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Mission-oriented research advocated for medical science

Despite a four-fold real-dollar increase in US government research support, the discovery of effective treatments for killer diseases like AIDS and Alzheimer's has declined in the last three decades compared with the preceding 30 years, says an article by an MIT physician researcher and a colleague.

The culprit, they say in the November 1 issue of Nature Medicine, is a misguided belief that mission-oriented research is not effective.

That the reverse is true, they assert, is borne out by their analysis of treatment discovery from 1935-65 compared with 1965-95. The analysis is the first historic review of such data, it is believed.

"Treatment discovery turns out to be very much a mission-oriented enterprise, requiring the participation of investigators committed to that task," they say. However, very little of the $11 billion in annual research support from the federal government backs investigations with a goal as specific as defeating a specific disease, they say.

The authors are Richard J. Wurtman, MD, director of the Clinical Research Center and a professor in the Department of Brain and Cognitive Sciences, and Robert L. Bettiker, currently studying at Georgetown Medical School. Mr. Bettiker has a master's degree in government administration from the University of Pennsylvania and an SB in chemistry (1990) from MIT.

They trace the aversion of the government to fund mission-oriented medical research to a "faulty formulation about how public investment in science should best be applied to conquer disease.. Implementation of this paradigm ultimately caused major distortions in the treatment-discovery infrastructure," and, they say, those distortions led to a decline in treatment discovery.

Dr. Wurtman and Mr. Bettiker say that the faulty view of how progress can best be made toward disease treatment "was born in 1945 when President Harry Truman's science adviser, Vannevar Bush, wrote a report, Science: The Endless Frontier. It held that the most effective strategy was not to require scientists to relate their research to specific societal missions-like finding treatments for pellagra or hypertension or AIDS or Alzheimer's disease-but instead to encourage them to work independently, follow their curiosity in choosing what to examine, and strive only for scientific excellence."

Moreover, the paradigm said the government "should not mount `Manhattan Projects' (or `Wars on Cancer') for individual diseases, similar to the one that Dr. Bush had so successfully directed for building atom bombs," Dr.Wurtman and Mr. Bettiker write.

The late Dr. Bush, a faculty member, dean, vice president and Corporation chairman of MIT, was a legendary figure in engineering and science. He mobilized US resources as World War II loomed and was named by President Roosevelt to head the National Defense Research Committee which coordinated the nation's science and technology efforts. Dr. Bush, who died in 1974, played a leading role in every subsequent scientific development during the war years, including the atom bomb, and beyond.

Dr. Wurtman, interviewed about the commentary article in Nature Medicine, said what is needed to get back on track in the discovery of treatment is "a great national conversation about what would be a more effective government policy.

"We need a new paradigm to replace the Bush paradigm. Mission-oriented research is not a national goal, and it should be," he said.

But in establishing a commitment to finding treatments for poorly treated diseases, the government "should not diminsh its presently excellent ability to fulfull the other national goal of accumulating new fundamental knowledge about how the body works," Dr. Wurtman said.

In the Nature Medicine article, the authors say: "Few effective treatments have been discovered for the diseases that contributed most to morbidity and mortality in 1965, or for newly recognized killers like Alzheimer's disease and AIDS."

Life expectancy has increased since 1965, but this, they say, has resulted not from discovering new effective treatment for previously untreatable diseases, "but from the widespread application of established preventive measures, such as management of hypertension and the continuing development of vaccines."

Improvements in diet and in the distribution of medical care have played roles, as has the invention of "novel diagnostic techniques, like those based on imaging, and major advances in surgery and anesthesia, particularly affecting cardiology, orthopedics and organ transplantation."

"None of these changes resulted principally from discoveries made in biomedical research laboratories. It may turn out that current, cutting-edge bench findings relating, for example, to gene therapy will indeed revolutionize treatment discovery in the future.

However, prophecy is notoriously unsuccessful in this arena, and attempts at analyzing why so few diseases have become treatable at a time of great growth in fundamental biomedical knowledge must focus on what actually has happened, not on what we hope will happen."

A version of this article appeared in MIT Tech Talk on November 1, 1995.

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