stanford medicine


Roger Kornberg portrait


A wake-up call to all who care about science — or for that matter, prosperity

Modern medicine is little over 100 years old. Until so very recently, disease was attributed to an imbalance of humors, and the only treatments were bleeding and violent purgatives.

Change began in Europe in the latter part of the 19th century, with the germ theory of disease and the work of Pasteur, Koch, Ehrlich and others. Medical science as we know it emerged early in the 20th century, with the establishment of great American institutions, such as The Johns Hopkins School of Medicine, The Rockefeller Institute and others that followed. An explosive growth of knowledge and capability over the past 50 years brings us now to a critical juncture: Arguably the greatest opportunity in human history, the cure of all disease, lies before us. Whether we will seize the opportunity is the question.

The experience of the past century shows the way forward. The major medical advances — X-rays, antibiotics, magnetic resonance imaging, genetic engineering, to name a few — have one thing in common: They resulted from discoveries made in the pursuit of knowledge for its own sake, not prevention or cure of disease. The lesson of this experience is counterintuitive. To solve a difficult problem in medicine, do not study it directly, but rather pursue a curiosity about nature and the rest will follow. Seek knowledge and understanding in all fields, from physics to biology. Do basic research.

But almost as soon as this lesson of the past is learned, it’s forgotten. The success of medical science threatens to become its undoing. Dazzled by the knowledge so far acquired, we are rushing to apply it to medical problems. Attention and resources are shifting worldwide from biomedical science to “translational medicine.” The shift is understandable but premature. Take the human genome, the font of all medical knowledge. Within it lies the answer to every question about human biology. The trouble is that the answers are written in a language we do not understand. It is a multidimensional and dynamic language. The products of the genome, both protein and RNA molecules, interact with one another and with the genome itself in a dance of dizzying complexity. At present, we can only dimly perceive the significance. We can grasp a small fraction of 1 percent of what there is to know and understand. If the medicine of today flows from this tiny bit of knowledge, imagine how much more would be possible if we knew the remaining 99 percent. What more persuasive call to the pursuit of basic research can there be?

The problem is not only scientific but also political. The support of basic research has traditionally come from government rather than the private sector, and for good reason. The time line is very long — basic problems take decades to solve. Only the public, with a lifelong interest, will support such an undertaking. Industry, with a short-term interest and eye on the bottom line, can hardly be expected to do so. What CEO could report to his or her board that a major investment has been made in research that may or may not become profitable in 10 to 20 years, or longer? Government clearly has a special responsibility and a unique role to play.

Our government has performed this role admirably in the past. Some 50 years ago, in perhaps the most farsighted action of any legislative body in history, the United States Congress established the National Institutes of Health to fund basic biomedical research. The genius of the NIH lay in its funding mechanism. In contrast with the time-honored system in Europe, where support flows from governments to universities to departments to professors and finally to researchers, the NIH provides support directly to researchers. Proposals are submitted by individuals, young and old alike, and are judged by panels of peers. The NIH is a form of scientific free enterprise, a marketplace of ideas, with selection on the basis of merit.

The return on this investment by the government has been huge. The eradication of polio and the cure of childhood leukemia and many other diseases have saved vast amounts in treatment and productivity, as well as human suffering. Not only has the investment been repaid many times over, but it was small to begin with. The annual budget for cancer research today is only $5 billion, less than 10 percent of our annual expenditure on soft drinks, less than a week of the war in Iraq.

Here, too, the lessons of the past are being forgotten. The NIH mechanism has been damaged by the diversion of funds from individual researchers to large programs. The NIH budget has been repeatedly cut. At a hearing on the budget last year, Sen. Arlen Specter, R-Penn., asked the reasonable question, “What’s going to happen to NIH if the budget is cut by $500 million?” The answer is that the amount of NIH-sponsored research will decline accordingly, by about 5 percent, but innovation will be stifled across the board. Innovation depends on risk-taking, which does not occur in a climate of fiscal conservatism. Funding cuts have a chilling effect that ripples through the system, deterring bold action and creativity on the part of established investigators, and discouraging young people from pursuing careers in basic research. In casual conversation at Stanford with three of the best young scientists I know, I learned that all three had lost NIH support. Not only is their brilliant research interrupted, but the morale of their many fine students is undermined.

Of all the adverse effects of cutting the NIH budget, the disillusionment of young people is the worst. The choice of a career in science already represents a great sacrifice. A passion for science must be weighed against a long period of training — 10 or more years of postgraduate study at low wages — and the possibility of no career at the end. The importance of young scientists cannot be overstated. Progress in science, and discovery in particular, is the work of young minds.

Research-intensive universities and scientific institutes along with nonprofit organizations already have vigorous efforts under way to raise public awareness and influence legislation. However, given the current fiscal environment, only a coordinated effort that includes scientists, university administrators, patients, patient-advocacy groups and industry can succeed.

Stanford and its sister institutions must play a leadership role in such a coalition, and many of us are ready to do so.

A call for action is timely, with regard both to legislation pending in the Congress and to the political season. Whereas President Bush has proposed another cut in the NIH budget for 2009, Specter and Sen. Tom Harkin, D-Iowa, have put forward a bill for additional funds to correct for previous cuts and inflation. Can such a bill stand in the face of current economic weakness and uncertainty? What lies in store with the next administration? So far, neither of the leading presidential contenders has taken a position or even responded to invitations from scientific organizations to be informed about the problem. [Editor's note: This piece was written prior to the publication of the Sept. 24 issue of Nature in which Democratic candidate Barack Obama responded to 18 science-related questions from the journal; Republican candidate John McCain declined to answer the questions.] The public has to understand, and to convey to Congress and the candidates, the importance of science and the NIH. Life-saving discoveries hang in the balance, and we must, especially in economic hard times, protect the basis for future prosperity.

Roger Kornberg, PhD, is a professor of structural biology at Stanford and the 2006 Nobel laureate for chemistry.






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