WINTER p.4 The science of large numbers p.16 Eric Lander & the cancer code 07 p.10 Hitting the bull’s-eye p.22 It starts with an embryo LensA New Way of Looking at Science Hot on cancer’s trail A PUBLICATION OF VANDERBILT UNIVERSITY MEDICAL CENTER – Cover: Cancer the crab scuttles across the beach, leaving behind a double-helical trail. Lens Photo illustration by Dominic Doyle. Photo credit: Science Faction/Getty Images. A New Way of Looking at Science WINTER 2007 VOLUME 5, NUMBER 1 EDITOR Bill Snyder CONTRIBUTING WRITERS Stephen Doster Leigh MacMillan Melissa Marino Bill Snyder PHOTOGRAPHY/ILLUSTRATION Dean Dixon Dominic Doyle Allen Garns David Johnson Jared Leeds Anne Rayner It is only the vision that can be new; DESIGN Diana Duren/Corporate Design, Nashville but that is enough. DIRECTOR OF PUBLICATIONS – EUDORA WELTY Wayne Wood COPY EDITOR Nancy Humphrey EDITORIAL OFFICE Office of News and Public Affairs D-3237A MCN Vanderbilt University Medical Center Nashville, Tennessee 37232-2390 615-322-4747 E-mail address: [email protected] Lens is published three times a year by Vanderbilt University Medical Center in cooperation with the VUMC Office of News and Public Affairs and the Office of Research. Lens® is a registered mark of Vanderbilt University. Our goal: to explore the frontiers of biomedical research, and the social and ethical dimensions of the revolution that is occurring in our understanding of health and disease. Through our Lens, we hope to provide for our readers – scientists and those who watch science alike – different perspectives on the course of discovery, and a greater appreciation of the technological, eco - nomic, political and social forces that guide it. © 2007 by Vanderbilt University Lens TABLE OF contents W0IN7TER 2 CLOSING IN ON CANCER 3 HIGH -TECH SURVEILLANCE Proteomics, the science of proteins, has raised hopes that doctors one day will be able to detect early cancer from tell-tale patterns of proteins in a single drop of blood. What will it take to bring these methods into the clinic? 4 THE SCIENCE OF LARGE NUMBERS From Shanghai, China, to the American South, modern-day gumshoes are hot on the trail of some of the worst miscreants afflicting the human race. By surveying thousands of participants enrolled in “cohort studies,” researchers are uncovering important clues to cancer and other diseases. 10 HITTING THE BULL ’S-EYE They’re not “magic bullets,” but targeted therapies have dramatically improved page 10 Explosion of drugs for cancer outcomes for many cancer patients. These drugs are not without side effects, however, and some of them cost $10,000 a month. Vanderbilt researchers give an update on the search for better treatments. 15 TURNING GENES ON TO TURN CANCER OFF Cancer can result not only when certain genes are “turned on,” but when others are “turned off” by the attachment of chemical “tags” to the DNA. This tag-driven con - trol of gene expression – called epigenetics – provides a new avenue for stopping tumor growth. 16 THE GREAT AMPLIFIER A driving force behind the sequencing of the human genome, Eric Lander is now tackling the “cancer genome.” More than that, this mathematical wunderkind wants to empower the next generation of scientists with new tools and information so they page 16 A new taxonomy for tumors can “change the world.” 22 IN THE BEGINNING It could be nature’s cruelest joke – the genes and proteins that help sculpt the fertil - ized egg into a complex multicellular organism are also responsible for the birth of many cancers. Understanding the fundamentals of developmental biology could lead to new treatments for patients. 28 A PROBLEM OF SOCIAL INJUSTICE Harold Freeman, M.D., former president of the American Cancer Society, and Jane Weeks, M.D., chief of Population Sciences at the Dana-Farber Cancer Institute, dis - cuss what needs to be done to reduce the disproportionate impact of cancer on racial and ethnic groups, the poor and the elderly. 32 LWALA DIARIES The previous issue of Lens chronicled the efforts of Vanderbilt medical student Milton Ochieng’ to construct the first health clinic in his village in Kenya. Abbie Foust, who spent her summer vacation surveying his village’s health needs, describes her life-changing experiences. page 22 The power of Wnt and Hedgehog LENS / WINTER 2007 1 B N A O X R I D C N A E E D H T G N I H C T A C the role that cigarettes play in the disease. Cohort studies, which track the development of disease in large groups over several decades, also may help solve l i the riddle of cancer disparities – why a r cancer incidence and death rates are t s disproportionately high, for example, ’ r among African-Americans. e c “It’s where research always starts,” n a says Jane Weeks, M.D., chief of c Population Sciences at Boston’s Dana- n o Farber Cancer Institute. “It generates t o Symphony of knowledge hypotheses. It generates ideas.” H Charting cancer in cohorts, uncover - Science closes in on cancer ing proteomic fingerprints, discovering clues to cancer in the development of an embryo – all avenues are important. By Bill Snyder “By pulling all of this information together into a symphony of knowledge, we will be able to exponentially expand the rate of effective cancer treatment over the next 10 or 20 years,” predicts Raymond he crab on the cover of this issue of Lens magazine represents all that is DuBois, M.D., Ph.D., director of the Told and new about cancer, the nation’s second leading cause of death after Vanderbilt-Ingram Cancer Center, who heart disease. later this year will become provost and Old, because cancer goes back to the dinosaurs; evidence of malignancies has been executive vice president of academic affairs found in fossils dating back 80 million years. at the University of Texas M.D. Anderson New, because fields as disparate as genomics and embryology are providing new Cancer Center in Houston. hope that a war declared 36 years ago by President Richard Nixon one day will be won. Continued support of cancer research In this issue, Eric Lander, Ph.D., a driving force behind the Human Genome is crucial, he adds. So is nurturing the Project, predicts that cancer patients soon will be able to have complete genomic next generation of scientists. workups to determine exactly what subtype of the disease they have, and which treat - “What makes me most impatient and ments are most likely to work. most frustrated is when I hear young peo - The sequencing of the 20,000 or so genes that make up the human being already has ple’s proposals being criticized for being improved our understanding of the genetic “switches” that turn on tumors. One benefit: too ambitious,” says Lander, who directs a discovery of new compounds that can switch off malignant growth without harming genomic research powerhouse, the Broad normal cells. Institute of MIT and Harvard. Also on the horizon: screening blood tests that harness the power of proteomic “There’s nothing wrong with young “fingerprints” to detect early cancer, even before symptoms occur. people being too ambitious. They should This issue of Lens focuses on the spectrum of research – from basic laboratory studies be too ambitious … the desire to try to do to clinical trials of new drugs – undertaken by scientists at Vanderbilt University Medical something important is a great fuel; it’s a Center, the Vanderbilt-Ingram Cancer Center and colleagues from Boston to Shanghai. great resource.” The story would not be complete, however, without mentioning epidemiology, This, incidentally, is the raison d’être that non-flashy field of medical research that is crucial to understanding what causes for Lens magazine – to explore, to explain, disease and how to prevent it. to inspire … to follow, if you like, the By recording the incidence of lung cancer among Americans over time and corre - double helical trail left in the sand by an lating the numbers with smoking rates, researchers were able to establish conclusively ancient animal. LENS 2 LENS / WINTER 2007 Liebler is heading up one of five The standardization effort mirrors E C teams across the country to standardize approaches being developed for early N A proteomic technologies and move them detection of colorectal cancer in the Jim L L forward. The project, part of the NCI’s Ayers Institute for Precancer Detection I Clinical Proteomics Technologies and Diagnosis. Liebler also directs this E V Initiative, was announced during last institute, part of the Vanderbilt-Ingram R fall’s news conference. Cancer Center. U S Richard Caprioli, Ph.D., co-director of Other Vanderbilt researchers have H the Vanderbilt team, directs the Mass found proteomic “signatures” that poten - C Spectrometry Research Center and has tially may improve the early diagnosis E T helped pioneer the technology used to and treatment of lung cancer, and they - H identify and analyze protein biomarkers in are scanning protein profiles found in the G tissue samples. blood of African-American and Caucasian I H Gordon B. Mills, M.D., Ph.D., direc - women for clues to why African-American s tor of the Kleberg Center for Molecular die more frequently from breast cancer. Markers at the University of Texas M. D. Proteomics “is an incredibly promis - High-tech Anderson Cancer Center, is collaborating ing field,” said Barker, “but until we get with the Vanderbilt researchers. some standardization here, it’s just not surveillance “A lot of the differences between going to move forward. proteins in disease states and normal “If we can move this field forward, we l The power of proteomics health are not differences in the amount s believe we can actually diagnose cancer i a of the proteins themselves, but in the very early,” she added.