The Power of Basic Science Applied to Medical Progress: Past Examples and Hope for Schizophrenia and Bipolar Illness

author: Edward Scolnick, Broad Institute
published: Aug. 7, 2012,   recorded: October 2009,   views: 2621

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An exemplar of the purpose-driven life in medical science, Ed Scolnick details research milestones from a remarkably varied career, revealing how scientific insight and collaborative effort translate into life-saving solutions for millions.

This physician turned biochemist has held distinguished positions at the National Institutes of Health, Merck, and now at MIT, but common themes unite his pursuits: “I’m always excited by the inherent beauty of molecular and biochemical insights into how biology works. Making scientific discoveries for me is tremendously emotionally satisfying and in fact addicting.”

In his talk, Scolnick touches on such research breakthroughs as identifying virus oncogenes, and developing treatments for cardiovascular disease, Hepatitis B, and osteoporosis, among others. He emphasizes that teasing out the biochemistry of diseases is “the key to success in drug discovery.” In Marfan syndrome, for example, investigators learned that a mutant gene leads to a malfunctioning aorta. Finding a cure flowed from understanding the underlying pathological processes. Scolnick proudly describes research on a gene involved with cholesterol buildup and an elevated risk for cardiovascular disease. This led to the development of statins, which has helped dramatically reduce the death rate in people with heart disease.

Scolnick offers a dramatic chronology of his pioneering work at Merck starting in 1981 to find an effective AIDS treatment, an effort leading to the protease inhibitor Crixivan. His timeline covers more than a decade of scientific collaboration to block the mechanism of HIV, and involves false starts, the death of a key scientist in the Lockerbie bombing, pressure from AIDS activists and corporate overseers, a “miracle” AIDS patient, breakthroughs in measuring viral protein, and more than one “twist of fate.”

In 2004, Scolnick turned in a new direction: toward mental illness, a field stalled for decades due to ignorance “about the underlying biochemistry and physiology of the disease.” Today, with the help of genomics and computative technologies, researchers are beginning to reveal the basic genetic architecture of schizophrenia and bipolar illness, says Scolnick. The “outline of their biochemistry” is starting to come clear for the first time, leading to the real possibility of novel therapeutics. While the challenges are formidable, he believes, consolidating MIT’s “first rate neuroscience, human genetics, chemistry (creates) a unique opportunity to do something in a field that desperately needs the kind of approach and change we were able to bring to the AIDS field.”

NOTE: Audio levels for Kastner and Horvitz are very low, but improve when Scolnick begins his talk. We apologize for the inferior audio capture in the field.

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