Convocation Talk at Lawrence University

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

April 30, 2002

In early December of last year, just three months after the horrific events of September 11, over two hundred Nobel Laureates, including one hundred Americans, gathered in Stockholm to commemorate the centenary of the first awards and to reflect on a century of accomplishments .

What Has Been Achieved?

For those of us in biological sciences and medicine, the retrospective on the past century was both a cause for celebration and a call to action. Over the past 100 years, biology and medicine have been transformed by discoveries in genetics, biochemistry, cell biology and many other fields, changing the study of living forms from an observational science---with the lone biologist seeking fossils on a limestone cliff---to an analytical one, with teams of technically sophisticated people studying the control of thousands of genes in a single cell.

The century opened with the rediscovery of Mendel's laws. The century's midpoint unveiled the role of DNA as the vehicle of genetic information and its double helical nature. Over the next two or three decades, the now classical flow of information from DNA to RNA to protein was elucidated. Then the tools were assembled for the Human Genome Project, and the sequence of most of the three billion nucleotides in human DNA was determined by the end of the century. We have also learned how cells grow, how they die, and how they differentiate, and how mutations occur and cause disease. We have learned to control infections by discovering drugs that interfere with the growth of bacteria and, more recently, interfere with the growth of viruses. We have made new vaccines to prevent infectious diseases. And we have isolated or made hormones to reverse endocrine deficiencies. We know how to transplant bone marrow and many kinds of organs; to fix heart valves and to prevent or reverse clogged arteries; and to treat many forms of mental illness with drugs. As a result of these things and many more, most people around the world---especially those in the advanced economies---United States, Europe, and Japan ---are living longer and healthier and happier lives.

What Has Failed?

Yet despite all these discoveries and medical advances, it is impossible to avoid the impression that the highest aspirations of scientists---like those of Alfred Nobel, who directed his prizes to be awarded for discoveries that bring "the greatest benefit to mankind"---have not been achieved. Although life expectancies have increased in most countries, especially in the later half of the 20th century, there continue to be dramatic differences between the rich and the poor countries and even between the rich and the poor within wealthy countries like our own. While average life expectancies in the wealthier countries----and a few interesting exceptions that are not so wealthy (Sri Lanka, Cuba, and the State of Kerala in India)--- have risen from less than fifty to nearly eighty years during the past century, the average life expectancies in the world's poorest countries are under forty years. As documented by the World Health Organization, the World Bank, and the Harvard School of Public Health in their monumental volume, The Global Burden of Disease, a grouping of nations by geographical area or economic status reveals dramatic differences when we compare not just years of life lost to disease, but years of life impaired by disabilities. As our own Centers for Disease Control have shown, even in the US there are variations of up to twenty years or more in life expectancy from county to county, and these differences have not changed over the past twenty years even as life spans have continued to lengthen.

Why is the world's health not better than this, despite the triumphs of biological science in the past century? One lesson is simple: discovery and understanding are not always followed by practical medical solutions. A Nobel prize was awarded in 1902 for discovery of the transmission of the malarial parasite by mosquitos, but a century later there are still almost 500 million cases of malaria each year and 1 to 2 million deaths. A Nobel Prize was awarded in 1905 for the discovery of the bacterium that causes tuberculosis, and a second was given about fifty years later for the isolation of an antibiotic that can treat it. But fifty years still later the incidence of tuberculosis is 8 million cases per year, and the disease still kills about two million annually.

Some Explanations for Failures

One reason that progress has not been more rapid, despite such seminal discoveries, is that the study of diseases that primarily affect the poor, especially the poor in poor countries, tends to be neglected in research efforts, which are largely carried out in rich countries. But there are other reasons too. Most obviously, even when science has found solutions to diseases, we often fail to apply them, especially to the poor. Many circumstances can affect delivery: The costs of health care. Political instability and warfare. Poor transportation and communication systems. Rapid expansion of the population. Illiteracy and inadequate instruction about healthy habits, especially to women. A nation's unwillingness or inability to invest in preventive practices, including clean water, adequate nutrition, and conventional vaccination programs.

A stunning example of the aggregation of these problems was recently described in a New York Times article about the Sudan. Protracted civil war and disrupted travel have kept even that fearless group, Doctors without Borders, from bringing the most elementary care to people of the Sudan. Parasites like the guinea worm and the agent of river blindness can usually be easily treated , but not when, as in the Sudan, medicines cannot reach the victims. A more complex example can be found in the epidemic of AIDS that is already decimating sub-Saharan Africa and threatening similar effects in Asia. Because AIDS also affects the advanced economies, albeit on a smaller scale, a major investment in research has produced an astounding set of discoveries: rapid isolation of the viral cause, HIV; a definition of the viral components required for growth of HIV; and the development of drugs that inhibit those components, suppress the virus, and restore health to most patients. But these expensive drugs are not available to most of the infected people in poor countries, and cheaper control measures are either not yet developed (vaccines) or often not very effective (counseling about the use of condoms).

What Should Be Done?

Why do these matters deserve our attention? I have met very few people who deny their importance on the grounds of our common humanity. And yet the wealthy parts of the world have shown relatively little interest in dealing with them. There are several reasons for this seemingly callous attitude. One, which I will address later, is that inadequate thought has been given to appropriate courses of action. Another is the alleged imperviousness of governments to arguments that would enhance their engagement with such issues.

To many of us, enhanced engagement in such humanitarian efforts seems to be essential , especially as we understand the world after September 11. To a very significant, if not measurable extent, terrorism is a manifestation of anger and resentment about the world's inequalities: The control of 85% of the world's resources by 15% of its people. The failure of globalization to provide its benefits to the poor as effectively as it has to the rich. The apparent insularity and arrogance of the wealthy countries towards the poor.

So this might seem like an opportune time to attempt to reverse the trends of recent decades and espouse more altruistic national policies. But this is far from a foregone conclusion. During a recent weekend, for example, I attended a meeting at a stately home near London to discuss with former and current members of American, British, and other governments how to make the case for greater attention by governments of rich countries to health in poor countries. While virtually all were sympathetic and concerned, many felt that policy makers---and the public---would be loathe to commit financial resources to improvements in health abroad without a solid, traditional case for national self-interest. But measuring how so many dollars for health will decrease by so much the risk of terrorism or increase the potential for trade with poor countries is not easy, if it is possible at all. Simple assertion of the probable truth---that efforts to improve health will enhance the stability of poor countries and improve attitudes towards the advanced countries---was thought to have limited potency.

What then should be done by those of us in the health sciences who believe that we have yet to do all that we can to improve health conditions for the more than 2 billion people who live on less than a thousand dollars a year? I would like to consider two avenues for action. One is advocacy, based on a rigorous analysis of what reasonable increases in spending on health can achieve in saved lives and improved quality of life. The other is a concerted effort to build health-related sciences in poor countries, in hopes of sustaining and expanding the benefits of greater spending on health.

Advocacy for Health Spending

I would like to report first on my own experience in helping to build a case for greater spending. Over two years ago, I was among those appointed by Gro Harlem Brundtland, the Director General of WHO, to the Commission on Macroeconomics and Health. Under the leadership of Jeffery Sachs, the well-known Harvard economist, and with the help of literally hundreds of staff from the WHO, WB, International Monetary Fund, and many other agencies, we put together a report (available via the Internet at http://www.cmhealth.org/ that does several things.

• First, true to the charge from Dr. Brundtland, it makes a powerful case that improvements in health should not simply follow other efforts to promote economic progress through traditional developmental investments in schools, roads, and businesses. Instead improved health has large economic and social benefits and should itself serve as a driver of development.
• Second, we could show that, despite a bewildering array of diseases in poor countries, a few disorders predominate and, for these, solutions often exist, and many lives could be improved or saved by using them. (These predominant conditions are vaccine-preventable diseases, maternal and perinatal illnesses, malnutrition, acute infections of the respiratory and gastrointestinal tracts, malaria and tuberculosis, tobacco-related diseases, and HIV/AIDS.)
• Third, we found that spending on health is terribly low in the poor countries---commonly less than $10 per person, in contrast to the $30 to 40 required to combat the common diseases in a minimally effective fashion, and in even starker contrast to the $1000 or more that is spent per person in the wealthier countries.
• Fourth, contributions from the advanced donor countries were found to be shockingly low. Only a few contributed the 0.7% of their gross national product to foreign assistance, as recommended in the United Nations Millenium Development goals. Our own country, sad to say, was at the bottom of the list of twenty-some major donors, with only 0.1% of our GNP (or 0.5% of our tax revenue) devoted to foreign assistance, only one-eighth of that provided for health expenses, and much of that to countries that are not among the poorest.

Total world wide foreign aid for health totals only $6 billion---note that we spend about a trillion dollars on health care in the US alone. A careful accounting of the impact of more spending on disease suggests that if the $6 billion were increased to $27 billion by 2007, with modest increases in spending by the recipient countries themselves, up to eight million lives could be spared each year. In future years, further gains could be achieved by increases of up to $50 billion or so by 2015, still a relatively modest sum in relation to the world's wealth.

In the long run, the Commission concluded, it will also be necessary to provide other, so-called "global public goods", including better disease surveillance, more research on diseases of the poor, and improved communications systems. Better and cheaper access to drugs will also be important, but that is a longer and more complex story for another time.

How can funds for health care be provided in the short run, without running the risk of creating an ineffective charity program? One vehicle the Commission recommended for distributing new money is the Global Fund for Malaria, Tuberculosis, and HIV/AIDS, proposed by Kofi Annan, the Secretary General of the UN. Although the Fund has yet to collect the $7 to 10 billion requested for its first year, it has received about $2 billion in pledges and several hundred million in cash. In late April, it displayed in public the competitive process used to evaluate proposals from many poor countries. The fact that fewer than 15% of requests were approved (and some only conditionally) suggests that the demand is great and that a merit-based system can prevail to insure responsible allocations.

The first steps taken to institute Kofi Annan's Global Fund are among the scattering of hopeful signs that the world is taking note of the urgency of health assistance. Many news accounts of the Commission's report have also helped. For example, on Christmas Day, 2001, Paul Krugman wrote in the NY Times, in a column entitled "The Scrooge Syndrome," that the objections of Treasury Secretary Paul O'Neill to increased foreign aid---that he'd like to see evidence of what works before making new commitments---was "pure humbug….For the truth is that we already know what works. Nobody expects….to turn Mozambique into Sweden overnight. But more modest goals, such as saving millions of people a year from diseases like malaria and tuberculosis, are quite reachable, for quite modest sums of money…. The key argument here is surely a moral one. A sum of money that Americans would hardly notice, a dime a day for the average citizen, would quite literally save the lives of millions."

Our course columnists don't make policy. A more influential event occurred a few months later, when Bono, the well known leader of the musical group known as U2, visited President Bush and Senator Jesse Helms. After this meeting, the President, on his way to a high level meeting about foreign aid in Monterray Mexico, pledged to increase our total annual contribution to foreign assistance from $10 to $15 billion within the next three years. This will still leave us near the bottom of the donor list as a fraction of GNP, but it is the first significant increase in our nation's spending for aid abroad in two decades. After seeing Bono, Senator Helms called for an additional $500 million to combat AIDS abroad, and said, surprisingly to many who have followed his career, "I know of no more heartbreaking tragedy in the world today than the loss of so many young people to a virus that could be stopped if we simply provided more resources." If Jesse Helms can be persuaded of this, there is hope for persuading many others.

Surely, fragile as they are, these are hopeful signs and should be spurs to continued enlightened advocacy by all of us.

Globalizing Science

The second component of the strategy we can undertake as health professionals is an effort to promote science and technology in developing countries. This is a means to perpetuate the impact of increased spending on health by creating a culture of science that is both global in nature---the good face of globalization----and responsive to local needs.

We health scientists are not alone in these aspirations. A leading plant biologist, Ismail Serageldin, now the head of the new library in Alexandria, Egypt, has made a powerful call to add science to the cultural repetoire of the poor countries, where young people are about 100 times less likely than their counterparts in the advanced world to enter a scientific career. As he wrote recently in Science magazine, "science can help to feed the hungry, heal the sick, protect the environment, provide dignity in work, and create space for the joy of self-expression. Yet, on the negative side, lack of opportunity to master science and the new technologies will accentuate the divide between rich and poor."

Over ten years ago, the UN began to advocate development of research programs (called Agenda 21), noting that the biological sciences, especially biotechnology, have special attractions for the poor countries of the world in which science has not usually thrived. Biotechnology is cheap and relatively easy to learn. It can be used to address many problems in developing countries, including health, agriculture, and environmental pollution. It is also an excellent vehicle for training scientists and can be a stimulus for foreign investment as well as commercially profitable. So why have such pleas and proposed programs gone unfulfilled? And what are the prospects for succeeding now?

A traditional impediment to progress in science, including health science, is the difficulty of sharing information, especially in the poor countries. As recently as a decade ago, all publication was on paper---printed in expensive journals and books that few could afford. Lengthy conversation among professionals occurred almost exclusively at meetings to which costly and time-consuming travel was required. Information contained in different places was hard to retrieve, combine, analyze, and mine for novel conclusions.

Now all this can be---and ultimately will be---changed with the arrival of electronic communication and the Internet. E-mail simplifies frequent exchanges with colleagues, even with those who are separated by many time zones. Enormous data sets can be organized, stored, scrutinized, and exchanged with remarkable ease. Important examples include the genome sequences made available by the NIH and other public-spirited organizations. At the other end of the spectrum, work in progress and individual viewpoints can be self-published on personal websites for the benefit of any who are interested. Technical methods and health trends can be conveniently posted and updated to encourage the formation of scholarly communities with shared interests and the production of results that can be meaningfully compared. Perhaps most importantly, the very nature of publishing of reports in science and medicine can be changed in an absolutely fundamental way---in a way that would allow anyone with a desktop computer and connection to the Internet to view for free any papers published in any of the leading journals and to make much better use of this literature.

Why is this possible and so attractive? What does the electronic format do for publishing? Most obviously, it makes universal distribution feasible---and at reduced cost. In contrast to the post-Gutenberg method, which requires the printing and shipping and delivery of a copy to each reader, the post-Internet method requires the creation of only one version that can serve anyone who connects. Electronic formats permit much more inclusive and informative presentation of data, improving the value of published work. The potential for convenient storage of old and new literature has enormous potential for reducing the space and funds now needed to maintain libraries. Methods for searching such archives for valuable, relevant information create unprecedented opportunities to use our legacy of knowledge more effectively.

Despite these attractions, progress towards a publishing utopia has been relatively slow---at least it seems slow to impatient idealists like me. It is true that many journals are available on line, but mostly to individuals or institutions who have subscribed, generally at rates that are no less than rates for publication on paper. When articles are provided for free on the Internet, it is generally only after a lag of six to 24 months after publication or in very poor countries where there are now very few scientists. Ultimately, we will need to find a way to make the biomedical literature available more quickly without bankrupting the journals. I believe this can and will be done by shifting the charges from readers to authors, but that is a longer story for another time. Still, even the limited changes that are occurring now could have a big impact in certain fields. For instance, in China, many people are obliged to travel large distances to visit the Shanghai Institute of Parasitology, which has one of the few large collection of the many expensive journals needed for work in that field. Greater access to them via the Internet would save lots of dollars and time.

Electronic connectivity is only one element in building a global culture of science. Financial resources, as recommended by the UN and many others, are essential. Young people from developing countries must not only be trained in the sciences, they must have incentives for working in those countries; this is often unlikely after they have been trained in sophisticated institutions in wealthy countries and then find there are no attractive places to work at home. The Millenium Science Initiative, coordinated by a small international group of eminent scientists and supported by the Packard Foundation and the World Bank, is attempting to rectify this situation by helping to develop modern science centers in middle income but relatively science-poor countries like Brazil, Mexico, and Vietnam, and in some of the world's poorest countries in Africa.

In my view, the prospects for the success of such ventures, especially those in the countries least accustomed to scientific institutions, could be dramatically improved by the presence of scientists, young or old, from developed countries. I envision a Global Science Corps---not unlike the US Peace Corps or a Medecins Sans Frontieres for scientists---helping to place scientists, both the newly trained or those nearing retirement, in appropriate settings to use their talents to work towards local scientific goals and to train those who work with them from the host country.

There is an historical model for such an effort in the life of the famous British geneticist, G.B.S. Haldane. In 1957, after a highly successful career in prominent English research institutions, Haldane---and his wife, also a geneticist--- headed for India, where he spent the rest of his life studying the genetics of corn and other agricultural organisms and lecturing throughout the country.

I believe that such service would be an appealing late phase in the careers of many American and European scientists and that an international effort to organize and pay for such scientific missions should be undertaken.

Obviously, a Global Science Corps---or whatever it is called---requires institutional settings of the kind the Millenium Science Initiative is trying to establish. I am convinced that such settings already exist, even in the very poorest countries, and can be attractive to prospective Corps members.

Consider one example that I have visited myself. In Bamako, the capital of Mali, with an average income of $300 per person per year, the National Institutes of Health and the US Agency for International Development have established a Malaria Research and Training Center that is staffed mainly by Malian scientists and technicians, has good Internet connectivity, serves as a regional institution for training, receives its own NIH grant money, and hosts scientific visitors from NIH and Tulane for collaborative projects. The Center is well known and well respected by the political leadership of Mali, is a source of public pride, and offers a positive view of health research to students at the adjacent school of medicine.

Another example is provided by an HIV/AIDS research center in Lusaka, Zambia, where scientists from the University of Alabama-Birmingham AIDS Center are studying with NIH funds and their Zambian colleagues the genetic characteristics of HIV variants that are transmitted from an infected marital partner to an uninfected partner. In the course of these studies, behavioral counseling reduces the rate of transmission by up to two thirds, while molecular studies are teaching us about the viral strains most likely to be transmitted---and thus the important targets for vaccine development.

Who would not find these to be exciting environments in which to work, to learn, and to train---with the added benefit of spreading the culture of science?

Reprise

I have tried to suggest that we are at a decisive moment in the history of our nation and the world. The events of September 11, dreadful though they were, have also alerted us to the resentments bred by the economic asymmetries in today's world. Those asymmetries are not purely economic; they affect every aspect of our lives, including that common bond and aspiration, a long and healthy life. We have the financial resources and the knowledge to do something---not everything, but something very significant---to change this situation now by provide health assistance. And over the longer haul, we can put the science we value so highly to work to help sustain improved health over many years.

As Ismael Serageldin said in the article I quoted earlier: "So let us start. If not us, who? If not now, when?"