Although the ethics of clinical investigation are currently based upon voluntary and informed consent of the subject, it was not until the mid-Twentieth Century that federal legislation provided ethical safeguards in biomedical research involving human subjects. Largely as a response to “reported abuses of human subjects in biomedical experiments, especially during the Second World War” and the Tuskegee experiments, the United States began to define basic ethical principles in medical research in the late 1970s (“The Belmont Report”). Until guidelines were provided by the American Medical Association and laws were enacted that created such entities as Institutional Review Boards, human research went largely unregulated in the United States leading to the exploitation of the infirmed, incarcerated, and ignorant.
The international cornerstone for research ethics came on the eve World War II: the Nuremberg Code. The first paragraph of the Code reads:
The voluntary consent of the human subject is absolutely essential. This means that the person involved should have legal capacity to give consent; should be so situated as to be able to exercise free power of choice, without the intervention of any element of force, fraud, deceit, duress, over-reaching, or other ulterior form of constraint or coercion; and should have sufficient knowledge and comprehension of the elements of the subject matter involved as to enable him to make an understanding and enlightened decision. This latter element requires that before the acceptance of an affirmative decision by the experimental subject there should be made known to him the nature, duration, and purpose of the experiment; the method and means by which it is to be conducted; all inconveniences and hazards reasonable to be expected; and the effects upon his health or person which may possibly come from his participation in the experiment.
Although the experiments of Mengele and Ishii receive great historical attention, the United States cannot claim ethical purity before or after the advent of the Nuremberg Code.
Concerns regarding human experimentation arose in the late nineteenth century, with the roots of the movement planted firmly in animal antivivisection soil. Humane organizations began to include child welfare in their aims in the 1870s, likening the innocence and helplessness of children to that of animals (Lederer 29). Although argued from fallacy, antivivisectionist warnings that animal experimentation would inevitably lead to human experimentation were, ultimately, not without credence. Multiple cases of human experimentation in the 1890s, both in the United States and abroad, fueled apprehension. Foremost was the case of an Italian bacteriologist, Giuseppe Sanarelli who, in 1897, claimed to have isolated the causative agent of yellow fever. During his research, Sanarelli inoculated five of his patients with the inactivated agent, claiming to have produced symptoms of yellow fever (Lederer 49). In another instance, Swedish researcher Carl Janson selected fourteen orphans as test subjects over calves, owning to affordability, in his experiments on smallpox (Lederer 51). In the United States, George Fitch’s syphilis experiments on young leper girls, Henry Berkley’s use of mental patients in thyroid extract trials, and Arthur Wentworth establishing the safety of spinal taps on children did nothing to allay concerns (Lederer 61).
By 1900 the first stirrings of regulation on human experimentation had reached the federal level. Closely linked to the issue of animal experimentation, the aforementioned cases of human experimentation appeared as Senate Document 78 which was entered into the minutes during a Senate hearing on a proposed animal cruelty bill (Lederer 62). Senator Gallinger of Ohio, the originator of Senate Document 78, later introduced Senate Bill 3424 — the first proposal on a federal level to regulate human experimentation (Lederer 71). As a precursor to future legislation, Senate Bill 3424 aimed to protect those incapable of informed consent and proposed procedural oversight (United States Cong.).
Although the American Medical Association’s Council on the Defense of Medical Research circulated a set of codes pertaining to animal research that were, in some form, adopted by fifty-nine of out of seventy-nine medical schools contacted in 1910, the American Medical Association (AMA) could reach no consensus regarding human subjects (Lederer 73). According to Susan Lederer, “Clinical investigators would continue to work without any formal guidelines until the 1940s, when the AMA amended the code to require voluntary consent of the subject and prior animal testing” (74).
At the heart of the ethical issues surrounding human experimentation lies informed, voluntary consent. By current standards, a subject must comprehend both the potential risks and potential benefits of participating in a study as well as feel no coercion to participate. While the nature of comprehension is still very much debated, the AMA’s Code of Ethics demands that:
Voluntary written consent must be obtained from the patient, or from the patient’s legally authorized representative if the patient lacks the capacity to consent, following: (i) disclosure that the physician intends to use an investigational drug or experimental procedure, (ii) a reasonable explanation of the nature of the drug or procedure to be used, risks to be expected, and possible therapeutic benefits, (iii) an offer to answer any inquiries concerning the drug or procedure, and (iv) a disclosure of alternative drugs or procedures that may be available. Physicians should be completely objective in discussing the details of the drug or procedure to be employed, the pain and discomfort that may be anticipated, known risks and possible hazards, the quality of life to be expected, and particularly the alternatives. Especially, physicians should not use persuasion to obtain consent which otherwise might not be forthcoming, nor should expectations be encouraged beyond those which the circumstances reasonably and realistically justify. (“Opinion 2.07 – Clinical Investigation”)
Of particular concern are those who, until National Research Act was signed into law in 1974, were exploited by researchers. These individuals, including the mentally defective, prisoners, and otherwise ignorant, were historically either not informed of or were incapable of ascertaining the risks posed, or were in positions where cooperation was, implicitly or otherwise, mandated. Breach of voluntary and informed consent can present in different ways: a violation of volunteerism by coercion or bribes, a violation of comprehension in instances where a subject is incapable of understanding the risks or their role, and the use of subjects without their knowledge. Each of these three flavors of violation occurred in the United States before the egregious human rights contraventions during the Second World War in Germany and Japan. More disturbing were the violations that occurred after the advent of the Nuremberg Code.
The volunteerism of prisoners in biomedical research is a contentious issue. Liberty is, by definition, curbed by incarceration. In 1915, the cause of pellagra was a matter of debate for researchers, and a serious problem in the state of Mississippi. It was suspected that the disease, which could lead to dementia and death, was caused by a nutritional deficiency rather than a bacterial infection. “U.S. Public Health Service investigator Joseph Goldberger,” Lederer writes, “approached Governer Earl Brewer of Mississippi for permission to conduct an experiment that would induce pellagra in male prisoners. . . Placing male prisoners on a pellagra diet for six months would provide a convincing demonstration of this theory” (110). Due to an incredibly generous offer of a full pardon many men volunteered; twelve prisoners “convicted of crimes ranging from bigamy [to] murder” participated and were released (Lederer 111). Although the incredible leniency toward felons is ethically questionable, the offer of a full pardon in exchange for a six month nutritional study constitutes bribery. Today, research using prisoners as subjects is limited to studies that deal directly with crime and imprisonment: the impact of incarceration, the possible causes of criminal behavior, drug and alcohol addiction, the effect of class, vaccines of prevalent diseases in the prison population, and studies that stand to improve the health of the subject (Macrina 104).
One of the more infamous cases of unethical research is the Willowbrook Scandal. New York Mental Hospitals in the early 1960s were dealing with overpopulation and a huge influx of patients. Struggling to make an arrangement for their mentally retarded children, parents eagerly accepted their children’s admittance to Willowbrook State School in exchange for the children’s participation in a hepatitis study. The consent forms parents signed indicated that their children would receive a hepatitis vaccine; instead, the study was on the natural progression of the disease, and previously healthy children were intentionally infected between 1963 and 1966 at the school (Goliszek 250). Arguing that the children would have contracted the disease within six months anyway — speaking volumes about the sanitary conditions of the hospital — researchers claimed a controlled study of the disease would be more beneficial to scientific progress. They proceeded, at first, to administer purified fecal samples from infected patients to the children orally; after further refinement of the process, intravenous injections took the place of ingestion (Goliszek 251). Current participation of children or the mentally ill, along with all other federally funded medical research on humans, is approved and overseen by an Institutional Review Board which has access to the research protocol and consent forms. In cases where and individual is incapable of granting their consent, a guardian or legal representative gives consent, and the consent must be documented and signed by a witness not of the investigational team, ideally a personal acquaintance the subject (Macrina 100).
The case drawing the most attention in the United States would be that of the Tuskegee syphilis study that took place from 1932 and continued for on for 42 years. Ironically, the university founded by Booker T. Washington became the scene for a long term study of the effects of untreated syphilis in black men. The men were, in fact, unaware that they were infected, were told that they were participating in a study on “bad blood,” and were offered neither heavy metal treatment for symptoms nor penicillin when it became widely available in the 1940s (Pence 279). After criticizing the experiment for six years, and concerned by the Center for Disease Control’s refusal to stop it, a doctor leaked the story to the press in 1972, leading to a congressional investigation and a civil suit that was settled out of court (Pence 283). The subjects of the study, their wives, and their children received restitution and free medical treatment (Pence 285). The case brings up numerous ethical issues concerning race, socio-economic status, education, and deception of patients. As a result of the Tuskegee experiments, the federal government began requiring all institutions receiving federal funds and conducting human research to have an Institutional Review Board (IRB) (Pence 295). Today, IRBs stand as the first line of defense for the subjects of research.
Aside from research conducted for the betterment of public health, United States weapons development opens a veritable Pandora’s Box of ethical issues. From the pardoning of Shiro Ishii, head of Japanese Unit 731 during World War II, in exchange for bacteriological warfare data obtained from unwilling participants under sadistic conditions (Goliszek 54) to the various radiation experiments performed on humans (Goliszek ch. 4), weapons research on humans in the States is an expansive subject that would set a conspiracy theorist alight.
With the advent of germ theory came a wave of research leading to vaccines and antibiotics. Undoubtedly, the sacrifices of the subjects, whether ethical or otherwise, have benefited both the public and modern science. Though today’s biomedical research subjects are protected by the guidelines of physician’s associations, federal legislation, and oversight committees, the history of medical research in the United States is steeped in exploitation. Regulation may guide scientists, but the choice of right versus wrong is ultimately an autonomous practice. When Stanley Milgram went about studying the role of authority in ethical decision making to better understand the events in Nazi concentration camps he discovered that otherwise average people would do harm to strangers if instructed to do so by an authority figure. The extent of evil experienced in the camps was not limited to Nazi potential, but human potential. “Each individual possesses a conscience which to a greater or lesser degree serves to restrain the unimpeded flow of impulses destructive to others. But when he merges his person into an organizational structure, a new creature replaces autonomous man, unhindered by the limitations of individual morality, freed of humane inhibition, mindful only of the sanctions of authority.” (Milgram)
Works Cited
“The Belmont Report: Ethical Principles and Guidelines for the protection of human subjects of research.” The National Institute of Health Office of Human Subjects Research. The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, 18 April 1979.Web. 9 November 2009.
“Code of Medical Ethics: Opinion 2.07 – Clinical Investigation.” American Medical Association. Report: Issued prior to April 1977; Updated June 1994 and June 1998. American Medical Association, 1998.Web. 9 November 2009.
Goliszek, Andrew. In the Name of Science. New York: St. Martin’s Press, 2003. Print.
Lederer, Susan E. Subjected to Science: Human Experimentation in America Before the Second World War. Baltimore: The Johns Hopkins University Press, 1995. Print.
Macrina, Francis L. Scientific Integrity. Washington, DC: ASM Press, 2005. Print.
“Memorable Quotes.” StanleyMilgram.com. Stanley Milgram, 1974. Web. 18 November 2009.
“The Nuremberg Code: Directives for Human Experimentation.” The National Institute of Health Office of Human Subjects Research. Reprinted from Trials of War Criminals before the Nuremberg Military Tribunals under Control Council Law No. 10, Vol. 2, pp. 181-182. Washington, D.C.: U.S. Government Printing Office, 1949.Web. 18 November 2009.
Pence, Gregory E. Classic Cases in Medical Ethics. New York: McGraw Hill, 2004. Print.
United States. Cong. Senate. A Bill for the Regulation of Scientific Experiments upon Human Beings in the District of Columbia. 56th Cong., 1st sess. S 3424. Washington: GPO, 1900.
There’s nothing quite so tiring as moving. Physically as well as emotionally. Over the past two days, what was MY space, is returning to a room in a house that is not my home.