THE PAYOFF FROM MEDICINE

Medical research is consuming far more funds than it was when the health sciences were making breathtaking advancements in the quality and quantity of human life. We spend billions of tax dollars, for instance, on the budget of the National Institutes of Health every year. When it comes to the control of disease, medicine gave us much less for much more money as the twentieth century progressed. It is true to some extent that the problems faced now are harder to solve, but it is also true that medical research is stuck in a rut. We can be confident only that the problems of the present are harder to solve using the approaches of the past. Little in the control of disease during the last half of the twentieth century involved fundamentally new approaches, in the same way that antibiotics are fundamentally different from vaccination, which is fundamentally different from hygienic improvements, which is fundamentally different from surgical removal of diseased tissue. Rather we are recycling each of these solutions. The major advances during this period were vaccines and antibiotics. The payoffs from vaccination dwindled from the successes against polio, measles, whooping cough, and mumps during the 1950s and 1960s to the more sporadic successes of the subsequent three decades. The generation of new antibiotics struggled to stay ahead of antibiotic resistance. The antibiotic strategy was broadened to encompass antiviral and antiprotozoal drugs, but these applications never generated the magic bullets that were anticipated from the successes of the 1940s. The positive effects of antivirals on AIDS, and antimalarials on malaria, never came close to the effects of penicillin on streptococcal pneumonia. When confronted with problems such as influenza, AIDS, and malaria, researchers kept applying the solutions that worked for other diseases, hoping that improved technology would improve the results of these marginally effective strategies. They did not use technology to generate any fundamentally different approaches.     In spite of this declining return on investment, one fact stands out. Though there has been much investment in studies of genetic causation of disease, the most significant returns were generated on the investments in studies of infectious diseases. Polio, measles, hepatitis, liver cancer, ulcers, and cervical cancer were all controlled or shown to be controllable during the last half of the twentieth century through the control of infectious agents. This track record provides a sense of how to invest in our future: focus on the germs.     The Human Genome Project serves as a test case. Many medical experts believe that the Human Genome Project will accomplish much of what the last half century of medical genetics failed to do: identify the genetic causes of the major diseases so that the harm from these diseases can be ameliorated. The genome project will surely illuminate genetic causes of disease, but evolutionary principles suggest that the most important disease-causing genes will belong not to the humans but to the pathogens. Human genes will become relevant not so much because they cause disease but rather because they protect or fail to protect against pathogen genes.     Specifically, analysis of the human genome should foster the discovery of genetic sequences that seem out of place in the human genome. These stretches will seem out of place because they are out of place, being viral rather than human. By facilitating an improved understanding of infectious agents in the human genome, these studies will help unmask potential agents of human diseases.*28\225\2*