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NYU School of Medicine Commencement Address

Harold Varmus
President and Chief Executive Officer
Memorial Sloan-Kettering Cancer Center

Carnegie Hall
New York
May 15, 2003

First and foremost: My hearty congratulations to the graduates -- and to their families, friends, and teachers. Medical school has not gotten any longer than it was when I was a student, but it certainly seems harder. There is more for you to learn about human biology; there are more career paths to contemplate; and the world you are now entering seems to present more daunting barriers to fulfilling the promise of medical science. So taking a day off to celebrate is good medicine.

Naturally I was flattered to be asked to speak to you on this happy, august, and also sobering occasion, especially in this revered place. I trust you knew that you have invited someone who hasn't practiced medicine for over 30 years; who let his license lapse more than 10 years ago; and who didn't graduate from NYU, but instead from a rival New York medical school.

I'd like to begin with a few words about my abandonment of medical practice. I have never viewed this as apostasy -- as an abandonment of conviction in the profession of medicine. Instead it has allowed me to fulfill the premise on which I entered medical school -- namely, that a medical degree and some knowledge of human biology could open doors to many careers. When I turned to medicine after an earlier literary education, I was not certain what I sought to do with medical training. It was only after two years of hospital residency, when the Vietnam draft compelled me to spend time in government service -- fortunately at the NIH in the Public Health Service -- that I discovered a latent passion for experimental work.

In response to that kindled passion, I conducted research and guided trainees for over twenty years at the University of California, San Francisco. I did this largely oblivious to the practical medical implications of what we were doing. Nevertheless, the implications have proven to be large. Our group and many colleagues around the world were building the foundations of the new kind of medicine that I hope you will all ultimately practice -- an approach based on a knowledge of genes, proteins, and molecular mechanisms of disease.

My own experience with foundation-building followed from two simple questions our lab was asking about retroviruses that cause cancer in chickens and mice: How do retroviruses grow? And how do they cause cancer?

Answers to the first question, from our lab and many others, defined the handful of viral genes, enzymes, and structural proteins required for these viruses to carry out the virus growth cycle -- to synthesize DNA copies of their RNA genomes, to integrate viral DNA into host chromosomes, and to produce new proteins and viruses particles. Ultimately, this knowledge allowed a rational response to the unexpected arrival of AIDS, the retroviral pandemic caused by HIV. Now, in the U.S. and Europe, death rates from AIDS have plummeted, because doctors can prescribe new drugs that specifically inhibit retroviral enzymes and can monitor the response to drugs with molecular markers.

Efforts to understand how retroviruses cause cancers uncovered a class of cellular genes, called proto-oncogenes. These genes are also present in the human genome, and they contribute to human cancer when they undergo mutations, forming active oncogenes. Recently developed drugs that inhibit the wayward proteins made from oncogenes have already proved to be highly effective against several uncommon cancers, with few side effects, encouraging hopes for more drugs aimed at molecular targets in other, more common cancers.

Similar advances are happening in many fields of medicine, in part because we now know something about nearly all the genes in the human genome, thanks to the Human Genome Project. Ultimately, such knowledge will allow doctors to assess an individual's risk of diseases; to detect diseases earlier; and to treat most diseases more effectively, based on a detailed, "molecular" evaluation of each patient.

So I look back on my abandonment of medical practice thirty years ago without regret, because I have witnessed something amazing: a profound transformation of our understanding of human biology and of the means to control human disease. But when I look out at the practice of medicine today, just when these exciting developments promise to revolutionize it, I see daunting obstacles.

  • The first and most obvious is our increasingly crippled and inequitable system for providing and paying for health care. On the one hand, costs will inevitably continue to rise for many patients, as medical care gets more sophisticated and more effective as a result of new knowledge and new methods. On the other hand, we seem unable to correct what should be unacceptable under-financing of care in a society like ours: at least 40 and perhaps as many as 60 million Americans still uninsured; inadequate coverage for elderly patients dependent on Medicare; and enormous disparities in access to care for the rich and the poor. In an editorial in Science magazine a few weeks ago, leaders at Duke University School of Medicine proposed that radical changes in care, based on new knowledge about personalized health risks, could turn things around. That would be great and deserves further discussion. If we can't solve the economics of care, pressures on places like NYU will leave doctors too busy to do the clinical research that is essential for validating new kinds of care, and the costs of such care will seem unaffordable.
  • Second, we have not been especially successful at reducing rates of disease and injury. One obvious way to afford more expensive and powerful treatments for those patients who develop terrible diseases like cancer and AIDS is to reduce the frequency of these diseases and others. We now have an increased awareness of the common causes of preventable illness, injury, and death -- smoking, obesity, and inadequate exercise; unsafe sexual practices; drug and alcohol abuse; accidents, homicides, and suicides; and (yes) medical error. But other than a moderate decline in tobacco use and the adoption of healthier habits in some segments of our society, there has been limited success in controlling these factors. Identifying genetic risks in some individuals might spur beneficial behavioral changes. But inadequate prevention is likely to vex us for many years to come.
  • Third, in good conscience, we cannot continue to focus intently on our own health in the advanced economies, while leaving large parts of the world behind. Despite amazing advances in science and medicine in the developed parts of the world, little has occurred to control common illnesses elsewhere, especially AIDS, TBC, dengue fever, childhood diarrhea, malaria, and several other parasitic diseases. I am heartened by the recent attention world leaders have given to these issues. Kofi Annan has championed the Global Fund for AIDS, Malaria, and TB; Bill Gates is funding vaccine distribution and research on neglected diseases; President Bush has advocated unprecedented increases in U.S. foreign aid to combat AIDS, albeit with some political compromises; and Bono and Doctors without Borders have provided inspiration for these efforts. Still, the sustained commitment required from all segments of a global society is far from secure.
  • Finally, we have not adequately exploited new methods to provide physicians and scientists with ready access to new knowledge. On this day above all others, it is appropriate to spend a few extra minutes talking about this problem, because, from now on, articles about medicine and science will replace your teachers at NYU as sources of crucial information. Happily, better access to knowledge is a problem that can be solved relatively easily and in the near future.

The dilemma boils down to this: on the one hand, we have an extraordinary opportunity -- offered by the Internet, by digital storage, and by powerful programs for searching the literature -- to allow physicians and scientists to keep pace with the rapid and profound changes occurring in medical science. On the other hand, the persistence of post-Gutenburg methods -- thousands of journals printed on paper and distributed only to subscribers -- is slowing conversion to more effective means of transmitting information.

The traditional publication system has enormous shortcomings. It has produced some excellent journals, but they are generally very expensive, yielding massive profit margins for private publishers and some societies, exhausting library budgets. Articles on paper are slowly processed and distributed relatively slowly. Only a few have been placed in the NIH's public electronic library, which allows a broad search for relevant information. Most significantly, the current system dramatically restricts access to knowledge -- favoring the few readers at well-heeled institutions that can usually afford to buy many expensive journals, and limiting access for the rest: physicians outside academic health centers; the public that has paid for the research, including patients and their families; and those living in less affluent countries.

I want to expand briefly on this crucial issue of access. The work described in the average paper in the medical sciences usually costs hundreds of thousands of dollars to carry out; in this country most of those funds have been provided by US taxpayers through the National Institutes of Health. Legislators and advocacy groups are keenly interested in guaranteeing that Federally supported research findings get widely disseminated to all who seek them.

Yet our publication process works in a contrary direction, and the only clear beneficiaries are the publishers. Remember that those physicians and scientists who did the work and wrote the articles seek only readers and recognition, not remuneration; they freely provide their work and cede full copyright to the journals. Academic colleagues review and often edit the papers, almost always without compensation. Then the publishers sell print and electronic subscriptions, mostly to institutional libraries and some medical scientists. This does not make access easy for the doctor in Idaho whose patient has just been diagnosed with a rare genetic disease; for a patient who wants to know the outcome of a recent trial of a new therapy for an auto-immune disorder; or for the high school student who is doing a science project on a cancer gene.

In short, we are far from achieving the goals of the director of the British Library who said, in 1836:

"I want a poor student to have the same means of indulging his learned curiosity, of following his rational pursuits, of consulting the same authorities, of fathoming the most intricate inquiry as the richest man in the kingdom…."

Fortunately there is now a much better way to publish and distribute, to store and search, the fruits of medical research. A new organization -- called Public Library of Science [], a group I helped to establish -- has advanced the idea that articles in the life sciences should become freely accessible as soon as possible and placed in a public digital library for unrestricted use. More recently, the Public Library of Science has become a non-profit publishing house, and two high-quality, flagship journals, PloS: Biology and PloS: Medicine, will soon be launched.

Of course, the development of free access, electronic journals does not mean that publishing has become cost-free. It will cost less and be better in many ways, but we propose that remaining expenses should be covered by modest fees charged to authors who have the financial support to afford them. These fees should be viewed at part of the cost of doing research. All articles that pass rigorous review will be available without charge to anyone with an Internet connection.

The success of free access publishing will depend on several things: The willingness of authors -- including, hopefully, some of you -- to honor this new movement by submitting their best work to such journals. The endorsement of free access publication by the agencies that fund research and by the institutions that perform it. (Indeed, the Howard Hughes Medical Institute has already done this.) And acknowledgement that improved distribution of research findings is important by the medical and scientific communities, the public, and the Congress.

I have argued today that we are beginning to see dramatic changes in medicine, propelled by genetics and other basic disciplines. But these changes will accelerate only if we pay attention to the cultural conditions of medicine and science -- to the way we use and pay for health care; to the way we approach preventable illness; to the way we assist the disenfranchised; and to the way we transmit new knowledge.

You, as new graduates, can help me justify my abandonment of medical practice. If you help to create a world in which new knowledge is freely shared and humanely used, the promise of improving health with modern science can be achieved. All of us will then have lived up to the traditional ideals of medical progress.

Congratulations again, and thanks for listening.