01/08/2007 - 22:00

Government oversight and the life sciences

Laura H. Kahn

Laura H. Kahn

A general internist who began her career in health care as a registered nurse, Kahn works on the research staff of Princeton University's ...

More

This fall, the Program on Science and Global Security at Princeton University hosted a series of biodefense seminars sponsored by the Carnegie Corporation of New York. The speakers included senior scientists and high-level government officials.

One of the themes that emerged from the series is the concern by some of the senior scientists that increased government oversight of basic life sciences research would “kill” the research. The oversight would be imposed in order to prevent unintended or nefarious uses of the research (e.g. the seven experiments of concern; please see the National Academy of Sciences (NAS) report on p. 5). The worry is that stringent mandatory oversight would become so onerous that people would stop pursuing it as a career and/or that much of the research would move overseas to countries where such oversight would be considerably weaker or nonexistent.

These scientists cite human subject research as an example of how strict oversight mechanisms has had a negative impact on those conducting the science and that much human subject research has now gone overseas. These concerns warrant examination of what happened with human subject research. Did increased oversight “kill” human subject research in the United States? Could this example serve as a predictor of what might happen to basic life sciences research since there are some parallels between them?

Protection for human subjects developed after a long, sorry history of abuses such as the Tuskegee syphilis experiments by the U.S. Public Health Service, in which poor black men were denied treatment for syphilis for decades. During the Nuremberg Trials, American judges issued the Nuremberg Code, a list of 10 principles to guide researchers doing human subject experimentation. This code was generally ignored in the United States. In 1964, the World Medical Association published the Declaration of Helsinki—guidelines for researchers to do ethical human subject research.

Mandatory oversight didn’t develop until the 1970s when the New York Times revealed the abuses of the Tuskegee syphilis study. The public uproar reached such a pitch that Congress passed the National Research Act (Public Health Law 93-348) in 1974, which created the National Commission for the Protection of Human Subjects in Biomedical and Behavioral Research. The commission advocated for local institutional oversight and accountability to ensure that vulnerable individuals were not placed at undue risk. At that time, much of the human subject research was funded by the federal government, so the regulations applied to all institutions that received federal funding. The system is far from perfect, and there have been high-profile cases in which research volunteers at respected institutions such as the University of Pennsylvania and Johns Hopkins University have died. In 1999, the National Institutes of Health’s Office for Protection from Research Risks shut down research at Duke University for four days while it investigated problems involving its human subjects protection policies and procedures.

To circumvent the regulations, many pharmaceutical companies have moved their human subject research and clinical trials overseas. According to a 2001 report by the Inspector General (IG) of the U.S. Department of Health and Human Services, the number of countries in which clinical investigators conduct drug research has increased from 28 in 1990 to 79 in 1999. In addition, the number of foreign investigators has increased from 271 to 4,458 during the same time span.

However, the reasons for moving human subject research overseas does not appear to be due solely to strict oversight. Reasons also include potential new markets for drugs, international agreements that ease FDA acceptance of foreign data, simultaneous approval in many countries, and perhaps most importantly, low costs. The accessibility of human subjects is only an added benefit. The 2001 IG report highlights the concern that the FDA cannot ensure human subject protections through international oversight boards. Indeed, the National Bioethics Advisory Commission and the World Health Organization have raised concerns that international human subject monitoring boards have insufficient monitoring practices and lack of experience.

There has been a move to standardize requirements for experimental quality and safety through the International Conference on Harmonization, which has ties with the United Nations. But until these requirements are implemented and enforced, concerns persist that people in developing countries who participate in the research might not receive full protections.

In addition, much human subject research has moved into doctor’s private offices, which are still regulated by federal human subjects oversight protections. Indeed, the number of private physicians involved in human subject research in the United States has almost tripled since 1990. But conflict of interest is enormous because these physicians get paid by pharmaceutical companies to participate in the research. Their roles as health care providers versus research investigators becomes blurred, and some patients—particularly the uninsured—receive free health care and medications only for the duration of the study. This trend likely has more to do with the economic impact of managed care than with mandatory human subject oversight. Before managed care, academic medical centers were able to subsidize clinical research with surplus dollars that have since dried up under imposed fiscal constraints. As a result, many physician researchers are moving into the pharmaceutical industry.  Therefore, it appears that the changes in human subject research have largely been due to economic reasons and not from strict government oversight.

Similar to human subject research, basic life sciences research has a checkered past. Japan used it for nefarious purposes during World War II, while the Soviet Union did the same during the Cold War. The United States jumped into bioweapons research for several decades until its program ceased in the late 1960s.

Public concerns were primarily focused on the dangers of genetic engineering rather than on bioterrorism, so a system of biosafety oversight developed. But there is evidence that this system of safety oversight is not rigorous at many institutions. Only after the 2001 anthrax attacks did a discussion on the oversight of the research begin—with the publication of the NAS report I previously mentioned.

However, a huge public outcry and demand for mandatory oversight after the anthrax attacks hasn’t materialized, unlike after the Tuskegee abuses were exposed. Some of this could be due to the fact that the anthrax perpetrator(s) haven’t been apprehended. The 109th Republican-led Congress also was not prone to responding to such concerns, but rather to protecting corporate interests; unless, of course, the crisis involved Terri Schiavo.

As it stands now, there are some who still believe that the threat of a bioattack by a scientist is a theoretical risk—although history has shown that the use of biological agents have been, and will continue to be, used against others. The NAS report recommended the creation of the National Science Advisory Board for Biosecurity (NSABB) whose mission is purely advisory. So far, the NSABB has not supported mandatory oversight for basic life sciences research. However, their concerns about mandatory oversight “killing” basic life sciences research is not supported by the human subject experience. We can only hope that a devastating biological attack will not serve as the impetus for oversight of basic life sciences research to be written into law.