New Life-Forms, No DNA Required Artificial Organisms Based on Man-Made Molecules Could Thrive and Evolve
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WORLD CHANGING IDEAS 10 innovations that are radical enough to alter our lives Illustrations by The Heads of State 34 Scientifi c American, December 2012 sad1212WCI4p.indd 34 10/17/12 4:39 PM Scientists and engineers dream about big advances that could change the world, and then they try to create them. On the following pages, Scienti c American reveals 10 innovations that could be game changers: an arti cial alternative to DNA, oil that cleans water, pacemakers powered by our blood, and more. These are not pie-in-the-sky notions but practical breakthroughs that have been proved or prototyped and are poised to scale up greatly. Each has the potential to make what may now seem impossible possible. —The Editors sad1212WCI3p.indd 35 10/16/12 7:28 PM New Life-Forms, No DNA Required Artificial organisms based on man-made molecules could thrive and evolve DNA IS PASSÉ. Synthetic biologists have invented an array of new molecules called ed truly synthetic life—life that does not XNAs that boast all the talents of deoxyribonucleic acid (DNA) and ribonucleic acid depend on what evolution has already (RNA), as well as some special powers. XNAs could allow scientists to safely create provided but on humankind’s inventions. Holliger emphasizes that XNA-based life-forms in the laboratory that do not depend on DNA to survive and evolve. life-forms are a long way off, but he al- “Life is inconceivable without a system thing no other artificial nucleic acids can ready recognizes a distinct advantage. If for genetic information storage and repli- do: they evolve. Inside living cells, en- such a creature escaped into the wild, it cation, but DNA and RNA are not unique,” zymes called polymerases cut, paste and would die without a steady supply of XNA- explains Philipp Holliger of the Medical splice DNA to access the genetic informa- specific enzymes. And XNA could not Research Council’s Laboratory of Molecu- tion. Without that interaction, DNA would weave itself into the genomes of natural lar Biology in Cambridge, England. “Relat- remain as inert as dusty encyclopedias on organisms, because their native enzymes ed polymers—at least six more—can do the a shelf. Holliger reprogrammed natural would not recognize it. XNA-based bacte- same function.” That the earth’s flora and polymerase enzymes to translate DNA ria designed to devour oil spills or turn fauna rely only on DNA and RNA, he says, into XNA and back again, establishing a wastewater into electricity, for example, is an “accident from the origin of life.” novel system for storing and transmitting could not interfere with native organisms. XNA stands for xeno nucleic acid (xeno genetic information, which is the founda- The fact that XNA is complementary to meaning “foreign”). Like DNA, XNA has a tion of evolution. One of the XNAs, HNA DNA, yet structurally unique, makes it im- structure that resembles a twisted ladder. (anhydrohexitol nucleic acid), reliably pre- mediately useful for medicine, biotechnol- In DNA, four different nucleobases, repre- served changes to its genetic code and ogy and biology research. Holliger imag- sented by the letters A, C, G and T, form evolved to attach to a protein with increas- ines XNAs that could be injected into the the steps. Phosphate groups and sugars ing precision. human body to detect early, subtle signs of form the ladders’ sides, also known as the Once Holliger improves the function- disease that current technologies miss. backbone. For 30 years scientists have ality of XNA and its enzymes, the set of Steven Benner, a fellow at the Founda- been tweaking the sugars to create artifi- molecules could replace DNA and RNA in tion for Applied Molecular Evolution in cial nucleic acids, which serve as research a living cell. Researchers might take a Gainesville, Fla., has also advanced the ef- tools in medicine that can bind to DNA. simple bacterium, for instance, suck out fort by expanding the genetic alphabet To make XNAs, Holliger and his col- its DNA and replace it with XNA. with two new nucleobases, Z and P. A larg- leagues did not simply alter the sugars in Alternatively, scientists could enclose er alphabet could form a wider array of DNA’s backbone—they substituted entire- XNA within protocells—the origin of a genes and, eventually, proteins. “The goal ly different molecules, such as cyclohex- new life-form that could evolve in ways no is to create chemically controlled systems ane and threose. Just as important, they one can predict. Whereas other synthetic that behave like biological systems, with- created enzymes that work with the XNAs biologists such as J. Craig Venter have out being biological systems,” Benner says. to form a complete genetic system. made remarkable advances in rewriting “We believe whatever you can draw on a The enzymes enable XNAs to do some- the existing genetic code, no one has creat- page, you can make.” —Ferris Jabr Only a few minutes after someone stops breathing— oxygen microbubbles, which the blood can absorb whether it is from a piece of meat stuck in the throat, within seconds. The bubbles are too small to cause Foam That a severe asthma attack or a lung injury—the brain an air embolism—a gas pocket that stops blood flow, starts to shut down. Cardiac arrest and death are thus causing a stroke or heart attack. Restores imminent. Emergency responders and hospital work- To create this lifesaving foam, John Kheir, a cardi- ers have one primary recourse: insert a breathing ologist at Boston Children’s Hospital, and his col- tube through a patient’s mouth. That procedure can leagues adapted existing medical nanotechnology. Breathing be risky and time-consuming. Microparticles with lipid membranes already deliver A new injectable solution could keep such people drugs, as well as dyes for ultrasound imaging. Kheir’s Injectable oxygen microbubbles alive for 15 minutes or more, buying crucial time to team propelled phospholipids through an oxygenated could give asthma and choking get victims to a hospital or to do some surgical gym- chamber and used sound waves to spur the ingredi- victims precious minutes nastics in an operating room. The solution contains ents to self-assemble into microparticles. The 36 Scientific American, December 2012 sad1212WCI4p.indd 36 10/17/12 4:59 PM researchers then used a centrifuge to superconcentrate have other organ damage than those who got saline overload that can cause heart failure. Kheir’s team is trying them into solution. Each four-micron-wide microbubble solution—despite not taking a single breath. to improve the formulation so that it requires less saline. contains pure oxygen, surrounded by a lipid film that is The approach is “a fairly innovative idea compared to Another concern is that without normal respiration, just a few nanometers thick. what we have now,” says Raymond Koehler of Johns carbon dioxide builds up in the body, which can be toxic. Because the bubbles contain oxygen at a pressure Hopkins University, who is not involved in the work, As Koehler notes, however, the body can handle a little that is higher than in the bloodstream, the gas diffuses because most emergency oxygen procedures require the excess carbon dioxide better than it can handle a total lack into red blood cells on contact. Once a bubble is deplet- pulmonary system to function at least at a minimal level. of oxygen. If the microbubbles prove successful in further ed, the shell collapses to a disk that is less than a micron One drawback is that because the blood absorbs the animal (and subsequent human) trials, the solution could wide, easily passing through the circulatory system. oxygen so quickly, a constant infusion is necessary, which help emergency crews or operating room technicians buy In a test, researchers blocked the airways of anesthe- involves a lot of saline to help the foam move smoothly into crucial minutes before they can implement other lifesav- tized rabbits for 15 minutes. Those injected with the solu- the bloodstream. The amount of solution that a patient ing treatments. In those situations, Koehler says, “you tion were much less likely to go into cardiac arrest or would receive after 15 minutes could lead to edema, a fluid want to have a backup plan.” —Katherine Harmon December 2012, ScientificAmerican.com 37 sad1212WCI3p.indd 37 10/16/12 7:28 PM Alzheimer’s disease remains virtually untreatable. tomography scans of living people’s brains, a recent More than 100 experimental drugs have failed to halt innovation, show that by the time symptoms appear, Early the condition that robs people of their memories, their amyloid has been silently accumulating for up to 20 relationships and, ultimately, their identity. Now scien- years. Perhaps by then the brain is irreversibly dam- Treatment for tists will be testing a new strategy for preventing this aged, making any drug useless. No one knows for sure, horrific condition from starting in the first place. Just as however, whether amyloid causes Alzheimer’s or is healthy people take statins to lower their cholesterol merely a by-product of the disease. The new study Alzheimer’s and avoid heart disease, people at risk for Alzheimer’s may provide an answer to this mystery. could conceivably pop pills to keep the disease at bay. Set to start early in 2013 if all approvals are grant- A drug trial of 300 Colombians Researchers will be investigating a drug that flush- ed, the investigation will involve 300 members of dis- could reveal a way to es away an intrusive protein called amyloid, suspected tantly related families in Colombia whose rare and par- as a primary contributor to Alzheimer’s.