nineteenth and early twentieth centuries included investigations of digestive processes (including the use of stomach tubes in infants), deliberate efforts to induce various sexually transmitted diseases to identify their causes and natural history, lumbar punctures, and studies of scurvy in orphaned infants that involved withholding of orange juice. A Swedish physician’s admission that he had used children provided by a foundling home rather than calves in a smallpox experiment because calves were costly prompted a U.S. pamphlet “Foundlings Cheaper than Animals” (Lederer, 1995, p. 50).
One American researcher who used institutionalized children in various studies commented in a 1914 publication that conditions in these institutions were similar to the “conditions which are insisted on in … [infection experiments] among laboratory animals, but which can rarely be controlled in a study of infection in man (Alfred F. Hess, quoted in Lederer and Grodin, 1994, p. 6). Despite considerable controversy, neither public action nor voluntary standards for human research won acceptance in the United States before World War II.
In 1931, the German government issued extensive new regulations protecting human participants in research after controversies over the use of healthy children in harmful studies on tuberculosis vaccines (Grodin, 1992). Among other provisions, the regulations stated that the potential adverse effects of research should be proportionate to the anticipated benefits and that disadvantaged individuals should not be exploited as research participants. The 1931 policies were both unprecedented for the era and profoundly ineffectual under the Nazi regime that took power in 1933.
Most current discussions of research ethics start with the Nuremberg Code’s Directives for Human Experimentation, which were announced by an American military tribunal in 1947 before the verdict in the trial of several Nazi physicians and others for atrocities in medical experiments (Annas and Grodin, 1992).9 (The tribunal convicted 16 of 23 defendants, most of them physicians, of war crimes and crimes against humanity and sentenced 7 of them to be executed.) These directives were the first internationally accepted statement of ethical principles in research. The lead principle stated that “the voluntary consent of the human subject is absolutely essential” meaning that “the person involved should have the legal capacity
The Nuremberg Code’s directives, by and large, reflect principles and advice provided in separate statements to the military prosecutors by Dr. Leo Alexander and Dr. Andrew Ivy. Ivy acted as the American Medical Association’s adviser to the prosecutors (ACHRE, 1995). The statement developed by Ivy applied to research with healthy volunteers, not sick patients. His principles also provided the foundation for a 1946 statement of policies for human experimentation by the American Medical Association.