AUTOEXPERIMENTATION

Autoexperimentation, which refers to the practice of intentionally utilizing oneself as an experimental subject, is not a rare event. Over the past four centuries, more than 135 examples have been documented, and the true incidence is undoubtedly much higher (Altman; Franklin and Sutherland). Although the preponderance of recorded autoexperimentation has been conducted in the name of biomedical research, investigators in the physical and social sciences have also engaged in this practice.

Autoexperimentation has long enjoyed a measure of romantic appeal in the scientific and popular tradition. "The experimenter, " wrote Sir George Pickering, "has one golden rule to guide him as to whether the experiment is justifiable. Is he prepared to submit himself to the procedure? If he is, and if the experiment is actually carried out on himself, then it is probably justifiable. If he is not, then the experiment should not be done" (p. 229). Henry K. Beecher suggested that any scientist wishing to engage in human experimentation ought to experiment on himself "as evidence of good faith."

Despite a reputation for nobility of purpose, the practice of autoexperimentation has been the focus of substantial scientific and ethical debate. The scientific controversy concerns the methodological limitations of autoexperimentation and its capacity to yield useful data. The ethical debate is more complicated. Superficially, it concerns the extent to which autoexperimentation ought to be regulated. At its heart, however, lies a fundamental conflict between two opposing views of scientific research. The libertarian view advocates a relatively laissez-faire policy toward all forms of scientific inquiry, including autoexperimentation. The paternalistic view, in contrast, emphasizes the importance of protecting experimental subjects from risk, whether self- imposed or imposed by others. While this entry presents various perspectives on the issue, the author is opposed to autoexperimentation in most cases and will make clear why this view is plausible as the entry unfolds.

Neither the methodological nor the ethical aspects of this debate can be fully understood without examining the historical and cultural context in which autoexperimentation developed.

Historical Perspectives

One important factor in the history of autoexperimentation, upon which many investigators have remarked, is the existence of an extremely powerful and deeply rooted obligation to pursue scientific knowledge regardless of personal risk. A good example is John Hunter's unfortunate experiment with venereal disease. Throughout the eighteenth century, physicians debated whether gonorrhea and syphilis were two separate entities or different manifestations of the same disease. Hunter, a prominent surgeon, anatomist, and fellow of the Royal Society, believed they were the same. In 1770, to prove the point, he inoculated his own penis with the fresh urethral discharge of a man with gonorrhea. When syphilitic chancres developed at the site of inoculation, Hunter erroneously concluded that his theory was correct. Even though he thought he had contracted gonorrhea, Hunter eventually died of syphilis (Franklin and Sutherland). It is clear, in retrospect, that the discharge most probably transmitted both diseases.

Closely related is the idea that the true scientist must always be prepared to engage in resolute acts of personal daring (including, though not necessarily limited to, auto-experimentation) to overcome impediments to research. There are two famous cases in point. In 1929, despite the direct prohibition of his department chief, Werner Forssmann surreptitiously passed an intravenous catheter into his own heart to prove the feasibility of cardiac catheterization in humans. He later shared the Nobel Prize for these experiments (Altman). The second case pertains to the thymidine experiments of Beppino Giovanella during the late 1970s. Thymidine had been shown to be a promising cancer drug in animals, but the U.S. Food and Drug administration (FDA) refused to authorize clinical trials on the grounds that its safety had not been established. Giovanella proceeded to ingest huge doses of thymidine, thereby proving its safety and overcoming the objections of the FDA (Franklin and Sutherland).

A third factor has to do with the problem of justifying human research before the safety of an experiment has been established. Experimenting on oneself or one's colleagues signals the conviction that the experiment is at least worthwhile, if not necessarily safe (see Beecher; Pickering; Bok). In 1997, the International Association of Physicians in AIDS Care (IAPAC) announced that many of its members had agreed to be subjects in trials of a live attenuated HIV-1 vaccine. Some AIDS researchers said the vaccine was too dangerous to be tested in people, but the head of the IAPAC initiative argued that 8, 500 new HIV infections every day made further delay in testing vaccines unethical (McCarthy). As of March 1998, more than 270 physicians, healthcare professionals, and healthcare advocates had volunteered for the trials, which had not yet commenced in early 2003 (IAPAC).

A fourth factor derives from the observation that auto-experimentation is usually the best, and sometimes the only, way to ensure absolute adherence to an exacting research protocol. In 1962, for example, Victor Herbert undertook an investigation to explore a possible link between nutritional folic acid deficiency and megaloblastic anemia. To deplete the body of folic acid reserves, he subsisted for eighteen weeks upon an extraordinarily insipid and unpalatable diet (Altman). Herbert commented that the experiment would probably have failed had he not experimented upon himself.

Finally, autoexperimentation has often been fostered when it appeared that certain researchers, by virtue of special training and experience, might extract significantly more from an experiment by participating than by observing. Data obtained uniquely through autoexperimentation proved critical, for example, in the development of protective clothing for ultrahigh-altitude airplane ejection, in studies of extreme acceleration and deceleration, in investigations of decompression sickness, and in studies of human physiology in space (Gibson and Harrison; Dille; Franklin and Sutherland).

Criticisms of Autoexperimentation

Critics of autoexperimentation object to the practice on both methodological and ethical grounds.

METHODOLOGICAL ISSUES. The worth of an experiment depends upon its scientific merit, upon its permissibility from ethical and legal perspectives, and upon its advisability on other grounds. Before any experiment is carried out, each of these elements must be assessed. Autoexperimentation suffers from three major methodological problems. First, there is an inherent difficulty in observing oneself dispassionately. This difficulty often leads to the confusion of objective and subjective data. Second, it is virtually impossible to establish adequate controls, particularly because autoexperiments tend to involve serial observations of one individual. Third, it is very difficult to extract statistically valid information because of the typically very small numbers of subjects and experiments. As a general rule, the likelihood that useful data will result from experiments on very small groups is determined by the likelihood that the data would not be materially affected by iterations (repetitions of the experiment) on larger groups.

Because of these weaknesses, autoexperimentation rarely proves to be a wholly satisfactory experimental method. There may be two important exceptions, however: pilot studies to establish the feasibility of a procedure or the safety of a pharmacological agent in normal subjects; and studies in which the scientist consents to be treated as an ordinary research subject and to remain under the supervision of other investigators for the duration of the experiment. It is worth noting that the second exception complies with the provisions of the Declaration of Helsinki stipulating that "the responsibility for the human subject must always rest with a medically qualified person and never rest on the subject of the research" (World Medical Association, p. 3).

ETHICAL ISSUES. Autoexperimentation is clearly often heroic, but the basis for the alleged obligation to engage in this practice is less clear, for it is not clear that there are good moral reasons to encourage—let alone require—autoexperimentation. As discussed above, autoexperimentation is not always good science, for it may lack adequate controls and sufficient subjects to generate meaningful results. Therefore, autoexperimentation makes sense more as a potential condition to involving noninvestigator subjects in further testing than as a substitute for using such subjects. However, autoexperimentation may not be sufficient to establish that lay persons may appropriately participate in an experiment, for the investigator may be more risk-accepting than other subjects, or may not be medically representative of all potential subjects, or may not meet the physiological qualifications for subjects in that experiment. It is also unclear that autoexperimentation is necessary to establish that noninvestigators should participate in an experiment, for the processes of institutional ethics review and informed consent are probably better ways to determine whether that is appropriate. Of course, these points may not apply when the risks are exceptionally high and the need for the research exceptionally urgent.

To the extent there is an obligation for researchers to engage in autoexperimentation, that obligation does not always outweigh the problems with autoexperimentation. The fundamental issue is whether any of the precautions required to protect the subject in other forms of human experimentation may be legitimately suspended in the case of voluntary autoexperimentation.

The three basic arguments that have been brought to bear on this question are not easily reconciled: (1) Individuals are entitled to assume voluntarily risks they may never impose on others; (2) under proper circumstances, both self-sacrifice (martyrdom) or assumption of high risk for good reason (heroism) are universally lauded; and (3) societies have a vested interest in protecting the welfare of their members, and some degree of regulation in recognition of this interest is required or, at the very least, ought to be permissible.

Libertarians argue that the principle of autonomy grants scientists the right to engage voluntarily in risky behavior. On this basis, they refute the applicability of regulations for the protection of human subjects in autoexperimentation. Champions of a more paternalistic approach, in contrast, oppose unlimited risk taking in any experimental context because of the following concerns:

1. Many risks have been undertaken for unimportant goals;
2. Habitual risk takers might turn to autoexperimentation even when other, more desirable forms of investigation exist;
3. Investigator–subjects may be at greater risk than other potential subjects because curiosity, enthusiasm, and other intangible factors may induce them to ignore risks that would otherwise deter a prudent individual from participation (Bok);
4. Certain levels of risk are, or ought to be, beyond consent (Bok);
5. Investigators reckless with respect to their own safety are wont to become reckless in other aspects of their investigations;
6. The autonomy of investigator–subjects might be tainted by various levels of institutional or peer coercion, or even by self-imposed psychological pressures (Dagi and Dagi); and
7. Large-scale, unregulated autoexperimentation might subvert accepted guidelines for the protection of human subjects under other experimental conditions.

The apparent contradiction between concerns (3) and (4), on the one hand, and the respect and admiration traditionally accorded to martyrs and heroes in Western society on the other, is not easily reconciled.

Finally, because most scientific research is now done in teams, the simple model from earlier days of a lone researcher experimenting upon himself does not fit all current autoexperimentation. "Group autoexperimentation" can involve vulnerable subjects when junior investigators, students, or laboratory technicians participate as subjects. Some recent research ethics policies addressing autoexperimentation reflect concern for such investigator–subjects.

Policies and Regulations

While it is generally agreed that institutions are ultimately responsible for the regulation of all forms of experimentation carried out within their jurisdiction, there is no consensus regarding how—or even whether—autoexperimentation should be regulated. The Nuremberg Code tacitly encourages autoexperimentation through the provisions of Article 5: Perilous human experimentation is prohibited "except, perhaps, in those experiments where the experimental physicians also serve as subjects" (Germany [Territory Under Allied Occupation]). The World Medical Association's Declaration of Helsinki does not address autoexperimentation directly, but does say that responsibility for the subject always rests with a "medically qualified person, " never on the subject (p. 15–16), and that, when the subject is in a dependent relationship with the researcher, informed consent should be obtained by a physician who is not engaged in the investigation and is "completely independent" of the relationship (p. 16). The U.S. National Institutes of Health promulgated a code for self-experimentation "to provide the same safeguards for physician–subjects as for the normal volunteer" (Altman). The Office for Protection of Research Risks of the U.S. Department of Health and Human Services has ruled that autoexperimentation is subject to the same regulations as other human research, including review by institutional review boards (IRB).

Some institutional ethics codes and policies now advise against or even prohibit autoexperimentation, even when it takes the form of "group" autoexperimentation, and involves residents, students, or employees. The IRB Guidebook issued by the Office for Human Research Protections of the U.S. Department of Health and Human Services suggests advertising for subjects, rather than recruiting students directly, and notes that some universities prohibit or severely restrict student participation. The research ethics policy of Massachusetts General Hospital is more stern: "Studies of volunteers in the investigator's own department or who are the investigator's students should be avoided and will usually be disapproved by the Human Research Committee because of the subtle coercive factors that could be present in even the most harmonious situations." The University of Maryland Baltimore County requires IRB approval to enroll students and employees.

Conclusion

No act of autoexperimentation, no matter how worthy or well intentioned, should be sanctioned until three conditions are fulfilled: (1) The proposed experiment has been fully described; (2) potential sources of coercion influencing the experimenter have been investigated and excluded; and(3) the institutional and social consequences of the experiment have been thoroughly explored, particularly with respect to risks such as the appearance of condoning inconsistent standards for the protection of human subjects. In most cases, fulfillment of these conditions will result in autoexperimentation being held to the same standard of review as any other forms of human investigation. These conditions are expressly designed to protect both the experimenter–subject and the institution, in equal measure.

The decision-making process associated with auto-experimentation should, therefore, involve peer review, and it should accord with established criteria for determining the acceptability of experimental protocols. At the very least, judgments about the permissibility of autoexperimentation must weigh questions of risk, benefit, voluntariness, and scientific significance, as well as the more elusive issues comprehended by the term institutional interests. While the requirement for institutional review may induce some scientists to experiment on themselves outside the scientific mainstream, this effect is unlikely to prevail and, as a practical matter, is virtually impossible to repress.

teodoro forcht dagi (1995)

revised by john k. davis

SEE ALSO: Autonomy; Harm; Paternalism; Research, Human: Historical Aspects; Research, Unethical

BIBLIOGRAPHY

Altman, Lawrence K. 1987. Who Goes First? The Story of Self-Experimentation in Medicine. New York: Random House.

Beecher, Henry K. 1959. "The Experimentation in Man." Journal of the American Medical Association 169(5): 461–478.

Bok, Sissela. 1978. "Freedom and Risk." Daedalus 107(2): 115–127.

Dagi, T. Forcht, and Dagi, Linda Rabinowitz. 1988. "Physicians Experimenting on Themselves: Some Ethical and Philosophical Considerations." In The Use of Human Beings in Research with Special Reference to Clinical Trials, ed. Stuart F. Spicker, Ilai Alon, André de Vries, and H. Tristram Engelhardt, Jr. Dordrecht, Netherlands: Kluwer.

Dille, J. Robert. 1984. "Introduction to the First of Two Aerial Voyages of Dr. Jeffires and Mons. Blanchard." Aviation, Space, and Environmental Medicine 55(11): 993–999.

Forssmann, Werner. 1964. "The Role of Heart Catheterization and Angiocardiography in the Development of Modern Medicine." In Physiology or Medicine, 1942–1962, vol. 3 of Nobel Lectures. Amsterdam: Elsevier.

Franklin, Jon, and Sutherland, John. 1984. Guinea Pig Doctors: The Drama of Medical Research Through Self-Experimentation. New York: Morrow.

Germany (Territory under Allied Occupation, 1945–1955: U.S. Zone) Military Tribunals. 1947. "Permissible Medical Experiments." In "The Nuremberg Code, " excerpted from vol. 2 of Trials of War Criminals before the Nuremberg Tribunals under Control Council Law No. 10. Washington, D.C.: U.S. Government Printing Office. Reprinted in Sugarman, Jeremy, Mastroianni, Anna C., and Kahn, Jeffrey P., eds. 1998. Ethics of Research with Human Subjects: Selected Policies and Resources. Frederick, MD: University Publishing Group.

Gibson, T. Mike, and Harrison, Mike H. 1984. Into Thin Air: A History of Aviation Medicine in the RAF. London: Robert Hale.

Herbert, Victor. 1962. "Experimental Nutritional Folate Deficiency in Man." Transactions of the Association of American Physicians 75: 307–320.

McCarthy, Michael. 1997. "AIDS Doctors Push for Live-Virus Vaccine Trials." The Lancet 350(9084): 1082.

Pickering, George W. 1949. "The Place of Experimental Method in Medicine." Proceedings of the Royal Society of Medicine 42(1): 229–234.

World Medical Association. 1998. "Declaration of Helsinki." In Ethics of Research with Human Subjects: Selected Policies and Resources, eds. Jeremy Sugarman, Anna C. Mastroianni, and Jeffrey P. Kahn. Frederick, MD: University Publishing Group.

INTERNET RESOURCES

Institutional Review Board, University of Maryland Baltimore County. 2003. "Enrollment of Participants and Use of Data." Available from <http://www.umbc.edu/irb/Enrollme.html>.

International Association of Physicians in AIDS Care (IAPAC). "IAPAC's HIV Vaccine Initiative." Available from <http://www.iapac.org>.

Massachusetts General Hospital. 2003. "Selection of Human Subjects." In "Responsible Conduct of Human Studies, " internal publication. Available from <http://healthcare.partners.org/phsirb>.

Office for Human Research Protections. 2003. IRB Guidebook. Available from <http://ohrp.osophs.dhhs.gov>.