Research, Unethical

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RESEARCH, UNETHICAL

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Unethical research is a concept inevitably relative to accepted views concerning research's ethical requirements. For Claude Bernard, an early French exponent of the scientific method in medicine who felt that the principle underlying medical morality requires that persons not be harmed, paradigm cases of unethical research are studies that offer their subjects risks that exceed their potential benefits. The Nuremberg Tribunal, by stating in its first principle of ethical research that the subject's free consent is absolutely essential, added as paradigmatic cases of unethical research those studies performed upon unconsenting persons (Germany [Territory Under Allied Occupation, …]). U.S. regulations that require an equitable selection of research subjects imply that a study that is otherwise ethical (e.g., a study with an acceptable risk-benefit ratio and whose subjects have freely consented) becomes unethical when it unfairly draws its research population from persons disadvantaged by reason of race, religion, or dependency, among others ("Federal Policy").

Examples of Unethical Research

Whichever ethical requirement may be chosen, the history of human research offers grim examples of its violation. During World War II, German researchers performed a large number of experiments in concentration camps and elsewhere. Subject-victims of Nazi research were predominantly Jews, but also included Romanies (Gypsies), prisoners of war, political prisoners, and others (Germany [Territory Under Allied Occupation … ]; Caplan). Nazi experimental atrocities included investigation of quicker and more efficient means of inducing sexual sterilization (including clandestine radiation dosing and unanesthetized male and female castration) and death (an area of study Leo Alexander [1949] termed "thanatology," which includes studies of techniques for undetectable individual assassination—i.e., murder that mimics natural death—as well as mass murder). Among the best-known cases were the hypothermia experiments, which investigated mechanisms of death by freezing and means of preventing it. These studies, motivated by the loss of German pilots over the North Sea, included immersing prisoners in freezing water and observing freezing's lethal physiological pathways.

Beginning in 1932, the U. S. Public Health Service funded a study of the natural progression of untreated syphilis in black men. Four hundred subject-victims were studied, along with 200 uninfected control subjects. The study, whose first published scientific paper appeared in 1936, continued until a newspaper account of it appeared in 1972. Its subject-victims were uninformed or misinformed about the purpose of the study, as well as its associated interventions. For example, participants were told that painful lumbar punctures were given as treatment, when in fact treatment for syphilis was withheld even after the discovery of penicillin (Brandt; Jones).

Numerous other examples of unethical research may be cited, though they have received far less attention. A New Zealand study on women that began in 1966 and was active for at least ten years had macabre similarities to the Tuskegee study. It concerned the natural history of untreated cervical carcinoma in situ (i.e., cancer that had not spread), and as in Tuskegee, its subject-victims were both uninformed and had treatment withheld for the study's duration (Paul). Parallel to the Nazi studies during World War II were those conducted by Japan. They included experimental attacks with biological weapons on at least eleven Chinese cities, and studies conducted on subject-victims that included efforts to induce gas gangrene by exploding fragmentation bombs near the exposed limbs and buttocks of 3,000 prisoners of war who were housed at a detention center known as Unit 731 (McNeill; Williams and Wallace).

Much unethical research comes to light only many years after its conduct, as is true of unethical military research conducted by the United States during and immediately following World War II. At that time, over 60,000U.S. servicemen were involuntarily enrolled in studies involving exposure to chemical warfare agents (mustard gas and lewisite); at least 4,000 of them were exposed to high concentrations in field experiments and test chambers (Institute of Medicine).

Information about experiments on human radiation response supported by the U.S. government beginning in 1945 came to public attention in 1993. In one study, conducted from 1945 to 1947, eighteen patients considered to be terminally ill were injected with high doses of plutonium to determine how long it is retained in the human body. Military secrecy surrounding atomic energy precluded informed consent. Rather than telling subject-victims they would receive an injection of radioactive plutonium, the investigators told subjects they would receive a "product." Experiments on intellectually handicapped teenagers in a Massachusetts institution involved feeding the subjects very small amounts of radioactive iron and calcium to study the body's absorption of these materials. While the radiation exposure in these studies was low and unlikely to result in harm, the subject-victims were all incompetent, and their parents, who consented on their behalf, were simply asked by the institution to agree to "nutritional experiments." In reaction to news accounts of these and other studies, orders were issued in 1993 to declassify documents relating to unethical exposure of U.S. service personnel and citizens to radiation from atomic-weapons testing after World War II; in 1994 President Bill Clinton appointed a panel to guide a federal investigation into the radiation studies (Mann).

Several themes emerge from the known examples of unethical research. Such studies are likely to be done using disenfranchised or disadvantaged populations as subjects. In the absence of public outcry, unethical research may continue for many years, despite the fact that readers of the scientific literature in many cases have had access to all the facts they need to expose unethical practice (see Beecher). The larger and more egregious studies are especially likely to have been motivated by national security concerns and funded by the military.

Use of Data from Unethical Research

Very early sources reflect differing views on the permissibility of making medical or other use of information derived from unethical practices. The Babylonian Talmud (Shabbat 67b) states that the prohibition on Amorite practices (pagan sorcery) does not forbid actions done for the sake of healing, and it cites several cases of permitted incantations and sympathetic magic. Robert Burton quotes Paracelsus's De occulta philosophia to similar effect: "It matters not whether it be God or the Devil, Angels or unclean Spirits cure him, so that he be eased" (Burton, 1628, p. 7). By contrast, Thomas Aquinas prohibits "inquiring of demons concerning the future." Even if demons should know scientific truths, he writes, it is improper to "enter into fellowship" with them in this way (Aquinas).

A large variety of empirical and ethical arguments have been marshaled to oppose the use of data from unethical research. Empirical arguments, which depend upon the facts of particular cases, question the scientific reliability of such data. For example, Robert Berger, through a close analysis of the Nazi hypothermia data, claims that even by then-current scientific standards, the information is unreliable. He describes incomplete and contradictory data reporting, the absence of a controlling scientific protocol, and the control of the research program by scientifically untrained personnel (including Heinrich Himmler, Commander of the SS). In fact, the principal investigator, Sigmund Rascher, had a previous record of deception and was arrested in 1944 and charged with crimes that included scientific fraud. Some commentators argue that such data may be used, but only when the information is exceptionally reliable and useful. Most or all instances known of data gathered unethically, however, fail to meet this test (see Schafer).

Ethical arguments opposing use of the data are especially numerous. From a consequentialist point of view, unethical studies should be "punished" by "non-use," to discourage future investigators tempted to resort to unethical research practices. Other theories of punishment may be appealed to as well: As a matter of justice, it is argued that unethical investigators should not be rewarded by having the data from their studies used. By expunging the records of unethical research, the society of scientists expresses its solemn condemnation of the methods employed to acquire it; failing to do so would make science complicit with the research studies. Appropriate symbolism may call for the "burial" of this data, as it calls for the burial of the subject-victims from whom the data was derived (see Caplan; Martin; Post).

Rebuttals of these ethical arguments are equally numerous, relying upon the premise that data from unethical research studies may be valuable in principle: Any coincidence between "good science" and "good ethics," these writers argue, is only contingently true. As a practical matter, it is argued, the most serious instances of unethical research could not have been deterred by the punishment of non-use; some of the most heinous research studies were commissioned by governments, especially national security apparatuses. Punishment should be visited upon the investigators who engaged in unethical research; by withholding the use of data, current patients whose care might have been improved by use of that data are made to bear the brunt. Arguments from complicity are rejected because there is no causal connection between the prior acquisition of the data and its current use (the Nazis did not gather information about hypothermia in anticipation of its use by Canadian researchers a generation later); and because the current use of the data, far from being a continuation of the Nazi project, is for humanitarian purposes antithetical to the original Nazi intentions. In that way, the symbolism associated with the use of these data is seen to have a positive, redemptive value, while retaining the data's possible value to science and society (Freedman; Greene).

The debate about the use of data from unethical studies should distinguish the different ways scientific results can be used. Three different meanings for data use have been suggested: reference to data, for example, by scientific publication or citation, to serve as grounding for a scientific argument; reliance upon data in establishing or validating a practice, scientific or technological (including clinical); and using data as suggestive of further areas for inquiry (Freedman). This last meaning, while the most common in practice, has been the least debated; it is unlikely that data, once disclosed, could fail to be used in this way.

Much debate has centered on the first meaning, use of data through publication or citation. Kristine Moe found that the Nazi hypothermia studies had been referenced at least forty-five times in the medical literature (Moe). The New England Journal of Medicine, among other publications, has taken the position that it will not publish studies considered unethical by its editor; moreover, it will allow references to unethical research only in articles that focus on ethical condemnation of the research in question (Ingelfinger). Robert J. Levine has argued that a preferable stance would permit the publication of scientifically sound but ethically questionable research, while requiring the simultaneous publication of editorial discussion of the ethical issues raised (Levine).

Use of data in the second sense, as grounding scientific or ethical practices, was central to a 1988 controversy. While considering air pollution regulations on phosgene, a chemical used in plastics manufacture and a component of pesticides, the U. S. Environmental Protection Agency (EPA) withdrew an analysis that made reference to data derived from Nazi experiments after some EPA scientists circulated a protest letter (Sun). Phosgene was a component of some chemical weapons, and the Nazis had studied the response of French prisoners to various levels of phosgene exposure. EPA officials, while recognizing scientific and technical flaws in the data's collection and reporting, held the data to be useful additions to the existing animal toxicology information. Nazi data is often said not to be generalizable to a normal population because it was derived from prisoners under horrible conditions of privation. However, even this aspect of the data was applicable because the EPA's recommendations were designed to minimize risk to those most physiologically vulnerable. Those opposed to use of the data presented arguments based on both fact and value. The data were said to be valueless because of their omission of consideration of vital variables like sex and weight of subject-victims. In addition, some agency scientists felt that data derived from this source, however valuable, should never be used.

In the majority of cases, the scientific value and impact of unethical research has been modest. Ethically, however, the Nazi, Tuskegee, and other studies have loomed large in raising both public awareness and ethical standards for the conduct of research. Unethical research has found its main use in ethics.

benjamin freedman (1995)

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Encyclopedia of Bioethics