Book Review

Lesser Harms: The Morality of Risk in Medical Research

N Engl J Med 2005; 353:2725-2726December 22, 2005

Article

Lesser Harms: The Morality of Risk in Medical Research
(Morality and Society Series.) By Sydney A. Halpern. 232 pp. Chicago, University of Chicago Press, 2004. $37.50. ISBN: 0-226-31451-0

The 1960s and 1970s are widely regarded as a watershed in the history of bioethics. The exposure of research scandals during these years generated widespread public controversy. The outcry was followed by a series of federal commissions and regulations that sought to make informed consent an integral part of clinical research. Yet this approach has hardly been perfect, as illustrated by such tragic accidents as the death of 18-year-old Jesse Gelsinger in a 1999 gene-therapy experiment.

A sociologist conversant with the methods of history and ethics, Sydney Halpern argues that medical researchers in the first half of the 20th century operated within an informal but sophisticated moral tradition governing human experimentation. According to this logic, any experiment involving humans first had to be scientifically sound. Experiments in animals and (on many occasions) members of the research team ought to precede studies in patients. And above all, no medical intervention should be considered ethical unless it posed less risk to the subject than the risk posed by the corresponding disease itself.

Halpern demonstrates how this moral tradition, which she designates the logic of “lesser harms,” operated on two levels. One was that of peer pressure. It was not uncommon for leading researchers to restrain their colleagues in the consideration of potentially dangerous research. For example, before 1935 there was a virtual moratorium on poliovirus-vaccine research, coordinated by scientists such as Simon Flexner, who considered the project simply too risky. Funding agencies provided a second level of enforcement. The President's Birthday Ball Commission (predecessor to the March of Dimes) and the Rockefeller Institute both took direct interest in protecting human subjects when considering grant awards.

Halpern explores the strengths and limitations of this informal ethics tradition with great subtlety. Her study, though wide-ranging, centers on how two investigators (Maurice Brodie and John Kolmer) broke the polio-vaccine moratorium in 1934 and 1935. Working independently, the two men inoculated tens of thousands of children with rudimentary polio vaccines that had just barely been tested in animals. Brodie's vaccine proved ineffective, and Kolmer's led to the paralysis of a number of children. Researchers like Flexner attempted to dissuade these investigators but were unable to stop them before it was too late. Kolmer, in particular, was an “outsider” with respect to the polio-virology community who felt little allegiance to Flexner and mainstream virologists. He was also able to find granting agencies willing to leave decisions involving risks in the hands of investigators.

One might assume that more uniform and formal rules among funding agencies could have prevented future debacles. Yet, even as this trend gained strength after World War II, research abuses became more widespread and consequential than ever. What went wrong? In the postwar years, agencies often alluded to the importance of obtaining consent from research subjects but used this language only superficially. What mattered more was how the context of war and its aftermath promoted a utilitarian ethos that subordinated individual rights to the good of society.

Halpern concludes by suggesting that regulations will be most effective if they build on the traditions of medical investigators, rather than antagonize them. This is a fascinating and timely book that deserves the attention of anyone interested in the complex questions accompanying the ethics of medical research.

Jeffrey P. Baker, M.D., Ph.D.
Duke University School of Medicine, Durham, NC 27713