, Germany (research) 38. Masahiro Furusawa, Seiko Epson Corporation, Japan (business) 4. Marin Soljaˇci´c, Massachusetts Institute of Technology Neurological Insights 39. Hanan Dery, University of California, San Diego (research) (research) 22. Itay Baruchi and Eshel Ben-Jacob, 5. Apple (business) Tel Aviv University (research) Making Them Whole 6. Robert Ghrist, University of Illinois 23. Richard D. Smith, 40. Todd A. Kuiken, at Urbana-Champaign, and Paciﬁ c Northwest National Laboratory, Rehabilitation Institute of Chicago (research) Vin de Silva, Pomona College (research) and Desmond J. Smith, 41. Dean Kamen, DEKA Research & Development University of California, Los Angeles (research) Getting from Here to There Corporation (research) 24. Stina M. Tucker, Esther Oh and 42. Cato T. Laurencin, 7. Manjunath N. Swamy, Immune Disease Juan C. Troncoso, University of Virginia (research) Institute, Harvard Medical School (research) Johns Hopkins University School of Medicine 8. Hans Boumans, (research) The Fastest Way to Get There Netherlands Organization 25. Beka Solomon, 43. Dominik Schultes, for Applied Research (research) Tel Aviv University (research) University of Karlsruhe, Germany (research) 44. Google (business) Fueling Alternatives Light Manipulation 45. IntelliOne (business) 9. James A. Dumesic, 26. Yurii A. Vlasov, University of Wisconsin–Madison (research) IBM Thomas J. Watson Research See-Through Technology 10. Radoslav R. Adzic, Center (research) and Better Sleep Brookhaven National Laboratory (research) 27. Takasumi Tanabe, 46. Brian Schulkin, 11. Shelley D. Minteer and Tamara Klotzbach, NTT Basic Research Laboratories, Japan Rensselaer Polytechnic Institute (research) Saint Louis University (research) (research) 47. Lawrence C. Rome, 28. E. Fred Schubert, University of Pennsylvania and Fighting Toxins in the Home Rensselaer Polytechnic Institute (research) Marine Biological Laboratory, Woods Hole, Mass. (research) 12. Patricia A. Hunt, 29. Eugene S. Polzik, Niels Bohr Institute, 48. Actelion Pharmaceuticals, Washington State University (research) University of Copenhagen, Switzerland (business) 13. American Pharmacists Association and and Ignacio Cirac, the U.S. Fish and Wildlife Service (policy) Max Planck Institute for Quantum Optics, 49. Conor R. Caffrey, University of California, Germany (research) San Francisco (research) Advances in Ultrameasurement 50. Ilaria Capua, Vialle University, Italy (policy) 14. Peter W. Sutter and Eli A. Sutter, Progress against Prions Brookhaven National Laboratory (research) 30. Giovanna R. Mallucci, 15. Groups of physicists at Institute of Neurology, London (research) Hokkaido University, Japan, and 31. Robert Rohwer, the University of Bristol, England (research) Veterans Affairs Medical Center, Baltimore (research) Mosquitoes Enlisted EDITORIAL CONTRIBUTORS to Beat Malaria Sun Power Gets a Boost Mark Alpert, Steven Ashley, Charles Q. Choi, 16. Marcelo Jacobs-Lorena, 32. Gregory S. Engel, Graham P. Collins, Mariette DiChristina, Johns Hopkins University (research) University of Chicago (research) Kaspar Mossman, George Musser, John Rennie, 17. Bruce A. Hay, 33. Steven Van Dessel, Ricki L. Rusting, Peter Sergo, Christine Soares, California Institute of Technology (research) Rensselaer Polytechnic Institute (research) Gary Stix, Philip M. Yam

TAMING VESSELS TO TREAT CANCER

Restoring order to the chaotic blood vessels hile still a graduate student in 1974, I had a chance to see malignant inside a tumor opens a window of opportunity for W tumors from a most unusual perspective. I was working at the National Cancer attacking it. Surprisingly, drugs meant to destroy Institute in the laboratory of the late Pietro M. Gullino, who had developed an innovative vasculature can make the repairs and may help experimental setup for studying cancer biolo- reverse conditions that lead to cardio vas c u lar gy—a tumor mass that was connected to the cir- culatory system of a rat by just a single artery disease and blindness By Rakesh K. Jain and a single vein. As a chemical engineer, I decided to use this opportunity to measure how much of a drug injected into the animal would ﬂ ow to the tumor and back out again. Amaz- ingly, most of the substance injected into the rat never entered the tumor. To make matters

56 SCIENTIFIC AMERICAN January 2008 © 2007 SCIENTIFIC AMERICAN, INC. worse, the small amount that did reach the mass ABNORMAL BLOOD VESSELS (left) add to the havoc was distributed unevenly, with some areas accu- inside a tumor and prevent treatments from mulating hardly any drug at all. reaching cancer cells. Normalizing those vessels My immediate concern was that even if a (above) makes them into functional weapons small fraction of the cancer cells in a human tu- that can be turned against the tumor. mor did not receive an adequate dose of whatev- KEY CONCEPTS er anticancer drug was being applied, those cells start testing this idea in cancer patients, and the ■ Abnormal and dysfunc- could survive—causing the tumor to grow back excitement in our lab was overwhelming when tional blood vessels are a sooner or later. Perhaps the engineer in me was we saw the first clinical evidence of tumors hallmark of solid tumors, also drawn to trying to understand and solve the shrinking in response to vascular normalization, one that contributes di- apparent infrastructure problem inside tumors just as we had anticipated. Much more work re- rectly to malignant prop- that posed a major obstacle to the delivery of mains before we can perfect this therapeutic ap- erties of a cancer as well cancer therapies. proach and gauge its usefulness in patients with as preventing treatments from reaching and attack- Over the subsequent decades my colleagues different types of malignancy. But what we have ing tumor cells. and I have investigated what makes the vascula- already learned about restoring blood vessels is ture within tumors abnormal and how these dis- also opening doors to treating other vascular ■ Normalizing tumor vessels ordered blood vessels not only stymie tradition- disorders, such as macular degeneration, the allows cancer therapies to al cancer treatments but also contribute directly leading cause of blindness in the U.S. penetrate the mass and to function more effectively. to some of the malignant properties of solid cancers. Building on these insights, we developed Tortuous Road ■ Unexpectedly, drugs origi- approaches to normalizing tumor blood vessels The journey that led to our recent successes nally designed to destroy and tested them successfully in mice. In the pro- began in earnest a few years after I completed my tumor blood vessels act to repair them for a time, cess, we also discovered a seeming paradox—a doctoral studies. Determined to ﬁ nd out why opening a new avenue for class of drugs designed to destroy the blood ves- drugs do not penetrate tumors uniformly, my cancer treatment as well sels of tumors actually acts to repair them, cre- colleagues and I started by monitoring every step as restoration of abnormal ating a window of opportunity to attack the of the process in rodents. Using a variety of tech- vasculature in other cancer most effectively. niques, we observed the progress of drugs as they diseases. —The Editors

KEITH KASNOT KEITH In recent years we have ﬁ nally been able to entered the tiny blood vessels of a tumor, crossed

www.SciAm.com SCIENTIFIC AMERICAN 57 © 2007 SCIENTIFIC AMERICAN, INC. the vessel walls into the surrounding tissue, of a tumor that will lack vessels altogether. entered into cancer cells and eventually exited Over the course of many years we managed the mass. Together with my students and collab- to delineate the processes that govern the move- orators, we developed methods for tracking mol- ment of fl uids, drugs and cells within this tortu- ecules, such as oxygen, within blood vessels and ous vasculature and gained insight into the con- tissues. Eventually we could even watch as genes sequences of the abnormalities. The picture that turned on and off inside cells. emerged was grim: the very fi rst thing we real- Early on it was apparent that the vessels with- ized was that tumor blood vessels are not just in tumors bear little resemblance to normal ones. disorganized in their appearance but highly ab- Healthy tissues are fed by straight vessels that errant in every aspect of their structure and branch predictably into successively smaller cap- function. We found that blood fl ows quite brisk- illaries and microvessels, creating a pervasive ly in some vessels within a tumor, whereas it is network for delivering oxygen and nutrients to static in others. In a given vessel, blood may cells. Tumors, which stimulate the growth of travel in one direction for a while and then renew vasculature of their own, tend to generate a verse direction. These fl ow patterns alone cre- tangle of vessels. These connect to one another ate a major obstacle to uniform drug delivery. randomly, with some oversize branches, many Moreover, some parts of the vessel walls are extraneous immature microvessels and areas overly leaky and others are unusually tight,

[THE PROBLEM] ABNORMAL VESSELS MAKE TROUBLE

Malformed vasculature inside a tumor VESSEL FUNCTION High turns a bad situation worse (boxes). interstitial ■ Flaws in the organization and function- Oversize pores in vessel walls leak fl uid into fl uid interstitial areas (between cells, vessels pressure ing of blood vessels create barriers and other structures) that prevent therapies from reaching ■ High interstitial fl uid pressure blocks tumor cells and foster an environment transport of drugs and oxygen out of vessels to tumor tissue where those treatments are less effec- Impaired Abnormal transport blood vessel tive. These unnatural internal condi- of drugs tions also contribute to malignant and oxygen properties of the cancer itself. Immature microvessel

VESSEL ORGANIZATION ■ Oversize diameter and chaotic layout create irregular blood ﬂ ow ■ Absent or immature vessels make some tumor regions impenetrable Leaky oversize pore

Tumor Endothelial cell

FLUID BUILDUP ■ Tumor tissue swells, causing TUMOR MICROENVIRONMENT Swelling painful symptoms ■ Dysfunctional vessels produce conditions of low ■ Fluid pressure oxygen (hypoxia) and high acidity Fluid and cells drives tumor- ■ Radiation and certain chemother a pies that require escape generated proteins oxygen to kill tumor cells are ineffective and cells toward ■ Immune cells that might attack cancer cells cannot Lymphatic vessel healthy tissues and function in an acidic environment and without oxygen into lymphatic ■ Hypoxia causes changes in gene activity that pro- vessels, increasing mote tumor cell migration toward healthy tissues risk of metastasis Healthy tissue KEITH KASNOT KEITH

58 SCIENTIFIC AMERICAN January 2008 © 2007 SCIENTIFIC AMERICAN, INC. which means that drugs and other molecules blood vessels are obstacles to treatment in even [THE AUTHOR] that managed to penetrate the vasculature more ways than I had initially imagined. In 1994 would be distributed into the surrounding tu- I described our fi ndings up to that point in-depth mor tissue unevenly. in this magazine [see “Barriers to Drug Delivery When we began investigating the causes of in Solid Tumors,” by Rakesh K. Jain; Scientif- this nonuniform porousness, we discovered that ic American, July 1994]. By that time, these in some tumors the pores in blood vessel walls observations were also beginning to suggest to could be as large as one or two microns in diam- my research collaborators and me that if we eter, which is more than 100 times the size of knew how to repair the structure and function pores in healthy vessels. As a result, these ves- of tumor-associated blood vessels, we would sels are unable to maintain normal pressure gra- have a chance to normalize the tumor microen- Rakesh K. Jain is Andrew Werk dients across their walls. Fluid pressure inside vironment and ultimately improve cancer treat- Cook Professor of Tumor Biology healthy blood vessels is typically much higher ment. To accomplish such a reversal, we fi rst had and director of the Edwin L. Steele than in the surrounding tissue. Because tumor to gain a better understanding of what makes tu- Laboratory for Tumor Biology in vessels are so porous, escaping fl uid raises the mor vessels abnormal and keeps them that way. the radiation oncology department of Massachusetts General Hospital outside—or interstitial—pressure until it nearly and Harvard Medical School. His equals that inside the blood vessels. Restoring Balance research incorporates biology, im- This unnatural pressure gradient is not just We began to look at the molecular factors aging, engineering and mathemat- an impediment to the ability of drugs to reach involved in normal blood vessel formation, ics in the study of blood and lym- tumor cells; the accumulation of interstitial fl u- known as angiogenesis, including the single phatic vessels and their tissue id produces swelling in and around tumor tis- most potent one, vascular endothelial growth environment, as well as the adaptation of basic fi ndings to patient sues. In patients with brain cancers, where tis- factor (VEGF). First discovered and named vas- treatment. He would especially sue expansion is limited by the skull, that swell- cular permeability factor by my Harvard Uni- like to acknowledge the National ing becomes a severe, often life-threatening versity colleague Harold Dvorak, VEGF pro- Cancer Institute for continuous problem in itself. In those with other types of motes the survival and proliferation of endothe- support of his work since 1980 and cancer, the exuded fl uid can also accumulate in lial cells, which form the inner lining of blood more than 200 graduate students, postdoctoral fellows and collabo- — body cavities. Wherever it goes, the fl uid oozing vessels. In excess, it also makes vessels leaky rators worldwide who have shared from a tumor carries with it tumor cells as well hence its original name. In normal tissues, how- his journey into the world of solid as various tumor-generated proteins that pro- ever, the collective action of VEGF and other tumors. Jain also serves as an ad- mote the growth of new blood and lymphatic growth-stimulating molecules like it is counter- viser to several pharmaceutical vessels in the surrounding normal tissue and balanced by the actions of natural antiangio- and biotechnology companies and is a member of both the National — lymph nodes which can then serve as conduits genesis molecules, such as thrombospondin, Academy of Engineering and the for the metastatic spread of the cancer cells to that inhibit blood vessel growth. Institute of Medicine. ) other parts of the body. Whether healthy or diseased, tissues that Beyond the difficulty of delivering drugs need new blood vessels increase their produc-

micrographs through chaotic tumor vasculature and the dan- tion of angiogenesis stimulators or reduce their gerous ﬂ uid buildup caused by leaky vascular production of inhibitors, or do both, tipping the walls, the abnormalities of tumor vessels create balance in favor of angiogenesis. In healthy pro- a highly unnatural microenvironment inside a cesses such as wound healing, a balance be- tumor as well. Because many areas of a tumor tween growth and inhibitory factors is eventu- lack vasculature and existing vessels are unable ally reinstated once the new vessels are estab- to deliver sufﬁ cient oxygen to surrounding tis- lished. But in tumors and a number of other sues, a general state of hypoxia (low oxygen) chronic diseases, an imbalance persists—and and high acidity prevails in the tumor. Hypoxia blood vessels grow increasingly abnormal. in turn makes tumor cells more aggressive and prone to metastasis. In addition, the body’s im- BLOOD VESSELS in a normal

); FROM “MOLECULAR REGULATION OF VESSEL MATURATION,” BY RAKESH K. JAIN, JAIN, RAKESH K. BY MATURATION,” VESSEL OF REGULATION “MOLECULAR ); FROM mune cells, which might help ﬁ ght a tumor, are mouse muscle’s capillary Jain ( hampered by acidity and cannot function in low bed (far left) and inside a oxygen. Nor can radiation treatments and a mouse tumor (left) differ subset of chemotherapy drugs that depend on distinctly. The tumor vessels branch erratically, vary in

VOL. 9; 2003. REPRINTED WITH PERMISSION FROM MACMILLAN PUBLISHERSchemical LTD. ( processes that require oxygen to kill diameter along their lengths

Harvard Medical School School Medical Harvard cancer cells. and are generally oversize— Thus, what began as an inquiry into seeming- all features that contribute ly simple aberrations in the ﬂ ow of drugs inside to irregular blood ﬂ ow. NATURE MEDICINE, NATURE LANCE L. MUNN MUNN L. LANCE IN IN tumors revealed that the abnormalities in tumor

Restoring tumor vasculature to a more normal state opti- mizes conditions for anticancer therapies to reach tumor NORMAL VASCULATURE ABNORMAL TUMOR VESSELS Balance between progrowth and Excessive amounts of proangiogene- cells and to work more effectively. Many abnormalities antigrowth factor signaling produc- sis factors, primarily VEGF, cause arise in tumor vessels because factors that stimulate ves- es an organized network, with large overgrowth, yielding haphazardly sel growth, or angiogenesis, overwhelm growth inhibitors vessels regularly branching into ever organized, oversize vessels and that usually check vessel proliferation. Antiangiogenesis smaller ones. many dysfunctional microvessels. drugs that suppress the primary progrowth factor, VEGF, tip the balance back toward normal vessel formation and maintenance. Normalization does not last indeﬁ nitely, because the drugs may ultimately destroy most vessels or a tumor may become resistant to them.

q HEALTHY VESSEL GROWTH AND MAINTENANCE Endothelial cells form blood vessels in response to signals from molecules that promote and inhibit growth. Pericyte cells straddle vessels, and a basement membrane surrounds them; both provide support.

Endothelial cell Anti Pro Anti Pro Pericyte Basement membrane Because VEGF is abun- bodies bound to the VEGF receptors themselves, dant in most solid tu- preventing the growth factor from making con- mors, I suspected that tact. Remarkably, both forms of VEGF inhibi- fi nding a way to mop up tion caused some of the immature and ineffi cient VEGF Receptor the excess V EGF or inter- blood vessels characteristic of many tumors to fere with the growth sig- be pruned away and induced the remaining ves- nals it generates could sels to remodel themselves so that they began to restore balance and cause resemble normal vasculature. Those normalized Antigrowth tumor vascula ture to re- blood vessels were less leaky, less dilated and less factors vert to a more normal state. tortuous. We could also detect functional im- Alternatively, increasing the provements in the tumors, including lower inter- Progrowth factors concentration of angiogenesis- stitial fl uid pressure, higher oxygenation and inhibiting factors could have the improved penetration of drugs.

same normalizing effect on the blood As excited as we were by these results and by 9; NO. SEPTEMBER 2001 VOL. 7, vessels. I also theorized that vessels treated the fact that they were later reproduced in ani- in either way would not remain normal forever— mals by other researchers, we still could not know they would be destroyed if the inhibitors were whether the same responses would occur in can- Normalized potent enough or would become abnormal again cer patients. And many researchers were under- MEDICINE, NATURE vessels make if the tumors developed the ability to make dif- standably skeptical of our approach. By the late ferent stimulators, such as basic fibroblast 1990s, when I ﬁ rst proposed the idea of tumor ); ); cells more growth factor (bFGF), which can mimic many vessel normalization publicly, scientists in aca-

of the effects of VEGF. The only way to ﬁ nd out demia and industry had been working on mak- seesaws vulnerable was to try angiogenesis inhibitors on tumors and ing drugs to destroy blood vessels. Their pursuit to the treat- see what happened. was based on the hypothesis put forward in In 1995 antibody-based drugs that could neu- 1971 by my Harvard colleague Judah Folkman

ments that tralize the effects of VEGF were already in devel- that tumor growth could be halted by starving ( CHRISTIANSEN JEN ); they can now opment, so we were able to use these to test our the mass using antiangiogenic drugs [see “Ves- approach in mice. Certain of the antibodies at- sels of Death or Life,” by Rakesh K. Jain and illustrations deliver more tached directly to VEGF, hindering its ability to Peter Carmeliet; Scientiﬁ c American, De- send a growth signal to endothelial cells by bind- cember 2001]. Indeed, the drug Avastin, ap- KEITH KASNOT ( KASNOT KEITH efficiently. ing to receptors on the cell surface. Other anti- proved by the U.S. Food and Drug Administra- THERAPY: ANTI-ANGIOGENIC WITH VASCULATURE TUMOR “NORMALIZING IN MUNN L. LANCE BY ILLUSTRATIONS ORIGINAL FROM ADAPTED A NEW PARADIGM FOR COMBINATION THERAPY,” BY RAKESH K. JAIN, IN

60 SCIENTIFIC AMERICAN January 2008 © 2007 SCIENTIFIC AMERICAN, INC. Two weeks after a single injection of Avastin, blood fl ow within the tumors did drop by 30 to 50 percent in six consecutive patients. The density of microvessels, the overall number of blood NORMALIZED VESSELS NORMALIZATION Inhibiting progrowth signals from WINDOW CLOSED vessels and the interstitial fl uid pressure in the tu- VEGF prunes immature vessels and A potent enough mors were all reduced as well. And a form of pro- restores the remaining ones to antiangiogenesis a more normal arrangement, size Anti Pro drug could prune grammed cell death known as apoptosis, charac- and functioning. so much vascula- teristic of oxygen and nutrient deprivation, in- ture that addition- creased among tumor cells that no longer had al therapies can no longer pene- access to the pruned vasculature. trate the tumor Surprisingly, however, there was no concur- (top). rent decrease in a sign of overall energy use by the Or, other growth tumor, its uptake of a glucose analogue, as might factors might be expected if the tumor were only being starved. surge to Instead it seemed that the remaining tumor ves- compensate for VEGF inhibition, sels had become more effi cient in supporting the making the tumor energy needs of the surviving cancer cells. Fur- resistant to antiangiogenesis thermore, the rate of proliferation of cancer cells therapy and increased in some tumors, refl ecting their access causing a return to better-functioning vessels and a more normal to abnormal vasculature. tissue microenvironment. Although increased Anti Pro Anti Pro proliferation is usually not desirable when it comes to cancer cells, that state would make them more sensitive to chemotherapy drugs, tion for use in cancer treatment in 2004, is a which generally target dividing cells. VEGF-neutralizing antibody originally devel- Together these results provided a fi rst glimpse oped as such an antiangiogenesis agent. of how a drug like Avastin works in patients and In laboratory testing and clinical trials, Avas- thereby revealed why it might improve the out- tin has been shown to destroy blood vessels in come of radiation or chemotherapy for a time. As animal and human tumors, although when used the drug blocks the effects of VEGF, some tumor alone it does not increase overall survival in can- vasculature is pruned away immediately, but the cer patients. In a pivotal clinical trial that led to vessels that remain become less abnormal. In ad- its approval, however, Avastin did increase the dition to improving the overall tumor microen- survival of patients with advanced colorectal TUMOR VESSELS cast in vironment, those normalized vessels also make polymer from a surgically cancer but only when it was used in conjunction the surviving cells more vulnerable to the treat- excised colon cancer form with standard chemotherapy. That positive out- ments that they can now deliver more effi ciently. a dense crystalline mass come seemed quite paradoxical at the time be- Restoring normal function to tumor vessels VOL. 4, NO. 1; 1997 representing a chaotic cause, in principle, a drug that was designed and profusion of microvessels. thereby creates a period during which treatment deployed to destroy blood vessels should reduce In contrast, large gaps with a variety of cancer therapies should be max- the effectiveness of chemotherapy, which re- indicate areas of the imally effective. quires functioning blood vessels to reach tumor tumor that lacked any MICROCIRCULATION, cells. Some published studies have in fact shown blood supply. that antiangiogenic agents can hinder radiation and chemotherapy. So how could these apparently contradictory fi ndings be reconciled? Our group had the chance to fi nd out by closely examining the structure and function of blood vessels in the tumors of rectal cancer patients receiving Avastin and combined chemotherapy and radiation in a 2002 clinical trial supported by the National Cancer Institute and led by Christopher Willett, now at Duke University Medical Center. Very quickly, we saw that the changes to tumor vasculature in those patients

FROM “GEOMETRIC RESISTANCE AND MICROVASCULAR NETWORK ARCHITECTURE OF HUMAN COLORECTAL CARCINOMA,” BY J. R. LESS, M. C. POSNER, C. SKALAK, T. N. WOLMARK AND R. K. JAIN, IN were not limited to simple vessel destruction.

www.SciAm.com SCIENTIFIC AMERICAN 61 © 2007 SCIENTIFIC AMERICAN, INC. Window of Opportunity that we were able to test it in another National To truly benefi t from this new insight into the Cancer Institute clinical trial, completed just over way that antiangiogenic therapy can work with a year ago. Led by my Massachusetts General radiation or chemotherapies, an oncologist Hospital colleagues Tracy Batchelor and Gregory would need to know when a patient’s tumor ves- Sorensen, the trial included 30 patients whose sels fi rst begin to normalize and how long they brain tumors, known as glioblastomas, had re- remain that way. My research group returned to grown despite aggressive surgery, radiation and experimenting with mice to better characterize chemotherapy. These patients had a life expec- this period we came to call the “normalization tancy of less than six months. window.” We treated brain tumors in the ani- They received a daily oral dose of Recentin, an mals with an antibody designed to block the experimental drug that potently inhibits the main VEGF receptor used by endothelial cells three primary cellular receptors for VEGF. Using and saw signs of vessel normalization begin after advanced imaging techniques, we were able to one day. During the normalization window— look for effects in their tumors and saw them al- which lasted only about fi ve to six days—tumor most immediately [see illustration on opposite oxygenation increased and radiation therapy page]. The signs of vascular normalization in- yielded the best therapeutic outcome. Other cluded reduced vessel diameter and leakiness, teams working with laboratory animals have which continued for at least 28 days, with some subsequently reported similar observations. normalized characteristics persisting for the en- Enough evidence supported this model, in fact, tire four-month duration of the study. Moreover, as anticipated by our original model, the normalization was accompanied by a rapid decrease in Vessel Repair: Beyond Cancer swelling in and around the tumor, an effect that undreds of millions of people around the world suffer from noncancerous conditions continued as long as the patients took the Recen- H that involve abnormal vasculature. Modifying blood vessel growth and function might tin. Because the side effects of VEGF inhibition become a key component of the therapeutic arsenal for those diseases as well, so drugs that can be severe, however, some patients asked for normalize blood vessels have the potential to vastly impact human health. a break from the treatment during the trial, Among the most widespread of problems in this category, for example, is atherosclero- which allowed us to observe the tumor vessels sis, an artery disease whose features include an accumulation of fatty plaques within the becoming abnormal again when Recentin was inner walls of blood vessels. Inside such plaques, infl ammation-inducing blood cells and discontinued, and renormalized when the drug other detritus accumulate, gradually enlarging the lesion. New blood vessels sprout within was resumed. this growing mass to feed it, much like a tumor. These new vessels also share many abnor- These results were the fi rst to defi ne how long mal features with tumor vessels, such as leakiness and disorganization. In principle, there- the period of vascular normalization can last in fore, applying antiangiogenic agents should normalize intraplaque vessels, stabilizing the humans and have led to a much larger ongoing lesions, halting their expansion and reducing their potential for rupture. clinical trial involving 300 patients to further Eye diseases such as diabetic retinopathy and the so-called wet form of age-related defi ne the role that Recentin, with and without macular degeneration (AMD) are also characterized by vascular abnormalities similar to chemotherapy, might play in the treatment of those seen in tumors. A hallmark of wet AMD is, in fact, the leakiness of blood vessels in the glioblastoma. We are also studying a number of retina at the back of the eye. As a result, blood oozes into surrounding tissue, causing partial antiangiogenic drugs in combination with tradi- or total vision loss. More than nine million Americans are currently affected. Not surprisingly, tional therapies in newly diagnosed and recur- the greatest progress outside the realm of cancer treatment in using antiangiogenesis to re- rent tumor cases in more types of cancer. pair vascular abnormalities has been in wet AMD. Two drugs, Lucentis and Macugen—both At the same time, we are also investigating inhibitors of VEGF—have already been approved for treating the condition and most likely ways of expanding the window of normalization work by normalizing the leaky vessels. so that survival improvements can be extended These same normalization principles may also be useful for controlling conditions that cause fl uid buildup (edema) and for tissue engineering and regenerative medicine, which from months to years. Any potential strategy to repair vessels must recognize that VEGF block- require the creation and maintenance of normally functioning vasculature. —R.K.J. ade alone may not always be suffi cient to achieve or sustain normalization, because tumors can WET AMD affects the macula, a region substitute other growth factors to get around of the retina at the back of the eye the loss of VEGF signaling. As tumors grow that appears slightly darkened in a healthy human eye (left) but can larger, for instance, they tend to make a diverse sprout excess blood vessels leading array of proangiogenic molecules in addition to to macular degeneration. The abnor- VEGF, so their vessels may gradually lose re- mal vessels leak blood (right) into sponsiveness to a treatment such as Avastin.

surrounding tissue, obscuring vision. In rectal cancer patients, for instance, our GILMAN JAMES AND ZHANG KANG

62 SCIENTIFIC AMERICAN January 2008 © 2007 SCIENTIFIC AMERICAN, INC. Before treatment After treatment 1 day 27 days 111 days BRAIN TUMOR response to antiangiogenesis therapy TUMOR SIZE The ability refl ects some effects of vascular normalization. MRI to use these images of a patient’s brain one day before beginning drugs for treatment and at subsequent intervals show a vascular shrinking white area corre- SWELLING sponding to the malignant repair makes tumor’s location (top row). them valuable Another set of views highlights accumulated fl uid tools for in the same area receding (middle row). As tumor- attacking generated edema diminish- WHITE MATTER es, reduced compression of tumors in brain tissue is visible in the rebounding of fi brous white more than matter tracts, which are one way. color-coded here by brain region (bottom row).

group discovered that blood levels of VEGF and delivering treatments. To that end, my colleagues PlGF (placental growth factor), a related mole- and I have been working to identify so-called cule, actually increased after VEGF was mopped biomarkers: readily identiﬁ able signs that reﬂ ect up with Avastin, suggesting that the tumor or what is happening inside the tumor and thereby other tissues began manufacturing more of those reveal the onset and duration of the normaliza- ➥

PATIENTS,” factors in response. And in recurrent glioblasto- tion window in individual patients. Such mark- MORE TO ma patients, blood levels of multiple proangio- ers might include, for example, proteins in the EXPLORE genic molecules rose as tumors escaped the Re- bloodstream or in urine whose levels rise or fall Normalization of the Tumor Vas- centin treatment. during this time window. culature: An Emerging Concept in This diversifi cation of progrowth signals il- Finding that antiangiogenesis drugs can nor- Anti-Angiogenic Therapy. Rakesh K. lustrates that the challenge for the oncologist malize vasculature should not suggest that the Jain in Science, Vol. 307, pages 58–62; January 2005. will be to formulate cocktails of agents specifi - original purpose for which they were developed cally tailored to the molecular profi le of each pa- is no longer valid. If a drug is suffi ciently potent Lessons from Phase III Clinical tient’s primary and metastatic tumors and to and specifi c to destroy enough tumor vasculature Trials of Anti-VEGF Therapy for changes in those profi les that will likely occur to starve the entire tumor and save a patient’s life, Cancer. Rakesh K. Jain, Dan G. over time. It is worth noting, however, that the then that would be a happy outcome for everyone. Duda, Jeffrey W. Clark and Jay S. Loeffl er in Nature Clinical Practice available tools for promoting vascular normal- But the ability to use these drugs for vascular re- Oncology, Vol. 3, No. 1, pages ization are not limited to drugs targeting VEGF pair as well makes them valuable tools for at- 24–40; January 2006. or other growth factors directly. We have shown tacking tumors in more than one way. In the lon- in mice, for example, that the drug Herceptin— ger term, this research can also benefi t the many Angiogenesis in Brain Tumors. an antibody that targets a tumor cell-surface millions of people around the world suffering Rakesh K. Jain et al. in Nature Reviews Neuroscience, Vol. 8, protein called HER2 and that is given to about from other diseases caused by abnormal vascu- pages 610–622; August 2007. a quarter of women with breast cancer—can lature, such as age-related macular degeneration mimic the responses produced by an antiangio- and atherosclerosis [see box on opposite page]. Antiangiogenic Therapy for Nor- genic cocktail and normalize tumor vessels. More than 30 years ago, when I fi rst set out malization of Atherosclerotic Herceptin indirectly lowers cellular manufac- to understand the tortuous and dysfunctional Plaque Vasculature: A Potential VOL. JANUARY 11; © 2007 2007. REPRINTED WITH PERMISSION OF ELSEVIER Strategy for Plaque Stabilization. ture of several proangiogenic molecules while blood vessels of tumors, I never imagined where Rakesh K. Jain et al. in Nature Clini- increasing the cells’ production of the antiangio- that road would lead. Nor could I have pictured cal Practice Cardiovascular Medicine,

CANCER CELL, CANCER genic thrombospondin-1. a day when a patient with a disease of abnormal Vol. 4, No. 9, pages 491–503; In addition to identifying new and existing blood vessels could walk into a clinic, have var- September 2007. medications that can foster vascular normaliza- ious biomarkers measured, then receive a tai- For more articles by Rakesh K. Jain tion, it will be important to ﬁ nd minimally inva- lored regimen of normalizing drugs to repair and animations explaining sive and affordable ways for doctors to monitor those vessels. But now that day looks closer than vessel normalization, go to ■ FROM “AZD2171, A PAN-VEGF RECEPTOR TYROSINE KINASE INHIBITOR, NORMALIZES TUMOR VASCULATURE AND ALLEVIATES EDEMA IN GLIOBLASTOMA IN ALLEVIATES EDEMA AND VASCULATURE NORMALIZES TUMOR KINASE INHIBITOR, TYROSINE RECEPTOR PAN-VEGF A “AZD2171, FROM BY T. BATCHELOR ET AL., IN the normalization process, to best exploit it when ever before. http://steele.mgh.harvard.edu/

By 2050 solar power could end U.S. dependence on foreign oil and slash greenhouse gas emissions By Ken Zweibel, James Mason and Vasilis Fthenakis

igh prices for gasoline and home heating oil are here to stay. The U.S. is at war in the Middle East at least in part to protect H its foreign oil interests. And as China, India and other nations rapidly increase their demand for fossil fuels, future fi ghting over energy looms large. In the meantime, power plants that burn coal, oil and natural gas, as well as vehicles everywhere, continue to pour millions of tons of pollutants and greenhouse gases into the atmo- sphere annually, threatening the planet. Well-meaning scientists, engineers, economists and politicians have proposed various steps that could slightly reduce fossil-fuel use and emissions. These steps are not enough. The U.S. needs a bold plan to free itself from fossil fuels. Our analysis convinces us that a KEY CONCEPTS massive switch to solar power is the logical answer. Solar energy’s potential is off the chart. The energy in sunlight ■ A massive switch from coal, oil, natural gas and striking the earth for 40 minutes is equivalent to global energy con- nuclear power plants to so- sumption for a year. The U.S. is lucky to be endowed with a vast re- lar power plants could sup- source; at least 250,000 square miles of land in the Southwest alone ply 69 percent of the U.S.’s are suitable for constructing solar power plants, and that land receives electricity and 35 percent more than 4,500 quadrillion British thermal units (Btu) of solar ra- of its total energy by 2050. diation a year. Converting only 2.5 percent of that radiation into elec- ■ A vast area of photovoltaic tricity would match the nation’s total energy consumption in 2006. cells would have to be To convert the country to solar power, huge tracts of land would erected in the Southwest. have to be covered with photovoltaic panels and solar heating Excess daytime energy troughs. A direct-current (DC) transmission backbone would also would be stored as com- have to be erected to send that energy effi ciently across the nation. pressed air in underground The technology is ready. On the following pages we present a caverns to be tapped dur- grand plan that could provide 69 percent of the U.S.’s electricity and ing nighttime hours. 35 percent of its total energy (which includes transportation) with ■ Large solar concentrator solar power by 2050. We project that this energy could be sold to power plants would be consumers at rates equivalent to today’s rates for conventional pow- built as well. er sources, about fi ve cents per kilowatt-hour (kWh). If wind, bio- ■ A new direct-current pow- mass and geothermal sources were also developed, renewable ener- er transmission backbone gy could provide 100 percent of the nation’s electricity and 90 per- would deliver solar elec- cent of its energy by 2100. tricity across the country. The federal government would have to invest more than $400 bil- ■ But $420 billion in subsi- lion over the next 40 years to complete the 2050 plan. That invest- dies from 2011 to 2050 ment is substantial, but the payoff is greater. Solar plants consume would be required to fund little or no fuel, saving billions of dollars year after year. The infra- the infrastructure and structure would displace 300 large coal-fi red power plants and 300 make it cost-competitive. more large natural gas plants and all the fuels they consume. The —The Editors plan would effectively eliminate all imported oil, fundamentally cutting U.S. trade defi cits and easing political tension in the Middle East HANDOUT/EPA/CORBIS AG/COMMERCIAL SCHOTT A 64 SCIENTIFIC AMERICAN © 2007 SCIENTIFIC AMERICAN, INC. Solar Grand Plan

© 2007 SCIENTIFIC AMERICAN, INC. and elsewhere. Because solar technologies are almost pollution-free, the plan would also re- U.S. Plan for 2050 TECHNOLOGY duce greenhouse gas emissions from power PHOTOVOLTAICS plants by 1.7 billion tons a year, and another 1.9 billion tons from gasoline vehicles would be dis- Solar Power Provides ... placed by plug-in hybrids refueled by the solar power grid. In 2050 U.S. carbon dioxide emissions would be 62 percent below 2005 levels, 69% 35% of electricity of total energy putting a major brake on global warming.

Photovoltaic Farms y 2050 vast photovoltaic arrays in the Southwest would COMPRESSED-AIR In the past few years the cost to produce photo- supply electricity instead of fossil-fueled power plants and B ENERGY STORAGE voltaic cells and modules has dropped signifi - would also power a widespread conversion to plug-in electric vehi- (with photovoltaic cantly, opening the way for large-scale deploy- cles. Excess energy would be stored as compressed air in under- electricity) ment. Various cell types exist, but the least expen- ground caverns. Large arrays that concentrate sunlight to heat sive modules today are thin films made of water would also supply electricity. A new high-voltage, direct-cur- cadmium telluride. To provide electricity at six rent transmission backbone would carry power to regional markets CONCENTRATED cents per kWh by 2020, cadmium telluride mod- nationwide. The technologies and factors critical to their success SOLAR POWER ules would have to convert electricity with 14 are summarized at the right, along with the extent to which the percent effi ciency, and systems would have to be technologies must be deployed by 2050. The plan would substan- installed at $1.20 per watt of capacity. Current tially cut the country’s consumption of fossil fuels and its emission modules have 10 percent efficiency and an of greenhouse gases (below). We have assumed a 1 percent annual installed system cost of about $4 per watt. Prog- growth in net energy demand. And we have anti cipated improve- ress is clearly needed, but the technology is ments in solar technologies forecasted only until 2020, with no fur- advancing quickly; commercial effi ciencies have ther gains beyond that date. —K.Z., J.M. and V.F. DC TRANSMISSION risen from 9 to 10 percent in the past 12 months. It is worth noting, too, that as modules improve, rooftop photovoltaics will become more cost- competitive for homeowners, reducing daytime electricity demand. In our plan, by 2050 photovoltaic technology ANNUAL U.S. FUEL CONSUMPTION would provide almost 3,000 gigawatts (GW), or 2007 billions of watts, of power. Some 30,000 square 2050 (Existing energy path) miles of photovoltaic arrays would have to be 2050 (Solar grand plan) erected. Although this area may sound enor- mous, installations already in place indicate that OIL 6.9 10.9 2.7 the land required for each gigawatt-hour of so- Billion barrels lar energy produced in the Southwest is less than that needed for a coal-powered plant when fac- ) toring in land for coal mining. Studies by the illustration

( NATURAL GAS National Renewable Energy Laboratory in 22.2 35.4 11.4 Trillion cubic feet Golden, Colo., show that more than enough land in the Southwest is available without re-

quiring use of environmentally sensitive areas, Mondolithic Studios population centers or difficult terrain. Jack COAL 1.2 1.9 0.5 Lavelle, a spokesperson for Arizona’s Depart- Billion tons ment of Water Conservation, has noted that more than 80 percent of his state’s land is not privately owned and that Arizona is very inter- ested in developing its solar potential. The be- ); KENN BROWN AND CHRIS WREN nign nature of photovoltaic plants (including no U.S. EMISSIONS graph water consumption) should keep environmental CARBON DIOXIDE 6.1 9.4 2.3 concerns to a minimum. Billion tons The main progress required, then, is to raise

module efﬁ ciency to 14 percent. Although the ( CHRISTIANSEN JEN

Land area 10 sq miles 30,000 sq miles Policies to develop large public land areas Thin-fi lm module effi ciency 10% 14% More transparent materials to improve light transmission; more densely doped layers to increase voltage; larger modules to reduce inactive area Installed cost $4/W $1.20/W Improvements in module effi ciency; gains from volume production Electricity price 16¢/kWh 5¢/kWh Follows from lower installed cost Total capacity 0.5 GW 2,940 GW National energy plan built around solar power

Volume 0 535 billion cu ft Coordination of site development with natural gas industry Installed cost $5.80/W $3.90/W Economies of scale; decreasing photovoltaic electricity prices Electricity price 20¢/kWh 9¢/kWh Follows from lower installed cost Total capacity 0.1 GW 558 GW National energy plan

Land area 10 sq miles 16,000 sq miles Policies to develop large public land areas Solar-to-electric efﬁ ciency 13% 17% Fluids that transfer heat more effectively Installed cost $5.30/W $3.70/W Single-tank thermal storage systems; economies of scale Electricity price 18¢/kWh 9¢/kWh Follows from lower installed cost Total capacity 0.5 GW 558 GW National energy plan

Length 500 miles 100,000– New high-voltage DC grid from Southwest to rest of country 500,000 miles

© 2007 SCIENTIFIC AMERICAN, INC. By 2100 effi ciencies of commercial modules will never they would if they were fueled by natural gas reach those of solar cells in the laboratory, cad- alone, and better heat recovery technology renewable mium telluride cells at the National Renewable would lower that fi gure to 30 percent. energy could Energy Laboratory are now up to 16.5 percent Studies by the Electric Power Research Insti- and rising. At least one manufacturer, First So- tute in Palo Alto, Calif., indicate that the cost generate lar in Perrysburg, Ohio, increased module effi - of compressed-air energy storage today is about 100 percent ciency from 6 to 10 percent from 2005 to 2007 half that of lead-acid batteries. The research in- and is reaching for 11.5 percent by 2010. dicates that these facilities would add three or of the U.S.’s four cents per kWh to photovoltaic generation, electricity and Pressurized Caverns bringing the total 2020 cost to eight or nine The great limiting factor of solar power, of cents per kWh. more than course, is that it generates little electricity when Electricity from photovoltaic farms in the 90 percent of skies are cloudy and none at night. Excess pow- Southwest would be sent over high-voltage DC er must therefore be produced during sunny transmission lines to compressed-air storage its energy. hours and stored for use during dark hours. facilities throughout the country, where tur- Most energy storage systems such as batteries bines would generate electricity year-round. are expensive or ineffi cient. The key is to fi nd adequate sites. Mapping by Compressed-air energy storage has emerged the natural gas industry and the Electric Power as a successful alternative. Electricity from pho- Research Institute shows that suitable geologic tovoltaic plants compresses air and pumps it formations exist in 75 percent of the country, into vacant underground caverns, abandoned often close to metropolitan areas. Indeed, a mines, aquifers and depleted natural gas wells. compressed-air energy storage system would The pressurized air is released on demand to look similar to the U.S. natural gas storage sys- turn a turbine that generates electricity, aided by tem. The industry stores eight trillion cubic feet burning small amounts of natural gas. Com- of gas in 400 underground reservoirs. By 2050 pressed-air energy storage plants have been op- our plan would require 535 billion cubic feet of erating reliably in Huntorf, Germany, since storage, with air pressurized at 1,100 pounds 1978 and in McIntosh, Ala., since 1991. The tur- per square inch. Although development will be

bines burn only 40 percent of the natural gas a challenge, plenty of reservoirs are available, COMPANY POWER ELECTRIC TUCSON

Photovoltaics In the 2050 plan vast photovoltaic farms would cover 30,000 square miles of otherwise barren land in the Southwest. They would resemble Tucson Electric Power Company’s 4.6-megawatt plant in Springerville, Ariz., which began in 2000 (left). In such farms, many photovoltaic cells are inter con nect- ed on one module, and modules are wired together to form an array (right). The direct current from each array fl ows to a transformer that sends it along high- voltage lines to the power grid. In a thin-fi lm cell (inset), the energy of incoming photons knocks loose electrons in the cadmium telluride layer; they cross a junction, fl ow to the top conductive layer and then fl ow around to the back conductive layer, creating current.

Hot Salt Another technology that would supply perhaps one fi fth of the solar energy in our vision is known as concentrated solar power. In this design, long, metallic mirrors focus sunlight onto a pipe fi lled with fl uid, heating the fl uid like a huge magnifying glass might. The hot fl u- Plentiful Resource ) id runs through a heat exchanger, producing Solar radiation is abundant in the U.S., especially the Southwest. The 46,000

illustrations steam that turns a turbine. For energy storage, the pipes run into a large, square miles of solar arrays (white circles) required by the grand plan insulated tank fi lled with molten salt, which re- Average Daily Total Radiation tains heat effi ciently. Heat is extracted at night, could be distributed in various ways; (kWh/sq m/day) creating steam. The molten salt does slowly one option is shown here to scale. cool, however, so the energy stored must be NOTE: ALASKA AND HAWAII NOT SHOWN TO SCALE 8 7 6 5 4 3 2 tapped within a day. Nine concentrated solar power plants with a electricity could be generated 24 hours a day. PAYOFFS total capacity of 354 megawatts (MW) have Existing plants prove that concentrated solar ■ been generating electricity reliably for years in power is practical, but costs must decrease. Foreign oil dependence cut from 60 to 0 percent the U.S. A new 64-MW plant in Nevada came Economies of scale and continued research online in March 2007. These plants, however, would help. In 2006 a report by the Solar Task ■ Global tensions eased and do not have heat storage. The fi rst commercial Force of the Western Governors’ Association military costs lowered installation to incorporate it—a 50-MW plant concluded that concentrated solar power could with seven hours of molten salt storage—is provide electricity at 10 cents per kWh or less by ■ Massive trade defi cit being constructed in Spain, and others are be- 2015 if 4 GW of plants were constructed. Find- reduced signifi cantly ing designed around the world. For our plan, ing ways to boost the temperature of heat ex-

SOURCE FOR MAP: COURTESY OF NATIONAL RENEWABLE ENERGY LABORATORY; DON FOLEY ( FOLEY DON LABORATORY; ENERGY RENEWABLE NATIONAL OF COURTESY MAP: FOR SOURCE 16 hours of storage would be needed so that changer ﬂ uids would raise operating efﬁ ciency, ■ Greenhouse gas emissions slashed

■ Domestic jobs increased

Photovoltaic array Electricity delivered to the grid Junction box

Sunlight (photons)

Current Electron ﬂ ow creates current Transparent conductive layer Cadmium sulﬁ de semiconductor Junction Cadmium telluride semiconductor Conductive metal Power conditioner and transformer Glass

www.SciAm.com SCIENTIFIC AMERICAN 69 © 2007 SCIENTIFIC AMERICAN, INC. too. Engineers are also investigating how to use PINCH POINTS Stage One: Present to 2020 molten salt itself as the heat-transfer fl uid, re- We have given considerable thought to how the ducing heat losses as well as capital costs. Salt ■ Subsidies totaling $420 solar grand plan can be deployed. We foresee is corrosive, however, so more resilient piping billion through 2050 two distinct stages. The fi rst, from now until systems are needed. 2020, must make solar competitive at the mass- ■ Political leadership needed Concentrated solar power and photovoltaics production level. This stage will require the to raise the subsidy, represent two different technology paths. Nei- government to guarantee 30-year loans, agree possibly with a carbon tax ther is fully developed, so our plan brings them to purchase power and provide price-support both to large-scale deployment by 2020, giving ■ New high-voltage, subsidies. The annual aid package would rise them time to mature. Various combinations of direct-current electric steadily from 2011 to 2020. At that time, the solar technologies might also evolve to meet de- trans mission system built solar technologies would compete on their own mand economically. As installations expand, profi tably by private merits. The cumulative subsidy would total engineers and accountants can evaluate the pros carriers $420 billion (we will explain later how to pay and cons, and investors may decide to support this bill). one technology more than another. About 84 GW of photovoltaics and concentrated solar power plants would be built by Direct Current, Too 2020. In parallel, the DC transmission system The geography of solar power is obviously dif- would be laid. It would expand via existing ferent from the nation’s current supply scheme. rights-of-way along interstate highway corri- Today coal, oil, natural gas and nuclear power dors, minimizing land-acquisition and regula- plants dot the landscape, built relatively close tory hurdles. This backbone would reach major to where power is needed. Most of the coun- markets in Phoenix, Las Vegas, Los Angeles try’s solar generation would stand in the South- and San Diego to the west and San Antonio, west. The existing system of alternating-cur- Dallas, Houston, New Orleans, Birmingham, rent (AC) power lines is not robust enough to Ala., Tampa, Fla., and Atlanta to the east. carry power from these centers to consumers Building 1.5 GW of photovoltaics and 1.5 everywhere and would lose too much energy GW of concentrated solar power annually in the over long hauls. A new high-voltage, direct- fi rst fi ve years would stimulate many manufac-

current (HVDC) power transmission back- turers to scale up. In the next fi ve years, annual POWERSOUTH ENERGY COOPERATIVE bone would have to be built. Studies by Oak Ridge National Laboratory indicate that long-distance HVDC lines lose far less energy than AC lines do over equivalent spans. The backbone would radiate from the Southwest toward the nation’s borders. The lines would terminate at converter stations where the power would be switched to AC and sent along existing regional transmission lines that supply customers. The AC system is also simply out of capacity, leading to noted shortages in California and other regions; DC lines are cheaper to build and require less land area than equivalent AC lines. About 500 miles of HVDC lines operate in the U.S. today and have proved reliable and effi cient. No major technical advances seem to be needed, but more experience would help refi ne operations. The Southwest Power Pool of Texas is designing an integrated system of DC and AC transmission to enable development of 10 GW of wind power in western Texas. And TransCanada, Inc., is proposing 2,200 miles of HVDC lines to carry wind energy from Mon- tana and Wyoming south to Las Vegas and beyond.

70 SCIENTIFIC AMERICAN January 2008 © 2007 SCIENTIFIC AMERICAN, INC. construction would rise to 5 GW apiece, help- domestic jobs—notably in manufacturing solar [THE AUTHORS] ing ﬁ rms optimize production lines. As a result, components—would be created, which is sever- Ken Zweibel, James Mason and solar electricity would fall toward six cents per al times the number of U.S. jobs that would be Vasilis Fthenakis met a decade kWh. This implementation schedule is realistic; lost in the then dwindling fossil-fuel industries. ago while working on life-cycle studies of photovoltaics. Zweibel more than 5 GW of nuclear power plants were The huge reduction in imported oil would is president of PrimeStar Solar in built in the U.S. each year from 1972 to 1987. lower trade balance payments by $300 billion a Golden, Colo., and for 15 years was What is more, solar systems can be manufac- year, assuming a crude oil price of $60 a barrel manager of the National Renew- tured and installed at much faster rates than (average prices were higher in 2007). Once solar able Energy Laboratory’s Thin-Film conventional power plants because of their power plants are installed, they must be main- PV Partnership. Mason is director of the Solar Energy Campaign and straightforward design and relative lack of en- tained and repaired, but the price of sunlight is the Hydrogen Research Institute in vironmental and safety complications. forever free, duplicating those fuel savings year Farmingdale, N.Y. Fthenakis is after year. Moreover, the solar investment would head of the Photovoltaic Environ- Stage Two: 2020 to 2050 enhance national energy security, reduce ﬁ nan- mental Research Center at Brook- It is paramount that major market incentives cial burdens on the military, and greatly de- haven National Laboratory and is a professor in and director of remain in effect through 2020, to set the stage crease the societal costs of pollution and global Columbia University’s Center for for self-sustained growth thereafter. In extend- warming, from human health problems to the Life Cycle Analysis. ing our model to 2050, we have been conserva- ruining of coastlines and farmlands. tive. We do not include any technological or Ironically, the solar grand plan would lower cost improvements beyond 2020. We also energy consumption. Even with 1 percent annu- assume that energy demand will grow national growth in demand, the 100 quadrillion Btu ally by 1 percent a year. In this scenario, by consumed in 2006 would fall to 93 quadrillion 2050 solar power plants will supply 69 percent Btu by 2050. This unusual offset arises because of U.S. electricity and 35 percent of total U.S. a good deal of energy is consumed to extract and Brilliant? energy. This quantity includes enough to supply process fossil fuels, and more is wasted in burn- Far-fetched? all the electricity consumed by 344 million plug- ing them and controlling their emissions. For a discussion with in hybrid vehicles, which would displace their To meet the 2050 projection, 46,000 square the authors about the solar grand plan, please visit our Community gasoline counterparts, key to reducing depen- miles of land would be needed for photovoltaic page at http://science- dence on foreign oil and to mitigating green- and concentrated solar power installations. That community.SciAm.com; click on

DON FOLEY house gas emissions. Some three million new area is large, and yet it covers just 19 percent of Discussions, then Technology.

Underground Electricity Electricity from to the grid Storage photovoltaic farm Generator Natural gas–fueled Excess electricity produced during combustion chamber the day by photovoltaic farms Exhaust heat would be sent over power lines to Recuperator compressed-air energy storage (pre-heats air) sites close to cities. At night the sites would generate power for Water-cooling tower consumers. Such technology is al- Compressors Low- ready available; the PowerSouth pressure Motor turbine Energy Cooperative’s plant in Mc- High- pressure Intosh, Ala. (left), has operated turbine since 1991 (the white pipe sends air underground). In these designs, incoming electricity runs motors and compressors that pressurize leased re te air and send it into vacant caverns, Air genera to icity mines or aquifers (right). When the ctr air is released, it is heated by burn- d ele mpe ing small amounts of natural gas; Air pu o cavern the hot, expanding gases turn int orage turbines that generate electricity. for st Cavern

www.SciAm.com SCIENTIFIC AMERICAN 71 © 2007 SCIENTIFIC AMERICAN, INC. Although the suitable Southwest land. Most of that land is ongoing research would improve solar efﬁ cien- barren; there is no competing use value. And the cy, cost and storage. $420 billion is land will not be polluted. We have assumed that Under these assumptions, U.S. energy de- substantial, only 10 percent of the solar capacity in 2050 will mand could be fulﬁ lled with the following capac- come from distributed photovoltaic installa- ities: 2.9 terawatts (TW) of photovoltaic power it is less than tions—those on rooftops or commercial lots going directly to the grid and another 7.5 TW the U.S. Farm throughout the country. But as prices drop, these dedicated to compressed-air storage; 2.3 TW of applications could play a bigger role. concentrated solar power plants; and 1.3 TW Price Support of distributed photovoltaic installations. Supply program. 2050 and Beyond would be rounded out with 1 TW of wind farms, Although it is not possible to project with any 0.2 TW of geothermal power plants and 0.25 exactitude 50 or more years into the future, as TW of biomass-based production for fuels. The an exercise to demonstrate the full potential of model includes 0.5 TW of geothermal heat solar energy we constructed a scenario for 2100. pumps for direct building heating and cooling. By that time, based on our plan, total energy The solar systems would require 165,000 square demand (including transportation) is projected miles of land, still less than the suitable available to be 140 quadrillion Btu, with seven times area in the Southwest. today’s electric generating capacity. In 2100 this renewable portfolio could gen- To be conservative, again, we estimated how erate 100 percent of all U.S. electricity and more much solar plant capacity would be needed un- than 90 percent of total U.S. energy. In the der the historical worst-case solar radiation spring and summer, the solar infrastructure conditions for the Southwest, which occurred would produce enough hydrogen to meet more during the winter of 1982–1983 and in 1992 than 90 percent of all transportation fuel de- and 1993 following the Mount Pinatubo erup- mand and would replace the small natural gas tion, according to National Solar Radiation supply used to aid compressed-air turbines. Data Base records from 1961 to 2005. And Adding 48 billion gallons of biofuel would cov- again, we did not assume any further techno- er the rest of transportation energy. Energy-re- logical and cost improvements beyond 2020, lated carbon dioxide emissions would be re-

even though it is nearly certain that in 80 years duced 92 percent below 2005 levels. COURTESY OF NREL

Concentrated Solar Large concentrated solar power plants would complement photovoltaic farms in the Southwest. The Kramer Junction plant in California’s Mojave Desert (left), using technology from Solel in Beit Shemesh, Isra- el, has been operating since 1989. Metallic parabolic mirrors focus sunlight on a pipe, heating ﬂ uid such as ethylene glycol inside (right). The mirrors rotate to track the sun. The hot pipes run alongside a second loop inside a heat exchanger that contains water, turning it to steam that drives a turbine. Future plants could also send the hot ﬂ uid through a holding tank, heating molten salt; that reservoir would retain heat that could be tapped at night for the heat exchanger.

72 SCIENTIFIC AMERICAN January 2008 © 2007 SCIENTIFIC AMERICAN, INC. Who Pays? ➥ MORE TO dies would end from 2041 to 2050. The HVDC Our model is not an austerity plan, because it EXPLORE transmission companies would not have to be includes a 1 percent annual increase in demand, The Terawatt Challenge for Thin subsidized, because they would fi nance con- which would sustain lifestyles similar to those Film Photovoltaic. Ken Zweibel in struction of lines and converter stations just as today with expected effi ciency improvements in Thin Film Solar Cells: Fabrication, they now fi nance AC lines, earning revenues by energy generation and use. Perhaps the biggest Characterization and Applications. delivering electricity. question is how to pay for a $420-billion over- Edited by Jef Poortmans and Although $420 billion is substantial, the an- Vladimir Arkhipov. John Wiley & haul of the nation’s energy infrastructure. One Sons, 2006. nual expense would be less than the current U.S. of the most common ideas is a carbon tax. The Farm Price Support program. It is also less than International Energy Agency suggests that a car- Energy Autonomy: The Economic, the tax subsidies that have been levied to build bon tax of $40 to $90 per ton of coal will be Social and Technological Case for the country’s high-speed telecommunications required to induce electricity generators to adopt Renewable Energy. Hermann infrastructure over the past 35 years. And it Scheer. Earthscan Publications, 2007. carbon capture and storage systems to reduce frees the U.S. from policy and budget issues carbon dioxide emissions. This tax is equivalent Center for Life Cycle Analysis, driven by international energy confl icts. to raising the price of electricity by one to two Columbia University: Without subsidies, the solar grand plan is im- cents per kWh. But our plan is less expensive. The www.clca.columbia.edu possible. Other countries have reached similar $420 billion could be generated with a carbon conclusions: Japan is already building a large, The National Solar Radiation tax of 0.5 cent per kWh. Given that electricity Data Base. National Renewable subsidized solar infrastructure, and Germany today generally sells for six to 10 cents per kWh, Energy Laboratory, 2007. has embarked on a nationwide program. Al- adding 0.5 cent per kWh seems reasonable. http://rredc.nrel.gov/solar/old_ though the investment is high, it is important to Congress could establish the fi nancial incen- data/nsrdb remember that the energy source, sunlight, is free. tives by adopting a national renewable energy There are no annual fuel or pollution-control The U.S. Department of Energy plan. Consider the U.S. Farm Price Support pro- Solar America Initiative: costs like those for coal, oil or nuclear power, and gram, which has been justifi ed in terms of na- www1.eere.energy.gov/solar/ only a slight cost for natural gas in compressed- tional security. A solar price support program solar_america air systems, although hydrogen or biofuels could would secure the nation’s energy future, vital to displace that, too. When fuel savings are factored the country’s long-term health. Subsidies would in, the cost of solar would be a bargain in be gradually deployed from 2011 to 2020. With Sunlight coming decades. But we cannot wait un-

DON FOLEY FOLEY DON a standard 30-year payoff interval, the subsi- til then to begin scaling up. Critics have raised other con- Pipe cerns, such as whether material ﬁ lled with constraints could stiﬂ e large-scale ethylene glycol installation. With rapid deployment, temporary shortages are Parabolic trough possible. But several types of cells exist that use different material combinations. Better processing and recy-

Heat exchanger cling are also reducing the amount of materials that cells require. And in the long term, Electricity to old solar cells can largely be recycled into new the grid solar cells, changing our energy supply picture from depletable fuels to recyclable materials. Superheated The greatest obstacle to implementing a re- Ethylene water fl ow glycol fl ow newable U.S. energy system is not technology or money, however. It is the lack of public Return awareness that solar power is a practical alter- water fl ow Steam native—and one that can fuel transportation as condensation well. Forward-looking thinkers should try to unit inspire U.S. citizens, and their political and scientifi c leaders, about solar power’s incredible potential. Once Americans realize that poten- Future plan: Steam turbine heat-holding tank tial, we believe the desire for energy self-suffi - (molten salt) ciency and the need to reduce carbon dioxide Generator emissions will prompt them to adopt a national solar plan. g

Second Thoughts about

New research indicates that a cavity-ﬁ ghting treatment could be risky if overused By Dan Fagin

ong before the passionate debates over cig- dents of 46 of the nation’s 50 largest cities. Out- KEY CONCEPTS arettes, DDT, asbestos or the ozone hole, side the U.S., fl uoridation has spread to Canada, ■ Researchers are intensify- L most Americans had heard of only one the U.K., Australia, New Zealand and a few ing their scrutiny of fl uo- environmental health controversy: fl uoridation. other countries. Critics of the practice have gen- ride, which is added to Starting in the 1950s, hundreds of communities erally been dismissed as gadfl ies or zealots by most public water sys- across the U.S. became embroiled in heated bat- mainstream researchers and public health agen- tems in the U.S. Some tles over whether fl uorides—ionic compounds cies in those countries as well as the U.S. (In recent studies suggest containing the element fluorine—should be other nations, however, water fl uoridation is that overconsumption of added to their water systems. On one side was rare and controversial.) The U.S. Centers for fl uoride can raise the risks of disorders affecting a broad coalition of scientists from government Disease Control and Prevention even lists water teeth, bones, the brain and industry who argued that adding fl uoride fl uoridation as one of the 10 greatest health and the thyroid gland. to drinking water would protect teeth against achievements of the 20th century, alongside decay; on the other side were activists who con- vaccines and family planning. ■ A 2006 report by a com- tended that the risks of fl uoridation were inad- Now, though, scientifi c attitudes toward fl uo- mittee of the National Research Council recom- equately studied and that the practice amount- ri dation may be starting to shift in the country mended that the federal ed to compulsory medication and thus was a where the practice began. After spending more government lower its cur- violation of civil liberties. than two years reviewing and debating hun- rent limit for fl uoride in The advocates of fl uoride eventually carried dreds of studies, a committee of the National drinking water because of the day, in part by ridiculing opponents such as Research Council (NRC) released a report in health risks to both chil- the right-wing John Birch Society, which called 2006 that gave a tinge of legitimacy to some dren and adults. fl uoridation a communist plot to poison Amer- longtime assertions made by antifl uoridation —The Editors ica. Today almost 60 percent of the U.S. popu- campaigners. The report concluded that the En-

lation drinks ﬂ uoridated water, including resi- vironmental Protection Agency’s current limit GOODMAN AARON

74 SCIENTIFIC AMERICAN January 2008 © 2007 SCIENTIFIC AMERICAN, INC. for fl uoride in drinking water—four milligrams uation is worrisome because there is so much p TOO MUCH OF A GOOD per liter (mg/L)—should be lowered because of uncertainty over how much additional fl uoride THING: Fluoride is in many health risks to both children and adults. In chil- we ingest from food, beverages and dental prod- foods, beverages and dental products. The dren, consistent exposure to fl uoride at that lev- ucts. What is more, the NRC panel noted that ubiquity of the cavity- el can discolor and disfi gure emerging perma- fl uoride may also trigger more serious health fi ghting chemical can nent teeth—a condition called dental fl uorosis. problems, including bone cancer and damage to result in overconsump- In adults, the same fl uoride level appears to in- the brain and thyroid gland. Although these ef- tion, particularly among crease the risk of bone fracture and, possibly, of fects are still unproved, the panel argued that young children. moderate skeletal fl uorosis, a painful stiffening they deserve further study. of the joints. Most fl uoridated water contains The largest long-running investigation of the much less fl uoride than the EPA limit, but the sit- effects of fl uoride is the Iowa Fluoride Study, di- www.SciAm.com SCIENTIFIC AMERICAN 75 © 2007 SCIENTIFIC AMERICAN, INC. 59% of the U.S. population received fl uoridated water [TRENDS] in 2002 FLUORIDATION ACROSS AMERICA Water fl uoridation has spread across the PERCENTAGE OF STATE POPULATIONS RECEIVING FLUORIDATED WATER, 2002

U.S. since its introduction in 1945. In 2002, < 25% 25%–49% 50%–75% >75% the latest year for which data are available, Americans receiving ﬂ uoridated water represented 67 percent of all people supplied WA ME by public water systems and 59 percent of MT ND VT the total population. Fluoridation is most NH MN OR NY MA prevalent in the District of Columbia (100 WI percent) and Kentucky (99.6 percent) and ID SD MI RI least common in Hawaii (8.6 percent) and WY PA CT IA NJ Utah (2.2 percent). NE OH DE IN MD NV IL UT WV CO VA FLUORIDATION RISING IN THE U.S. CA KS MO KY Total U.S. population NC 300 Supplied by public water systems* TN Receiving fluoridated water OK SC AZ NM AR 200 MS AL GA

TX LA 100 AK FL Number of People (millions) 0 1945 1965 1985 2002 HI Year

*Data on public water systems not available before 1964

rected by Steven M. Levy of the University of is not as strong as it used to be. “Instead of just Iowa College of Dentistry. For the past 16 years pushing for more fl uoride, we need to fi nd the Levy’s research team has closely tracked about right balance,” Levy says. 700 Iowa children to try to tease out subtle effects of fl uoridation that may have been over- The Advent of Fluoride [THE AUTHOR] looked by previous studies. At the same time, Framed toothpaste advertisements from more Levy is also leading one of the most extensive than half a century ago hang on the walls of ) efforts ever to measure fl uoride concentrations Levy’s conference room. One touting Pebeco

in thousands of products—including foods, Toothpaste reads: “Do you want your teeth to clip paper drinks and toothpastes—to develop credible es- ache and get ugly?” Another asserts that “Col- timates of typical ﬂ uoride intake. gate Chlorophyll Toothpaste Destroys Bad It is a maddeningly complex area of research Breath.” They are artifacts of the preﬂ uoride because diets, toothbrushing habits and water era, when tooth decay—called caries in the par-

ﬂ uoridation levels vary so much and also be- lance of dentistry—was pervasive and tooth- ( MOODBOARD/CORBIS );

cause genetic, environmental and even cultural pastes were marketed with questionable medi- graph and and is an associate profes- factors appear to leave some people much more cal claims.

Dan Fagin map sor of journalism and director of susceptible to the effects of fl uoride—both pos- The introduction of fl uoride changed all that. the Science, Health and Environ- itive and negative—than others. Despite all the In 1945 Grand Rapids, Mich., became the fi rst mental Reporting Program at New uncertainties, however, Levy and some other city to fl uoridate its water supply. Ten years lat- York University. A former environ- fl uoride researchers have come around to the er Procter & Gamble introduced Crest, the fi rst mental and science writer for Newsday, his articles on cancer view that some children, especially very young fl uoridated toothpaste, which contained stan- epidemiology won the AAAS ones, are probably getting more fl uoride than nous fl uoride (a compound with one atom of tin READING-IKKANDA); LUCY (

Science Journalism Award in 2003. they should. Most of those scientists, including and two of fluorine). Colgate-Palmolive fol- Fagin Fagin is co-author of Toxic Decep- Levy, still support water fl uoridation as a proved lowed in 1967 by modifying its Colgate brand tion (Common Courage Press, method of controlling tooth decay, especially in with what has become one of the dominant cav- 1999) and is working on a book about gene-environment interac- populations where oral hygiene is poor. But the ity-fi ghting ingredients in toothpastes: sodium tions and the childhood cancer researchers also believe that in communities monofl uorophosphate. Instead of sticking with

cluster in Toms River, N.J. with good dental care the case for ﬂ uoridation the ﬂ uoride salts found in toothpastes and fa- ( FAGIN ANNA OF COURTESY

76 SCIENTIFIC AMERICAN January 2008 © 2007 SCIENTIFIC AMERICAN, INC. [FOCUS ON TEETH] vored by dentists in offi ce treatments, most water suppliers eventually switched to the cheaper FIGHTING CAVITIES option of fl uoridating with silicofl uorides such Fluoride’s role in combating tooth decay is rooted in the ion’s powerful as hexafl uorosilicic acid, a by-product of a fer- attraction to enamel, the hard, white outer layer of the teeth. tilizer manufacturing process in which phosphate ores are treated with sulfuric acid. Fluoride ions Calcium ions Enhanced applied to teeth By the 1970s and 1980s America was awash Phosphate ions deposition of calcium and in various forms of fl uoride, and fl uoridation Fluoride ions phosphate had become the cornerstone of preventative Calcium and dentistry in most English-speaking countries. phosphate ions Exactly why and how much caries incidence de- creased during the same period is a matter of fi erce debate, but the consensus among dental Enamel Acid excreted researchers is that the decline was steep and that by bacteria fl uoride deserved much of the credit. That was the culture in which Levy got his Gums start in public health dentistry in the mid-1980s. Blood Food vessels remnant Colgate-Palmolive funded his early research, which had the effect of encouraging more fl uoride use in dental offi ces. But as American dentists began to see fewer cavities and more fl uorosis on the teeth of their young patients, Levy started to wonder whether children were getting too much of a good thing. “There was a transition in my own thinking from ‘more fl uoride is defi nitely our goal’ to making sure we understand where the right balance is between p Without Fluoride p With Fluoride caries and fl uorosis.” The primary mineral in enamel is hydroxylap- The topical application of fl uoride to the Fluoride’s role in causing one disease and de- atite, a crystal composed of calcium, phos- teeth has two effects. First, the fl uoride phorus, hydrogen and oxygen. When food ions replace some of the hydroxyl groups in terring another is rooted in the fl uorine ion’s pow- remnants become lodged between teeth, the hydroxylapatite molecules, creating erful attraction to calcium-bearing tissues in the bacteria consume the sugars and excrete lac- fl uorapatite crystals that are slightly more body. In fact, more than 99 percent of ingested tic acid, which can lower the pH of the mouth resistant to the enamel-dissolving acid ex- enough to dissolve the hydroxylapatite. If creted by the bacteria. Second, the fl uoride fl uoride that is not quickly excreted ends up in the rate of dissolution is higher than the rate on the surface of teeth serves as a catalyst bones and teeth. Fluoride inhibits cavities through of remineralization—the deposition of calci- that enhances the deposition of calcium um and phosphate ions from saliva onto the and phosphate, thus remineralizing dam- two separate mechanisms. First, fl uoride that enamel—then cavities will form in the teeth. aged enamel and combating decay. touches the enamel—the hard, white outer layer of the teeth—becomes embedded in the crystalline structures of hydroxylapatite, the main min- Debating the Effects eral component of teeth and bones. The fl uorine ions replace some of the hydroxyl groups in the The U.S. Centers for Disease Control and TOOTH DECAY INDEX hydroxylapatite molecules of the enamel, and this Prevention has hailed fl uoridation as one (number of decayed, missing of the 10 greatest public health achieve- or filled teeth in 12-year-olds) substitution makes teeth slightly more resistant 8 to the enamel-dissolving acid excreted by bacte- ments of the 20th century, claiming that Fluoridated the addition of the chemical to drinking 7 U.S. ria in the mouth as they consume food remnants. Australia New Zealand ) water has been one of the main reasons Second, the fl uoride on the surface of teeth serves 6 for the decline in tooth decay over the

graph Unfluoridated as a catalyst that enhances the deposition of cal- past three decades (measured here by the 5 Belgium Finland cium and phosphate, making it easier for the body number of decayed, missing or ﬁ lled 4 Italy to continually rebuild the enamel crystals that the teeth in 12-year-olds). Rates of tooth 3 bacteria are dissolving. decay have also plunged, however, in Fluoride has a very different effect, however, many countries where public water sys- 2

); LUCY READING-IKKANDA); LUCY ( when large doses are ingested by young children tems are not ﬂ uoridated. In some of 1

teeth these nations, ﬂ uoride added to foods, whose permanent teeth are still developing and 0 have not yet erupted. The key proteins in early beverages and dental products may 1975 1985 1995 2005 Year tooth formation are called amelogenins, which account for part of the decline.

ANDREW SWIFT ( SWIFT ANDREW regulate the formation of hydrox ylapatite crys-

www.SciAm.com SCIENTIFIC AMERICAN 77 © 2007 SCIENTIFIC AMERICAN, INC. [AREA OF CONCERN] IS FLUORIDE WEAKENING BONE? Scientists have focused on ﬂ uoride’s effects on bone because so much of the chemical is stored there. Studies have shown that high doses of ﬂ uoride can stimulate the proliferation of bone-building osteo- Periosteum Marrow blast cells, raising fears that the chemical may induce malignant tumors. Fluoride also appears Spongy bone to alter the crystalline structure of bone, possibly increasing the risk of fractures. Compact bone Osteoblasts forming Proliferation of Layer of new new bone Existing bone osteoblasts weak bone

Fluoride ions

Blood vessels

p Normal Bone Formation p Effects of Excessive Fluoride

tals. As a crystal matrix forms, the amelogenins weight per day. In the early 1990s, when the break down and are removed from the matur- children in Levy’s study were infants, he found ing enamel. But when some children consume that more than a third of them were ingesting high doses of fluoride, which is absorbed enough fl uoride—mostly via water-based infant through the digestive tract and delivered by the formula, baby foods and juice drinks—to put bloodstream to the developing teeth, the bio- them at a high risk of developing mild fl uorosis Scientifi c chemical signaling goes awry and the proteins in their permanent teeth. That fraction dropped remain inside the budding tooth longer than only slightly as their diet changed during their attitudes usual, thereby creating gaps in the crystalline toddler years—a critical period for enamel for- toward enamel structure. As a result, when a fl uorosed mation in preemergent teeth. Typical fl uoride tooth fi nally erupts it is often unevenly colored, ingestion stayed high during the toddler years, fl uoridation with some portions whiter than others—a visu- in part because toothpaste replaced formula as may be al effect caused by light refracting off the po- a key source. Although both children and adults rous enamel. In more severe cases, the surface are supposed to spit out their toothpaste after starting of the tooth is pitted and the stains are brown. brushing, Levy had found in an earlier study Nutrition and genetics can infl uence the risk of that toddlers on average actually swallowed to shift in fl uorosis, but the most important factor by far more than half of their toothpaste. the country is the amount of fl uoride ingested. By the time the Iowa children were nine With grant money from the National Insti- years old and their permanent front teeth had where the tute of Dental and Craniofacial Research, Levy emerged, it was obvious that the earlier expo- practice set out to determine how much fl uoride children sures to fl uoride had literally left their mark. consume and how it affects their teeth and The front teeth of children who had been in the began. bones. There is no universally accepted optimal high-intake group as infants and toddlers were level for daily intake of fl uoride—that is, a level more than twice as likely to show the telltale that maximizes protection against tooth decay staining of fl uorosis than the teeth of children while minimizing other risks—but the range who had ingested less fl uoride when they were most often cited by researchers is 0.05 to 0.07 younger. And as their diet broadened, so did

milligram of fluoride per kilogram of body their sources of ﬂ uoride. Tests performed in SWIFT ANDREW

78 SCIENTIFIC AMERICAN January 2008 © 2007 SCIENTIFIC AMERICAN, INC. Levy’s lab found, for example, that many kinds osteoporosis—a bone disease that increases the of juice drinks and soda pop contain enough risk of fractures—have shown that high doses fluo ride (generally about 0.6 mg/L) so that of fl uoride can stimulate the proliferation of drinking a little more than a liter a day would bone-building osteoblast cells, even in elderly put a typical three-year-old at the optimal in- patients. The exact mechanism is still unknown, take level, without counting any other daily but fl uoride appears to achieve this by increas- sources. ing the concentrations of tyrosine-phosphory- Dozens of food items tested by Levy’s team lated proteins, which are involved in biochemi- contained even higher concentrations of fl uo- cal signaling to osteoblasts. As with tooth ride: an average of 0.73 mg/L in cranberry-juice enamel, however, fl uoride not only stimulates cocktail, 0.71 mg/L in ice pops, 0.99 mg/L in bone mineralization, it also appears to alter the beef gravy and 2.10 mg/L in canned crabmeat, crystalline structure of bone—and in this case, for example. In most cases, the fl uoride came the effects are not merely aesthetic. Although from water added during processing, although fl uoride may increase bone volume, the strength higher levels also got into grapes and raisins via of the bone apparently declines. Epidemiologi- pesticides, into processed chicken products via cal studies and tests on lab animals suggest that ground-up bone, and into tea leaves via absorp- high fl uoride exposure increases the risk of bone tion from soil and water. fracture, especially in vulnerable populations Levy found that exposure to fluoridated such as the elderly and diabetics. Although drinking water was an even more important risk those studies are still somewhat controversial, factor for fl uorosis. Iowa children who lived in nine of the 12 members of the NRC panel con- communities where the water was fl uoridated cluded that a lifetime of exposure to drinking were 50 percent more likely to have mild fl uoro- water fluoridated at 4 mg/L or higher does SIGNS OF sis on at least two of their eight permanent front indeed raise the risk of fracture. The committee FLUOROSIS teeth at nine years of age than children living in noted that lower fl uoridation levels may also When young children consume nonfl uoridated areas of the state (there was a 33 increase the risk, but the evidence is murkier. large amounts of fl uoride, the percent prevalence in the former versus 22 per- As the Iowa children in his study enter ado- chemical can disrupt the develop- cent in the latter). Similar results appeared in lescence, Levy hopes that analyses of the ment of their permanent teeth. the NRC report, which found that infants and strength of their spine, hips and overall skeleton When the teeth emerge, their toddlers in fluoridated communities ingest will point to possible connections between fl uo- enamel may be discolored (top) or, in more severe cases, disfi g- about twice as much fl uoride as they should. ride intake and bone health. He presented some ured (bottom). Researchers have Furthermore, the committee noted that adults preliminary data in 2007, fi nding little differ- found that this condition, called who drink above-average amounts of water, in- ence in the mineral content of the bones of 11- dental fl uorosis, is more common cluding athletes and laborers, are also exceed- year-olds based on how much fl uoride they had in communities where the drinking the optimal level for fl uoride intake. ingested as young children. As they go through ing water is fl uoridated. But enamel fl uorosis, except in the severest adolescence, however, Levy thinks that cases, has no health impact beyond lowered trends may emerge. self-esteem: the tooth marks are unattractive The even bigger question looming over and do not go away (although there are mask- the fl uoride debate is whether these known ing treatments). The much more important cellular effects in bones and teeth are clues question is whether fl uoride’s effects extend be- that fl uoride is affecting other organs and yond altering the biochemistry of tooth enamel triggering other diseases besides fl uorosis. formation. Says longtime fl uoride researcher The biggest current debate is over osteosar- Pamela DenBesten of the University of Califor- coma—the most common form of bone can- nia, San Francisco, School of Dentistry: “We cer and the sixth most prevalent cancer in certainly can see that fl uoride impacts the way children. Because fl uoride stimulates the pro- proteins interact with mineralized tissue, so duction of osteoblasts, several researchers what effect is it having elsewhere at the cellular have suggested that it might induce malignant level? Fluoride is very powerful, and it needs to tumors in the expanding cell population. A be treated respectfully.” 1990 study conducted by the U.S. government’s National Toxicology Program found

University of Iowa of University Fluoride and Bone a positive dose-response relation for osteo- Bone is an obvious place to look for fl uoride’s sarcoma incidence in male rats exposed to fi ngerprints because so much fl uoride is stored different amounts of fl uoride in drinking wa-

STEVEN M. LEVY M. STEVEN there. What is more, studies of patients with ter (all those amounts, as is typical for ani-

www.SciAm.com SCIENTIFIC AMERICAN 79 © 2007 SCIENTIFIC AMERICAN, INC. mal studies, were far above the actual expo- mechanism: the formation of aluminum fl uo- sures found in fl uoridated communities). But ride complexes—small inorganic molecules that other animal studies as well as most epidemio- mimic the structure of phosphates and thus in- logical studies in human populations have been fl uence enzyme activity in the brain. There is ambiguous at best. also some evidence that the silicofl uorides used A FLUORIDE DIET The latest dustup over fl uoride and osteosar- in water fl uoridation may enhance the uptake The optimal range for daily intake coma was instigated by a young researcher of lead into the brain. of fl uoride—the level that maxi- named Elise B. Bassin of the Harvard School of The endocrine system is yet another area mizes protection against tooth Dental Medicine. Bassin collected information where some evidence exists that fl uoride can decay but minimizes other risks— about fl uoride exposures among 103 osteosar- have an impact. The NRC committee conclud- is generally considered to be 0.05 to 0.07 milligram for each kilo- coma patients and 215 matched control subjects ed that fl uoride can subtly alter endocrine func- gram of body weight. Consuming and concluded that fl uoride is a risk factor for tion, especially in the thyroid—the gland that foods and beverages with large the cancer among boys (the results were ambig- produces hormones regulating growth and me- amounts of fl uoride can put a diet uous for girls). Bassin’s report appeared in 2006 tabolism. Although researchers do not know above this range. Below are typi- in the journal Cancer Causes and Control; in how fl uoride consumption can infl uence the cal trace levels of fl uoride, measured in parts per million (ppm), the same issue, however, her dissertation advis- thyroid, the effects appear to be strongly infl u- found in foods and drinks tested er at Harvard, Chester Douglass, wrote a com- enced by diet and genetics. Says John Doull, at the University of Iowa College mentary warning readers to be “especially cau- professor emeritus of pharmacology and toxi- of Dentistry. tious” in interpreting her fi ndings because, he cology at the University of Kansas Medical Cen- said, better data, still unpublished, contradict ter, who chaired the NRC committee: “The thy- 3.73 ppm Brewed black tea them. Antifl uoridationists and some envi- roid changes do worry me. There are some ppm Raisins u ronmental groups quickly rushed to things there that need to be explored.”

2.34 ) 2.02 ppm White wine Bassin’s defense, demanding that Har-

vard investigate Douglass, professor The Controversy Continues cream ice 1.09 ppm Apple- and chair of epidemiology at the den- The release of the NRC report has not triggered fl avored juice drink tal school, for allegedly misrepresent- a public stampede against fl uoridation, nor has ing Bassin’s work and for having a con- it prompted the EPA to quickly lower its fl uoride 0.91 ppm Brewed fl ict of interest because he is editor in limit of 4 mg/L (the agency says it is still study- coffee chief of a newsletter for dentists funded by ing the issue). Water suppliers who add fl uoride 0.71 ppm Tap water Colgate. The university’s investigation of Doug- typically keep levels between 0.7 to 1.2 mg/L, (U.S.-wide lass, completed in 2006, concluded that there far below the EPA limit. About 200,000 Ameri- average) ); C SQUARED STUDIOS/GETTY IMAGES (

was no misconduct or conﬂ ict of interest. cans—and several million people in China, beer ( 0.61 ppm Chicken soup Clashes over the possible neurological effects India, the Middle East, Africa and Southeast broth of ﬂ uoride have been just as intense. Phyllis Asia—drink concentrations higher than the lim-

0.60 ppm Diet Coke Mullenix, then at the Forsyth Institute in Bos- it, but their excess fl uoride comes from natural- Getty Images (U.S.-wide ton, set off a fi restorm in the early 1990s ly occurring runoff from fl uoride-containing average) when she reported that experiments on rocks and soils near water sources. 0.48 ppm Hot dog lab rats showed that sodium fl uoride The report is, however, prompting some re-

0.46 ppm Grapefruit can accumulate in brain tissue and af- searchers to wonder whether even 1 mg / L is too KITCHEN JONATHAN );

juice fect animal behavior. Prenatal expo- much in drinking water, in light of the growing raisins sures, she reported, correlated with hy- recognition that food, beverages and dental 0.45 ppm Beer u peractivity in young rats, especially products are also major sources of fl uoride, es- 0.45 ppm Baked russet males, whereas exposures after birth had pecially for young children. The NRC commit- potatoes the opposite effect, turning female rats tee did not formally address the question, but 0.35 ppm Cheddar cheese into what Mullenix later described as its analyses suggest that lower water fl uorida- 0.33 ppm Flour “couch potatoes.” Although her research tion levels may pose risks, too. “What the com- tortillas was eventually published in Neurotoxicology mittee found is that we’ve gone with the status ); IMAGE SOURCE PINK/GETTY IMAGES ( and Teratology, it was attacked by other quo regarding fl uoride for many years—for too 0.32 ppm Creamed corn hot dog hot (baby food) scientists who said that her methodolo- long, really—and now we need to take a fresh ( gy was fl awed and that she had used un- look,” Doull says. “In the scientifi c community, 0.23 ppm Chocolate realistically high dosages. Since then, people tend to think this is settled. I mean, when

ice cream u Getty Images however, a series of epidemiological the U.S. surgeon general comes out and says this 0.13 ppm Brewed studies in China have associated high is one of the 10 greatest achievements of the chamomile tea ﬂ uoride exposures with lower IQ, and 20th century, that’s a hard hurdle to get over.

0.03 ppm Milk (2%) research has also suggested a possible But when we looked at the studies that have DAVID ROSENBERG

80 SCIENTIFIC AMERICAN January 2008 © 2007 SCIENTIFIC AMERICAN, INC. [BACKGROUND] FLUORIDE HISTORY he risks of fl uoride were known long before its benefi ts. Starting in the fi rst decade of the 20th century, a T dentist named Frederick McKay traveled the American West investigating reports of what was then known as Colorado Brown Stain. With a collaborator, G. V. Black, dean of the Northwestern University Dental School, McKay discovered that children born in Colorado Springs, Colo., had stained teeth, but adults who moved there did not. They hypothesized that young children whose permanent teeth had not yet erupted or developed enamel faced the highest risk of developing the stain. McKay, who guessed that the stain was caused by some unknown compound in the local drinking water, also noticed a curious fact: the mottled teeth were surprisingly resistant to decay. The cause remained a mystery until 1930, when McKay went to Arkansas to investigate reports of tooth staining in Bauxite, a company town owned by the Aluminum Company of America (Alcoa). Worried that aluminum might be blamed, Alcoa’s chief chemist, H. V. Churchill, tested the local water and discovered something McKay had never suspected: high levels of naturally occurring fl uoride. McKay quickly tested other sus- ➥ pect water supplies and found that wherever fl uoride levels were high—typically 2.5 milligrams per liter or MORE TO higher—Colorado Brown Stain was prevalent. A new disease entered the EXPLORE lexicon: fl uorosis. Patterns of Fluoride Intake from Spurred by Churchill’s and McKay’s discoveries, a researcher named Birth to 36 Months. Steven M. Henry Trendley Dean, head of the dental hygiene unit at the National Levy, John J. Warren, Charles S. Institute of Health (which later changed its name to the National Insti- Davis, H. Lester Kirchner, Michael J. tutes of Health), tried to determine how much fl uoride was enough to Kanellis and James S. Wefel in Jour- trigger fl uorosis. By the late 1930s he had concluded that levels below nal of Public Health Dentistry, Vol. 61, No. 2, pages 70–77; June 2001. 1 mg/L would pose little risk. Dean remembered that McKay had found that fl uorosed teeth were resistant to decay, and so he began Patterns of Fluoride Intake from pushing for a citywide test of a revolutionary idea: deliberately add- 36 to 72 Months of Age. Steven M. ing fl uoride to water at levels that would deter cavities without trig- Levy, John J. Warren and Barbara gering fl uorosis. He got his wish in 1945 in Grand Rapids, Mich., Broffi tt in Journal of Public Health and Dean went on to become fl uoridation’s leading advocate as the Dentistry, Vol. 63, No. 4, pages 211– 220; December 2003. fi rst director of the newly formed National Institute of Dental Re- search from 1948 until his retirement in 1953. —D.F. Timing of Fluoride Intake in Rela- tion to Development of Fluorosis t COLORADO DENTIST Frederick McKay, on Maxillary Central Incisors. whose investigations led to the discovery Liang Hong, Steven M. Levy, of fl uoride’s effects on teeth. Barbara Broffi tt, John J. Warren, Michael J. Kanellis, James S. Wefel and Deborah V. Dawson in Commu- been done, we found that many of these ques- its fi ndings. He acknowledges, however, that nity Dentistry and Oral Epidemiology, Vol. 34, No. 4, pages 299–309; tions are unsettled and we have much less infor- the argument for water fl uoridation is not as August 2006. mation than we should, considering how long strong in affl uent areas with good nutrition and this [fl uoridation] has been going on. I think dental care. “Today it depends on what the car- Age-Specifi c Fluoride Exposure in that’s why fl uoridation is still being challenged ies level is in the community. If the disease is Drinking Water and Osteosarco- so many years after it began. In the face of igno- low, the return on investment [for fl uoridation] ma. Elise B. Bassin, David Wypij, Roger B. Davis and Murray A. rance, controversy is rampant.” may not be all that great.” Mittleman in Cancer Causes and Con- Some longtime fl uoride researchers, however, Opponents of fl uoridation, meanwhile, have trol, Vol. 17, No. 4, pages 421–428; remain unimpressed by the evidence of effects been emboldened by the NRC report. “What May 2006. beyond teeth and bones, and they continue to the committee did was very, very important, be- push for an expansion of water fl uoridation in cause it’s the fi rst time a truly balanced panel Caution Needed in Fluoride and Osteosarcoma Study. Chester W. the U.S. and elsewhere. Their view remains the has looked at this and raised important ques- Douglass and Kaumudi Joshipura in offi cial position of the American Dental Asso- tions,” says Paul Connett, a chemistry professor Cancer Causes and Control, Vol. 17, ciation and the U.S. Public Health Service. “We at St. Lawrence University and the executive di- No. 4, pages 481–482; May 2006. feel there are enough communities out there rector of the Fluoride Action Network, one of with high caries rates to justify additional fl uo- the most active antifl uoridation groups world- Fluoride in Drinking Water: A Scientifi c Review of EPA’s ridation,” says Jayanth V. Kumar, director of wide. “I absolutely believe it’s a scientifi c turn- Standards. National Academy oral health surveillance and research at the New ing point because now everything’s on the table. of Sciences, 2006. Available at York State Department of Health and a member Fluoride is the most consumed drug in the U.S., www.nap.edu/catalog. g BETTMANN/CORBIS of the NRC panel who dissented from some of and it’s time we talked about it.” php?record_id=11571

Self-Powered

Nanotech By Zhong Lin Wang

Nanosize machines need still tinier power plants

he watchmaker in the 1920s who de- them into the realm of the possible. Just think vised the self-winding wristwatch was of the potential power sources a human body T on to a great idea: mechanically har- provides: mechanical energy, heat energy, vi- vesting energy from the wearer’s moving arm bration energy, chemical energy (in the form of and putting it to work rewinding the watch glucose) and the hydraulic energy of the circu- spring. latory system. Converted into electricity, just a Today we are beginning to create extremely small fraction of this energy could be suffi cient small energy harvesters that can supply electri- to power many types of small devices [see box cal power to the tiny world of nanoscale devices, on page 86]. where things are measured in billionths of a meter. We call these power plants nano generators. Power to the Tiny KEY CONCEPTS The ability to make power on a minuscule scale Work on power generation for small devices has ■ Nano technology has huge allows us to think of implantable biosensors that moved quickly since the late 1990s, when the potential—but those mi- can continuously monitor a patient’s blood glu- proliferation of portable electronic gadgets nuscule devices will need a cose level, or autonomous strain sensors for attracted researchers to the problem of fi nding power source that is better structures such as bridges, or environmental new ways to power them. Experimenters at the than a battery. sensors for detecting toxins—all running with- Massachusetts Institute of Technology’s Media ■ Waste energy, in the form out the need for replacement batteries. Energy Lab, for example, devised an energy-scavenging of vibrations or even the sources are desperately needed for nanorobotics, shoe using the piezoelectric effect, whereby cer- human pulse, could pro- microelectromechanical systems (MEMS), tain crystalline materials produce a voltage vide suffi cient power to homeland security and even portable personal when mechanically stressed. But the diffi culty run such tiny gadgets. electronics. It is hard to imagine all the uses such of producing useful amounts of power soon ■ Arrays of piezoelectric infi nitesimal generators may eventually fi nd. drove scientists to explore generators that could nano wires could capture Researchers are pursuing several different meet the much smaller electrical power needs of and transmit that waste routes toward power generation on a miniature MEMS. These silicon-based devices, whose energy to nano devices. scale. Options include exploiting random vibra- dimensions are measured in microns (millionths ■ Medical devices will likely tions or motions (such as those near a roadway), of a meter) to millimeters (thousandths of a be a major application. temperature gradients (for example, ground meter), have found many uses, including as A pacemaker’s battery temperature is fairly constant several meters be- accelerometers for automobile air-bag systems could be charged so it low the surface), biochemistry, and external en- and as ink-jet printer nozzles. Biology and would not need replacing, ergy sources such as ultrasonic waves or even au- chemistry also offer opportunities for produc- or implanted wireless dible noises. ing power [see box on page 87]. nanosensors could moni- A key advantage of nano devices and nano- In recent years, scientists have built small vi- tor blood glucose for systems is that they usually operate at a very low bration-based generators using both piezoelec- diabetics. —The Editors power level, in the range of nanowatts to micro- tric and electromagnetic transducers. The electro-

watts, bringing nanogenerators for powering magnetic microgenerator utilizes a moving mag- QUESTELL ADAM

© 2007 SCIENTIFIC AMERICAN, INC. AMERICAN, SCIENTIFIC © 2007 glucose or pressure in this conceptual image. conceptual this in pressure or glucose environment, a sensor measures blood that draws energy from the ambient POWERED BY a nano a nano SCIENTIFIC AMERICAN generator ( foreground 83 ) ZINC OXIDE NANO WIRES, typically 30 to 100 nanometers in diameter and one to three microns in length, are seen in this scanning electron microscope image (above). The voltage output in millivolts of an array shows variability (below).

mV 6.5

3.2

[THE AUTHOR] net or coil for inducing an alternating electric relatively large, gravity is important in driving current in a circuit. Although some microgene- its oscillating mass. rators have been fabricated at the scale of Now my research group at the Georgia Insti- MEMS, the technology tends to require struc- tute of Technology is working on piezoelectric tures ranging from one to 75 cubic centimeters, power generation at the nanoscale. And at the which work in vibration ranges from 50 hertz nano scale, things change. Gravity, which plays (cycles per second) to ﬁ ve kilohertz. A typical such a critical role in the larger world, is a very piezoelectric vibration-based generator uses a minor actor in the nanoworld as compared with two-layered beam of lead zirconium titanate, the forces of chemical bonding and intermolec- with a mass located at its unsupported end, ular attraction. Zhong Lin Wang is director of the Center for Nanostructure somewhat like a swimmer poised at the end of a Characterization at the Georgia diving board. When gravity causes the beam to Where Gravity Doesn’t Matter Institute of Technology. He bend downward, the upper piezoelectric layer is The force of gravity is not available to us on a discovered the nanobelt in 2000 under tensile strain and the lower layer is under useful scale in the nanoworld. If one attempted and the world’s smallest balance, compressive strain. The result is a positive and to construct a piezoelectric generator with a the nanobalance, in 1998. Among his many honors, he received negative voltage across the beam. As the mass nano meter-scale beam, gravity would make the 1999 Burton Medal of the oscillates back and forth, an alternating voltage almost no contribution to sustaining the beam’s

Microscopy Society of America. is created. But because this energy generator is motion, and the device would not work. There- WANG LIN ZHONG OF COURTESY

84 SCIENTIFIC AMERICAN January 2008 © 2007 SCIENTIFIC AMERICAN, INC. fore, we need another method to build a nano- zinc oxide nanowires, each of them a perfect six- size generator for powering autonomous devic- sided, columnlike crystal that is grown on a sol- es. Our team has been exploring innovative nano- id conductive substrate using a standard vapor- technologies for converting mechanical energy liquid-solid process in a small tube furnace. We (such as body movement and muscle stretching), deposit gold nano particles, which serve as cata- vibration energy (such as acoustic and ultrason- lysts, on a sapphire substrate. An argon gas car- ic waves) and hydraulic energy (such as the fl ow rier fl ows through the furnace as a zinc oxide of blood and other bodily fl uids) into electric powder is heated. The nano wires then grow un- energy to power nanodevices. derneath the gold particles. The typical diameter My research focused on carbon nanotubes in of the nanowires is 30 to 100 nanometers, and the late 1990s. We invented a few techniques for they measure one to three microns in length. measuring the mechanical, electrical and fi eld- The idea of converting mechanical energy emission properties of individual carbon nano- into electricity came to my mind around Au- tubes using in situ microscopy. But we could not gust 2005, when we were measuring the elec- control a nanotube’s electrical properties. I im- tromechanical coupled properties of the wires. mediately realized that metal oxides are a new Using an atomic force microscope (AFM), we world—and why not explore those nanostruc- observed some voltage output peaks, but we tures? In 2000 I started with nano belts, white were not sure what they were. We did system- woollike products made by baking a metal oxide atic work through November of that year and such as zinc in the presence of argon gas at 900 learned that the voltage was from the piezoelec- to 1,200 degrees Celsius, and with nanowires. tric effect of the zinc oxide; our results exclud- Our research has become focused on aligned ed the contribution from friction, contact or

[THE BASICS] MECHANICAL ENERGY TO ELECTRICITY A nanogenerator (below left) consists of an array of vertical zinc oxide forces such as vibration, the human pulse or acoustic waves. In this nano wires, hexagonal crystals with both piezoelectric and semicon- example, the generator’s output is stored in a capacitor and periodi- ducting properties. A rectangular electrode with a ridged underside cally sent to a sensor, which could be measuring blood glucose or sits atop the nanowires and moves side to side in response to external pressure. A tiny radio-frequency transmitter reports the results.

Nano wire

n n i i a a r Atomic force r t t s s microscope

e e l v i i

s s

s n

e e r

Wireless sensor m

Capacitor

BENDING BACK AND FORTH, the piezoelectric nano wires develop a voltage from the compressive and tensile strains on their sides. The semiconductor nano wires and conductive electrode rectify the alternating voltage and release it as direct current. GEORGE RETSECK GEORGE

www.SciAm.com SCIENTIFIC AMERICAN 85 © 2007 SCIENTIFIC AMERICAN, INC. other confounding arti facts. The next step was optimum packaging of the nano generator to en- determining what the process was for the charge hance its output. By the end of the year we real- output from a single nanowire. After studying ized that the nano generator could at last be re- a book on semiconductor devices, I proposed ported to the scientifi c community. the working mechanism of what would become Our experimental setup provided the fi rst the nano generator. demonstration of continuous direct current pro- Zinc oxide has the rare attribute of possessing duced by a piezo electric nano generator. It con- both piezoelectric and semiconducting proper- sists of an array of parallel zinc oxide nanowires ties, which we put to use in creating and accumu- and a platinum-coated silicon electrode with a lating piezoelectric charges in the nanowires. We ridged surface in place of the microscope’s tip. have shown that when the conductive tip of an Coating the electrode with platinum both en- AFM bends a straight, vertical nanowire, a strain Just How hances its conductivity and causes it to act like a fi eld is established, with the stretched surface Much Energy diode that allows current to fl ow in only one di- showing positive strain and the compressed sur- Does Your rection, from metal to semiconductor. The elec- face showing negative strain. As the tip scans over Body Prod uce? trode is placed above the nano wire array at a the top of the zinc oxide nano wires, we observe controlled distance and can be moved laterally Blood fl ow many peaks in the corresponding voltage output 0.93 watts of mechanical so that it bends the nano wires from side to side. image for each contact position [see box on page energy Thanks to its surface ridges, the electrode acts 84]. The piezoelectric effect creates an electric 0.16 W electrical energy like an array of aligned microscope tips [see box field inside the nano wire’s volume, with the available on preceding page]. 0.16 joules of electrical energy stretched and compressed sides of the wire show- per movement ing positive and negative voltages. Flexible Future Exhalation The idea came fi rst, but we needed experi- Since January 2007 we have been fully involved 1.00 W mechanical energy mental support. Just before Christmas 2005, I 0.17 W electrical energy in improving our nanogenerator. The ceramic designed an experiment to visualize directly the available or semiconductor substrates that we initially voltage output of a large wire under optical and 1.02 J electrical energy used for growing zinc oxide nano wires are hard AFM microscopy. My student and I did the ex- per movement and brittle, for instance, making them unsuit- periments, and one evening in late December, we Inhalation able for applications that require a foldable or were rewarded with several videos that directly 0.83 W mechanical energy fl exible power source, such as biosensors 0.14 W electrical energy proved my model. The next day I worked with implanted in muscles or joints, or power available Jinhui Song in my offi ce to edit the movie. Then 0.84 J electrical energy generators built into shoes. we sent the paper to Science for publication. per movement Here is where conductive polymers To be useful in practical applications, our Upper limbs can provide a substrate that is likely to nanogenerator needs to contain an array of nano- 3.00 W mechanical be biocompatible. In experiments we wires, all of them continuously generating elec- energy discovered that many available fl exible tricity that can be collected and delivered to a 0.51 W electrical energy plastic substrates are suitable for growing the available device. And the energy to be converted into elec- zinc oxide nanowire arrays, which ultimately 2.25 J electrical energy tricity has to come in the form of a wave or vi- per movement could fi nd applications in portable and fl exible bration from the environment so the nano- electronics. Because of the fl exibility of the sub- Walking generator can operate independently and wire- 67.00 W mechanical energy strate, the nano wire surface profi le was wavy, ) lessly. We have developed a novel design that 11.39 W electrical energy causing some missed contacts. We believe that addresses these requirements. available providing suitable bonding strength between the 18.90 J electrical energy The next challenge was to increase the power nano wires and substrate as well as optimizing typing laptop on per movement of the nano generator. Three objectives have to the wire spacing will be important in increasing be achieved: eliminate the use of the AFM, make Fingers typing discharge effi ciency. 6.9–19.0 milliwatts many nano wires generate electricity simul- Although our approach has demonstrated the mechanical energy taneously and continuously, and excite the 1.2–3.2 mW electrical principle of the nanogenerator, we must drasti- nano wires in an indirect wave, such as an energy available cally improve its performance to make it practi- ultra sonic wave. I came out with a new design 226–406 microjoules cal. All the nano wires must generate electricity IMAGES/GETTY); PM ( IMAGES using a ridged electrode to replace the AFM tips electrical energy simultaneously and continuously, and all the yoga poseyoga

per movement ( and presented the idea to my postdoctoral assis- electricity must be effectively collected and distant, Xudong Wang. It took him about four tributed. A large-scale method for growing zinc

months of experiments before compiling the oxide nano wires can be cost-effective because it Getty Images ﬁ rst group of data. The signal was rather small. does not require expensive high-temperature

From May to October 2006 we focused on the manufacturing processes. Hurdles that lie ahead TIM PLATT

86 SCIENTIFIC AMERICAN January 2008 © 2007 SCIENTIFIC AMERICAN, INC. [OTHER IDEAS] Ambient-Energy Harvesters Nano generators that use vibration-driven piezoelectrics show promise, but other ways to siphon energy from the environment also exist

he most effective energy-harvesting processes are in nature, such as fect, wherein an electric potential exists at the T in microorganisms that must perform this task to survive. Derek R. junction of two dissimilar metals that are at dif- Lovley of the University of Massachusetts Amherst and his colleagues, ferent temperatures. The voltage produced is for instance, have reported that a marine organism, Desulfuromonas proportional to the temperature difference be- acetoxidans, can transfer electrons to a graphite electrode from acetate tween the two ends; thermocouples based on produced in sea sediments by other organisms. The result is an electric this principle are often used to measure tem- current that ﬂ ows through water to another electrode. Such “sediment perature. When a temperature differ- batteries” might be used for bioremediation of toxic wastes, for exam- ence is applied, charge carri- ple. Similarly, the catalytic action of microorganisms can produce elec- ers in the material diffuse Thermoelectric module trical output from different carbohydrates and substrates. from the hot side to the cold Heat In 2004 a group of researchers led by A. K. Shukla of the Central side. Mobile charge carriers ﬂ o w Electrochemical Research Institute in Resistor migrating to the cold side India demonstrated biological fuel leave behind their oppositely

cells that use organic substances and charged and immobile nuclei Arm meta bolic processes to generate cur- at the hot side, giving rise to rent. It is possible to tap into the a thermoelectric voltage. THERMOELECTRIC generator exploits body’s own resources, including the Thermoelectrics is an ex- temperature differences. metabolic properties of our cells, to citing ﬁ eld, but the genera- generate enough energy to power an Water tors are fairly large because array of medical devices, including of the need to maintain an appreciable temperature difference be- drug delivery systems, cardiac pace- tween the two ends of the device. Consequently, thermoelectric gen- makers and diagnostic devices. The erators may have limited applications as power sources that can be in- drawback of microbial fuel cells is tegrated into nano systems. Yet they have already found some that their size is rather large and their commercial applications, such as the Seiko Thermic wristwatch, intro- Sediment power output may not be adequate duced in 1998, which used thermoelectric modules to generate sufﬁ - for nonbiological applications. cient microwatts to run its mechanical workings from the small gradi- Another option, a thermoelectric SEDIMENT battery is pow- ent between the wearer’s body heat and the ambient temperature. generator, relies on the Seebeck ef- ered by marine organisms. —Z.L.W.

in our research include learning how to grow generator that is about six square millimeters in perfectly uniform arrays of nanowires that all size. We have also shown that nanogenerators produce electricity and how to extend their can be arranged in series to improve the output working life. The lifetime of the current nano- voltage and in parallel to improve the output generator is about 50 hours. The main reason for current, as is commonly done with power sourc- the device’s failure is likely the packaging tech- es such as batteries or fuel cells. But to produce ➥ MORE TO nology for assembling the top electrode and the higher voltages, we need to make nanowires EXPLORE nano wire arrays. If the electrode presses on the with identical height and diameter. nano wires too fi rmly, for example, no current Nano generators may never power our homes Direct-Current Nano generator Driven by Ultrasonic Waves. will be generated. We are working hard to im- or even our fl ashlights; the amount of power Xudong Wang, Jinhui Song, Jin Liu prove the packaging. available from them will be quite small. But and Zhong Lin Wang in Science, Vol. The process used to produce the arrays in- nano wire arrays can be ideal generators for de- 316, pages 102–105; April 6, 2007. volves evaporating a thin layer of gold onto the vices that need to work only intermittently, such substrate, where it acts as a catalyst for nano- as sensors that collect and transmit data for one Nano wire Piezoelectric Nano- generators on Plastic Substrates wire growth. The zinc oxide crystals look some- second of every minute. In the years to come, as Flexible Power Sources for thing like a forest without branches. To improve nano generators will be used to harvest and re- Nano devices. Pu Xian Gao, Jinhui the adhesion of the nanowires with the sub- cycle the energy wasted in our daily life, such as Song, Jin Liu and Zhong Lin Wang in strate, we have added a thin layer of polymer that created by pressure changes in a car tire, a Advanced Materials, Vol. 19, pages onto the substrate after growth so that the roots moving vehicle’s mechanical vibration or even 67–72; 2007. of the nanowires are partially embedded. We the fl uttering surface of a camper’s tent. Con- Zhong Lin Wang’s Web site is have achieved electrical output of about 10 milli- sider how many small energy resources are all available at www.nanoscience. ■ GEORGE RETSECK GEORGE volts and 800 nano amperes from a nano- around us. gatech.edu/zlwang

LAVA erupting from an active volcano in Hawaii comes from a hotspot, akin to a ﬂ ame burning through the earth’s crust. HOT By John A. Tarduno

here was the cone? We had just pulled up our drill pipe, replaced its worn W drill bit, and lowered it back down to the seafl oor, a mile under our ship. Crowding into the control room, we watched images from a camera attached to the end of the pipe, looking for a cone we had left as a marker to guide the pipe back to the hole we were drilling. The team had gone through this exercise many times before. Usually we would see a fi sh swim by or a squid momentarily grab the pipe, and then the cone would appear. This time we saw only fi sh and squid. What had gone wrong? We had come to the northwestern Pacific Ocean to extract core samples from the submerged extinct volcanoes, known as the Emper- or seamounts, that form the northernmost leg of the Hawaiian-Emperor volcanic chain. The neat pattern formed by the chain is apparent on any world map and, along with the jigsaw-puzzle shape of South America and Africa, has long stood as a testament to plate tectonics—the principle that our planet’s surface is an ever shifting mosaic of rocky puzzle pieces. Not only do the islands and seamounts form an uncannily straight line for 3,500 kilometers across the Pacifi c, their rocks get steadily older as you move northwest up the chain: from the Big Island (which is still growing) through Maui, Oahu, Kauai and on up to the Midway atoll, whose long-extinct volcano

has subsided so much that it barely sticks up Getty Images above the sea surface. Past Midway, the line makes a sharp bend, continuing northward

along the Emperor seamounts and stretching RENE FREDERICK

88 SCIENTIFIC AMERICAN January 2008 © 2007 SCIENTIFIC AMERICAN, INC. Long considered ﬁ xed founts of molten material from deep within the planet, hotspots now SPOTS join the list of moving parts Unplugged

nearly as far as the tip of the Aleutian Islands. measure past climate and rocks used to gauge the The standard explanation for this pattern, motion of the solid earth relative to the planet’s based on ideas put forward by geophysicist spin axis. So it has come as a shock to geologists J. Tuzo Wilson in 1963, is that the islands record that hotspots may not be all they appear to be. motion of the Pacifi c plate over a volcanic hot- My colleagues and I have recently demonstrat- KEY CONCEPTS spot [see “Hot Spots on the Earth’s Surface,” by ed that they are not, in fact, fi xed. In a sense, they Kevin C. Burke and J. Tuzo Wilson; Scientifi c are like the cone we left at the bottom of the Pa- ■ Volcanic hotspots, such as the one creating the American, August 1976]. The hotspot can be cifi c as a reference marker. When we failed to fi nd Hawaiian Islands today, thought of as a candle within the earth whose it in place, we realized that ocean currents must have long been consid- fl ame burns through the crust, pumping lava to have swept it away. The team repositioned the ered fi xed points in the the surface and building an island. The ever ship, located the drilling hole, and entered it with- scheme of slowly moving moving plate pulls the island off the hotspot, the out a cone to guide us. Similarly, geophysicists tectonic plates that form the earth’s outer surface. hotspot generates a new island, and the cycle now have to fi gure out why hotspots drift and continues. Together the hotspot and plate tec- have to develop a new way to get our bearings. ■ New evidence that hotspots can instead be tonics produce islands like an assembly line. mobile comes from study In 1971 Jason Morgan of Princeton Universi- Magnetic Filings of Hawaii’s chain of is- ty went a step further. He proposed that the The evidence that clinched the case for plate tec- lands and submerged de- “candle” was the molten tip of a plume of hot tonics in the 1960s, and that has since refi ned our funct volcanoes. The rock rising from deep within the earth’s mantle. understanding of hotspots, is the record of plate chain’s elbowlike geometry has traditionally Pinned down in the planet’s interior, the hotspot movement provided by rock magnetization. been attributed only to a itself did not move; only the plate did. In this When lava cools, magnetic minerals within it, change in the motion of view, the Hawaiian hotspot has remained at a principally magnetite and titanomagnetite, crys- the Pacifi c plate. Now it latitude of about 19 degrees north, while the Pa- tallize. These miniature bar magnets lock in the is in part credited to hot- cifi c plate has moved northwest at about 10 cen- direction of the earth’s magnetic fi eld at that spot migration, itself an expression of movement timeters a year. The great bend in the hotspot’s moment in time and that location on the surface. in the earth’s mantle track suggests that the direction of plate motion Because the earth’s magnetic fi eld varies in deep below the surface. suddenly changed some 47 million years ago. both time and space, rock magnetization pro- ■ Implications include Beyond accounting for the evolution of vides two ways to determine how plates have textbook rewrites, as Hawaii and other island chains, the fi xed posi- moved. First, geologists can study the time varia- well as new views on tion of hotspots has given earth scientists a very tion. At irregular time intervals, the planet’s fi eld paleo climate records and powerful set of landmarks. These landmarks reverses polarity: the North and South magnetic the stability of the entire have allowed geologists to reconstruct plate mo- poles switch places. Consider what that means earth on its spin axis. tions and determine the original location of geo- for lava erupting at mid-ocean ridges. When the —The Editors logic samples, such as sediment cores used to rock emerges and cools, the magnetization of its

www.SciAm.com SCIENTIFIC AMERICAN 89 © 2007 SCIENTIFIC AMERICAN, INC. [CASE STUDY] THE OLD VIEW OF HAWAII’S ORIGIN Textbooks say that the chain composed of Hawaii’s islands and the Emperor seamounts (right) formed as the Pacifi c tectonic plate passed over a fi xed hotspot. Venting lava built an island; then the plate carried the island to the northwest, to be replaced by another Detroit, formed 75–81 million years ago (Mya) (below). The chain’s sharp bend was ascribed to a shift in plate motion. But varied fi ndings indicate the scenario is incomplete. If it were Suiko, 61 Mya correct, for instance, the chain geometry would Emperor seamounts match that predicted by the study of hotspots Nintoku, 56 Mya (submerged, defunct in the Indian and Atlantic basins (dashed line). volcanoes) Hawaiian chain Koko, 49–50 Mya Daikakuji, 47 Mya

Midway, 28 Mya

Necker, 10 Mya Prediction based on Indo-Atlantic hotspots Kauai, 5 Mya Hawaii, recent Paciﬁ c plate Hotspot

minerals lines up like magnetic fi lings pointing, distance that the plate must have moved since say, to the north. Plate tectonics then carries the then. (It does not reveal the longitude.) rocks away from the ridge. After several hundred Using these approaches is not entirely straight- [THE AUTHOR] thousand years or so, the polarity fl ips, and from forward. The earth’s magnetic fi eld does not John A. Tarduno is thankful that that moment newly formed rocks are magnetized point purely north-south. It has a more complex only a single sandstorm struck his the opposite way. These, too, are carried away shape that geophysicists think refl ects the fl ow expedition to northeastern Mauri- tania last year. He had gone to the from the ridge. The polarity eventually fl ips back, of liquid iron in the planet’s core. When aver- Sahara to recover 200-million-year- and the cycle continues. The result is a series of aged over several millennia, however, these de- old rocks, whose ancient magnetic horizontal stripes recorded in the oceanic crust, viations cancel out. Thus, researchers can com- signatures reveal how the earth’s alternating between north-pointing and south- pensate for the complexity of the fi eld by sam- plates have moved over the eons. pointing magnetic minerals—a geologic version pling a large number of rocks representing a long Then he hauled his drilling equipment up 800-foot cliffs on Cha- of tree rings. Geologists date the stripes by enough span of time. Few islands still have old tham Island off New Zealand, this matching them against the timeline of polarity rocks that date back far enough, so geologists time to obtain 85-million-year-old reversals. They then use time and distance data have to drill into the ocean fl oor. rocks. The North Pole and South Af- to calculate a plate’s direction and speed rela- That process presents its own complications. rica have also been on his recent tive to an adjoining plate. Oceanic crust can be tilted, which can be mistak- itinerary. Tarduno is a professor in the departments of earth and envi- The second technique exploits the fact that en for magnetic inclination. The best rock sam- ) ronmental sciences and of physics the direction of the earth’s magnetic fi eld has ples come from areas that seismic data confi rm and astronomy at the University of two components: horizontal (declination) and lie fl at. Geologists have drilled deeply into only illustration Rochester and is founder of its pa- vertical (inclination). When you rely on a com- a few of these areas. Another approach is to tow leomagnetism laboratory. pass to fi nd the direction of north, you use the a magnetometer behind a ship and measure the declination, but if you look closely at the com- magnetization of the seafl oor rock remotely. Un- ( HAND KEVIN );

pass needle, you will see that it is also tilted fortunately, such measurements reﬂ ect not only Tarduno slightly with respect to the horizontal. As Neil the magnetization imprinted when the rock Opdyke of the University of Florida demon- formed but also the induced magnetizations im- strated in a classic study in the late 1960s, the parted by the earth’s present-day ﬁ eld, as well as inclination is directly related to latitude. Mea- the magnetization acquired over geologic time suring inclination reveals the latitude where the as some of the magnetic domains within the

rock originally formed and hence the minimum crystals spontaneously reoriented themselves. ( TARDUNO A. JOHN OF COURTESY

90 SCIENTIFIC AMERICAN January 2008 © 2007 SCIENTIFIC AMERICAN, INC. Magnetometer readings therefore still need to be tate like interlocking gears, potentially changing calibrated against directly sampled rocks. the way that geographic features in the Atlantic relate to those in the Pacific. Unfortunately, Wide Latitude much of the geologic history of Antarctica re- The fi rst hint that the Hawaiian hotspot might mains a mystery, buried under thick ice caps. not be fi xed came in the early 1970s from studies This uncertainty prevented geologists from re- conducted by Tanya Atwater and Peter Molnar, constructing the plate motions fully. both then at the Massachusetts Institute of Tech- The only way to settle the matter was to go nology. They looked at two phenomena to deduce back to the rock samples. My University of Roch- plate motion: seafl oor stripes and island chains. ester colleague Rory Cottrell and I took up this When two plates meet at a mid-ocean ridge, their challenge in 1995. We visited the Ocean Drilling motions create a series of seafl oor stripes and, if Program (ODP) at Texas A&M University and each plate is underlain by a hotspot, a pair of examined archived cores of sediment and rock island chains. Researchers can predict what the collected over several decades. The most prom- hotspot track of an island chain should look like ising had been collected in 1992 from one of the on one plate by examining the track of the corre- Emperor seamounts, known as Detroit, which sponding chain on the other plate. formed between 75 million and 81 million years Atwater and Molnar reported that the predic- ago. The rock type was basalt—similar to that — tions for several hotspot tracks failed to match erupting on Hawaii’s Big Island today which Å DRILL RIG towering over the the location of the actual volcanoes, suggesting carries the best-understood type of magnetic deck of the JOIDES Resolution that the hotspots had moved. The technique has signal. The core had drawn little attention be- lowered and raised the long since been refi ned and extended by Joann Stock cause researchers thought it was too short in drill pipe (foreground) that the of the California Institute of Technology and her length to provide enough accurate readings of author and his team sent to the colleagues, with essentially the same results. magnetic inclination. seafl oor to extract rock cores Predictions for the Hawaiian-Emperor chain A new analysis proved otherwise. To remove from seamounts. made using hotspots in the Atlantic Ocean are the effects of induced magnetization and spon- in rough agreement with the portion of the chain taneous reorientation of large magnetic mineral formed over the past 30 million years, but they domains so that we could identify the minerals’ deviate further back in time. At 60 million years original magnetization, we measured the sam- ago the offsets are very large. ples in a shielded superconducting quantum in- These conclusions did not convince many ge- terference device (SQUID) magnetometer and ologists, however. Other effects could explain went through an exhaustive demagnetizing pro- the disagreement between the two data sets. The cedure. It turned out that the core was just long Pacifi c and Atlantic basins consist of plates that enough to provide precise readings of magnetic abut the continent of Antarctica, which itself is inclination and hence the latitude at which the made of at least two plates. These plates can ro- minerals formed: 36 degrees north.

[RESEARCH TOOL] CLUES FROM ROCK MAGNETISM Magnetic studies were key to revealing ﬂ aws in the old view of the Hawaiian-Emperor chain’s evolution. 90˚ When lava solidiﬁ es, certain minerals lock in the

) inclination, or angle, of the earth’s magnetic ﬁ eld 45˚ at that latitude (white arrows in details). The illustration minerals line up parallel to the planet’s surface at the equator (bottom), perpendicular to it at the magnetic poles,

); KEVIN HAND ( HAND KEVIN ); and at intermediate angles at mid- drill latitudes (top). Should a rock move, it will retain its original magnetic inclination. If 0˚ the chain developed as a plate moved over a ﬁ xed hotspot, magnetic inclinations in seamount rocks would have matched those in rocks from Hawaii, but they did not.

COURTESY OF JOHN A. TARDUNO ( TARDUNO A. JOHN OF COURTESY Magnetic ﬁ eld line

www.SciAm.com © 2007 SCIENTIFIC AMERICAN, INC. We compared our new result with a study lava layers, eliminating one source of potential done in 1980 by Masaru Kono, then at the To- error. Once we got the samples on deck, a cadre kyo Institute of Technology, using ODP’s pre- of experts helped us analyze them, including decessor, the Deep Sea Drilling Project. He had Robert Duncan of Oregon State University, taken samples of the 61-million-year-old Suiko Thorvaldur Thordarson, then at the University seamount of the Emperor chain and found that of Hawaii at Manoa, Frederick Frey of M.I.T. it had formed at 27 degrees north. These were and Clive Neal of the University of Notre Dame. startling results. If the Hawaiian hotspot, now To estimate the rock’s ages, we examined micro- located at a latitude of 19 degrees north, were fossils in sediments lying on top of or intermixed fi xed, the Detroit and Suiko seamounts would with the lavas. The ship had a magnetism lab have formed at the same latitude. The three lat- where we gauged the rock’s magnetization. It itude values differed, suggesting that the Em- would take many months of follow-up work in peror seamounts marked the trace of a moving shore-based laboratories, including critical iso- plume. Among our colleagues, though, the re- tope geochronological work, to confi rm our sults met with a reception notable for its air of fi ndings. But the overall picture was apparent by indifference. All our thousands of laboratory the time we returned to port in Yokohama. Å CONE is being dispatched measurements condensed down to a mere two The hotspot had clearly moved rapidly south. to the seafl oor through an points on a graph. Skeptics required more be- Its inferred velocity during the period from 81 opening, called a moon pool, fore they would reconsider the textbook plate- million to 47 million years ago was more than in the center of the JOIDES motion explanation of the Hawaiian chain. four centimeters a year, comparable to that of Resolution. Such cones helped tectonic plates. Corroborating this fi nding, we to position the drill pipe that A Leg Up found no coral debris at the Detroit or Nintoku brought up rock cores for In late 1997 Cottrell and I began thinking about seamounts and only a smattering at the Koko magnetic analysis. ) a new ocean drilling expedition. We chose drill- seamount. If these islands had formed at Ha- ing sites with the help of David Scholl of Stanford waii’s tropical latitude, we would have expected illustration University and also invited Bernhard Steinberger, coral reefs to have taken shape around them. who had been modeling mantle fl ow for his Ph.D. The implications are now rippling through

dissertation at Harvard University, to join the the earth sciences, answering old questions and ( HAND KEVIN );

effort. We sailed off onboard the Ocean Drill- raising new ones. For example, one other geolog- cone ing Program’s JOIDES Resolution in the sum- ic indicator of latitude is the type of sediments de- mer of 2001 on a two-month expedition—called posited in the deep oceans. Near the equator, sed- Leg 197—that took us to three of the Emperor iments are rich in the calcium carbonate shells of seamounts: Detroit, Nintoku and Koko. plankton, which accumulate because of the high Before drilling, we conducted short seismic biological productivity of this region. Outside

surveys to ensure we would recover ﬂ at-lying the equatorial zone, the sediments are carbonate- ( TARDUNO A. JOHN OF COURTESY [CASE STUDY REVISITED] WHAT REALLY HAPPENED

The magnetic work showed that OLD VIEW NEW VIEW the seamounts arose at progressively lower latitudes, 80 Mya with Detroit forming at about 36 degrees north and Koko at about N NW 22 degrees north. So, although S the old view of the Hawaiian- Emperor chain’s evolution held that the hotspot stood still while 50 Mya the Paciﬁ c plate crossed over it (left), it is now clear that the N NW hotspot migrated, too (right), S heading south. (Arrow sizes represent relative speed.) 47 Mya to present Plate motion Hotspot motion NW NW S

Discovery that hotspots can travel OLD NEW has revised understanding of what VIEW VIEW they are. They are still deﬁ ned as Crust Hotspot the tip-tops of mantle plumes that originate near the boundary between Upper mantle the earth’s liquid core and the overlying Lower mantle viscous mantle. In the old view (left), though, the plumes remained ﬁ xed relative to the deep interior. In the new view (right), the plumes are swayed by convection Outer core within the mantle. The base of the plume can also move, as shown in a movie at http://earth. uni-muenster.de/dyn/plumedynamics.shtml Inner core

poor. Sediments in cores from the Pacifi c Ocean tive positions of the plates would remain the same. up to 50 million years old do not fi t the carbon- In the 1980s geologists used the assumption ate-rich pattern that one would expect if hotspots of hotspot fi xity to reconstruct plate motions were fi xed. Josep M. Pares and Ted C. Moore of and pinpoint the past locations of the earth with the University of Michigan at Ann Arbor recent- respect to its spin axis. The data suggested the ly found that this paradox would be resolved if earth had migrated up to 20 degrees relative to the Hawaiian hotspot was drifting southward. the axis over the past 130 million years. Our Geologists may need to rewrite their text- fi ndings refute that claim: the hotspots moved, books about North America, too. Experts have not the entire earth. So hotspots can be a false known for a long time that large tracts of the beacon for plate motions and polar wander. American West did not form where they are now. The deepest implication of hotspot mobility ➥ These landmasses were pushed into their present relates to the earth’s mantle. The hotspot may MORE TO positions by the long-gone plates that once com- still be rooted in the deep mantle, but its base EXPLORE posed the Pacifi c Ocean basin. Interactions be- may move around, and the rising plume may be Fixed Hotspots Gone with tween oceanic and continental plates are also re- bent by the mantle fl ow. More radically, the con- the Wind. Ulrich Christensen in sponsible for the formation of major geologic cept of plumes itself has come under scrutiny. Nature, Vol. 391, pages 739–740; February 26, 1998. features such as the Rocky Mountains. But the Don Anderson of Caltech has argued that hot- plate interactions have been estimated assuming spot plumes may not, in fact, be rooted in the The Emperor Seamounts: South- that Hawaii’s hotspot was a fixed reference lower mantle. They may instead be shallow phe- ward Motion of the Hawaiian point. Because it is not, geologists must revisit nomena, emerging from the upper layers of the Hotspot Plume in Earth’s Mantle. how western North America was built. mantle or lower layers of the crust. Others think John Tarduno et al. in Science, Vol. 301, pages 1064–1069; plumes come in all shapes and sizes and origi- August 22, 2003. Pole Position nate at various layers within the planet. On a still larger scale, hotspot motion affects As dramatic as our discoveries on hotspot Geophysics—Hotspots Come how researchers think about polar wander— mobility have been, they do not mean that all of Unstuck. Joann Stock in Science, rotation of the entire solid earth relative to the present geologic understanding must be over- ibid., pages 1059–1060. planet’s spin axis. Polar wander is a confusing turned. Science seldom works like that. The re- Animations of plate tectonics term in geophysics, because the phrase implies markable age progression and the sheer volume processes are available in the that the pole itself moves around. In fact, both of magma marked by the Hawaiian-Emperor Chapter 8 section at the Web site the spin and magnetic axes remain almost fi xed chain show that the Hawaiian hotspot is still “Exploring Earth Visualizations”: in absolute space; it is the land and seafl oor that closest to the ideal envisioned by Wilson and www.classzone.com/books/ earth_science/terc/navigation/ wander. The sinking of tectonic plates might Morgan. But rather than being fi xed in the deep visualization.cfm shift the earth’s mass distribution and cause an mantle, it has had an unexpected mobility. A imbalance of forces, like a washing machine with simple picture has given way to a complicated Tarduno’s University of Rochester a lopsided load of clothes. To rebalance itself, the one. Both plates and hotspots move, and the ob- Paleomagnetic Research Group Web site is at www.earth. entire planet would rotate. In the extreme case, served effects can refl ect a combination of both— rochester.edu/pmag, and more Florida might wind up at the North Pole or Green- challenging scientists to determine the contribu- information on the Integrated land might become a tropical island. This pro- tion of each. Underappreciated until now, tur- Ocean Drilling Program is at g KEVIN HAND HAND KEVIN cess differs from plate tectonics because the rela- moil in the mantle deserves new respect. www.iodp.org

www.SciAm.com SCIENTIFIC AMERICAN 93 © 2007 SCIENTIFIC AMERICAN, INC. PHYSIOLOGY The Human Instru me nt When judged by its size, our vocal system fails to impress as a musical instrument. How then can singers produce all those remarkable sounds? By Ingo R. Titze

he human vocal system would not to describe how great singers produce those receive much acclaim if instrument amazing sounds. KEY CONCEPTS T makers placed it in a lineup of tradi- ■ Although the human vocal tional orchestral instruments. Arranged by size, Music-Making Keys system is small, it manages to for example, the voice box (larynx)—and the Structural and operational shortcomings in the create sounds as varied and airway it sits in—would be grouped with the human vocal apparatus are apparent in all its beautiful as those produced piccolo, among the smallest of mechanical parts. To make music, an instrument needs by a variety of musical music makers. And yet experienced singers three basic components: a sound source that instruments. compete well with all man-made instruments, vibrates in the air to generate a frequency that ■ All instruments have a sound one on one and even paired with full orchestras. we perceive as pitch, together with higher fre- source, a resonator that Recent investigations of how our singing voice quencies that defi ne the timbre (sound color); reinforces the basic sound and generates a remarkable range of sounds have one or more resonators that reinforce the fun- a radiator that transmits the revealed surprising complexity in the behavior damental frequency by increasing its vibration sound to listeners. of the vocal system’s elements and in the ways strength; and a radiating surface or orifi ce that ■ A human’s sound source is the they interact. transfers the sounds to free air space and, even- vibrating vocal folds of the For more than half a century, scientists ex- tually, to a listener’s ear. larynx; the resonator is the plained the voice’s ability to create song by invok- In the case of, say, a trumpet, a player’s lips sound-boosting airway above ing a so-called linear theory of speech acoustics, vibrate as lung-pumped air rushes between them the larynx; and the radiator is whereby the source of sound and the resonator into a cup-shaped mouthpiece to create a funda- the opening at the mouth. of sound (or amplifi er) work independently [see mental frequency and several higher frequencies ■ The human voice can create “The Acoustics of the Singing Voice,” by Johan that are called overtones. The instrument’s met- such an impressive array of Sundberg; Scientific American, March al tubes serve as the resonators, and the expand- sounds because it relies on 1977]. Researchers have now learned, however, ing aperture of the horn radiates the sound. nonlinear effects, in which that nonlinear interactions—those in which Trumpeters alter fundamental frequency by small inputs yield surprisingly source and resonator feed off each other—play modifying the lip tension and by pressing the large outputs. an unexpectedly crucial role in generating hu- valves to change the effective length of the tubes. —The Editors man sound. Such insights now make it possible Or take a violin: the strings vibrate to create

AARON GOODMAN AARON much smaller equipment.

© 2007 SCIENTIFIC AMERICAN, INC. [THE BASICS] pitches, the central air cavity and wooden top supply resonance, and the f holes in the top plate HOW INSTRUMENTS MAKE MUSIC help to send the sound into the surrounding air. Nearly all musical instruments, both man-made A singer, on the other hand, relies on vibrat- and biological, share three basic elements: ing vocal folds, blowing air across them to gen- VIOLIN ●1 a sound source that vibrates in air to create a erate the sound frequencies. Vocal folds are two certain fundamental frequency (which is perceived small bundles of specialized tissue, sometimes Tuning pegs as pitch) and its related harmonic frequencies called “vocal cords,” that protrude pouchlike (integral multiples of the basic frequency), which from the walls of the larynx. They generate a defi ne the timbre, or sound color; ●2 a resonator fundamental frequency by rapidly oscillating as that reinforces or amplifi es the fundamental they contact each other, separate and come in frequency and its harmon ics; and ●3 a sound contact again. The glottis (the space between the radiator that transfers the sound to free air space folds) opens and closes. The laryngeal vestibule, and on to a listener’s ear. an airway passage just above the larynx, acts Fingerboard like the mouthpiece of the trumpet to couple the sound to the remaining part of the resonator known as the vocal tract. The lips radiate the sound outward like the bell of the trumpet. Instrument manufacturers examining the vo- ●1 SOUND SOURCE (string) cal folds, which are collectively the size of your thumbnail, would not fi nd their potential for making orchestral musical sounds impressive. ●2 SOUND RESONATOR (top plate) Beyond their small size, one immediate objec- tion would be that they would seem too soft and spongy to sustain vibration and create a variety of pitches. Bridge Nature, biology’s instrument maker, might ●3 SOUND RADIATOR (f hole) respond that although the folds are certainly undersized, the airways can produce enough resonance to reinforce the sound of the larynx substantially. But here, too, the musical instrument maker would probably still fail to be per- suaded: the typical air tube extends just 15 to 20 centimeters above the larynx and 12 to 15 centimeters below it, no more than the length of a piccolo. The rest of the body contributes little or nothing. Wind instruments that approximate the pitches created by the human voice (trom- frequencies via a square root relation. Thus, to bones, trumpets, bassoons) typically contain make a steel string of a given length double its much longer tubes; the bell and valves of a trum- LINEAR VS. frequency (raise the pitch by an octave), one must pet, for instance, uncoil to about two meters NONLINEAR quadruple the string tension. This rather strin- and those of a trombone to about three meters. Voice scientists used to gent requirement may limit the range of frequen- explain the performance of cies that can reasonably be obtained by altering Source Design the human vocal system in a source’s stiffness or tension. To understand how nature the instrument maker terms of linear effects, ones Fortunately, a player can also change the fre- has developed the vocal folds that perform in which the outputs of a quency of a sound source’s vibration by effec- beyond expectations, fi rst consider some stan- function are proportional to tively lengthening or shrinking the oscillating dard requirements for sound sources. For a reed the inputs (and so can be rep- element. Within a vibrating string, for instance, resented as a line, for exam- or string to sustain its vibration, it needs to be frequencies are inversely proportional to the ple). More recently, research- made of an appropriately elastic material so it length of the vibrating segment. By pinning the ers have concluded that the can snap back when deformed. Elasticity is mea- human vocal system behaves string on one end with the fi nger, a player selects sured by its stiffness (or, conversely, fl exibility) different frequencies. If a string’s vibrating length nonlinearly. In a nonlinear iStock Photo or its tension: a reed has a bending stiffness; a feedback system, small is cut in half without changing the tension, for string vibrates under tension. Generally, a sound changes can result in dispro- example, the vibration frequency doubles. To

source’s stiffness or tension determines the sound portionately large effects. produce a wider range of frequencies, a single STEVE DIBBLEE

HUMAN VOCAL SYSTEM

Ingo R. Titze, a world leader in the scientiﬁ c study of the human voice, has published more than 500 articles on the topic. He currently serves as the University of Iowa Foundation Distinguished Professor in that institution’s department of speech pathology and audiology, and he directs the ●3 SOUND RADIATOR National Center for Voice and (mouth) Speech (www.ncvs.org) at the Oral cavity Denver Center for the Performing Arts. Titze, who received his Ph.D. Pharynx (throat) in physics from Brigham Young University in 1972, teaches singing and sings in multiple styles, includ- ●2 SOUND RESONATOR ing opera, Broadway and pop. Larynx (airway)

●1 SOUND SOURCE (vocal folds of larynx)

Trachea

musical instrument often uses multiple strings. cles to shift its end points. But should we length- String instruments, then, have three distinct en or shorten the vocal folds to raise frequency? mechanisms for changing frequency: altering An argument could be made for either adjust- the length of a string, modifying its tension, or ment. Longer vocal folds would vibrate at lower skipping to another string. Players of stringed frequency, but tenser folds would vibrate at instruments typically set the tensions by turn- higher frequency.

) ing pegs around which the strings are wrapped; The physics formula describing the frequen- the strings retain this same tension between end cy of a string ﬁ xed at both ends under tension

illustration points. Players almost never can manipulate says that to get the maximum increase in fre- both the length and tension simultaneously. quency, one should increase the tension (actually the tensile stress, or tension per cross-sec-

); GEORGE PIMENTEL PIMENTEL GEORGE ); The Little Source That Could tional area) while decreasing the length. Such a

); ADAM QUESTELL ( QUESTELL ADAM ); SHRIEK ROCKER Titze Steven Tyler is In playing the human vocal folds, in contrast, response requires an unusual material, because Tyler celebrated for his ability to ( singers must do what no other string instrument most materials can increase tension (stress) only scream tunefully. Aerosmith’s can do: vary the length and tension of the vibrat- when they are elongated. Think of a rubber lead singer creates that ex- ing material simultaneously to change frequency. band; pull on it, and it tightens up. Thus, length treme sound by using a large Rather than pinning down a vocal fold with a and tension are in competition for changing amount of nonlinear effects in WireImage/Getty Images COURTESY OF INGO R. TITZE ( TITZE R. INGO OF COURTESY ﬁ nger to shorten its effective length, we use mus- frequency. his vocalizations.

www.SciAm.com SCIENTIFIC AMERICAN 97 © 2007 SCIENTIFIC AMERICAN, INC. [HUMAN SOUND SOURCE] HOW OUR VOCAL FOLDS WORK Unlike violin strings, the human sound source—the vocal folds (or vocal cords) in the larynx—has a complex, three-part structure that allows us to generate several octaves of frequencies. At the core of each fold is a stringlike ligament (cross section). Internal to the ligament are contractile muscles. And covering it all is a highly ﬂ exible mucous membrane. Each component brings a special capability to the whole. The ligament’s tensile stress rises rapidly with elongation (by muscles that move the cartilages attached to the folds), which helps to produce higher frequencies. The vocal-fold muscle can increase tensile stress as it contracts. In doing so, it generates an even larger frequency range. The soft, pliable surface of the outer membrane, which oscillates like a ﬂ ag in the wind as air from the lungs passes over it, exchanges vibrational energy with the airstream to create sound waves.

LARYNX VIEWED FROM MOUTH

Airﬂ ow Vocal folds

LARYNX

Ligament Vocal folds Muscle Mucous membrane

VOCAL-FOLD Glottis CROSS SECTION

Nature has addressed these problems by con- Complex Cords structing the vocal folds out of a three-part mate- Biology has also found a second way to expand rial that displays properties not found in standard the pitch range of the vocal folds, including a instrument strings. One component is a ligament material that can increase in tension as it short- that looks somewhat stringlike, which is why ens, namely, muscle tissue. The internal con- the folds came to be called “cords” popularly. traction of muscle ﬁ bers can raise the stress Scientists have shown in biomechanical tests that between a vocal fold’s end points, even when the stress in this ligament rises nonlinearly when the fold itself shortens. About 90 percent of the it is stretched just a little; it can be virtually limp volume of the vocal fold is muscle tissue. In when short but impressively tense when elongat- essence, nature has solved the pitch problem

ed. Stretching its length from 1.0 to just 1.6 cen- largely by growing a group of strings side by ) timeters, for example, can raise its internal stress side as a laminate, with some layers having con-

BROADWAY STAR Ethel Merman by a factor of 30, which would yield a frequency tractile properties and others not. But how can illustration belted out songs with precise change ratio of more than 5 to 1 (recall the this complex tissue be kept in vibration when it enunciation and pitch so the square root relation mentioned earlier). But the cannot be bowed or repeatedly plucked inside audience could hear her even fact that the length increases by 60 percent low- the larynx? The only source of energy available

without amplifi cation. The ( QUESTELL ADAM ); ers the vibration rate, bringing the true frequency to deform the folds and thereby induce vibra- female “belt” voice gains resonance from vocal-tract inertive ratio back to around 3 to 1, about one and a half tion—the way that wind passing across a fl ag Merman reactance [see box on opposite octaves in musical terms. Most of us speak and makes it fl ap—is air fl owing from the lungs. A page], which boosts the sec- sing in this frequency range, but some singers can muscle and a ligament alone would be too stiff ond harmonic frequency (dou- produce as much as four to fi ve octaves, which to develop such vibrations as air passes over

ble the fundamental). is still considered extraordinary by scientists. their surfaces. For the needed air-driven oscil- ( BETTMANN/CORBIS

98 SCIENTIFIC AMERICAN January 2008 © 2007 SCIENTIFIC AMERICAN, INC. lation to occur, a soft, pliable surface tissue is natural (freely vibrating) frequencies compete in DID YOU KNOW? required, one that can respond to the airstream these tissues for dominance. This competition by generating waves akin to those the wind may result in unexpected pitch jumps or rough- Humans tend to think of the forms at the surface of the ocean [see “The ness in the sound [see “The Throat Singers of entire body as the human instrument, which would Human Voice,” by Robert T. Sataloff; Scien- Tuva,” by Levin Edgerton; Scientifi c Ameri- make it comparable in size tifi c American, December 1992]. can, September 1999]. to a double bass. But most And indeed, the folds have a third layer, a For low pitches and moderate-to-loud sound of the human body contrib- mucous membrane that stretches over the mus- volumes, the singer activates the vocal fold mus- utes nothing to the sound— cle-ligament combination to provide this ener- cle and sets all the layers into vibration. The vo- neither the chest, the back, gy-transfer function. This mucosa, which con- cal folds are short, and the muscle stress largely the belly, the buttocks nor sists of a very thin skin (epithelium) with a fl u- determines the pitch. In this case, the mucosa the legs. All the sound comes idlike substance underneath, is easily deformed and the ligament are both relaxed and serve from the voice box (larynx) and can support a so-called surface wave. My mainly to propagate the desired surface waves and the air passages. colleagues and I have shown mathematically for self-sustained oscillation. For the sound vol- that this airstream-driven wave sustains vibra- ume to be reduced at these pitches, the muscle tion. The buckling, ribbonlike motion often does not vibrate and is used only to adjust the makes the tissue look like it is folding bottom to vocal-fold length. It is the combined elasticity of top, which is how the name “vocal fold” arose. the mucosa and ligament that determines the frequency. To create high pitches, the singer Playing the Vocal Folds elongates the vocal fold; ligament stress alone How can this triple-decker system be played then dictates the frequency while the mucosa over several octaves so as to produce a single carries the surface wave. frequency? Only with much experience and It is not hard to imagine the complicated con- dexterity. Chaotic effects always lurk in the trol system and innervation of the laryngeal background during vocalizations as multiple muscles needed to fi nely regulate these tensions

[HUMAN SOUND RESONATOR] HOW THE VOCAL AIRWAYS AMPLIFY SOUND Singers use a nonlinear energy-feedback process in the laryngeal vesti- presses against the motionless air column in the vestibule. The inertia bule (the airway above the larynx) to resonate, or amplify, sounds cre- of the stationary air column raises the air pressure in the glottis, which ated by the vocal folds. This process, called inertive reactance, occurs drives the folds even farther apart (2). Then the lungs begin to accel- when singers create special conditions in the vestibule to provide an erate the air mass upward. As the air column moves, the elastic recoil extra, precisely timed “kick” to each cyclic opening and closing of the of the folds begins to send them back together to close the glottis, folds that reinforces their vibration to create stronger sound waves. cutting off the airﬂ ow from the lungs (3). Those responses leave a The kick comes in when the motion of the air column in the vesti- partial vacuum in the glottis that acts to slam the folds together bule lags with respect to the movement of the vocal folds. When the strongly (4). Thus, like a well-timed push on a kid’s swing, the inertive vocal folds start to separate at the beginning of an oscillation (1), reactance—the push-pull action—of the air in the laryngeal vestibule lung-driven air ﬂ ows into the glottal space between the folds and augments each swing of the vocal folds, creating resonance.

GLOTTIS OPENING GLOTTIS CLOSING

Mobile air column Stationary air column

Laryngeal Rising pressure Falling pressure vestibule

●1 ●2 ●3 ●4 Folds closing Larynx Vocal fold Folds opening Glottis Decreasing Increasing airﬂ ow airﬂ ow High pressure ADAM QUESTELL QUESTELL ADAM

www.SciAm.com SCIENTIFIC AMERICAN 99 © 2007 SCIENTIFIC AMERICAN, INC. [HUMAN SOUND RADIATOR] BIG MOUTHS AND SMALL MOUTHS Acting as a tube resonator, the vocal tract adopts certain shapes to better project certain pitches and resonant overtones. To produce powerful high notes, belters often open their mouths as wide as possible. This so-called MEGAPHONE megaphone conﬁ guration resembles a trumpet (top), Vocal fold with the vocal folds and vestibule serving as the “lips and mouthpiece” and the mouth as the “horn.” Other Vestibule Mouth singing styles are better produced when the vocal tract Trachea of larynx takes on an inverted megaphone shape—that is, with the mouth narrowed (bottom).

INVERTED MEGAPHONE

Vocal fold

Vestibule Trachea of larynx Mouth

to produce a desired frequency and volume lev- many brass and woodwind instruments, the el. Laryngeal muscles outside the vocal folds horn (with its valves) is designed to match many precisely coordinate length changes in the vocal of the source frequencies at whatever pitch is fold. During these complicated manipulations, played. voice quality may suddenly change, a phenom- Because physical law dictates that all steady enon known as registration. It is caused to a (continuous) sounds are composed of source large extent by overusing or underusing the vo- frequencies that are harmonically spaced— cal-fold muscle to regulate tension. Singers use meaning that all source frequencies are integer registration artistically to present two contrast- multiples (2:1, 3:1, 4:1, ...) of the fundamen- ing sounds to the listener, as in yodeling. If a tal—the resonator must often be quite large to singer involuntarily or accidentally changes reg- accommodate these wide frequency spacings. ister, however, it can cause embarrassment, be- This physical law dictates that trumpet horns cause such a slip suggests a lack of control of the are 1.2 to two meters long, trombone horns singer’s instrument. stretch three to nine meters, and French horn tubing uncoils from 3.7 to 5.2 meters. Resonating Airways Nature is stingy with the size of the singer’s In musical instruments, the resonator for the resonator. The total size of the human airway most part determines the instrument size, but above the vocal folds is only about 17 centime- singers have to make do with a pint-size resona- ters long. The lowest frequency that can be res- tor. The human resonator, however, performs onated is around 500 hertz (cycles per second)— ) effectively despite its overt limitations. and half that when certain vowels are sung, In a musical instrument, boards, plates, ket- such as /u/ or /i/ (as in “pool” or “feel”). Be- illustration tles, horns or tubes typically act to reinforce cause the vocal tract is a resonant tube that is DAME Joan Sutherland knew and amplify the frequencies that the sound nearly closed at one end, its resonant frequen- instinctively that some vowels source produces. In the violin, for instance, the cies include only the odd-integer multiples (1, 3, cannot be used when singing strings pass over a bridge support that connects 5, ...) of the lowest resonance frequency. There- ( QUESTELL ADAM ); certain pitches. The Australian to the top plate, which has been carefully fash- fore, this short tube can resonate simultaneous- soprano changed some of the Sutherland vowels in her opera lyrics ioned to vibrate sympathetically at many of the ly only the odd harmonics of a 500-Hz source ( same natural frequencies that the strings can frequency (500 Hz, 1,500 Hz, 3,500 Hz, ...). (even to the point of mispro- Corbis nouncing the words) to best produce, thereby boosting them. The air mass And because the vocal tract cannot change tube match them with the between the top and bottom plates can also os- length with valves or slides (other than a few

desired pitches. cillate at the strings’ natural frequencies. In centimeters by protruding a lip or lowering the IRA NOWINSKI

100 SCIENTIFIC AMERICAN January 2008 © 2007 SCIENTIFIC AMERICAN, INC. larynx), our resonator seems as if it should be Megaphone Mouth hopelessly restricted in what it can do. Different singing styles rely on different vocal tract shapes to make optimal use of inertive Resonating a Short Tube reactance. In producing an /æ/ vowel (as in Here again recent studies indicate that nonlinear “mad”), the vocal tract approximates a mega- effects come to the rescue. This time it is a non- phone shape. A small cross section at the glottis linear interaction among the system’s elements. is paired with a large opening at the mouth [see Rather than reinforcing each harmonic with a box on opposite page]. Singers can fi nd inertive specifi c tube resonance (as occurs, for example, reactance as high as 800 or 900 Hz for males in organ pipes of different sizes, each of which and 20 percent higher for females. At least two resonates certain harmonics), our short vocal harmonic source frequencies can achieve tract reinforces a cluster of harmonics simulta- inertive reactance for fairly high pitches, and neously by using an energy-feedback process. several more can for low pitches. This fact The vocal tract can store acoustic energy in one means that one strategy for obtaining powerful part of the vibration cycle and feed it back to the high notes is for the singer to open the mouth as source at another, more advantageous time. In ITALIAN TENOR Luciano Pavarotti, wide as possible, as in belting or calling. When famed for the brilliance and effect, the vocal tract gives a “kick” to each cycle the vocal tract adopts this megaphone confi gu- beauty of his tone, produced of oscillation of the vocal folds so as to increase ration, it approximates the shape of an ampu- the rich resonance in his voice the amplitude of vibratory motions. In analogy by fi ne-tuning nonlinear tated trumpet (with no coiling tube or valves, to pushing someone on a playground swing, this inertive reactance in his throat. but with a bell, or horn). cyclic kick resembles a carefully timed push to An alternative approach to reinforcing vocal- boost the amplitude (travel distance) of the fold vibration with inertive reactance is to adopt swing’s oscillations. the so-called inverted-megaphone shape, in The ideal timing of the kick comes when the which the laryngeal vestibule, the “mouthpiece,” movement of the air column in the tube is de- is kept narrow, the pharynx (the part of the layed with respect to the movement of the vocal throat situated immediately behind the mouth folds. Scientists say that the air column then has and nasal cavity) is expanded as widely as pos- inertive reactance (slow or sluggish response to sible and the mouth is narrowed somewhat. This an applied pressure). Inertive reactance helps to confi guration is approximated to verbalize the sustain the fl ow-induced oscillation of the vocal /u/ vowel (as in “took”). The inverted-mega- folds in a profound way [see box on page 99]. phone technique is ideal for female classical When the vocal folds begin moving apart at ➥ MORE TO singers who wish to sing in the middle of their the inception of a vibratory cycle, air from the EXPLORE pitch range and male classical singers who wish lungs starts to fl ow into the glottal space between The Physics of Small-Amplitude to sing in the high part of their pitch range. Clas- them and begins pushing on the stationary air Oscillation of the Vocal Folds. sical training involves fi nding more regions of column located just above in the laryngeal vesti- I. R. Titze in Journal of the Acoustical the singing range where the vocal tract provides bule. Air pressure in and above the glottis rises Society of America, Vol. 83, No. 4, inertive reactance for the source frequencies, at pages 1536–1552; 1988. as the air column accelerates upward to allow all pitches and for many different vowels. The new air to fi ll in behind it. This pressure increase Acoustic Systems in Biology. training also involves getting a “ring” into the pushes the folds even farther apart. When elastic Neville H. Fletcher. Oxford Universi- voice, which is accomplished by the combination recoil springs the folds back from the walls to ty Press, 1992. of the narrow vestibule and the wide pharynx. close the glottis, the fl ow of air through the glot- Singing teachers use terms such as “covering” Vocal Tract Area Functions from tis subsides. Because of inertia, though, the air the voice or “turning it over” to describe the Magnetic Resonance Imaging. column continues to move up, leaving a partial B. Story, I. Titze and E. Hoffman in process of choosing just the right vowel for the vacuum in and above the glottis that acts to slam Journal of the Acoustical Society of given pitch so that most of the source frequen- the folds more strongly together. Thus, like a America, Vol. 100, No. 1, pages cies experience inertive reactance. well-timed push on a kid’s swing, the inertive re- 537–554; 1996. Singing styles are based on what human bi- actance of the air in the vocal tract augments each ology can offer to produce an acoustically effi - Principles of Voice Production. swing of the vocal folds with a push-pull action. Reprint. I. R. Titze. National Center cient instrument. Researchers who study the el- Still, the vocal tract does not automatically for Voice and Speech, 2000. ements of the human vocal system, and the un- behave in this inertive way for all vocal shapes. www.ncvs.org expected ways in which it functions, are A singer’s task is to adjust the shape of the vocal garnering an ever greater understanding of how Corbis The Physics of Musical Instru- tract (by carefully selecting favorable “singing” accomplished singers ply their art. Both scien- ments. Second edition (corrected vowels) so that inertive reactance is experienced fi fth printing). N. H. Fletcher and tists and singers will benefi t substantially from g ETHAN MILLER MILLER ETHAN over most of the pitch range—no easy task. T. D. Rossing. Springer, 2005. continued close cooperation and study.

www.SciAm.com SCIENTIFIC AMERICAN 101 © 2007 SCIENTIFIC AMERICAN, INC. INSIGHTS ■ ■ ■ ■ PALEOANTHROPOLOGY Cooking Up Bigger Brains Our hominid ancestors could never have eaten enough raw food to support our large, calorie-hungry brains, Richard Wrangham claims. The secret to our evolution, he says, is cooking BY RACHAEL MOELLER GORMAN

ichard Wrangham has tasted chimp In the 10 years since coming on his the- evolution. He is out of his league. Further- food, and he doesn’t like it. “The ory, Wrangham has stacked up consider- more, archaeological data does not sup- R typical fruit is very unpleasant,” able evidence to support it, yet many port the use of controlled fi re during the the Harvard University biological anthro- archaeologists, paleontologists and anthro- period Wrangham’s theory requires it to. pologist says of the hard, strangely shaped pologists argue that he is just plain wrong. Wrangham, who first encountered fruits endemic to the chimp diet, some of Wrangham is a chimp researcher, the skep- chimps as a student of Jane Goodall’s in which look like cherries, others like cock- tics point out, not a specialist in human 1970, began his career looking at the way tail sausages. “Fibrous, quite bitter. ecological pressures, especially food Not a tremendous amount of sugar. distribution, affect chimp society. He Some make your stomach heave.” famously conducted research into After a few tastings in western Ugan- chimp violence, leading to his 1996 da, where he works part of the year on book Dem onic Males. But ever since his 20-year-old project studying wild staring into that fi re 10 years ago, he chimpanzees, Wrangham came to the has been plagued with thoughts of conclusion that no human could sur- how humans evolved. “I tend to think vive long on such a diet. Besides the about human evolution through the unpalatable taste, our weak jaws, tiny lens of chimps,” he remarks. “What teeth and small guts would never be would it take to convert a chimpan- able to chomp and process enough zeelike ancestor into a human?” Fire calories from the fruits to support our to cook food, he reasoned, which led large bodies. to bigger bodies and brains. Then, one cool fall evening in And that is exactly what he found 1997, while gazing into his fi replace in Homo erectus, our ancestor that in Cambridge, Mass., and contem- fi rst appeared 1.6 million to 1.9 mil- plating a completely different ques- lion years ago. H. erectus’s brain was tion—“What stimulated human evo- 50 percent larger than that of its pre- lution?”—he remembered the chimp decessor, H. habilis, and it experi- food. “I realized what a ridiculously enced the biggest drop in tooth size in large difference cooking would human evolution. “There’s no other make,” Wrangham says. Cooking RICHARD WRANGHAM time that satisfi es expectations that could have made the fi brous fruits, FLAME ON: Argues that the practice of cooking we would have for changes in the along with the tubers and tough, raw food, beginning with Homo erectus, ultimately body that would be accompanied by meat that chimps also eat, much enabled the human brain to evolve to its current cooking,” Wrangham says. more easily digestible, he thought— large size. The problem with his idea: proof is they could be consumed quickly and slim that any human could control digested with less energy. This inno- INTO THE FRYING PAN: His theory has many fi re that far back. Other researchers vation could have enabled our chimp- skeptics because only scattered signs of fire use believe cooking did not occur until like ancestors’ gut size to shrink over by H. erectus exist. One example: a Chinese site perhaps only 500,000 years ago. Con- evolutionary time; the energy that where H. erectus may have spat hackberry seeds into sistent signs of cooking came even lat- would have gone to support a larger early campfires (producing spectacular sparks). er, when Neandertals were coping gut might have instead sparked the ON THE IMPORTANCE OF THE STOVE: “Everywhere, with an ice age. “They developed earth evolution of our bigger-brained, larg- everyone expects a cooked meal every evening.” oven cookery,” says C. Loring Brace,

er-bodied, humanlike forebears. an anthropologist at the University of DOOHER KATHLEEN

Michigan at Ann Arbor. “And that only making enzymatic breakdown easier. goes back a couple hundred thousand Wrangham’s theory would fi t together years.” He and others postulate that the nicely if not for that pesky problem of con- introduction of energy-rich, softer animal trolled fire. Wrangham points to some products, not cooking, was what led to H. data of early fi res that may indicate that erectus’s bigger brain and smaller teeth. H. erectus did indeed tame fi re. At Koobi So Wrangham did more research. He Fora in Kenya, anthropologist Ralph examined groups of modern hunter-gather- Rowlett of the University of Missouri– ers all over the world and found that no Columbia has found evidence of scorched human group currently eats all their food earth from 1.6 million years ago that con- raw. Humans seem to be well adapted to tains a mixture of burned wood types, eating cooked food: modern humans need indicating purposely made fire and no a lot of high-quality calories (brain tissue requires 22 times the energy of skeletal muscle); tough, fibrous fruits and tubers cannot provide enough. Wrangham and his colleagues calculated that H. erectus (which was in H. sapiens’s size range) would have to eat roughly 12 pounds of raw plant food a day, or six pounds of raw plants plus raw meat, to get enough calories to survive. Studies on modern women show that In contemplating the question those on a raw vegetarian diet of what stimulated human often miss their menstrual periods because of lack of evolution, “I realized what energy. Adding high-energy a ridiculously large difference raw meat does not help much, either—Wrangham found cooking would make,” data showing that even at Richard Wrangham says. chimps’ chewing rate, which can deliver them 400 food calories per signs of roots having burned underground hour, H. erectus would have needed to (a tree struck by lightning would show chew raw meat for 5.7 to 6.2 hours a day only one wood type and burned roots). to fulfi ll its daily energy needs. When it was The discoveries are consistent with human- not gathering food, it would literally be controlled fi re. Rowlett plans next to study chewing that food for the rest of the day. the starch granules found in the area to see To prove that cooking actually does if food could have been cooked there. save energy, Wrangham partnered with Still, most researchers state that unless Stephen Secor, a University of Alabama evidence of controlled fi re can be regularly biologist who studies the evolutionary confi rmed at most H. erectus sites, they design of the digestive system. They found will remain skeptical of Wrangham’s the- that the python—an animal model with ory. Moreover, other food-based theories easily studied gut responses— expends can explain the body and brain expansion less effort breaking down cooked food without fl ames. One is the expensive tissue zefa/Corbis than raw. Heat alters the physical struc- hypothesis, proposed in 1995 by Leslie C.

ture of proteins and starches, thereby Aiello, professor emeritus of biological LYTTLE C.

anthropology at University College Lon- don, and physiologist Peter Wheeler of Liverpool John Moores University in Eng- land. The main idea of the hypothesis— that smaller guts correlate with bigger brains in primates—fi ts with Wrangham’s theory, but Aiello and Wheeler think that energy-dense animal-derived foods, such as soft bone marrow and brain matter, were the reason humans developed these characteristics, not cooking. Lacking the proof for widespread fi re use by H. erectus, Wrangham hopes that DNA data may one day help his cause. “It would be very interesting to compare the human and Homo erectus genetics data to see when certain characteristics arose, such as, When did humans evolve improved defenses against Maillard reaction products?” he says, referring to the chemical products of cooking certain foods that can lead to carcinogens. Even without such evidence yet, some think Wrangham’s theory is just the thing to shake up the fi eld of human evolution. “It doesn’t matter who develops these ideas,” says Aiello, who is also president of the Wenner-Gren Foundation, which supports anthropological research. “You have to listen to what Richard is saying because he has some very interesting, original data. Sometimes the most creative ideas come from unexpected places.” She points to Goodall, who surprised the world by prov- ing that humans were not the only tool- makers. “It’s one of the best illustrations I know of the value of primate research informing our knowledge of human evolution and adaptation,” Aiello says. If Wrangham’s strange ideas turn out to be true, we can thank an early hominid Emeril Lagasse who picked a charred tuber out of a campfi re and swallowed it. With- out that person, we might never have been able to examine our origins—or enjoy a good grilled steak—in the fi rst place. g

Rachael Moeller Gorman is a writer based in Boston. A Q&A version of her interview with Wrangham is at www.SciAm.com/ontheweb

SCIENTIFIC AMERICAN Digital WORKING KNOWLEDGE ■ ■ ■ ■ BOWLING PINSETTERS

Perpetual Reset Machine By Mark Fischetti

busy bowling alley might seem noisy, but behind the lanes tion in Lake Forest, Ill., later offered a competing “pinsetter,” and the cacophony is signiﬁ cantly louder. As the heavy balls the two companies still dominate the market today with technol-

A crash into the wooden pins, hefty motors, conveyor belts, ogy that is strongly reminiscent of the original. ); pulleys and cams clatter behind each “pit,” grabbing the wreckage What has changed most are the bells and whistles designed to from one collision while hoisting and arranging pins so they are expand bowling’s popularity. In the 1980s cameras were placed pinsetters ready for the next one. between the lanes, pointed at the pins, and wired to computers For years pin boys stood at the lane ends, manually resetting that automatically calculated bowlers’ scores and displayed them pins and rolling the balls back to bowlers. Machines did not ap- overhead. More recently, a system of blacklights, fl uorescent pins, pear until 1946, when AMF Bowling, Inc., now in Richmond, Va., laser beams, loud music and video screens has turned the ordinary introduced the fi rst “automated pinspotter.” Brunswick Corpora- routine into a dazzling late-night dance party promoted as cosmic, disco or “Xtreme” bowling. A visit to the back end of a typical 24-lane alley, such as Cove DID YOU KNOW... Bowling Lanes in Great Barrington, Mass., reveals a mechanical ) engineer’s paradise. Twenty-four steel, wood and rubber pinspotter machines relentlessly chunk along shoulder to shoulder; each illustrations one is about fi ve feet tall, weighs about 2,000 pounds and collects, sorts and resets 10 pins in around eight seconds. Racks of spare

belts, cams, rods, levers, oils and rags line the rear wall, looking ( RETSECK GEORGE ); pins like a cluttered auto repair garage. Cove Bowling Lanes head me- ( chanic DJ Marks must inspect, clean and lubricate each machine every week. “It’s pretty much a constant job,” he says happily. “I Getty Images do ﬁ ve machines a day—four on Fridays.” He shows them off to enthusiastic patrons and says most proprietors will do the same. So on your next trip to the lanes, if you are not compiling a marvel-

ous score, ask for a peek at the mechanical marvels instead. LIBRARY OF CONGRESS, PRINTS AND PHOTOGRAPHS DIVISION, NATIONALC SQUARED CHILD STUDIOS LABOR COMMITTEE COLLECTION (

HUMAN TARGET: Pin boys reset pins before machines came along. Balls are most often made of resin. A “You really had to work fast, or the bowlers would yell at you, core denser at the center (shown) creates a low radius of gyration; the ball ‘Hey, get moving!’” recalls Paul Retseck, 84, who set pins in the rotates sideways more easily as it rolls 1930s for $1 a night in Michigan City, Ind. Drunken patrons forward and therefore hooks gently and sometimes tried to hurl balls at boys who were stooped over steadily along the lane. Pushing core picking up pins: “We learned to hop up quick onto the side wall,” density outward creates a high radius of gyration; the ball rolls straight down the Retseck says. Subway Bowling Alleys in Brooklyn, N.Y., at Above: lane but then hooks sharply as its angular 1 A.M., April 1910. momentum builds.

LOST BALL: Occasionally a ball does not return to the bowler. The most likely culprit is a pin that becomes lodged in the ball-return inlet hole, wedged under the return lever. An attendant must remove the pin, although a second bowled ball might knock it free, too.

RESET: At times the sweep bar may stall on the lane. This usually Ball lift propels a occurs because the table did not receive all 10 pins. The missing pin ball back to the bowler. prompts the arm to stay above the table instead of returning to its A ball enters the inlet hole, guided by a tipped plate under neutral position, which signals the sweep cycle to continue. A bowler the conveyor. A lever hoists it can request help from an attendant by pressing the reset button. upward against a belt that rolls it to the top. Gravity then takes over.

●1 Camera ■➔ BOWLING CYCLE A charge-coupled-device camera sees which pins remain standing A bowler throws two balls per frame. After the ﬁ rst after a ball has struck, informing the automatic scoring computer. ball, a rack descends over the pins; two rods The computer then initiates clamp onto the neck of each standing pin and lift the reset cycle. It also calculates ball speed based on them while downed pins are cleared. The rods the ball’s elapsed time between then descend and release the pins they picked two side beams. up. After the second ball [shown in illustrations], all pins are cleared, and 10 new ones are reset.

●4 Cushion Pins pass underneath a wood slat, but the ball stops against the ●3 Pit rubber face and rolls toward the ball-return hole (not shown). Ball and pins fall onto a ●2 Sweep conveyor belt. Fiberglass bar sweeps ●5 Elevator backward to clear Rod locks a pin into remaining pins. a pocket as the wheel revolves upward.

●6 Distributor arm Pin drops into a pan that orients it base-ﬁ rst. A telescoping belt places it into a cup. Actuators advance the arm to empty cups. In other models, pins drop from a stationary arm into a rotating basket that ﬁ lls cups.

●7 Table A full table descends. Cups pivot to vertical and set pins on the lane. The cups retract, and the table rises; the sweep lifts, too.

Tenpin is 15 inches tall and weighs up to three pounds, 10 ounces. Wood, primarily hard rock maple, is shaped on a lathe and coated with plastic.

SEND IDEAS to [email protected]

Beasts with Soul ■ Machines with Brains ■ Bubble Baths with Meaning BY MICHELLE PRESS

■➜ THE SOUL OF THE RHINO: A Nepali the beast’s blood in a prayer for peace and pros- NEW AND NOTABLE BOOKS: Adventure with Kings and Elephant perity, takes center stage. Mishra, a Nepalese wildlife biologist trained in the West, is not a HOLLYWOOD SCIENCE Drivers, Billionaires and Bureaucrats, 1 Don’t Try This at Home: The Physics of Shamans and Scientists, and the professional writer, but his intelligence and wit make this a mesmerizing account that inter- Hollywood Movies Indian Rhinoceros by Adam Weiner. Kaplan Publishing, 2007 twines politics, conservation and tensions be- by Hemanta Mishra. Lyons Press, 2008 (paperbound, $17.95) tween the traditions of East and West. ($24.95) 2 Stereoscopic Cinema and the Origins of 3-D Film, 1838–1952 by Ray Zone. University Press of Kentucky, The subtitle may sound like hype, ■➜ 2007 ($42) but it is a rare case of truth in label- THE DESIGN OF FUTURE THINGS 3 Hollywood Science: Movies, Science, and ing. Against the backdrop of politi- by Donald A. Norman. Basic Books, 2007 the End of the World cal violence in Nepal—beginning ($27.50) by Sidney Perkowitz. Columbia University Press, with the massacre of the king’s fami- 2007 ($24.95) ly in 2001 by the eldest son and end- A computer scientist who is the author of The De- 4 What’s Science Ever Done for Us? What The Simpsons Can Teach Us about Physics, ing with the Maoist insurgency this sign of Everyday Things and many other articles Robots, Life, and the Universe crisis spawned—Mishra tells the story of trying and books on design and technology, Norman as- by Paul Halpern. John Wiley & Sons, 2007 to save the greater one-horned Asian rhino from serts that the intelligence of so-called smart sys- (paperbound, $14.95) extinction. Kings did indeed play a pivotal role in tems is fundamentally limited: a machine cannot 5 The Physics of Star Trek the creature’s conservation, and the murder of begin to know all the factors that go into human by Lawrence M. Krauss. Revised and updated. the recent king led to its now uncertain future. decision making. In fact, machines have become Foreword by Stephen Hawking. Basic Books, 2007 (paperbound, $15) The exotic Tarpan ceremony, in which the Nepal- too smug, he says. From cars to refrigerators to ese king must hunt and kill a male rhino and offer scales, they misread our intentions. But of course, he argues, this doesn’t mean we should reject their help. Instead we EXCERPT need to fi gure out a way to “social- ize” them, to see that they recog- ■➜ EVOLUTION nize their limitations and improve their interactions with humans. Text by Jean-Baptiste de Panafi eu. Photographs by Patrick Gries. Much of what he has to say will be Translated by Linda Asher. Seven Stories Press, 2007 ($65) familiar to those who have read his previous work, but if you are new to Norman, the The Natural History Museum of Paris collaborated on these astonishing photographs book provides an enjoyable antidote to a lot of from Gries to provide visual affi rmation of evolution. Fleshing out the skeletal current hyperbole. evidence are brief essays by de Panafi eu and an even more succinct 250-year-old observation from the Comte de Buffon: ■➜ EINSTEIN’S ENIGMA OR BLACK HOLES IN MY BUBBLE BATH by C. V. Vishveshwara. Springer, 2006 ($27.50)

The author blends ﬁ ction, fanta- sy, physics and philosophy to tell the story of gravitation theory, focusing on Einstein’s general relativity and the astrophysics of black holes. He not only succeeds at doing this; he entertains readers with delight- ful digressions and illustrates key concepts with wonderful cartoons, some pur- portedly scribbled on paper napkins. A theoreti- “Take the skeleton of a man. Tilt the pelvis, shorten the femur, legs, and arms, cal physicist, Vishveshwara received his doctor- elongate the feet and hands, fuse the phalanges, elongate the jaws while shortening ate and taught in the U.S. before returning to the frontal bone, and ﬁ nally elongate the spine, and the skeleton will cease to his native India, where he has been a professor represent the remains of a man and will be the skeleton of a horse.” —Buffon, 1753 at the Raman Research Institute and the Indian

Institute of Astrophysics. GRIES; PATRICK PHOTOGRAPH BY BARRAL,2007; XAVIER EDITIONS PARIS COPYRIGHT HORSE SPECIMEN FROM THE NATURAL HISTORY MUSEUM, TOULOUSE, FRANCE

How do we remember smells for so long if olfactory sensory neurons only survive for about 60 days? —A. A. Bozorgi, Irvine, Calif.

Donald A. Wilson, a zoology professor at the combination of sensory neurons activated at any given University of Oklahoma and co-author of Learn- time and interprets that pattern; the brain’s interpre- ing to Smell (Johns Hopkins University Press, tation is what you perceive as smell. With so many 2006), replies: inputs contributing to the formation of a scent pat- We recognize an old scent, despite having re- tern, the absence of a small number of con- placed at least a subset of the olfactory sensory neu- stituents does not appreciably change the rons that fi rst interacted with that odor, because the pattern or the brain’s perception. overall pattern of activity within the olfactory system remains relatively constant over time. OLFACTORY neuron (orange) Olfactory sensory neurons, which sit in the mucus in the back of the nose and relay data to the brain via axons (fi ngerlike projections that transmit information out from the cell body), are one of an increasingly large number of neuron types that are Why do migratory birds known to die and be replaced throughout life. Fortunately, they do not all die at the same time, and there are many thousands of fl y in a V formation? olfactory sensory neurons that respond to any given scent. —J. F. Bowman, Corte Madera, Calif. The 2004 Nobel Prize in Physiology or Medicine went to Lin- da B. Buck and Richard Axel for their 1991 research showing Bruce Batt, who retired in 2007 as chief biologist for Ducks that there is a huge family of genes that encode proteins called Unlimited, a wetlands conservation group based in Mem- olfactory receptors. One of their important observations was phis, Tenn., offers this explanation: that individual olfactory sensory neurons typically express just There are two well-supported and complementary explana- one of those genes. That is, signals from a given neuron provide tions for why birds fl y in formation. (Both V and J structures are information about odors that activate the specifi c receptor pro- typical and readily recognizable fl ight formations for migratory tein expressed by that cell. In fact, when an olfactory sen- birds; studies have shown that a J formation is, in fact, more sory neuron expressing a particular receptor gene dies common than a true V-shaped structure.) One way to ac- and a new neuron expressing that same gene matures, count for the phenomenon is that followers benefi t from the new neuron’s axons plug into the same group of a supportive upwash of air created by the lead birds. olfactory bulb neurons that its predecessor did. This The other is that regimented fl ight formation fa- phenomenon results in remarkable pattern stability cilitates proper spacing, directional orientation over years, despite continual rewiring. and group communication. )

A single receptor protein, however, appears to The relative importance of each geese bind (or recognize) many different odors. Thus, benefit undoubtedly shifts along rather than having neurons that respond selective- with changes in various factors, such ); ly to coffee or vanilla or Bordeaux, most individ- as the season of the year or the purpose ); DLILLC/CORBIS ( DLILLC/CORBIS ); ual cells respond (via their receptors) to submo- of an individual fl ight. During local feeding olfactory neuron olfactory ( ng wine ng lecular features of the volatile chemicals coming fl ights, for example, energy conservation is fi from those objects. For example, an olfactory sen- probably much less important than careful ori- woman snif woman

sory receptor neuron may respond to a hydrocar- entation and collision avoidance are. During long- ( bon chain of a particular length or to a specifi c distance migration, on the other hand, each mem- functional group such as an alcohol or aldehyde. ber of the fl ock gains a great deal by optimizing its Researchers,Photo Inc. Therefore, any given sensory neuron will respond position to conserve energy. g Getty Images to many different odors as long as they share a common feature. The brain (specifi cally, the olfactory HAVE A QUESTION?... Send it to [email protected] HORST NEUMANN NEUMANN HORST bulb and the olfactory cortex) then looks at the or go to www.SciAm.com/asktheexperts GSCHMEISSNER STEVE

Does Inﬁ nity Come in Different Sizes?

BY JOHN MATSON

n the 1995 fi lm Toy Story, the gung-ho space action fi gure partner rn. The reals can then be listed in order of their corre- Buzz Lightyear tirelessly incants his catchphrase: “To infi n- sponding naturals: r1, r2, r3, and so on. I ity ... and beyond!” The joke, of course, is rooted in the per- Then Cantor’s wily side comes out. He created a real number, fectly reasonable assumption that infi nity is the unsurpassable called p, by the following rule: make the digit n places after the absolute—that there is no beyond. That assumption, however, is decimal point in p something other than the digit in that same not entirely sound. As German mathematician Georg Cantor decimal place in rn. A simple method would be: choose 3 when demonstrated in the late 19th century, a variety of infi nities ex- the digit in question is 4; otherwise, choose 4. ist—and they can be classifi ed by their relative sizes. For demonstration’s sake, say the real-number partner for the natural number 1 is 27 (or 27.00000...), the pair for 2 is pi Natural Logic (3.14159...) and that of 3 is President George W. Bush’s share of Take, for instance, the so-called natural numbers: 1, 2, 3, and so the popular vote in 2000 (0.47868...). Now create p following on. These numbers are unbounded, and thus the collection, or set, Cantor’s construction: the digit in the fi rst decimal place of p of all the natural numbers is infi nite in size. But just how infi nite should not be equal to that in the fi rst decimal place of r1 (27), is it? Cantor used an elegant argument to show that the naturals, which is 0. Therefore, choose 4, and p begins 0.4.... (The number though infi nitely numerous, are actually less numerous than an- before the decimal can be anything; 0 is used here for simplicity.) other common family of numbers: the real numbers. This set com- Then choose the digit in the second decimal place of p so that it prises all numbers that can be represented as a decimal, even if that does not equal that in the second decimal place of r2 (pi), which is decimal representation is infi nite in length. Hence, pi (3.14159. . . ) 4. Select 3, and now p = 0.43.... Finally, choose the digit in the is a real number, as is 27 (which is both natural and real). third decimal place of p so that it does not equal the one in the cor- Cantor’s argument used the logic of contradiction: he fi rst as- responding decimal place of r3 (President Bush’s percentage), sumed that these sets are the same size; next he followed a series which is 8. Write 4 again, making p = 0.434.... Thus, you have: of logical steps to fi nd a fl aw that would undermine that assump- r = 27.00000... p = 0.4... tion. He reasoned that if the naturals and the reals have equally 1 many members, then the two sets can be put into a one-to-one r2 = 3.14159... p = 0.43... correspondence. That is, they can be paired so that every element r3 = 0.47868... p = 0.434... in each set has one—and only one—“partner” in the other set. This mathematical method (called diagonalization), continued Think of it this way: even in the absence of numerical count- infi nitely down the list, generates a real number (p) that, by the ing, one-to-one correspondences can be used to measure relative rules of its construction, differs from every real number on the list amounts. Imagine two crates of unknown sizes, one of apples in at least one decimal place. Ergo, it cannot be on the list. and one of oranges. Withdrawing one apple and one orange at a In other words, for any pairing of naturals and reals, there ex- time thus partners the two sets into apple-orange pairs. If the ists a real number p without a natural-number partner—an apple contents of the two crates are emptied simultane- without an orange. Therefore, any one-to-one correspondence ously, the two boxes contain an equal number between the reals and the naturals fails, which means that the ) of fruits; if one crate is exhausted before the infi nity of real numbers is somehow greater than the infi nity of Cantor other, the one with remaining food is more natural numbers. g ); CORBIS ( CORBIS ); plentiful. John Matson is a copy editor at Scientifi c American. nity symbols nity fi Crafty Math in Cantor thus began by presuming that the natu- MORE ONLINE . . . Find more investigations into popular myths rals and the reals are in such a correspondence. at www.SciAm.com/factorfi ction

Accordingly, every natural number n has a real To suggest a topic, write to factorﬁ [email protected] LOGAN PARSONS (