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Molecular Fingerprints the Search for Individualized Medicine WINTER03 p.8 The Power of Proteins p.22 One protein’s story p.16 Discovery science p.26 The future of proteomics LensA New Way of Looking at Science Molecular fingerprints The search for individualized medicine. A PUBLICATION OF VANDERBILT UNIVERSITY MEDICAL CENTER Lens – A New Way of Looking at Science WINTER 2003 VOLUME 1, NUMBER 1 Lens is published by Vanderbilt University Medical Center in cooperation with the VUMC Office of News and Public Affairs and the Office of Research. © Vanderbilt University EDITOR Bill Snyder DIRECTOR OF PUBLICATIONS MEDICAL CENTER NEWS AND PUBLIC AFFAIRS Wayne Wood CONTRIBUTING WRITERS Mary Beth Gardiner Leigh MacMillan Bill Snyder PHOTOGRAPHY/ILLUSTRATION Dean Dixon Dominic Doyle The voyage of Dana Johnson Anne Rayner Pollo Brian Smale discovery consists DESIGN Diana Duren/Corporate Design, Nashville not in seeking new COVER ILLUSTRATION Dean Dixon landscapes, but in EDITORIAL OFFICE Office of News and Public Affairs having new eyes. CCC-3312 Medical Center North Vanderbilt University Nashville, Tennessee 37232-2390 615-322-4747 – MARCEL PROUST About the cover: Need help deciphering the fingerprint 'code?' Please turn to the back inside cover. Lens TABLE OF contents WINTER03 2 PUBLICATION OVERVIEW 3 EDITOR’S LETTER 4 MOLECULAR FINGERPRINTS The search for patterns of proteins in blood and tissue one day may help doctors diagnose diseases like cancer earlier and more accurately than ever before. These “molecular fingerprints” also may lead to new, more effective medicines and the ability to tailor treatments to individual patients. The ultimate aim: a more thor- ough understanding of disease and how to prevent it. 13 MINING FOR PROTEINS Recent technological advances are helping scientists isolate and identify proteins, determine their three-dimensional structures, and figure out how they interact. The result is a much clearer picture of how the cellular “factory” operates, and how tiny changes in protein function can lead to disease. 16 DISCOVERY SCIENCE Leroy Hood is known as the father of biotechnology for the development of groundbreaking biomedical instrumentation. Now he’s calling for a revolution of thought – an interdisciplinary, systems approach to biological discovery that challenges conventional wisdom about how research is conducted. A lifetime of influences, opportunities, and challenges has led Hood to this, his meridian hour. 22 ONE PROTEIN’S STORY What exactly are proteins? How are they made? What do they do? Join us on a journey of discovery deep into the cell to find the answers. Our tour is hosted by the epidermal growth factor receptor, a protein that plays a key role in signaling cell division. When this protein’s message goes awry, cancer can occur. 26 THE FUTURE OF PROTEOMICS Two of the nation’s most prominent leaders in biotechnology, Tony White and Michael Hunkapiller, sit down with Lens for a wide-ranging interview on the challenges facing the field of proteomics, the growing need for collaboration between government, universities and private companies, and the potential impact that the debate over stem-cell research may have on scientific progress. LENS/ WINTER 2003 1 Lee Limbird, Ph.D. Associate Vice Chancellor for Research Vanderbilt University Medical Center OVERVIEW Dr. Limbird is professor and former chair of the Department of Pharmacology at Vanderbilt, and a guiding force behind Lens. ANNE RAYNER POLLO ANNE RAYNER Capturing light. Providing focus. One goal of Lens is to whet the Altering perspective. That is the intent of appetite for a greater understanding of our new publication, Lens. We are trying biomedical research for those who have not to give our readers – scientists and those had the opportunity for formal scientific who watch science alike – an appreciation training. Yet another is to provide a Fingerprints of the revolution that is occurring in our synthesis of the different perspectives on the understanding of health and disease. same topic for experts and the lay public. Much like the maturation of our Hopefully, you will come to appreciate children, scientific discovery occurs in two through our Lens that discoveries that interrelated ways – an incremental, step- affect the quality of human life are part of by-step grasp of new insights intertwined the fabric of our society. They are about with fundamental changes and paradigm public policy, economics, and the balance of shifts in our appreciation of life and its these issues in a world that is threatened by underlying processes. more than disease. We hope you will come to appreciate It is our hope that Lens will provide through our Lens that discoveries that enjoyable yet thought-provoking reading could improve our health are not just for a broad audience – from participants in about biology and medicine. They are the discovery enterprise to its benefactors, both accelerated and detoured by the the public at large. motivation and peculiar perspective of investigators. They are catapulted by technological advances. For example, if the promissory notes of genome-wide science are fulfilled, a therapeutic revolution will result, and we will begin to treat “We are trying to give our readers – scientists and underlying diseases rather than simply the symptoms of diseases. Society’s definition those who watch science alike – an appreciation of health and disease will, of course, of the revolution that is occurring in our influence the direction that this discovery process takes. understanding of health and disease.” - LEE LIMBIRD, PH.D. 2 LENS/ WINTER 2003 “It is appropriate that the magazine’s inaugural issue should focus on proteomics, for the science of proteins – many experts believe – will be one of the most important fields influencing 21st Century medicine.” - BILL SNYDER LETTER FROM EDITOR Imagine yourself driving in the them more successfully than we ever have country in a convertible, watching the before, and ultimately to prevent them grassy fields roll by, feeling the wind in your from occurring in the first place. face. Much of what you’re experiencing – This lens is not the private property DEAN DIXON including the ability to grasp the steering of doctors or scientists. It is available to wheel and hear the music on the radio – is all who would look through it. due to the actions and interactions of That is why we at Vanderbilt microscopic protein molecules in your University Medical Center have produced nerves, your muscles, your eyes and ears. a new publication accessible to the general Now imagine the interior of your public. In this and future issues, we will body: the antibodies (also proteins) that examine the frontiers of biological science fight infection, the complex symphony of and medical research, and how the new protein messages that tell your tissues to knowledge gained from these inquiries Fingerprints grow or not to grow, the signals transmitted may affect our lives. by proteins across synaptic junctions in It is appropriate that the magazine’s your brain that enable you to think. inaugural issue should focus on proteomics, Imagine if something goes wrong for the science of proteins – many experts with some of your proteins, and your believe – will be one of the most important body’s immune system mistakes your own fields influencing 21st Century medicine. tissues for bacterial invaders, or because of Richard Caprioli, director of the Mass Bill Snyder poorly translated instructions some cells Spectrometry Research Center at Vanderbilt Editor, Lens Magazine begin to grow out of control, or the and a member of this magazine’s editorial For more than 20 years, Snyder signaling across the synapse is disrupted. board, puts it this way: “We’re on the covered health care and medical You may develop an illness like multiple threshold of the journey to cure disease.” research for daily newspapers, sclerosis or cancer or depression. As we marvel at the advances that are including The Tennessean and Just as the development of the micro- coming our way, we should not forget the Nashville Banner in Nashville. scope in the 17th Century enabled people scientists of centuries past who first opened to see what was previously un-seeable, today up new worlds of wonder beyond the reach we’re going through a similar perceptual of our eyes. “If I have seen further,” said Sir revolution. Our modern medicine currently Isaac Newton, “it is by standing on the can address only the symptoms or conse- shoulders of giants.” quences of many illnesses, ranging from dementia to diabetes. But now, through advances in genomics and computer science, we are beginning to appreciate the pervasive role that proteins play in maintaining health or causing disease. Thanks to technologies like mass spectrometry, protein “chips” and bioin- formatics, we are now able to examine nature through a new lens, one that may enable us for the first time to understand the root causes of many diseases, to stop LENS/ WINTER 2003 3 Molecular fingerprints The search for individualized medicine. BY BILL SNYDER 4 LENS/WINTER 2003 Proteomics – the science of proteins – is opening up a new world of discovery and understanding of diseases as diverse as cancer and dementia. Using a variety of rapidly developing technologies, and knowledge gleaned, in part, from the successful effort to sequence the human genome, researchers the world over are developing new drugs and diagnostic tests based on proteins that are key to health as well as disease. One of those methods, called “molecular fingerprinting,” attempts to identify patterns of proteins in the blood and tissues that can be used to detect diseases like cancer much earlier and MOLECULAR FINGERPRINTS monitor therapy much better than is now possible. This is the story of some of the research – and the essential involvement of a patient – that are helping to make that hope a reality. wo months ago, Art Haag joined a various cancers – unique patterns of proteins small, but rapidly growing number that may signal the presence of tiny tumors Tof cancer patients who are helping not yet detectable by X-rays.
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