While human experimentation is now regulated by the oversight of university and professional ethics boards and recognized as fraught with ethical risks, this is a relatively recent shift in the history of medicine and biomedical research. Eugenics arose and was sustained prior to our contemporary views of human experimentation, and thus sheds light on a period of time that saw the use and misuse of populations that were deemed socially unfit or undesirable. First, an overview of some experimental approaches with human subjects in clinical research from the late 19th to the mid 20th century shall be provided, drawing on preceding scholarship by American historian of science, Susan Reverby (2000). Second, an overview of the special development of research and therapies for persons with ‘feeble-mindedness’ and ‘mentally ill patients’ is provided, which gave rise to distinct social and ethical problems at the beginning of the 20th century (Pressman, 1998). Those changes influenced the ways in which scientists, physicians, and public health administrators informed patients on the prognosis of their disease, the depth of the applied treatments, along with the nature of the proposed experimental and clinical treatment options, which did often not step out of implicit or explicit eugenics contexts.

Anatomical and pathological approaches to human bodies
By the end of the 18th-century as a biological basis for medicine became widely accepted, the concept of function rose to prominence within physiology and biomedical research. When physiologists attempted to study the physiological functions, then they had to start experimentally where such functions resided: this being the physiology of the living body and observations from pathological dissections of human cadavers (Stahnisch, 2012). Their research subjects were often taken from the poorer classes of society; they were orphans from children’s hospitals and orphanages, as well as mentally ill patients and––quite importantly for the Canadian and American eugenics context––aboriginal peoples. This means that either such deprived individuals had to pay with their bodies, meaning that they were used in human experimentation, in order to receive medical care at all, or they were deliberately subjected to experimental testing without their knowledge and consent. Later analogous cases of coercive human subject experimentation with captive patient populations were for example the Yellow Fever experiments in the southern United States and in Mexico (on soldiers and incarcerated prisoner groups), or the Venereal Disease experiments pursued by Albert Neisser (1855–1916) in Germany (with a group of prostitutes, who had reduced legal rights as patients) (Lederer, 1995). Already during the 18th-century and the time of the French Revolution, anatomists and physiologists, such as Xavier Bichat (1771–1802), had had no qualms about replicating their experimental observations on test animals also in “fresh” human bodies, which they received for example in the form of prisoners sentenced to death; or they attended execution procedures to work on the poor individuals’ organs and try the latest “blessings” of Galvanic electropunctures and other devices.

Clinical human subject research from the 19th to the 20th centuries
During the latter parts of the 19th century and the beginning decades of the 20th century, two major discourses dominated the field of human experimentation, namely those of “anatomical localism” and “constitutional physiology” (Stahnisch, 2012): pathological localists held that all human diseases had a distinct substrate in the morphological organs of the living body––such as in tuberculosis, cancer, or liver cirrhosis. The physiological constitutionalists were convinced that the conditions and causes of diseases had to follow the vital properties of the organism and its parts, while they were often ready with the view that particularly individuals from the lower classes had an innately fragile body constitution and suffered from degeneracy and inherited weakness––also with regard to their social environments, in often-deprived urban dwellings and the reproduction of bad bodily traits (i.e. bad eugenic stock). This was for example advocated for by American neurologist Silas Weir Mitchell (1829–1914) in his book “Rest in the Treatment of Nervous Disease” (1875).

At the beginning of the following century––quite prominently in the case of Imperial Germany––medical investigators came ever closer to conduct military-related research and unethical human experimentation (from today’s perspective). This emanates particularly from recent 20th-century scholarship, such as on the director of the Kaiser Wilhelm Institute for Physical Chemistry Fritz Haber (1868–1934) and his support for chemical warfare in WWI. Historians have looked at scientists’ participation in the construction of race and ethnicity during the interwar period or the analysis of how Nazi racial policies had influenced medical doctors in the widening of the moral boundaries of clinical human experimentation. These assumptions were often based on larger-scale international exchanges in science and medicine, in which the marginalization of patients as well as those of particular racial and social groups was taken for granted (often in the context of widespread colonialism). It should be pointed out that the often underlying assumption of racial hygiene and biological anthropology––along with the emerging field of medical genetics––had been highly international in their scope. This is signified in the tight exchanges of researchers, students, materials, and literature between Britain, Germany, Scandinavia, the US, and other countries, as exemplified in the prominent Canadian eugenics cases of the Torontonian psychiatrist Clarence B. Farrar (1874–1970), who had worked before with Emil Kraepelin (1856–1926) at the University of Heidelberg, and Edmonton psychologist John M. MacEachran (1877–1971), who had trained with Wilhelm Wundt (1832–1920), a prominent founding figure of experimental psychology at the University of Leipzig.

Human experimentation under Nazism and Fascism
Biomedical science under Nazism and Fascism in Europe was largely pursued in conjunction with distinct research fields that encompassed racism and eugenic medical philosophies. What can be interpreted as a natural step for a clinician of the time, wanting to test his animal experiments in humans to consolidate scientific hypotheses, was often an attempt “to jump the experimental queue.” This murderous shift of biomedical research rendered many experiments unethical, even when these are compared to the pre–1930s ethical standards in the German medical community (laws that had been the first explicit medical misconduct regulations worldwide). While actively seeking party officials’ support to continue their experiments in human subjects, for example neurologist George Schaltenbrand (1897–1979) did not wait to address the Action T4—the infamous Nazi euthanasia program—but emphasized in despising ways that the “idiots” and “demented patients” of psychiatric asylums were well suited for his experiments. For him, they just represented “life not worth living,” as Karl Binding (1841–1920) and Alfred Hoche (1865–1943) had previously stated in their medico-legal eugenics text “Allowing the Destruction of Life Unworthy of Life” (1920).

It is telling that Schaltenbrand at the University of Wuerzburg refrained from pursuing the planned experiments on his own neurological patients, apparently conceptualizing the high–risk character of such research. What was particularly at stake, was the contemporary moral relapse to pre–1900 standards within the overarching medical framework of racial hygiene (Rassenhygiene) (Proctor, 1988). At the place of the personal value of the individual, the biologistic view of racial fitness now came to reign exclusively over scientific conduct. Schaltenbrand’s laboratory had previously emerged outside of the Nazi–dominated health care system. However, it tried to build connections with high–profile institutions beyond the confines of the medical schools, such as the big science-network of the German Research Council along with alliances with the Reichs Ministry of Health. This close alliance between science and politics became quite typical for research minded scientists in Fascist Europe during the 1930s and 1940s. Even the atrocious war crimes (e.g. military–related research in pharmacology, aviation physiology, and chemical warfare) and human experimentation in mental asylums, penitentiaries, and the concentration camps (e.g. malnutrition, stress testing, and siblings research) need to be contextualized within the framework of deadly Nazi medical philosophy. In this transformed social and political order, physicians and academics acted as intellectual planners, administrative protagonists, and beneficiaries from support and awards in the Nazi- and Fascist-dominated societies (Weindling, 1989). The social and biological forms of eugenics, which rose to central awareness of physicians, biologists, and sociologists in the 1900s, played thus an important role in the development of clinical human research, while many protagonists of the eugenics movement had previously been active in social medicine and psychiatry during the interwar period.

A modern outlook on human subject experimentation
The atrocities of the crimes committed by Nazi scientists led to the social and juridical realization of “informed consent” during the time of the Nuremberg Doctors’ Trials in 1947, as well as the Declaration of Geneva in 1948. These events drew the public attention to the fact that patients were selected for their specific use in biomedical research programs. Often, explicit preference was given to severe cases in which no ethical consent could be obtained nor opposition expected, while the research results became interpreted and presented in an overly positive light. This can also be seen in the prominent case of human experimentation that went on in the Provincial Training School in Alberta, during the immediate postwar period (Muir, 2014). The working group around the medical superintendent Dr. Leonard Jan Le Vann (1915–1987) conducted research with psychotic patients, who were administered with ‘trifluoperazine dihydrochloride’ and ‘chlordiazepoxide.’ No specific consent of these patients or of their families was obtained, at a time when the pharmacological and physiological properties of these drugs were still largely unknown.

Quite generally, it is important to note that coercive human subject experimentation further continued in Canada and the United States after WWII. A central historical development—which was hardly an exception from many other drastic examples—was the research program of the American Tuskegee Syphilis Study. It continued from 1930 to 1972, despite surfacing knowledge about the scope of the Nazi medical war crimes and the application of the guidelines of the World Health Organization (WHO) being in place since the late 1940s. Hundreds of black syphilis patients had been refused effective drug treatments, in order to gain “objective knowledge” about the natural history of infectious disease (Guerrini, 2003). Likewise critical were other forms of medical research with new technological advances in psychiatry coming into being, including surface and deep brain stimulation, new psycho- and neuropharmacological substances, and electroshock therapies. Since the early days of hospitalizing the mentally ill in psychiatry and mental health along with the shock therapies and electrostimulation programs of the 1900s to the 1930s, the gap between the physicians’ healing intentions and the harm produced in patients was enormous (Stahnisch, 2014). This general development became exacerbated largely through the research advances of the biomedical field since the 1940s and 1950s. The technological properties of the new therapeutic options make it clear that the manipulative operations on human subjects need to be regarded as two sides of the same biomedical coin: therapeutic technologies versus experimental investigations with hospital patients.

By placing these developments in a comparative perspective, the often-differing positions on patients’ consent, their relation to public perception (Roelcke, 2004), and the preparation of research funding are all major factors in modern biomedical research. In mapping out the social conditions of clinical and technological advances, some significant connections, important co-developments and ethical problems become visible. They point to the meandering course that reshaped the boundaries between biomedical research interests, clinical, and therapeutic work. The historical examples presented here can make us aware of the continuingly problematic opposition between medical progress and patient ethics (Lederer, 1995), along with the blurred conceptual boundary between research and guiding social ideas. These had been––and some continue to be––mixed with eugenic, racial, and pejorative assumptions in the framework of human subject experimentation.

-Frank W. Stahnisch

• Harrington, Anne, 1996, Reenchanted Science, Holism in German Culture from Wilhelm II. To Hitler. Princeton, NJ: Princeton University Press, 1996.

• Guerrini, Anita, 2003, Experimenting with Humans and Animals. From Galen to Animal Rights. Baltimore, MD: Johns Hopkins University Press.

• Lederer, Susan E., 1995, Subjected to Science: Human Experimentation in America before the Second World War. Baltimore, MD: Johns Hopkins University Press.

• Roelcke, Volker and Maio, Giovanni (eds.), Twentieth Century Ethics of Human Subjects Research: Historical Perspectives on Values, Practices and Regulations. Stuttgart: Franz Steiner Verlag.

• Pressmann, Jack D., 1998, Last Resort: Psychosurgery and the Limits of Medicine. New York: Cambridge History of Medicine.

• Proctor, Robert, 1988, Racial Hygiene: Medicine under the Nazis. Cambridge, MA: Harvard University Press.

• Reverby, Susan M. (ed.), 2000, Tuskegee Truths. Rethinking the Tuskegee Syphilis Study. Chapill Hill: University of North Carolina Press.

• Stahnisch, Frank W., 2012, Medicine, Life and Function: Experimental Strategies and Medical Modernity at the Intersection of Pathology and Physiology. Bochum, Freiburg: Projektverlag.

• Weindling, Paul, 1989, Health, Race and German Politics between National Unification and Nazism, 1870–1945. Cambridge History of Medicine. Cambridge, UK, and New York: Cambridge University Press.

• Zimmerman, Andrew, 2001, Anthropology and Antihumanism in Imperial Germany. Chicago, IL: University of Chicago Press.

• Muir, Lailani, 2014, A Whisper Past: Childless after Eugenic Sterilization in Alberta. Victoria, BC: Friesen Press.

• Stahnisch, Frank W., 2014, Non Restraint, Shock Therapies, and Brain Stimulation Approaches: Patient Autonomy and the Emergence of Modern Neuropsychiatry. In: Clausen, Jens and Levy, Neil (eds.), Handbook of Neuroethics. New York: Springer, pp. 519–533.