 CHAPTER ONE PART THREE THE DEPARTMENT OF DEFENCE CONSENT IS FORMALIZED The story of research involving human subjects in the U.S. military began at least a century ago. Well before 1944, the beginning of the period of special interest to the Advisory Committee, the military needed healthy subjects to test means to prevent and treat infectious diseases to which military personnel might be exposed. The notion that consent should be obtained from human subjects was clearly part of this tradition. Less clear is how consistently this was applied and what consent actually meant to those in authority. The most famous example of the early use of subject consent in the military took place at the turn of the century. Walter Reed's successful research on yellow fever, the mosquito-borne disease that bedeviled Panama Canal construction efforts, employed healthy subjects who signed forms indicating their agreement. Whether the practice was required by the army or self-imposed by Reed is unknown. In 1925 an army regulation to promote infectious disease research noted that volunteers should be used in experimental research. The Navy also provided early requirements for human subject research. In 1932 the Secretary of the Navy granted permission for the conduct of an experiment involving divers on condition that the subjects were informed volunteers. In 1943 the Secretary of the Navy also required that all investigators seeking to conduct research with service personnel obtain prior approval from the Secretary. As we have noted in the introduction, during World War II federally funded biomedical research related to the war effort, outside the Manhattan Project, was coordinated by the Committee on Medical Research, CMR, of the Office of Scientific Research and Development, which was part of the Executive Office of the President. The CMR supported a program of human research during which the question of the rules for the conduct of human research was addressed. In 1942 a University of Rochester researcher seeking to work out a human experiment on the chemical prophylaxis of gonorrhea asked the CMR for an opinion that such human experimentation is desirable. In an October 9, 1942 response the CMR's Chairman offered the following general statement which was endorsed by the full committee. Human experimentation is not only desirable but necessary in the study of many of the problems of war medicine which confront us. When any risks are involved volunteers only should be utilized as subjects and these only after the risks have been fully explained and after signed statements have been obtained which shall prove that the volunteer offered his services with full knowledge and that claims for damage will be waived. An accurate record should be kept of the terms in which the risks involved were described. In spite of the CMR's statement in response to this researcher's query it supported other experiments that involved subjects whose capacity to give valid consent to participation was doubtful, including institutionalized people with cognitive disabilities. During the war the Navy used consent forms in wartime experiments using prisoners and conscientious objectors as a proposal for research on an influenza vaccine with prisoners at San Quentin in 1943 shows. The form used in this case indicates that the subject is acting freely and voluntarily without any coercion on the part of any person whomever. To be sure the forms located by the advisory committee were called waiver or release rather than consent forms. Thus the attestation to voluntary participation was punctuated by the release of experimenters from liability. However, at a time when free young men were routinely conscripted into the military the requirements that subjects including prisoners and conscientious objectors must be volunteers seems remarkable. In sharp contrast with these procedures the Navy too sometimes functioned in a manner inconsistent with a voluntary consent policy for healthy subjects. Surviving subjects have reported that harmful mustard gas experiments on naval personnel at the Naval Research Laboratory in Washington D.C. during World War II failed to adequately inform subjects and seemed to have involved manipulation or coercion of volunteers. The lack of medical follow-up on the subjects of these experiments was sharply criticized in a 1993 report by the Institute of Medicine of the National Academy of Sciences. The NEPA debate on the ethics of prisoner experiments. Many of the researchers and officials who had been involved in Manhattan Project human experiments during the war and then in the 1947 AEC deliberations about human research policy were also engaged, in 1949 and 1950, in discussions of the ground rules for research with human subjects in the development of new military technology. This time the forum was the joint AEC-DOD project on nuclear energy for the propulsion of aircraft, NEPA. The DOD convened an advisory panel of private and public officials to determine how to obtain data needed to answer questions such as whether the air crew would be put at undue risk by the nuclear-powered engine. The participants in the discussion included university researchers Heimer Friedel, Stafford Warren, Robert Stone, and Joseph Hamilton, and AEC officials Shields Warren and Alan Gregg. Shields Warren argued that human experimentation was not appropriate because the research could be done on animals and human data was not likely to produce scientifically valid results. See introduction. Robert Stone, the recipient of the November 1947 letter in which AEC General Manager Wilson called for informed consent, emerged as the primary proponent of human experiments. In a January 1950 discussion paper he focused on the ethics of human experimentation. After a recitation of a tradition that included Walter Reed's experience and the historical use of prisoners and medical students as research subjects, Stone cited requirements that had been publicized by the American Medical Association in 1946. These rules provided that subjects must give voluntary consent, that animal experimentation must precede human experimentation, and that human experiments should be performed under proper medical protection and management. See chapter 2. Stone argued that it would be possible to conduct NEPA related experiments with prisoners in compliance with all three of these requirements. Stone's proposal generated considerable discussion among DOD and AEC experts and officials. In April 1950 the DOD's joint panel on the medical aspects of atomic warfare endorsed the use of prisoners of true volunteer status as meeting the requirements of accepted American standards for the use of human subjects for research purposes. However, AEC officials were less than enthusiastic. Doesn't the prisoner proposal, ACBM Chairman Alan Gregg asked a military official in the course of one discussion, fall in the category of cruel and unusual punishment? Not, the official replied, if they carry out the work as they proposed. It would be on an absolutely voluntary basis and under every safety precaution that could be built up around it. It didn't strike me as being cruel and unusual. To which Shields Warren retorted, It's not very long since we got through trying Germans for doing exactly the same thing. In December 1950 the AEC convened a panel to discuss what was known about potential radiation effects on service personnel and whether human research was needed. Joseph Hamilton, Robert Stone's colleague at the University of California, was unable to attend the meeting and in his regrets he offered his thoughts on the matter. In a letter to Shields Warren he noted that the proposal to use prisoner volunteers would have a little of the Buchenwald touch and reported that he had no very constructive ideas as to where one would turn for such volunteers should this plan be put into effect. He suggested using large primates, even though from a purely scientific viewpoint the data collected would not be as useful as data from humans. Apparently Stone lost the debate. A decision was made not to conduct experiments with prisoners or other healthy subjects in connection with the NEPA project. However, as will be discussed in more detail in Chapter 8, the military contracted with a private hospital to study patients who were being irradiated for cancer treatment in the hopes of answering the same kinds of questions that would have been addressed if NEPA research with prisoners had gone forward. This provides for DOD contractor indemnification in the case of injury. In the aftermath of World War II the military continued its long-standing program of infectious disease research using human subjects. During the late 1940s and early 1950s the Army Epidemiological Board, AEB, and its 1949 successor, the Armed Forces Epidemiological Board, AFEB, which was established to advise on medical research funded by the DOD and to direct some research undertaken with Army funds sponsored studies with healthy subjects that focused on hepatitis, dengue fever, and other infectious diseases. Consistent with military tradition at least some AEB-sponsored researchers were using written permission forms. The forms, frequently referred to as an agreement with volunteer, or a release, outlined the study and the risks to the subject and protected the DOD from liability. In the late 1940s some university researchers expressed concern that they were not adequately protected from liability in the case of injury or death of their prisoner subjects. The ensuing dialogue provides a window on the role of the written releases and the understanding of the rules governing human subject research. In response to a researcher's request to be reimbursed by the Army for a disability policy for the subjects, the Army lawyers replied that the Army could not provide indemnification in the absence of clear congressional authority. Army legal advisers recommended that the researcher protect himself, the state of New Jersey, the research locale, and the government by means of the usual waiver. In a February 1948 letter the AEB director, John R. Paul, explained that the world situation had placed the rules for human experimentation up for grabs. At this stage in the world situation one should proceed cautiously until standards are set by what everybody is in authority. I am not sure just what the rules are, but I understand that some type of vigilance committee has laid down certain principles about volunteers in order to protect this country from the criticisms brought up in Germany during the Nuremberg trials. During the war we more or less made our own policies on this, but I am not sure that this is possible today. The allusion to a vigilance committee is unclear. It may be a reference to a committee established by the Governor of Illinois to examine the use of prisoners as research subjects in that state, and chaired by Andrew Ivy, the principal expert witness for the prosecution at the Nuremberg Medical Trial. C. 2 Given the date of the letter, February 18, 1948, it seems likely that Paul had just skimmed through his new copy of the Journal of the American Medical Association. The report of Ivy's committee was published in the February 14, 1948 issue. In April 1948 an AEB official made it plain to the researchers that the fact that state authorities or the prison warden gave permission for the experiment should be of little comfort to them. In case of a lawsuit, responsibility would devolve entirely upon the individual experimenter. Only Congress could provide a solution, but it would be a dangerous course to raise the matter publicly. I have, the AEB official wrote, given considerable thought to the matter of whether it would be advisable to approach individuals or groups in Congress with the idea of having laws passed related to payment of compensation for disability or release of the experimenter from liability. I am afraid that this would be a dangerous course and that it might, in fact, injure clinical investigations generally. There is a very real possibility that unfavorable publicity would quickly result. It appears that the relief sought by researchers was provided by Congress in 1952, however. Under the umbrella of a law that provided indemnification for DOD research and development activities as a whole. In October 1952, following the death of a prisoner subject in an AFEB sponsored hepatitis study and questions raised by the Army Chemical Corps about release forms for human guinea pigs, the AFEB administrator queried the DOD legal office about a recently passed federal law. The law provided authority for the military to indemnify contractors for risks undertaken in research and development situations. Did the new law afford relief to the immediate dependence of prison volunteers when, as a result of these experiments, they should die? The answer was yes, but only by providing relief to the researchers first. From the wording of the law and from the legislative history, the legal office replied, it is a direct indemnification to the contractor and not to the individual human guinea pig. Thus, what appears to have been the first Cold War congressional enactment to deal with human subjects of research addressed the government's obligation to its contractors, not the government's and its researchers' obligations to the subjects. Moreover, the record indicates that a more direct approach was not sought by the DOD because of concerns about public relations. At the same time Congress was acting, however, the DOD itself was secretly debating a new policy for human experiments. The Secretary of Defense issues the Nuremberg Code in top secret. As the Korean War began in mid-1950, the military's interest in human experimentation, in connection with chemical and biological as well as atomic and radiation warfare, intensified. The need for a DOD-wide policy on the use of human subjects in research was noted by Colonel George Underwood, the Director of the Office of the Secretary of Defense, in a February 1953 memorandum to the incoming administration of Dwight D. Eisenhower. There is no DOD policy on the books which permits this type of research, human experiments in the field of atomic, biological, and chemical warfare. From 1950 to 1953, discussions about human research and human research policy were held in several high-level DOD panels, including the Armed Forces Medical Policy Council, AFMPC, the Committee on Medical Sciences, CMS, and the Joint Panel on the Medical Aspects of Atomic Warfare. These groups were headed by civilian researchers, and, in at least the latter two cases, included representatives of the AEC, CIA, NIH, VA, and Public Health Service. At its September 8, 1952 meeting, the AFMPC heard a presentation from the Chief of Preventative Medicine of the Army Surgeon General's Office on the topic of biological warfare research. It was pointed out that the research had reached a point beyond which essential data could not be obtained unless human volunteers were utilized for such experimentation. Following detailed discussion, it was unanimously agreed that the use of human volunteers in this type of research be approved. At its October 13, 1952 meeting, the AFMPC again took up the question of human experimentation. It was resolved, the Chairman wrote to the Secretary of Defense, that the ten rules promulgated at the Nuremberg trials be adopted as the guiding principles to be followed. An eleventh rule, barring experiments with prisoners of war, was added by the legal advisor to the Council, Mr. Stephen S. Jackson. The OD Attorney Jackson evidently was responsible for the inclusion of the Nuremberg Code in the AFMPC's proposed policy. In an October 13, 1952 memo to the Chairman of the AFMPC, Jackson recommended that the attached principles and conditions for human experimentation, which were laid down by the tribunal in the Nuremberg trials, be adopted, instead of those previously submitted by me. As an addendum to the Nuremberg Code, Jackson proposed a requirement that consent be expressed in writing before at least one witness. This recommendation followed from the suggestion of Anna Rosenberg, Assistant Secretary of Defense for Manpower and Personnel, who was an expert on labor relations. A letter written by the Administrator of the Armed Forces Epidemiological Board documents Mr. Jackson's role and motivation. It was on Mr. Jackson's insistence that the Nuremberg principles were used in Toto in the document, since he stated, these already had international judicial sanction, and to modify them would open us to severe criticism along the line, see, they use only that which suits them. Thus, the DOD's Council cited the 1947 Nuremberg Military Tribunal ruling as establishing an international legal precedent to which American researchers should be held. It appears that in succeeding months the AFMPC proposal was received unenthusiastically by other DOD committees that reviewed it. In a November 12, 1952 memorandum, the Executive Director of the Committee on Medical Sciences pointed out that human experimentation has been carried on for many years. He contended that, to issue a policy statement on human experimentation at this time would probably do the cause more harm than good, for such a statement would have to be watered down to suit the capabilities of the average investigator. Human experimentation, the CMS Executive Director asserted, has, in years past, and is at present governed by an unwritten code of ethics, which is administered informally by fellow workers in the field and is considered to be satisfactory. To commit to writing a policy on human experimentation would focus unnecessary attention on the legal aspects of the subject. Notwithstanding the reservations of the CMS and others, the Nuremberg Code Proposal had the support of President Truman's Secretary of Defense, Robert A. Lovett. However, the Secretary's aide, George V. Underwood, wrote in January 1953, Since the consequences of this policy will fall upon Mr. Wilson, President Eisenhower's nominee for Secretary of Defense, Charles Wilson, it might be wise to pass to him as a unanimous recommendation from the alumni. In a January 13, 1953 memorandum for the new Secretary, the AFMPC strongly recommended that a policy be established for the use of human volunteers, military and civilian employees in experimental research at armed forces facilities. The policy would render the research subject to the principles and conditions laid down as a result of the Nuremberg Trials. The Nuremberg Code 1. 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, overreaching, 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. The 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 reasonably to be expected, and the effects upon his health or person which may possibly come from his participation in the experiment. The duty and responsibility for ascertaining the quality of the consent rest upon each individual who initiates, directs, or engages in the experiment. It is a personal duty and responsibility which may not be delegated to another with impunity. 2. The experiment should be such as to yield fruitful results for the good of society, unprocurable by other methods or means of study, and not random or unnecessary in nature. 3. The experiment should be so designed and based on the results of animal experimentation and a knowledge of the natural history of the disease or other problem under study that the anticipated results will justify the performance of the experiment. 4. The experiment should be so conducted as to avoid all unnecessary physical and mental suffering and injury. 5. No experiment should be conducted where there is an a priori reason to believe that death or disabling injury will occur, except, perhaps, in those experiments where the experimental physicians also serve as subjects. 6. The degree of risk to be taken should never exceed that determined by the humanitarian importance of the problem to be solved by the experiment. 7. Proper preparation should be made and adequate facilities provided to protect the experimental subject against even remote possibilities of injury, disability, or death. 8. The experiment should be conducted only by scientifically qualified persons. The highest degree of skill and care should be required through all stages of the experiment of those who conduct or engage in the experiment. 9. During the course of the experiment the human subject should be at liberty to bring the experiment to an end if he has reached the physical or mental state where continuation of the experiment seems to him to be impossible. 10. During the course of the experiment the scientist in charge must be prepared to terminate the experiment at any stage if he has probable cause to believe in the exercise of the good faith, superior skill, and careful judgment required of him that a continuation of the experiment is likely to result in injury, disability, or death to the experimental subject. 13. For more information or to volunteer please visit LibriVox.org. Final Report of the Advisory Committee on Human Radiation Experiments. Ethics of Human Subjects Research. A Historical Perspective. Chapter 1. Part 4. The Wilson Memorandum. 26 February 1953. Memorandum for the Secretary of the Army. Secretary of the Navy. Secretary of the Air Force. Subject. Human Volunteers in Experimental Research. 1. Based upon a recommendation of the Armed Forces Medical Policy Council that human subjects be employed, under recognized safeguards, as the only feasible means for realistic evaluation and or development of effective preventative measures of defense against atomic, biological, or chemical agents, the policy set forth below will govern the use of human volunteers by the Department of Defense in experimental research in the fields of atomic, biological, and or chemical warfare. 2. By reason of the basic medical responsibility in connection with the development of defense of all types against atomic, biological, and or chemical warfare agents, armed services personnel and or civilians on duty at installations engaged in such research shall be permitted to actively participate in all phases of the program. Such participation shall be subject to the following conditions. A. The voluntary consent of the human subject is absolutely essential. 1. 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, overreaching, 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 reasonably to be expected, and the effects upon his health or person which may possibly come from his participation in the experiment. 2. The consent of the human subject shall be in writing. His signature shall be affixed to a written instrument setting forth substantially the aforementioned requirements, and shall be signed in the presence of at least one witness who shall attest to such signature in writing. 3. In experiments where personnel from more than one service are involved, the Secretary of the Service which is exercising primary responsibility for conducting the experiment is designated to prepare such an instrument and coordinate it for use by all the services having human volunteers involved in the experiment. 3. The duty and responsibility for ascertaining the quality of the consent rests upon each individual who initiates, directs, or engages in the experiment. It is a personal duty and responsibility which may not be delegated to another with impunity. B. The experiment should be such as to yield fruitful results for the good of society un-porcurable by other methods or means of study, and not random and unnecessary in nature. C. The number of volunteers used shall be kept at a minimum, consistent with item B, above. D. The experiment should be so designed and based on the results of animal experimentation and a knowledge of the natural history of the disease or other problem under study that the anticipated results will justify the performance of the experiment. E. The experiment should be so conducted as to avoid all unnecessary physical and mental suffering and injury. F. No experiment should be conducted where there is an a priori reason to believe that death or disabling injury will occur. G. The degree of risk to be taken should never exceed that determined by the humanitarian importance of the problem to be solved by the experiment. H. Proper preparation should be made and adequate facilities provided to protect the experimental subject against even remote possibilities of injury, disability, or death. I. The experiment should be conducted only by scientifically qualified persons. The highest degree of skill and care should be required through all stages of the experiment of those who conduct or engage in the experiment. J. During the course of the experiment, the human subject should be at liberty to bring the experiment to an end if he has reached the physical or mental state where continuation of the experiment seems to him to be impossible. K. During the course of the experiment, the scientist in charge must be prepared to terminate the experiment at any stage if he has probable cause to believe in the exercise of the good faith, superior skill, and careful judgment required of him that a continuation of the experiment is likely to result in injury, disability, or death to the experimental subject. L. The established policy, which prohibits the use of prisoners of war in human experimentation, is continued, and they will not be used under any circumstances. 3. The secretaries of the Army, Navy, and Air Force are authorized to conduct experiments in connection with the development of defenses of all types against atomic, biological, and or chemical warfare agents involving the use of human subjects within the limits prescribed above. 4. In each instance in which an experiment is proposed pursuant to this memorandum, the nature and purpose of the proposed experiment, and the name of the person who will be in charge of such experiment, shall be submitted for approval to the secretary of the military department in which the proposed experiment is to be conducted. No such experiment shall be undertaken until such secretary has approved in writing the experiment proposed, the person who will be in charge of conducting it, as well as informing the secretary of defense. 5. The addresses will be responsible for ensuring compliance with the provisions of this memorandum within their respective services. Signed, C. E. Wilson. Copies furnished, Joint Chiefs of Staff, Research and Development Board. Top Secret. Downgraded to Unclassified, 22 August, 75. On February 26, 1953, Secretary of Defense Wilson signed off on the AFMPC policy. It was issued in a top secret memorandum to the secretaries of the Army, Navy, and Air Force. The Wilson memorandum reiterates the principles of the Nuremberg Code, requires written and witnessed informed consent of research subjects, and prohibits the use of prisoners of war. The policy was to govern the use of human volunteers by the Department of Defense in experimental research in the fields of atomic, biological, and or chemical warfare for defensive purposes. The basis for the classification of the 1953 memorandum is not clear. Since the memorandum dealt with atomic and other unconventional forms of warfare, its classification may have been routine. There is evidence that the DOD had a general desire to keep hidden from public view any indication that it was involved in biological and chemical warfare-related research. The Wilson memorandum, of course, was just such an indication. In September 1952, the Joint Chiefs of Staff advised the services to ensure, in so far as practicable, that all published articles stemming from BW, biological warfare, and CW, chemical warfare, research and development programs are disassociated from anything which might connect them with U.S. military endeavor. In one sense, the memorandum is a landmark in its official recognition of the Nuremberg Code, but in another sense it also generates important questions. Having determined to recognize international principles of human rights, why, or how, could the Secretary have limited their application to some but not all human experiments? Why was the policy directed exclusively to experiments related to atomic, biological, and chemical warfare? Moreover, was the policy intended to govern such research wherever it was conducted, for example, when it was performed by private contractors as well as by intramural researchers? How was a directive issued in secret implemented? Communicating the 1953 Wilson memorandum. That there were problems in the dissemination of Secretary Wilson's top secret memorandum is evidenced in a memorandum containing queries by officials of the Armed Forces Special Weapons Project, AFSWP, within a year of the Wilson memorandum's issuance. The AFSWP, now the Defense Nuclear Agency, DNA, was at the hub of DoD nuclear weapons research. In the course of a routine review of research reports, an AFSWP official learned that volunteers were injured as a consequence of taking part in a field experiment of flash blindness conducted at an atomic bomb test before the Wilson memorandum was issued. C. CHAPTER X The AFSWP reviewer immediately concluded that a definite need exists for guidance in the use of human volunteers as experimental subjects. On further inquiry the AFSWP reviewer found that a policy already existed but had not been disseminated to investigators. A follow-up memorandum, evidently written in early 1954, records, In November 53 it was learned that there existed a TS, top secret, document signed by the Secretary of Defense, which listed various requirements and criteria which had to be met by individuals contemplating the use of human volunteers in biomedical or other types of experimentation. It was learned that although this document details very definite and specific steps, which must be taken before volunteers may be used in experimentation, no serious attempt has been made to disseminate the information to those experimenters who have a definite need to know. The lowest level at which it had been circulated, the AFSWP reviewer learned, was that of the three Secretaries of the Services. Efforts by an Assistant Secretary to downgrade the document had not been able to obtain concurrence. The reviewer hoped that this letter shall point up the need for some relaxation of the grip in which this document is now held, at least on a definite need to know basis. The application of the Wilson memorandum to further experiments conducted at atomic bomb tests is discussed in Chapter 10. Implementation in the Army The Army did take substantial steps to put into effect the Wilson memorandum. In June 1953, the Army Chief of Staff, John C. Oakes, issued a memorandum implementing the Secretary of Defense's policy in TOTO. Referred to in the Army as CS385, this memorandum was initially classified top secret, but was declassified the following year. In addition to the provisions of the Wilson memorandum, the Army document required the prior review and approval of both the Surgeon General and the Secretary of the Army. The Army's memorandum also contained legal analysis that explained the source of the Army's authority to perform human experiments in the first place and the limits that this authority put on the selection of subjects. Even in the midst of the Korean War, the Army did not view it as self-evident that the DoD could engage in human experiments or choose any subjects it wished. The memorandum explained that the authority to experiment on humans came from congressional enactments, including provisions for research and development. Interestingly, the choice of subjects was to be governed by the Army's ability to ensure compensation in the case of death or disability. This could be provided, the lawyers declared, only upon express congressional action. In the case of military personnel and contractor employees, there was such provision. But there was no such authority in the case of private citizens who offered their services. The Army lawyers recommended, and the CS385 policy provided, that private citizens not employed by Army contractors could not serve as research subjects. On March 12, 1954, the Army Office of the Surgeon General, OSG, issued an unclassified statement entitled, Use of Volunteers in Medical Research Principles, Policies, and Rules. This document, too, restated the Nuremberg principles. In contrast with the Wilson and Oaks memorandums, it was not restricted to medical research related to atomic, biological, or chemical warfare. Instead, the OSG statement was directed to medical research with human volunteers generally. Moreover, while CS385 did not state directly whether it applied to contract researchers, the 1954 OSG statement was transmitted to at least some university researchers, with the prefatory note, to be used, as far as applicable, as a non-mandatory guide for planning and conducting contract research. There is evidence that the OSG's requirements were sometimes more than non-mandatory guides. For example, in a June 27, 1956, letter to the Armed Forces Epidemiological Board, a Tulane University public health researcher agreed that his vaccine experiments with prisoner subjects would be conducted only after written consent was obtained from the subjects. The Tulane researcher indicated that, with respect to his application for funding, I have held it up, since Dr. Dingell indicated I be familiar with the statement of the Office of the Surgeon General, read the use of human volunteers. I have read it, and believe that our past and future work have and will comply with the rules stipulated. Moreover, this researcher provided a written statement to supplement his original proposal that explained how the OSG requirements would be met. In another case, a proposal involving measles and normal children, an AFEB official advised the researcher to take the OSG policy into consideration in writing the proposal. As discussed earlier, in 1952 the Army obtained congressional authority to indemnify contract researchers in the event that an experiment caused injury or death. There is evidence that the Army sought to link the grant of an indemnification clause, ASPR 7.203.22, insurance, liability to third persons, to a contractor acceptance of the principles stated by the Army Surgeon General. In a March 1957 letter to the University of Pittsburgh, which was proposing to use medical student volunteers in a non-radiation experiment, the Army told Pittsburgh that the provision of the clause was contingent upon your adhering to the following, March 1954, Office of the Surgeon General, principles, policies, and rules for the use of human volunteers in performing subject medical research contracts. While the evidence clearly shows that Army officials sought to apply the Nuremberg Code policy to contractors, it did not meet with complete success, and the full extent of its efforts remains unclear. As we see in Chapter 2, in the early 1960s Harvard successfully resisted the inclusion of the Nuremberg Code language in its medical research contracts with the Army. As we see in Chapter 8, which discusses DOD funding of research on the effects of total body irradiation, the indemnification language was included in at least some contracts in which the Surgeon General's policy was not mentioned. By 1969, however, the policy may have become standard in Army contracts under the authority of the Medical Research and Development Command. There are several possible explanations for the seeming substance of widespread inclusion of the Surgeon General's memo as a contractual requirement, at least where indemnification was provided for. First, as discussed below, it is possible that the 1954 policy was meant to apply to research with healthy subjects and not sick patients. However, even if that were generally the case, the provision of indemnification might be expected to have a reflection on this limitation. Second, as a related matter, the evidence we are reviewing shows a tension between the government's declaration of a principle and its readiness to actively insist that the principle be honored within the privacy of the doctor-patient relationship. Finally, Army imposition of the Surgeon General's principles may also have depended on the nature of its interest in the research being applied. An April 3, 1957 memo distinguished cases where the institution because of its primary interest would conduct the research even without the support of the OSG from cases where the study is conducted at the insistence of the OSG. In the former case, the strategy would be to seek cost-sharing contracts in which the institution would assume all responsibility for any possible effects resulting from the experimentation. In the latter case the indemnification clause would be provided but the March 1954 policy would also be required and included in the contract directly or by reference. It is not clear that the 1954 OSG policy on human volunteers was intended to apply to research with patients. The term volunteer is ambiguous but at the time it was commonly used to refer to healthy subjects. Nonetheless, a 1962 Army Memorandum that declared that since World War II by and large research has been conducted in strict accordance with the Nuremberg Code mentions patients. The memo reported that a recent survey of contract research found that the volunteers treated in accord with the Nuremberg Code included 3,000 students and 250 patients and 300 prisoners. It is not known what kind of research these 250 patients were involved in, nor is it known what proportion of the patients who had been subjects of research supported or conducted by the Army since World War II were represented by these 250. Unfortunately the 1962 Reviews Confident Declaration that Army research complied with the Nuremberg Code was too sanguine. In 1975 following public revelations that the Army and the CIA had conducted LSD experiments on unwitting subjects the Army Inspector General reviewed the application of the June 1953 policy to drug testing. The Inspector General's review led to the declassification of the 1953 Wilson Memorandum. The Inspector General found that the Army had with one or two exceptions used only volunteers for its drug testing program. However the volunteers were not fully informed as required prior to their participation and the methods of procuring their services in many cases appeared not to have been in accord with the intent of department of the Army policies governing the use of volunteers in research. Additional DOD research requirements While the Navy is not known to have taken specific action in response to the 1953 Wilson Memorandum we have already noted that the Navy had long since provided for prior review and voluntary participation in some cases. The 1951 Navy Manual of the Medical Department required secretarial approval of human experimentation and the use of volunteers. These requirements applied to experimental studies of a medical nature involving personnel of the Naval establishment military and civilian. Participation was to be on a voluntary basis only. The manual also mandated prior review for research with patient subjects. Clinical research including research projects and therapeutic trials was to be authorized by the Board of Medicine and Surgery. At least for research with radioisotopes the requirement for voluntary participation may have applied to patient subjects as well as healthy subjects. In 1951 the Navy debated adoption of a permission form for the use of radioisotopes for patients at Naval hospitals. This form to be signed by either the patient or the responsible next of kin authorized the use of tracer therapeutic doses obtained from the Atomic Energy Commission for research purposes. Although it is not clear that the Army rules implementing the 1953 Wilson memorandum applied to patient subjects there is some evidence that consent forms that were usually used for surgical procedures were used in patient-related experimental settings involving radioisotopes. In 1955 an official from the Letterman Army Hospital in San Francisco asked the Walter Reed Hospital about the need for written permission forms for test doses of radioisotopes. In response the Army indicated that a standard form used for operations in anesthesia should also be employed at the physician's discretion when authorization for administration of radioisotope therapy is desired. In the Air Force a 1952 regulation on clinical research mandated safety and administrative procedures for the use of humans in experiments at Air Force medical facilities. This regulation required prior group review but did not mention consent provisions or refer to the subjects as volunteers. In 1958 a letter from the Air Force's Air Research and Development Command describes the policy for the use of humans in hazardous research and development tests. This policy reiterated the requirement for prior review discussed in the 1952 regulation. In this context however subjects were to be volunteers who understood the degree of risk involved in the experiment. What then were the operative rules in the Department of Defense for research involving human subjects in the 1940s and 1950s? By the mid-1950s for the entire DoD for research related to atomic biological and chemical warfare and for all research involving human volunteers in the Army, the formal rules were the ten principles of the Nuremberg Code and the additions included in the Secretary of Defense's 1953 policy. According to the 1975 testimony of the Surgeon General of the Army before the U.S. Senate and the internal review conducted by the Army Inspector General these principles were Army policy. At the same time, as the Inspector General reported in 1975 and as we discuss further in Chapter 10 these requirements were not always known or followed. While there were attempts to implement the Army Surgeon General's 1954 policy, it is not known how the policy's provisions including the requirement to obtain voluntary consent were interpreted. The Navy's 1951 requirements for prior review and voluntariness applied to all research involving Navy personnel. The extent to which research rules apply to patient subjects in the clinical setting is less clear. There is some indication that in some cases standard consent forms akin to the surgical permits in use at the time were employed with patients at military hospitals who were administered test doses of radioisotopes. End of Section 14 Section 15 of Final Report of the Advisory Committee on Human Radiation Experiments. This is a LibriVox recording. All LibriVox recordings are in the public domain. For more information or to volunteer please visit LibriVox.org. Final Report of the Advisory Committee on Human Radiation Experiments. Ethics of Human Subjects Research. A Historical Perspective. Chapter 1. Part 5 The National Institutes of Health and the Veterans Administration. During the late 1940s and 1950s the AEC and DOD were by no means the only agency sponsoring research involving human subjects. The Department of Health Education and Welfare DHEW through two of its components, the Public Health Service and the NIH was emerging during this period as the dominant government agency sponsoring human biomedical research. The Veterans Administration, VA, as well conducted a large medical research program that involved the use of radioisotopes in numerous human experiments. In the early 1950s NIH participated in some of the discussions preceding the issuance of the 1953 Secretary of Defense Memorandum. At the request of a DOD official for information on NIH's approach to the use of human subjects NIH responded with an April 1952 letter that included a draft statement on the ethical principles underlying investigations involving human beings. Among its other provisions the April 28, 1952 draft states that the person who is competent to give consent to an investigative procedure must do so. He must have legal capacity to give consent and be able to exercise free choice without the intervention of any element of force, fraud, deceit, duress, constraint, or coercion. He must have sufficient knowledge and comprehension of the nature of the investigation to enable him to make an understanding and enlightened decision. He must therefore be told the nature, duration, and purpose of the experiment, the method and means by which it is to be conducted, the inconveniences and hazards reasonably to be expected, and the effects upon his health or person will reasonably be expected to come from his participation in the investigation. He should understand furthermore that by his participation he becomes a co-investigator with a physician. Although it is not known what became of this draft statement, around this time NIH had good reason to develop a policy on the use of human subjects. In 1953 NIH opened the Clinical Center, of the Science Research Hospital. The Center adopted a policy requiring voluntary agreement based on informed understanding from all research subjects and written consent from some patient subjects involved in research that the physician believed to be unusually hazardous. Written consent was required from all healthy, normal subjects of research, beginning in 1954. Additionally, NIH began a system of group review of proposed research that became a model for today's institutional review boards, IRBs. Thus, the NIH policy appears to be the first instance of a single policy that expressly provides for consent from all subjects, be they healthy or sick. Even so, the policy was still limited to research at the Clinical Center and did not apply to the considerable amount of NIH-funded research being undertaken by grantees extramural research. The question of whether patients as well as healthy, normal volunteers should give written consent arose in the development of the NIH policy. Legal counsel at NIH advised that from a legal point of view there should be a written statement indicating the patient's awareness of the nature of the particular investigation in which the NIH was to participate an acceptance of any particular inconvenience or risk inherent in his participation. Assigned form offered the best proof that a policy of informed consent was followed for all subjects enrolled in studies at the center. The NIH attorney wrote that while the Clinical Center's Medical Advisory Board did not disagree with the principal, it did disagree with the need of the members that expressed their views and most did so all rejected such a proposal. The rejection was due, as I understand it, not to any particular detail but rather a more basic objection to written as opposed to oral statements. There was apparently no objection to providing the patient with enough information to permit him to exercise an informed choice of participation or refusal as long as not reduced to writing for his signature. Nonetheless, the principal that all research subjects including healthy subjects in the normal volunteer program and patient subjects should make an informed choice seems to be acknowledged in the Medical Advisory Board's position. The NIH Clinical Center approach adopted by the mid-1950s, written consent from healthy subjects and from only certain patient subjects persisted through the early 1960s and was paralleled in policies of the DOD and the AEC. The view that written consent from patients might unnecessarily interfere with doctor-patient relationships prevailed. Within the NIH dialogue continued throughout the 1950s, setting the stage for the leading role DHEW was to take in formulating human research regulations in the 1960s. See Chapter 3 Although the NIH was by far the dominant agency in research involving human subjects, a significant amount of radioisotope research occurred at the VA. The VA research program employing radioisotopes at VA medical centers began in 1948. This program was limited to VA hospitals affiliated medical schools. From its inception this program involved a system of prior group review by local radioisotope committees, normally composed of non-VA affiliated teaching staff of the affiliated medical school. These committees reviewed all research proposals and approved all research conducted at VA radioisotope units. In its formative years the advisors to the new VA program included Stafford Warren, Shields Warren, and others who were likely to be familiar with the consent principles articulated by the AEC. Nonetheless, the earliest evidence of a consent policy at the VA comes in the form of a 1958 General Counsel's opinion on whether the VA could participate in certain research. The General Counsel asserted that persons who participate in human subject research must voluntarily consent to the experiment on themselves. Such consent must rest upon an understanding of the hazards involved. The volunteer may withdraw from the experiment at any time. Moreover, before the experiment steps to reduce the hazard, as for example, indicated research on animals must be made. This opinion was written in response to two proposed research projects and it is not known if it was implemented in the projects or applied to others. Conclusion Records now available show that at the highest reaches of Cold War bureaucracies officials discussed conditions under which human experimentation could take place. These discussions took place earlier and in greater, although by today's standards uncritical and less searching were assumed. Nonetheless, the stated positions that resulted were often developed in isolation from one another were neither uniform nor comprehensive in their coverage and were often limited in their effectuation. Several interrelated factors seem to have been prominent in causing these discussions to take place and in determining the scope of the requirements that were declared and the efforts that were undertaken to implement them. Conclusion Administrative and legal circumstance The creation of new programs or the qualitative expansion of old ones impelled officials, lawyers, and researchers to reflect on the rules to govern them. While these rules were sometimes cast as legal or financial requirements, they often included provisions such as a requirement for written consent that appear similar to statements and requirements that govern the conduct of research today. The language used to describe these rules was often that of law or administration, such as waiver or release forms, or it may have had particular meaning to researchers at the time, such as clinical testing. As a result, it is often hard to compare these rules to current requirements, which have benefited from intervening decades of linguistic and conceptual refinement. Professional cultures Differing professions brought their own tools and perspectives to discussions of conditions under which human subjects' research could proceed. For example, lawyers were likely to insist on obtaining documented evidence of patient consent, while medical professionals emphasize the importance of the trust that underlay the relationship between doctor and patient. They sometimes objected to the use and implications of written consent forms. If consent procedures were a source of disagreement, the need to minimize risk to subjects was not. In creating and administering the AEC's Radioisotope Distribution Program, physician investigators and other researchers placed a premium on controlling and minimizing risk in the human use of radioisotopes. This emphasis on the establishment of administrative and educational procedures to control risk, the details of which are discussed in Chapter 6, embodied an essential principle of ethical research. The requirement for prior review included in the Radioisotope Distribution Program was, as we have seen, also present elsewhere. Even before 1944, approval of the Secretary of the Navy was required for research with human subjects. The Secretary of the Army required prior approval of research related to atomic, biological, and chemical warfare in 1953. In the Air Force, secretarial approval of human experiments was codified in 1952. At NIH, prior group review was employed as a policy from 1953 on. The VA, whose program developed under the eyes of AEC experts and advisors, relied on local isotope committees. The Nature of the Subjects While voluntary consent was acknowledged as a condition of human research by some government agencies well before 1944, it was not as broadly applied as it is today. Requirements of voluntary consent were asserted most clearly and consistently where the subjects were healthy. As a practical matter, healthy subjects are not likely to participate in experiments without specific request, and as a legal matter the invasion of a person's body in the absence of a prior relationship that might justify it has long been unacceptable. Still more important, the arbitrary use of people in experiments is incompatible with respect for human dignity. The use of patients in medical research appeared in a different historical context from that of healthy subjects, and the agencies appear to have responded accordingly. From the perspective of the medical profession, the age-old tradition of the doctor-patient relationship, as we shall see in the next chapter, provided a justification for research with the potential to benefit patients, but not of course for healthy subjects who were not under medical care. There is little evidence that the AEC's questioned whether research with patients that did not offer a prospect of benefit warranted a different response. An exception is the position articulated by the AEC's general manager in 1947, which made the possibility of benefit to the patient's subject a condition of permissible research, at least where the research involved poisonous or harmful substances. However, there is little indication that this provision was ever implemented. The period we reviewed in this chapter led to considerable public disquiet about the use of healthy subjects and about the use of ill and institutionalized people in research from which they could not possibly benefit. It was this disquiet in the wake of several well publicized incidents that formed the basis of the mid-1960s reforms of federal policy governing research with human subjects. See Chapter 3 The focus on the way that patient subjects were used in clinical research that offered some prospect of benefit and particularly on consent issues came much later. The latter discussion is one that continues today, as is evident from the advisory committee's work on current research regulation that is described in Part 3. The Degree of Risk To the extent that there was discussion in the 1940s and the 1950s of consent for patient subjects it seemed to arise mainly in circumstances in which those who were ill would be put at unusual risk from the research. As we have seen the AEC's Radioisotope Distribution Division concluded that consent was required where patients were being subjected to larger doses for investigative purposes that apparently posed unusually hazardous or unknown risks. Similarly from its establishment at mid-century the AEC's Hospital at Oak Ridge which focused on new and potentially risky experimental cancer treatment did have routine requirements for consent. Likewise from its 1953 birth the NIH's Clinical Center established a policy that recognized that patient choice was important for all kinds of research with patients and written consent was required when an experiment involved an unusual hazard formal policies and public morality. It is important not to get lost in the details of the various documents we have cited in this chapter. What is most significant about the discussions that took place in federal agencies from the mid-1940s through the 1950s is the fact that so many of the ideas and values with which we are familiar were apparent then. This does not mean that the same words were used or that when they were used they had the same meaning as they do for us today. But it does mean that there were certainly more or less rough ideas about voluntary consent and minimization of risk. As we have seen in this chapter these ideas were very much in play in the culture of the time. End of section 15 Section 16 of Final Report of the Advisory Committee on Human Radiation Experiments This is a LibriVox recording. All LibriVox recordings are in the public domain. For more information or to volunteer please visit LibriVox.org Recording by Melanie Young Final Report of the Advisory Committee on Human Radiation Experiments Ethics of Human Subjects Research, A Historical Perspective Chapter 2 Part 1 Post-war professional standards and practices for human experiments In Chapter 1 we explored government discussions of research involving human subjects in the 1940s and 1950s. We found that at several junctures government officials exhibited an awareness of the Nuremberg Code the product of an international war crimes tribunal in 1947. If a requirement of voluntary consent of the subject was endorsed by the Nuremberg judges and was recognized at the highest reaches of the new Cold War bureaucracy then how a citizen might now ask can there be any question about the use of this standard to judge the experiments conducted during this time in the United States and yet precisely this question has been raised in connection with human radiation experiments. Did American medical scientists routinely obtain consent from their subjects in the 1940s and 1950s including those who were patients and if not how did the scientists square their conduct with the demands of the Nuremberg Code. This chapter describes the advisory committee's efforts to answer these questions and what we learned. We began with an examination of what in fact was argued at Nuremberg. We focus particularly on the testimony of Andrew Ivy the American Medical Association's AMA official consultant to the Nuremberg prosecutors and on the AMA's response to the report Dr. Ivy prepared about the trial for the organization. We turn next to an analysis of the actual practices of American medical scientists during this period. In addition to reviewing contemporary documentation and present-day scholarship, the advisory committee conducted interviews with leading medical scientists and physicians who were engaged in research with human subjects in the 1940s and 1950s. These sources suggest a different, more nuanced picture of the principles and practices of human research than that presented at Nuremberg. Of particular importance in this picture are the practical and moral distinctions that many researchers made between investigations with healthy subjects and those with sick patients. Those working with healthy subjects could cite a tradition of consent that dated at least to Walter Reed's turn of the century experiments. Those working with sick patients were in a clinical context that was conditioned by a tradition of faith in the wisdom and beneficence of physicians. A tradition that was dominant until at least the 1970s. Closely related to these distinctions was the tension between being a scientist and being a physician. This tension confronted members of a new and rapidly growing breed of medical professionals in the United States working to make careers in clinical research. The chapter goes on to explore whether these distinctions and tensions were reflected in the Nuremberg Code and why the trial may not have had much impact on the treatment of patient subjects. The rest of the chapter explores the emerging awareness of the moral complexities of research at the bedside and the limitations of the Nuremberg Code to address them. We close with a brief discussion of the declaration of Helsinki. The international medical communities attempt to produce a code of conduct compatible with the realities of medical research. The American expert, the American Medical Association and the Nuremberg Medical Trial. In the fall of 1943 the United States, Great Britain and the Soviet Union agreed that once victorious they would prosecute individuals among the enemy who might have violated international law during the war. On August 8, 1945 exactly three months after VE Day and two days after the bombing of Hiroshima representatives of the American, British, French and Soviet governments officially established the International Military Tribunal in Nuremberg, Germany. An assemblage of Allied prosecutors presented cases against 24 high-ranking German government and military officials including Hermann Görig and Rudolf Hess before this international panel of judges. Quite early in the course of these initial Nuremberg trials which ran from October 1945 to October 1946 it became apparent according to the recent recollections of American prosecutor Telford Taylor that the evidence had disclosed numerous important Nazis military leaders and others who should also be tried. In January 1946 President Harry Truman approved a supplementary series of war crimes trials. These trials were to take place in the same Nuremberg courtroom and international law which continued to be the standard by which guilt or innocence would be determined. Americans wartime allies would not however participate. Responsibility for prosecuting and judging defendants in the second set of Nuremberg trials was left exclusively to the United States. The first of 12 cases that would eventually make up this second series of trials in Nuremberg is technically called the United States v. Carl Brandt et al. More popularly this trial is known by a variety of other names such as the Doctor's Trial and the Medical Case. For the sake of convenience and consistency, we will refer to the trial by another common name the Nuremberg Medical Trial. This case began on December 9, 1946 when U.S. Chief of Council for War Crimes, Telford Taylor delivered the prosecution's opening statement against the 23 defendants 20 of whom were physicians to one degree or another Taylor charged the defendants with murders, tortures and other atrocities committed in the name of medical science. The trial ended in late August 1947 when the judges handed down a ruling that included the so-called Nuremberg Code and seven death sentences. In the spring of 1946 the American prosecution team preparing for the medical trial which was made up of lawyers commissioned in the Army cabled Secretary of War Robert P. Patterson with a request for a medical expert. Patterson consulted with Army Surgeon General Norman T. Kirk who suggested turning to the American Medical Association. Kirk contacted the AMA and after some internal consultation the Associations Board of Trustees voted in May 1946 to appoint Dr. Andrew C. Ivey as the AMA's official consultant to the Nuremberg prosecutors. Dr. Ivey was one of America's leading medical researchers at the time. Early in the war Ivey was the civilian scientific director of the Naval Medical Research Institute in Bethesda, Maryland. During the summer of 1946 he was in the process of moving from a position as head of the division of physiology and pharmacology at Northwestern University Medical School to the University of Illinois where he would serve as a vice president with the responsibility for the university's professional schools in Chicago. The precise rationale behind Ivey's selection as the AMA's advisor to the Nuremberg prosecutors remains unclear but it is likely that the AMA turned to Ivey for at least two reasons. First, his wartime research interest corresponded in topic though not in style to some of the most shocking experiments that had taken place in the Nazi concentration camps. Ivey supervised and carried out experiments in seawater desalination sometimes using human subjects with the intent of developing techniques to aid allied pilots and sailors lost at sea. He also conducted some pioneering human experiments in aviation medicine dealing with the physiological challenges posed by high altitudes. These are two of the areas which Nazi researchers had conducted especially gruesome human experiments. Second, Ivey was well known for his energetic defense of animal experimentation against American anti-vivisectionists. For example, he served for eight years as the founding secretary treasurer of the National Society for Medical Research an organization formed by scientists in 1946 to ward off challenges to medical research posed by anti-vivisectionists. It seems likely that the AMA Board of Trustees would have recognized Ivey as someone who possessed an unusual combination of familiarity with the scientific aspects of experiments carried out in the aviation camps and broad understanding of the moral issues at stake in medical research, whether the experimental subjects were animals or humans. Also, Ivey was almost certainly perceived as someone who could be trusted to look out for the interest of the American medical research community during the Nuremberg Medical Trial. The AMA Board of Trustees probably realized that the entire enterprise of medical research would to some degree be on trial in Germany. In July or early August of 1946, Ivey went to Germany to meet with the Nuremberg prosecution team. Ivey offered technical assistance to the lawyers struggling with the scientific details of the experiments, but he also recognized, as he put it, that the prosecutors appeared somewhat confused regarding the ethical and legal aspects of human experimentation. After returning from his initial trip to Europe in aid of the Nuremberg prosecutors, Ivey offered a preliminary oral report to the Board of Trustees of the American Medical Association at the Board's August 1946 meeting. After his presentation, the trustees asked Ivey to provide a written summary of his findings, so that the AMA's Judicial Council, a committee of five whose duties included deliberating on matters of medical ethics, could make a report as to the manner in which these Nazi experiments were infringements of medical ethics. In mid-September Ivey submitted a written report to the AMA as he had been directed. At roughly the same time, he also turned over a copy of the 22-page TypeScript to the Nuremberg prosecution team. In this piece, Ivey laid out the rules of human experimentation. He stated without equivocation that these standards had been well established by custom, social usage and the ethics of medical conduct. Ivey's rules read as follows. One, consent of the human subject must be obtained. All subjects must have been volunteers in the absence of coercion in any form. Before volunteering, the subjects have been informed of the hazards, if any. In the USA, during war, accident insurance against the remote chance of injury, disability and death was provided. This was not true in all cases. Two, the experiment to be performed must be so designed and based on the results of animal experimentation and a knowledge of the natural history of the disease under study that the anticipated results will justify the performance of the experiment. That is, the experiment must be such as to yield results for the good of society unprocurable by other methods of study and must not be random and unnecessary in nature. Three, the experiment must be conducted A, only by scientifically qualified persons and B, so as to avoid all unnecessary physical and mental suffering from injury and C, so that on the basis of the results of previous adequate animal experimentation, there is no a priori reason to believe that death or disabling injury will occur, except in such experiments as those on yellow fever where the experimenters serve as subjects along with non-scientific personnel. A comparison of these roles with the Nuremberg Code, which the Nuremberg Tribunal issued of its judgment on August 19th, 1947, reveals that the three judges extracted important elements of Clause 1 from Ivy's first rule and clauses 2, 3, 4, 5 and 8 almost verbatim from the rest of Ivy's formulation. Significantly, the judges also reiterated Ivy's assertion that these rules were already widely understood and followed by medical researchers. It is possible that the Nuremberg judges never read Ivy's report directly. During his testimony at the trial, Ivy essentially read his set of rules into the court record. Also, the judges could have gained exposure to Ivy's thinking through two additional indirect sources. First, another medical expert who aided the prosecution. An American Army psychiatrist named Leo Alexander admitted on April 15, 1947 a memorandum to the prosecutors entitled Ethical and Non-Ethical Experimentation on Human Beings. In this memorandum, which would have been passed to the judges, Alexander repeated in very similar languages significant portions of Ivy's rules as outlined in the September 1946 report. Second, American prosecutor James McHaney closely followed the text of Ivy's rules when setting before the judges the prerequisites to a permissible medical experiment on human beings. During the prosecution's closing statement on July 14, 1947. But Ivy's standards for human experimentation served as even more than the primary textual foundation for the Nuremberg Code. His set of rules also undergirded the AMA's first formal statement on human experimentation. As the Board of Trustees had directed when asking Ivy to prepare his written report, the finished document was immediately forwarded to the AMA Judicial Council. The Board gave the Judicial Council three months to prepare a presentation for the House of Delegates. The large policymaking body of the AMA that was scheduled to hold an annual meeting in early December 1946. Unfortunately, records of the Judicial Council's consideration of Ivy's report have not survived. But published proceedings of the House of Delegates meeting reveal the results of the Council's deliberations. Dr. E. R. Cuniff, Chair of the Judicial Council, summarized his panel's response to Ivy's report at an executive session of the House of Delegates on December 10th, 1946. The day immediately following the prosecution's opening statement in the Nuremberg Medical Trial. Cuniff condemned the Nazi experiments described in Ivy's report as gross violations of standards that were already inherent in the existing principles of medical ethics of the American Medical Association. Which had undergone only minor revisions that the AMA adopted them in 1847, the first year of the Association's existence. But in recognition of the fact that guidelines for human experimentation were not explicitly laid out in these principles, the Judicial Council offered the following distillation of Ivy's rules. In order to conform to the ethics of the American Medical Association, three requirements must be satisfied. One, the voluntary consent of the person on whom the experiment is to be performed must be obtained. Two, the danger of each experiment must be previously investigated by animal experimentation. And three, the experiment must be performed under proper medical protection and management. These three rules became the official policy of the AMA when the House of Delegates noted its approval, section by section and as a whole, on the morning of December 11th, 1946. The AMA's official governing body also added a general admonition. This House of Delegates condemns any other manner of experimentation on human beings than that mentioned herein. It is worth noting that in 1946 roughly 70% of American physicians belonged to the AMA. In absolute terms, 126,835 physicians belonged to the Association. But it must be acknowledged that membership in the National Association came automatically with membership in county and state medical societies, which was often necessary for professional privileges at local hospitals. Each member of the AMA would have received a regular subscription to the Journal of the American Medical Association. And all of these subscribers would have had an opportunity to read the three rules for human experimentation approved by the House of Delegates. At the same time, however, these rules were not published prominently. They were set in small type along with a variety of other miscellaneous business items in the lengthy published minutes of the meeting. Only an exceptionally diligent member or one with a special interest in medical ethics is likely to have located this item. In mid-June 1947, Ivy took the stand late in the Nuremberg Medical Trial as a rebuttal witness for the prosecution. To counter the claims of the defense that standards for proper conduct in human experimentation were being clearly established before the initiation of the trial. The contents of Ivy's September 1946 report and the AMA standards that arose from it played a major role during his three days of testimony. At one point, prosecution associate counsel Alexander G. Hardy carefully walked Ivy through a verbatim oral recitation of the rules for human experimentation contained in Ivy's report and the condensed version of his rules as approved by the AMA. After a reading of the AMA principles, Hardy and Ivy had the following exchange. Question. Now, do these rules purport to be the principles upon which all physicians and scientists guide themselves before they resort to medical experimentation on human beings in the United States? Answer. Yes, they represent the basic principles approved by the American Medical Association for the use of human beings as subjects in medical experiments. Hearing this specific and obviously important claim about research with human subjects in the United States, Judge Harold E. Sebring interjected with a broad question about the international significance of Ivy's assertion. How do the principles which you have just enunciated comport with the principles of the medical profession over the civilized world generally? Ivy responded. They are identical according to my information. Later in his testimony, Ivy faced cross-examination by Fritz Sodder, counsel for two of the German medical defendants. Sodder pushed Ivy to acknowledge that the AMA guidelines had come into formal existence only as the Nuremberg Medical Trial was getting underway. In response to this attempt to diminish the legal force of the AMA standards with the obvious suggestion that the rules had been made up too recently to be of relevance, Ivy made an explicit claim in court that the ideas inherent in the AMA standards significantly predated their official formulation. Question You told us that an association had made a compilation regarding the ethics of medical experiments on human beings. Can you recall what I am referring to? Answer Yes. Question. That was in December 1946, I believe. Answer. Yes. I remember question. Did that take place in consideration of this trial? Answer. Well, that took place as a result of my relations to the trial, yes. Question. Before December of 1946 were such instructions in printed form in existence in America? Answer. No. They were understood only as a matter of common practice. Thus, if Ivy is to be taken literally, the standards he forcefully articulated during the Nuremberg Medical trial, which were affirmed by the AMA House of Delegates as the trial was just beginning and codified by three American judges as the trial came to an end were the standards of practice at the time. End of section 16 Recording by Melanie Young.