2006 : WHAT IS YOUR DANGEROUS IDEA?

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Professor of Biology, Amherst College; Author, Plague Time
A New Golden Age of Medicine

My dangerous idea is that we have in hand most of the information we need to facilitate a new golden age of medicine. And what we don't have in hand we can get fairly readily by wise investment in targeted research and intervention. In this golden age we should be able to prevent most debilitating diseases in developed and undeveloped countries within a relatively short period of time with much less money than is generally presumed. This is good news. Why is it dangerous?

One array of dangers arises because ideas that challenge the status quo threaten the livelihood of many. When the many are embedded in powerful places the threat can be stifling, especially when a lot of money and status are at stake. So it is within the arena of medical research and practice. Imagine what would happen if the big diseases — cancers, arteriosclerosis, stroke, diabetes — were largely prevented.

Big pharmas would become small because the demand for prescription drugs would drop. The prestige of physicians would drop because they would no longer be relied upon to prolong life. The burgeoning industry of biomedical research would shrink because governmental and private funding for this research would diminish. Also threatened would be scientists whose sense of self-worth is built upon the grant dollars they bring in for discovering miniscule parts of big puzzles. Scientists have been beneficiaries of the lack of progress in recent decades, which has caused leaders such as the past head of NIH, Harold Varmus, to declare that what is needed is more basic research. But basic research has not generated many great advancements in the prevention or cure of disease in recent decades.

The major exception is in the realm of infectious disease where many important advancements were generated from tiny slices of funding. The discovery that peptic ulcers are caused by infections that can be cured with antibiotics is one example. Another is the discovery that liver cancer can often be prevented by a vaccine against the hepatitis B virus or by screening blood for hepatitis B and C viruses.

The track record of the past few decades shows that these examples are not quirks. They are part of a trend that goes back over a century to the beginning of the germ theory itself. And the accumulating evidence supporting infectious causation of big bad diseases of modern society is following the same pattern that occurred for diseases that have been recently accepted as caused by infection.

The process of acceptance typically occurs over one or more decades and accords with Schopenhauer's generalization about the establishment of truth: it is first ridiculed, then violently opposed, and finally accepted as being self-evident. Just a few groups of pathogens seem to be big players: streptococci, Chlamydia, some bacteria of the oral cavity, hepatitis viruses, and herpes viruses. If the correlations between these pathogens and the big diseases of wealthy countries does in fact reflect infectious causation, effective vaccines against these pathogens could contribute in a big way to a new golden age of medicine that could rival the first half of the 20th century.

The transition to this golden age, however, requires two things: a shift in research effort to identifying the pathogens that cause the major diseases and development of effective interventions against them. The first would be easy to bring about by restructuring the priorities of NIH — where money goes, so go the researchers. The second requires mechanisms for putting in place programs that cannot be trusted to the free market for the same kinds of reasons that Adam Smith gave for national defense. The goals of the interventions do not mesh nicely with the profit motive of the free market. Vaccines, for example, are not very profitable.

Pharmas cannot make as much money by selling one vaccine per person to prevent a disease as they can selling a patented drug like Vioxx which will be administered day after day, year after year to treat symptoms of an illness that is never cured. And though liability issues are important for such symptomatic treatment, the pharmas can argue forcefully that drugs with nasty side effects provide some benefit even to those who suffer most from the side effects because the drugs are given not to prevent an illness but rather to people who already have an illness. This sort of defense is less convincing when the victim is a child who developed permanent brain damage from a rare complication of a vaccine that was given to protect them against a chronic illness that they might have acquired decades later.

Another part of this vision of a new golden age will be the ability to distinguish real threats from pseudo-threats. This ability will allow us to invest in policy and infrastructure that will protect people against real threats without squandering resources and destroying livelihoods in efforts to protect against pseudo-threats. Our present predicament on this front is far from this ideal.

Today experts on infectious diseases and institutions entrusted to protect and improve human health sound the alarm in response to each novel threat. The current fears over a devastating pandemic of bird flu is a case in point. Some of the loudest voices offer a simplistic argument: failing to prepare for the worst-case scenarios is irresponsible and dangerous. This criticism has been recently leveled at me and others who question expert proclamations, such as those from the World Health Organization and the Centers for Disease Control.

These proclamations inform us that H5N1 bird flu virus poses an imminent threat of an influenza pandemic similar to or even worse than the 1918 pandemic. I have decreased my popularity in such circles by suggesting that the threat of this scenario is essentially nonexistent. In brief I argue that the 1918 influenza viruses evolved their unique combination of high virulence and high transmissibility in the conditions at the Western Front of World War I.

By transporting contagious flu patients into a series of tightly packed groups of susceptible individuals, personnel fostered transmission from people who were completely immobilized by their illness. Such conditions must have favored the predator-like variants of the influenza virus; these variants would have a competitive edge because they could ruthlessly exploit a person for their own replication and still get transmitted to large numbers of susceptible individuals.

These conditions have not recurred in human populations since then and, accordingly, we have never had any outbreaks of influenza viruses that have been anywhere near as harmful as those that emerged at the Western Front. So long as we do not allow such conditions to occur again we have little to fear from a reevolution of such a predatory virus.

The fear of a 1918 style pandemic has fueled preparations by a government which, embarrassed by its failure to deal adequately with the damage from Katrina, seems determined to prepare for any perceived threat to save face. I would have no problem with the accusation of irresponsibility if preparations for a 1918 style pandemic were cost free. But they are not.

The $7 billion that the Bush administration is planning as a downpayment for pandemic preparedness has to come from somewhere. If money is spent to prepare for an imaginary pandemic, our progress could be impeded on other fronts that could lead to or have already established real improvements in public health.

Conclusions about responsibility or irresponsibility of this argument require that the threat from pandemic influenza be assessed relative to the damage that results from the procurement of the money from other sources. The only reliable evidence of the damage from pandemic influenza under normal circumstances is the experience of the two pandemics that have occurred since 1918, one in 1957 and the other in 1968. The mortality caused by these pandemics was one-tenth to one-hundredth the death toll from the 1918 pandemic.

We do need to be prepared for an influenza pandemic of the normal variety, just as we needed to be prepared for category 5 hurricanes in the Gulf of Mexico. If possible our preparations should allow us to stop an incipient pandemic before it materializes. In contrast with many of the most vocal experts I do not conclude that our surveillance efforts will be quickly overwhelmed by a highly transmissible descendent of the influenza virus that has generated the most recent fright (dubbed H5N1). The transition of the H5N1 virus to a pandemic virus would require evolutionary change.

The dialogue on this matter, however, continues to neglect the primary mechanism of the evolutionary change: natural selection. Instead it is claimed that H5N1 could mutate to become a full-fledged human virus that is both highly transmissible and highly lethal. Mutation provides only the variation on which natural selection acts. We must consider natural selection if we are to make meaningful assessments of the danger posed by the H5N1 virus.

The evolution of the 1918 virus was gradual, and both evidence and theory lead to the conclusion that any evolution of increased transmissibility of H5N1 from human to human will be gradual, as it was with SARS. With surveillance we can detect such changes in humans and intervene to stop further spread as was done with SARS. We do not need to trash the economy of southeast asia each year to accomplish this.

The dangerous vision of a golden age does not leave the poor countries behind. As I have discussed in my articles and books, we should be able to control much of the damage caused by the major killers in poor countries by infrastructural improvements that not only reduce the frequency of infection but also cause the infectious agents to evolve toward benignity.

This integrated approach offers the possibility to remodel our current efforts against the major killers — AIDS, malaria, tuberculosis, dysentery and the like. We should be able to move from just holding ground to institution of the changes that created the freedom from acute infectious diseases that have been enjoyed by inhabitants of rich countries over the past century.

Dangerous indeed! Excellent solutions are often dangerous to the status quo because they they work. One measure of danger to some but success to the general population is the extent to which highly specialized researchers, physicians, and other health care workers will need to retrain, and the extent to which hospitals and pharmaceutical companies will need to downsize. That is what happens when we introduce excellent solutions to health problems. We need not be any more concerned about these difficulties than the loss of the iron lung industry and the retraining of polio therapists and researchers in the wake of the Salk vaccine.