Paradigm Shifts: From Biology to Technology to Medical Applications
Richard O. Hynes, PhD '71, Daniel K. Ludwig Professor for Cancer Research, Department of Biology; Investigator, Howard Hughes Medical Institute; Eric S. Lander, Professor of Biology
; Founding Director, Broad Institute of MIT and Harvard
; Member, Whitehead Institute; Lee Hood, Affiliate Professor of Immunology, University of Washington; President, Institute of Systems Biology; Susan L. Lindquist, Professor of Biology, MIT
Description: After years of working out the genetic and molecular machinery of cancer, scientists are gaining significant ground on the disease, and are on the verge of a new generation of diagnostic and therapeutic approaches. Three researchers who have spearheaded this biomedical revolution describe how increasingly fast and cost"effective technology has helped make sense of ever"growing data on different cancers, offering 'big picture' views that may lead not merely to more effective treatments, but to an entirely new kind of medical care.
When exposed to environmental stress such as high temperatures, cells in all organisms respond with proteins called heat shock factors (HSFs), and endure all sorts of damage. Years ago, Susan Lindquist speculated that the stress response, an "ancient survival pathway," might have something to do with cancer. She set this work aside, until she was "enticed" by MIT and its multidisciplinary and computational approach to the disease. In recent studies, Lindquist has learned that a central protein, HSF1, promotes malignancy in many ways. She tested different strains of cancer cells from many MIT labs, and found that "cancer is aided and abetted by the stress response." In human breast cancer cells, for example, "the more deranged and metastatic and oncogenic the cell line is, the more it seems to depend on stress response," Lindquist says. Conversely, knocking out HSF1 can protect against cancer growth. With the help of the Broad Institute and its screening technology, Lindquist has explored 350 thousand compounds to see whether they inhibit or potentiate HSF1, and turned up herbal remedies that interfere with the stress response and slow the advance of some cancers.
Only recently has it been possible to step back and get the big picture on cancer, says Eric Lander. This increasingly comprehensive perspective comes courtesy of Lander's own enterprises, including the Human Genome Project (1990"2003), and relentlessly improving DNA sequencing technology. MIT's own sequencing output has grown from 70 billion bases per year in 1999 to 125 billion bases, with the cost down 100 thousand fold _ "a stunning pace," concludes Lander, with major implications for cancer research. Lander has launched a cancer genome atlas that will assemble from hundreds of thousands of patient samples of normal and cancerous DNA, and permit the analysis of important cancer cell lines. He envisions the capacity to "knock out every gene in the genome" to build cellular models in order to predict "how a tumor will become resistant to drugs. "It's already time to start asking what is the standard of care for cancer patients," says Lander. "It should be soon for anybody that I loved that they could have this information."
Leroy Hood figures he has participated in four paradigm changes in biomedical science, and is leading the charge on the fifth: the drive toward P4 medicine (for "predictive, preventive, personalized and participatory"). Hood was behind the automated DNA sequencer that made the Human Genome Project a reality, and has subsequently developed other devices for translating RNA, protein and other biological information. He says he came to realize that "cross"disciplinary biology was essential for the future," accompanied by a systems approach to disease. Hood imagines patients someday "surrounded by a cloud of virtual data points," which may be distilled to render "simple hypotheses about health and disease." With medicine increasingly an informational science, researchers will be able to map diseases as networks perturbed by precisely delineated genetic or environmental factors. Hood is developing a blood diagnostics system for detecting different types of disease, and developing genomes of families to track genes coding for these diseases. The ultimate goal: creating individualized patient "data spaces" in order to "deal with disease in powerful new ways," and to shift the future focus toward wellness.
About the Speaker(s): Richard Hynes received his B.A. in biochemistry from the University of Cambridge, U.K., and his Ph.D. in biology from MIT. After postdoctoral work at the Imperial Cancer Research Fund in London, where he initiated his work on cell adhesion, he returned to MIT as a faculty member.
Hynes is a fellow of the Royal Society of London, the American Academy of Arts and Sciences, and the American Association for the Advancement of Science, and a member of the National Academy of Sciences and the Institute of Medicine. He has received the Gairdner Foundation International Award for achievement in medical science and recently served as president of the American Society for Cell Biology.
Host(s): Office of the President, MIT150 Inventional Wisdom
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