Infectious Disease

The ability to understand and manipulate the basic molecular constituents of living things has created an extraordinary opportunity to improve human health.

Excerpted from The Future Postponed, Massachusetts Institute of Technology, 2015

Chris A. Kaiser: Amgen Inc. Professor of Biology

The ongoing revolution in molecular biology has shown that all forms of life contain the same basic set of molecular parts and operate by the same biochemical rules, which scientists increasingly understand and can manipulate. That has created an extraordinary opportunity to improve human health, both by preparing for and thus preventing epidemics of emerging infectious disease such as Ebola and by finding solutions to the even more deadly threat from drug resistant bacteria.

Ebola outbreaks have occurred periodically in rural Africa for many decades, and the cause of this highly transmissible and deadly disease— the Ebola virus—has been known since 1976. As the world struggles to contain the current epidemic in Western Africa, it is clear that
there have been many missed opportunities to prepare the tools we now desperately need to detect, treat, and immunize against this still poorly understood disease. How did we come to be so little prepared to confront a disease that posed such an obvious risk to global health?

The answer, in part, may have been over-confidence in the established alliance between publicly funded university and hospital based research and privately funded research in pharmaceutical and biotechnology companies that has been so successful in developing drugs,
tests, and procedures needed to combat the diseases of the developed world. It now seems clear that existing priorities and incentives are not sufficient to prepare for diseases that emerge by jumping from animals to humans in impoverished parts of the developing world— of which Ebola is only one of at least half a dozen equally dangerous threats.

How viruses invade and multiply within human cells is generally understood. But basic research is needed to delineate the exact molecular mechanism for each virus, because develop- meant of drugs to combat infections depend on these specifics. Likewise, the development of effective vaccines also requires extended basic research into the structure of the virus, and specifically into how it evolves by changing proteins on its surface to evade the body’s immune system: then it is possible to identify surface proteins that do not change, and which become the targets for vaccines. If we are to be prepared for the next viral epidemic, we need to invest in the basic research to characterize and understand all known viruses with the potential to be highly infectious. It is not that long a list; this is a task well within the capacity of the U.S. biomedical research system; and, since these diseases threaten all countries, it would be easy to make common cause with partners in Europe and Asia.

Drug-resistant bacteria infect at least two million people in the U.S. every year, with growing fatalities. If we don’t begin a major basic research effort soon, the threat to U.S. public health a decade from now may well look very challenging.

As dramatic as exotic emerging viral diseases seem, they are not the only or even the most serious infectious disease threat that the world faces. Potentially more deadly to most Americans is the spread of antibiotic resistance that undercuts our ability to treat bacterial infections we have long considered to be under control, from tuberculosis to staphylococcus and streptococcus. In fact, drug-resistant bacteria infect at least two million people in the U.S. every year, a growing number of them fatally.

The development of antibiotics – drugs that kill specifically bacterial cells by targeting differences between bacteria and the cells in our body – is one of the great achievements
of modern medicine and we now take it for granted that if a child has strep throat we can cure it within days with the right antibiotic. But it is now clear that the more widely an anti- biotic is used, the more rapidly that bacteria will evolve to acquire a resistance to it—and the bacteria are increasingly winning this war. Especially alarming is the spread of drug-resistance forms of staph and strep bacteria, especially in hospitals; the emergence of resistance to two “last resort” antibiotics, Methicillin and Vancomycin, used to treat infections resistant to other drugs; and the spread of a multi-drug resistant form of tuberculosis, for which no other treatment options now exist.

Development of entirely new antibiotics is at present the only way to keep ahead of the threat of incurable bacterial infectious disease. But the pharma industry has developed very few new antibiotic drugs in the past two decades—economic incentives are clearly insufficient. The alternative strategy is basic research into new bacterial processes, so that it would be possible to attack multiple tar- gets within a bacteria, making it much harder for resistance to evolve. For that we need an infusion of fresh ideas and incentives for independent investigators—in effect, investments in a major basic research effort in the physiology and genetics of pathogenic bacteria that will attract new talent to this area. If we don’t begin this effort now, the threat to U.S. public health a decade from now may well look very challenging.