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Home , Nuremberg, Nuremberg Code

DOCTORS' TRIAL

Informed consent in human experimentaton before the

Jochen Vollmann, Rolf Winau

T7his Nuremberg issue of the The issue ofethics with respect to medical experi- BMJ comprises seven mentation in during the 1930s and 1940s papers in this special was crucial at the and related section, editorials by trials of doctors and public health officials. Those Jennifer Leaning and involved in horrible crimes attempted to excuse Donald Acheson, two themselves by arguing that there were no explicit personal views,four news rules governing medical on human items and three book beings in Germany during the period and that reviews. In addition, we are research practices in Germany were not different publishing on from those in allied countries. In this context the pp 1448-9 the Nuremberg Nuremberg code of 1947 is generally regarded as codefrom 1947 and the the first document to set out ethical regulations in Declaration ofHelsinki that human experimentation based on informed was derivedfrom it. All the consent. New research, however, indicates that Nuremberg material is ethical issues of in guidelines available on the BMJ's for human experimentation were recognised as homepage: http:I/ early as the nineteenth century. These guidelines www. bmj. com shed light on the still contentious issue ofwhen the concepts of , informed consent, and therapeutic and non-therapeutic research first emerged. This issue assumes renewed importance in the context of current attempts to assess liabil- ity and responsibility for the abuse of people in various experiments conducted since the second world war in the United States, Canada, Russia, and other nations.

First Prussian directive on informed consent Albert Neisser, 1855-19fi6 The introduction of scientific and experimental methodology into clinical medicine in the nineteenth century brought with it an increased demand for method of syphilis prevention he injected cell free experimentation on human subjects, particularly in serum from patients with syphilis into patients who bacteriology, immunology, and physiology. This were admitted for other medical conditions. Most of research was done mainly on patients in hospital, often these patients were prostitutes, who were neither without their consent, under an "ethos of science and informed about the experiment nor asked for their con- medical progress." As a result of injury to some patients sent. When some of them contracted syphilis Neisser subjected to non-therapeutic research, however, contro- concluded that the "vaccination" did not work. versy and public debate ensued about the ethics of However, he argued that the women did not contract human experimentation.1 syphilis as a result ofhis serum injections but contracted In 1891 the Prussian minister of the interior issued a the disease because they worked as prostitutes. Liberal directive to all prisons that tuberculin for the treatment newspapers published these and other cases, triggering of tuberculosis "must in no case be used against the public debate. patient's will."' But the first detailed regulations about Most academic physicians at the time supported non-therapeutic research in Western medicine came Neisser. An exception was Albert Moll,6 a psychiatrist in from the Prussian minister for religious, educational, private practice in , who collected in his and medical affairs in 1900. They were issued after Physicians'Ethics 600 cases ofunethical non-therapeutic critical public discussion and political debate on the research on humans and emphasised the need for Neisser case in the Prussian parliament and set forth the informed consent. Moll also developed a legally based, Institute ofthe History of legal basis of disclosure and unmistakable consent.' 2 Of positivistic contract theory of the patient-doctor Medicine, Free University particular interest is the debate within the medical pro- relationship, which is widely ignored in current bio- ofBerlin, 12203 Berlin fession and the political circumstances. Jochen Voilmann, professor ethics publications.7 RolfWinau, director and In 1898 the public prosecutor investigated the case, professor and Neisser was fined by the Royal Disciplinary Court. The Neisser case The court ruled that, though Neisser as a well known Correspondence to: In 1898 Albert Neisser, discoverer of the gonococcus medical authority may have been convinced that the tri- Professor Vollmann. and professor of dermatology and venereology at the als were harmless, he should have sought the patients' University of Breslau, published clinical trials on serum consent. Not questionable science but lack of patients' BMJ 1996;313:1445-7 therapy in patients with syphilis. In order to find a consent was the principle for the legal judgment.

BMJ voLuME 313 7 DECEMBER 1996 1445 GOVERNMENT ACTION explanation of the possible negative consequences" of The Prussian parliament also discussed the case sev- the intervention. All research interventions could be eral times and in 1899 asked the government to act. As performed only by the medical director or with his or a result the minister for religious, educational, and her authorisation. In all cases fulfilment of these medical affairs commissioned a detailed report from the requirements as well as all further circumstances of the Scientific Medical Office of Health, which was case had to be "documented in the medical history."' composed ofleading German physicians such as Rudolf Despite all this, however, the directive was not legally Virchow. The commission directed its attention to binding and little is known of its impact on human and autonomy. It concluded that a experimentation. physician who recognised that an injected serum might cause infection had no right to inject such a serum. In any case, both informing the subject and obtaining the Circular ofthe Reich minister ofthe interior: subject's consent were preconditions to experimenta- guidelines for new therapy and human tion. In a handwritten report Emil von Behring argued experimentation, 1931 that, particularly with reference to the Neisser case, self Because of criticism of unethical human experimen- experimentation should always precede experiments on tation in the political press and in parliament as well as patients. He personally held that purely scientific in the context of a political reform of criminal law in experimentation on human subjects was unethical even Germany, in 1931 the Reich government issued if they gave voluntary consent.'4 detailed "guidelines for new therapy and human experi- The minister also sought legal advice on the Neisser mentation." The guidelines clearly distinguished case. Lawyers stated that conducting non-therapeutic between therapeutic ("new therapy") and non- research on a subject without consent fulfilled the crite- therapeutic research ("human experimentation") and ria for causing physical injury in criminal law. The set out strict precautions. scientific validity of the experiment did not serve as Besides the principles of beneficence and non- mitigation. Informed consent was a mandatory precon- maleficence, the regulations were based on patient dition for any non-therapeutic research. Problems of autonomy and a legal doctrine of informed consent. "New therapy may be applied only if consent or proxy coercion, persuasion, and the unequal authority consent has been between doctor and patient were discussed in detail, given in a clear and undebatable man- and the lawyers concluded that respect for rights and ner following appropriate information. New therapy morality had the same importance for the good of man- may be introduced without consent only if it is urgently kind as medical and scientific progress. Written required and cannot be postponed because of the need documentation and clear responsibility of the medical to save life or prevent severe damage to health. . . ." In director for all human experimentation became legal those cases a written report must clearly outline the doctrine. preconditions. But non-therapeutic research was Finally, in 1900 the minister for "under no circumstances permissible without religious, 18 Written and medical affairs a to consent."8 documentation and a clear educational, issued directive all structure of hospitals and clinics. Medical directors were advised responsibility for each clinical trial were that all medical interventions other than for diagnosis, required. Though an early model of institutional review healing, and immunisation were excluded under all cir- boards was discussed, the official guideline adopted the cumstances if "the human subject was a minor or not hierarchical model from the directive of 1900, in which competent for other reasons" or if the subject had not the medical director was responsible for all clinical given his or her "unambiguous consent" after a "proper research in the institution. As later formulated in the Nuremberg code, a careful cost-benefit calculation and a detailed research plan with animal experimentation beforehand were already required to minimise risk to human subjects. Some regulations were even stricter and more detailed than those contained in the Nuremberg code and the much later . Human experimentation on dying patients was absolutely prohibited. Publication of the results of new therapy must respect the patient's dignity and the mandate of humanity. In academic teaching every opportunity should be taken to emphasise the special responsibilities of a physician undertaking clinical trials. Even further, any exploita- tion of social or economic need in testing new therapies was rejected.

Discussion This paper shows that explicit directives concerned with the welfare of people subjected to medical experi- mentation in Germany were in place long before the Nuremberg code was devised in 19479-12 Critical press reports and debate in parliament forced the Prussian government to issue the first directive concerned with medical experimentation in humans in 1900. This directive was based on medical and legal scientific reports. A clear distinction was made between therapeutic and non-therapeutic research, but regula- tions were issued only for non-therapeutic research. The regulations were based on the principle of I autonomy and represented an early model of informed i_ _ consent. A "proper explanation of the possible negative Medical experimentation on a metabolic ward of the Kaiserin Auguste Victoria Haus, Berlin, in consequences" of the intervention and "unambiguous the 1920s consent" became the mandatory standard. In addition,

1446 BMJ VOLUME 313 7 DECEMBER 1996 legal reports carefully discussed aspects of coercion, persuasion, and imbalance of authority between patient Key messages and doctor just as in contemporary work.'3 Minors and incompetent subjects were generally excluded from * The Nuremberg code of 1947 is widely regarded non-therapeutic research, as they could not give valid as the first document providing ethical regulations informed consent. in human research on the basis of informed We conclude that at the turn of the century informed consent consent was already a legal doctrine in medical experi- * New research has uncovered ethical issues of mentation in Germany, being based on "unambiguous informed consent in human experimentation as consent" of the subject after "proper" information had as the nineteenth been given by the doctor, including negative conse- early century quences and side effects. Interestingly, the regulations * Regulations were not initiated by the medical were not initiated by doctors or research institutions but profession but were issued after critical public dis- were issued by government authorities. However, it cussion and political debate remains an open question how informed consent was * Basic elements of the modern legal concept of applied by doctors in research and clinical practice and informed consent can be found in these early regu- how it shaped the individual doctor-patient lations relationship. 14-16 * These early regulations were not binding in the The guidelines issued by the Reich government in legal sense and little is known about their actual 1931 regulated therapeutic and non-therapeutic impact on research in human subjects. Whereas without exception non-therapeutic research could be performed only with the subject's informed consent, therapeutic research could be performed without explicit consent but only in at the time, these did not prevent crimes against a medical emergency and if it was deemed to be in the humanity by part of the German medical profession.9'2 patient's best interest. The second part of the Prussian directive of 1900 defined a structure of responsibility in medical We thank Mrs M A Shiffman for help with the English trans- institutions. Because of the hierarchical structure in lation and Dr Thomas Lennert (department of paediatrics, German hospitals only the medical director and Free University of Berlin) for the photograph of the medical physicians authorised by the medical director were experiment at the Kaiserin Auguste Victoria Haus. allowed to conduct research on human subjects. Funding: Deutsche Forschungsgemeinschaft (German However, in no case of injury to a patient by Research Council; grant Vo 625/1-3). experimentation was the issue of responsibility contro- Conflict of interest: None. versial, as all medical directors and professors declared their personal responsibility. This hierarchical model of 1 Tashiro E. Die Waage der Venus. Venerologische Versuche am Menschen zwischen responsibility, also found in the Reich government's Foruschritt und Moral. Husum: Matthiesen, 1991. guidelines of 1931, differs from the modern concept of 2 Elkeles B. Medizinische Menschenversuche gegen Ende des 19. responsibility in clinical research. Under current Jahrhunderts und der Fall Neisser. Rechtfertigung und Kritik einer wissenschaftlichen Methode. Med HistY 1985;20:135-48. concepts the individual researcher is personally respon- 3 Winau R. Vom kasuistischen Behandlungsversuch zum kontrollierten sible for his or her actions and ethical issues are assessed klinischen Versuch. In: Helmchen H, Winau R, eds. Versuche mit Menschen. Berlin: de Gruyter, 1986. by peers on institutional review boards. 4 Lederer SE. Subjected to science. Human experimentation in America before the For the first time in history informed consent, the second world war. Baltimore: Johns Hopkins University Press, 1995. research process, and explicit clarification of personal 5 Official Regulations as to Tuberculin in Germany and . JAMA 1891;16:492. (Original German publication: Ministerial-Blatt Par die responsibility for the experiment were required to be gesamte innere Verwaltung in. den Koniglich Preup5ischen Staaten 1891;52:27.) included in the medical record. In addition, issues of 6 Moll A. Arztliche Ethik. : Enke, 1902. 7 Schultz JH. Albert Moils Arztliche Ethik. Ziirich: Juris, 1986. written research plans with a risk-benefit assessment, 8 Luther E, B. Das hippokratische Ethos. Untersuchungen zu Ethos und the need for previous animal experimentation, and Praxis in der deutchen Arzteschaft. (Saale): Wissenschaftliche Beitrage der Martin-Luther-Universitat Halle-Wittenberg, 1967. medical self experimentation were raised. Though a 9 Mitscherlich A, Mielke F. Wissenschaft ohne Menschlichkeit. Medizinische und system ofpublic health insurance existed in Germany in eugenische Irrwege unter Diktatur, Burohratie und Krieg. : 1931 and health care for all Lambert Schneider, 1949. (English translation: Doctors ofinfamy. The story provided good citizens, ofthe Nazi medical crimes. New York: Schuman, 1949.) issues of social and the protection ofpoor people 10 Muller-Hill B. Todliche Wissenschaft. Die Aussonderung von Juden, Zigeunern in medical research were regulated. We question und Geisteskranken 1933-1945. Reinbeck bei : Rowohlt, 1984. 11 Kater MH. Doctors under Hitler. Chapel Hill: University of North Carolina whether the healthcare system in the United States Press, 1989. would meet these regulations, many patients without 12 Caplan AL (ed). When medicine went mad. and . Totowa: Humana Press, 1991. health insurance having no access to regular medical 13 Faden RR, Beauchamp TL. A history and theory of informed consent. New treatment. In order to obtain medical help these patient York: Oxford University Press, 1986. must rely on free experimental treatment in research 14 Katz J. The silent world ofdoctor and patient. New York: Free Press, 1984. 15 Pernick MS. The patient's role in medical decisionmaking: a social history of institutions without having a choice whether to give free informed consent in medical therapy. In: President's Commission for Study and autonomous informed consent. of Ethical Problems in Medicine and Biomedical and Behavioral Research, ed. Making health care decisions. Vol 3. Washington, DC: US Though present conceptions of informed consent Government Printing Office, 1991. differ from those in the Prussian directive of 1900 and 16 Vollmann J. Das Informed Consent-Modei als Politikum in derMedizin. Patien- tenauflerung und Einwidligung aus historischer und medizinethischer the Reich government's guidelines of 1931, some basic Perspektive. am Main: Suhrkamp (in press). elements can be identified in postwar regulations"7 18 17 Annas GJ. The changing landscape of human experimentation: with issues of human Nuremberg, Helsinki and beyond. Health Matrix Law Med 1992;2:119- together many ethical 40. experimentation."92' Our primary objective was to show 18 Sass HM. Reichsrundschreiben 1931: pre-Nuremberg German regulations that the basic concept of informed consent was concerning new therapy and human experimentation. J Med Philos 1983;8:99-1 11. developed long before the second world war and before 19 Beecher HK. Ethics and clinical research. NEnglJMed 1966;274:1354-60. Nazi crimes in Germany, not on the initiative of the 20 Katz J. Experimentation with human beings: the authority of the investigator, subject, professions and the state in the human experimentation process. New medical profession or research community but as a legal York: Russell Sage Foundation, 1972. doctrine by government authorities. The guidelines of 21 Jones JH. Bad blood2 the Tushegee syphilis experiment. New York: Free Press, 1931 were not annulled in , when unethi- 1981. 22 Advisory Commnittee on Human Radiation Experiments. Final repr. cal experiments were performed by German doctors in Washington, DC: Government Printing Office, 1995. concentration camps. Though no other nation seems to 23 Smith R. Time to face up to research misconduct. BMJ 1996;312:789-90. have had such ethically and legally advanced regulations (Accepted 28 October 1996)

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