Doing Research on People

Nowhere is the potential for conflicting obligations more worrisome than in situations where doctors simultaneously deliver medical care to patients and use them as research subjects. The idea of experimenting on patients conjures up two quite different pictures. The first depicts persons who are sick and suffering—perhaps even dying—being subjected to the manipulations of clinical investigators who use patients in their efforts to contribute to scientific knowledge, as well as to promote their own careers. The second picture portrays untold numbers of present and future patients receiving the benefits of miraculous cures resulting from painstaking research in hospitals and laboratories. Neither of these pictures is an accurate rendering of the actual conduct of research involving human subjects, yet both contain partial truths. The actual contribution to medical knowledge gained by most clinical trials is only a pale rendering of the image of miraculous breakthroughs in scientific understanding and control of disease. The ethical dilemma created by the need to experiment on sick patients in order to advance the frontiers of biomedical science and conquer diseases is sometimes stated in the form of two unacceptable extremes. To allow unfettered experiments on human beings would open up the prospect of new abuses such as those known to have occurred in the past. The atrocities committed by the Nazis in the name of medical research are the worst example but not the only instance of unethical research conducted on human subjects. However, to prohibit research on human subjects altogether would be to close off the only avenues that could provide the scientific knowledge and technological capabilities for preventing and curing diseases. A particular experiment or an entire line of research can be judged ethically acceptable or unacceptable for different reasons. These reasons rest on general moral principles, the same moral principles used to evaluate therapeutic practices in medicine. The utilitarian moral principle underlies the concept of the “risk-benefit equation,” requiring that the beneficial consequences of research outweigh the risks of harm. The “principle of beneficence,” as it has come to be known, was defined in The Belmont Report, one of several publications issued by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research in 1979. The National Commission, created by the National Research Act of 1974, treated beneficence as an igation that embraces two general rules: do no harm, and (2) maximize possible benefits and minimize possible harms. Applying a nonconsequentialist moral principle would lead to a rather different assessment of at least some research involving human subjects. Kant’s categorical imperative, which states that persons are never to be treated merely as means but always as ends in themselves, might rule out all nontherapeutic research. It would surely prohibit experiments involving individuals who will receive no direct benefit and who lack the capacity to grant informed consent to participate. A plausible interpretation of the categorical imperative is that it would permit some research in which there is no direct therapeutic benefit, but only when the consenting subjects have an interest in the success of the research for a reason other than benefit to themselves—for example, if the research is investigating an illness from which a relative suffers, or if the subject participates out of altruistic motives. A problem remains, however, when this principle is applied to research involving children and other individuals with diminished autonomy. If the research holds out no prospect of direct benefit to them, these human subjects are being used “merely as a means” to the ends of others. Does that make it unethical to conduct nontherapeutic research on individuals who cannot consent on their own behalf? The answer is yes if the governing moral principle is Kant’s categorical imperative, and no if the applicable concept is the principle of beneficence. The National Commission for the Protection of Human Subjects chose the latter ethical principle as the appropriate standard for judging the acceptability of risks in human experimentation. Another reason for judging various lines of research to be unethical is that they wrong human subjects. even if those subjects are not at risk for physical or psychological harm. This charge has been leveled against the use of deception in social science research and also against research projects in which the investigator engages in cover observations. To deceive subjects is to wrong them by failing to respect their dignity as persons. To observe people without their knowledge and consent is an invasion of their rights of privacy. The concept of wronging the subjects of research rests on the respect-for-persons moral principle, central to the non- consequentialist ethical perspective. The Belmont Report states: Respect for persons incorporates at least two ethical convictions: first, that individuals should be treated as autonomous agents, and second, that persons with diminished autonomy are entitled to protection. The principle of respect for persons thus divides into two separate moral requirements: the requirement to acknowledge autonomy and the requirement to protect those with diminished autonomy The leading application of this principle is in the doctrine of informed consent. Failure to obtain voluntary, informed consent from subjects or their legally authorized representatives violates the respect-for-persons principle in the research setting as well as in the context of performing therapy on patients. A widely publicized case of violation of the respect-for-persons principle occurred in a research project conducted in 1964 at the Jewish Chronic Disease Hospital in Brooklyn, N.Y. Twenty-two elderly patients, 19 suffering from some form of nonmalignant terminal iliness and three cancer patients used as experimental controls, were approached by a researcher who wished to study the body’s immune mechanisms. The material actually injected into these unwitting patients was tissue consisting of live cancer cells, but the patients were told only that some tissue would be injected, that a lump would form, and that it would disappear in a few days. The researcher was certain that injecting cancer cells into the subjects would not cause cancer, but he wanted to determine how quickly and in what manner the patients’ immune systems would reject the cancer cells. The main charge brought against the research and the director of the hospital, in a hearing conducted by the New York State Board/of Regents, was that the patients had not been given sufficient, accurate information to grant properly informed consent. Probing questions were also raised about the competency of these patients to grant consent at all, since they were elderly and debilitated, some frankly senile, and others deaf or blind. The researcher told the hearing board that he saw no reason to use the word “cancer in describing the procedures to the patients. He said the term “has a tremendous emotive value, disvalue to everybody ... What the ordinary patient, what the nonmedical person, and even many doctors ... whose knowledge of the basic science behind transplantation is not great—to them the use of a cancer cell might imply a risk that it will grow and produce cancer, and the fear that this word strikes in people is very great.” Acting under its responsibility for licensing the medical profession, the regents found the researcher and the medical director of the hospital guilty of “unprofessional conduct” and of “fraud and deceit in the practice of medicine.” Surprising as it may seem, the charge of “unprofessional conduct” is more devastating than calling a doctor “unethical.” Several years ago some questions were raised by the institutional review board on which I serve about the conduct of one physician whose research protocols are regularly reviewed by the IRB. The majority of committee members are doctors, most of whom are involved in research themselves. Despite their conscientious efforts to protect the subjects of research, they are reluctant to make trouble for one of their fellow physicians. The committee also includes nurses, social scientists, members of the hospital administration, one person drawn from the local community, and myself as ethicist. On this occasion a physician on the IRB suggested that a motion to censure the researcher was called for, and I became involved in formulating the wording of the motion. The wording included both charges—"unethical practices” and “unprofessional conduct.” I was advised by a colleague to drop the second charge, as it was a “red flag,” more damaging to the researcher than an accusation of unethical practices. Much less surprising was the outcome of this episode. Only one other member of the IRB was willing to vote for censuring or reprimanding the unethical investigator, and the matter was quickly dropped. Macklin is professor of bioethics at the Albert Einstein College of Medicine, Bronx, NY 10461. Copyright © 1987 by Ruth Mackiln. Reprinted by permission of the publisher, Pantheon Books, A division of Random House, Inc.

Doing Research on People

Interested in reading more?

Become a Member of