- - Hans-Martin Sass, M.D.
Zentrum Medizinische Ethik, Ruhr Universitaet
Postfach 102148, D-44780, Bochum, , GERMANY
Eubios Journal of Asian and International Bioethics 13 (2003), 102-4.
At the end of the 19th century the Prussian government on December 29, 1900, issued regulations on human experimentation . The directives were published in the official publication of the Prussian Ministry of Religious, Educational and Medical Affairs, a publication similar to the Federal Register in the United States. These directives are the first modern regulations by a state authority. They are specifically and exclusively directed at medical research and point out 'that medical interventions for purposes other than diagnosis, therapy, and immunization are absolutely prohibited, even though all other legal and ethical requirements for performing such interventions are fulfilled if: (1) the person in question is a minor or is not fully competent on other grounds; (2) the person concerned has not declared unequivocally that he consents to the intervention (3) the declaration has not been made on the basis of a proper explanation of the adverse consequences that might result from the intervention' [8; 2:217]. For purposes of diagnosis, therapy and controversial immunization programs other guidelines had been issued before. Given the bureaucratic character of the Prussian state and culture, it would be unthinkable that those ministerial directives would not have been treated with the utmost respect and introduced and obeyed in the most rigid way. The rigidity of the directives is shown by the fact that research on children and noncompetent persons under no circumstances would be allowed and that bending those rules be absolutely prohibited.
While the Prussian directive covered most of the northern part of the German Reich and the majority of the German population, the Reich Health Council (Reichsgesundheitsrat), a central political body advising the Reich government and including representatives of the chambers of physicians, surgeons, and pharmacists, and also Sickness Fund representatives and various representatives of central ministries issued more detailed guidelines on new therapy and an human experimentation in 1931. Forms to be signed by all physicians seeking employment in open or closed health care facilities included these regulations, thus were part of the employment contract. Membership in medical professional organizations was mandatory and health care institutions and professional organization were required to implement those guidelines after they were published by the Reichsminister of the Interior. The 'Final Circular of the Reich Minister of the Interior concerning Guidelines for New Therapy and Human Experimentation', dated February 28, 1931, was binding law throughout the existence of the German Reich. For still unknown reasons, the Reich regulations were not included in the Omnibus Law (Ueberleitungsgesetz) passed by the Bundestag after 1948, which transported hundreds of laws and regulations of the Reich into the Federal Republic's legal structure.
The Nazi experiments on prisoners, children and other vulnerable populations thus violated the Reich regulations on legal grounds and on grounds of professional self-regulation. While the Reich regulations were more detailed than the Prussian instructions, they accepted experimentation with children if minimal risk could be guaranteed, not outlawing those altogether as the Prussian instructions did, but calling them impermissible 'if it endangers the child or minor in the slightest degree'.
The Reich regulations included another paragraph never repeated in subsequent regulations or, guidelines: 'Experimentation with dying persons conflicts with the principles of medical ethics and therefore is impermissible'[9:106]. To my knowledge, no other national or international legal or professional guidelines on medical research has addressed the immorality of experimenting on dying fellow humans, even though there is ample anecdotal evidence that clinical trials, experimental surgery, and even teaching and hands-on medical training do not respect the dignity of the dying. Also, the Reich Regulations expressively address the importance of research ethics to be taught in medical education, an issue not mentioned in recent guidelines or regulations on medical research [9:14].
Elsewhere I have described other groundbreaking features of the 1931 Reich Regulations [9;12]; in general, they were more strict than the Nuremberg Code of 1946, the various editions of the Helsinki-Tokyo Declaration and other regulations [13;15]. They, as the Prussian directive before, make the medical head of the institution personally and professionally unequivocally responsible for the design, implementation, and review of human experimentation [8;9], a remarkable difference to regulations in force today. The approval of a committee or other collective body was not mandated; the Prussian instruction writes: 'interventions of this nature may be performed only by the director of the institution himself or with his special authorization' [8:II.1].
Medical Research Tribunals In Nuremberg And Japan
Starting in October 1946, after the conclusion of the Nuremberg Military Tribunal under Control Law of the four victorious countries Britain, France, Soviet Union and United States, the United States with approval of the other allied powers in 'United States vs. Karl Brand et al.'  began prosecuting 23 German physicians who during the Third Reich ordered, performed or probably were aware of cruel and immoral human experimentation. The court judges were exclusively United States judges, so were the expert witnesses Ivy and Alexander . But they did not prosecute on the basis of German laws and regulations governing human experimentation and criminal activity in force during the Third Reich, as the defendant physicians requested and, given the existence of those laws and regulations, as legal experts and reasonable people would have expected .
In the absence of specific laws or regulations within their own country, the judges referred instead to the 'Hippocratic Oath' and the principle of 'crime against humanity'. Ivy and Alexander went at length to elaborate on the Hippocratic principle of no-harm. Alexander wrote a memorandum 'Ethical and Non-Ethical Experimentation on Human Beings' [2:135]. This memorandum and sections of Ivy's statement were incorporated in the closing arguments in July 1947 by James McHaney, the chief prosecutor. McHaney mentioned the absence of animal experimentation, the lack of consent, poor design, and unproven expectations 'to yield results for the good of society'. He also held: 'If there is a priori reason to believe that death or disabling injury might occur, the experimenters must serve as subjects themselves, along with the nonscientific personnel. .. But important as these other considerations are, it is the most fundamental tenet of medical ethics and human decency that the subject volunteer for the experiment after being informed of its nature and hazards. This is the clear dividing line between the criminal and what may be noncriminal. If the experimental subjects cannot be said to have volunteered, then the inquiry need proceed not further. Such is the simplicity of the case' [2:137]. In their final judgment the court used the language in Alexander's memorandum to summarize its position in what is now known as the Nuremberg Code [18, vol 2:181-182; 2:2]. In its judgment the court had edited out of Alexander's memorandum the issues of proxy consent and of incompetent patients involved in research [2:135,139].
In retrospect, the origins of the now famous Nuremberg Code are associated with legal ambiguity and questionable legal and moral authority. The court proceedings violated essential principles of legal philosophy and conduct: (a) they did not prosecute on the basis of existing German law; (b) they arbitrarily and high-handedly wrote a 'code' and published that code on which they based their judgment only together with that judgment; (c) they thus violated the legal maxime 'nulla poena sine jus', no punishment without a law established prior to the persecution based on that particular law. A court decision based on existing German law at the time when the Nazi crimes were performed would have been the correct and only legal remedy; it might have resulted in higher sentences than 7 death penalties and 16 convictions for crimes against humanity. It is still a mystery why the Nuremberg Code has been eulogized as the most prominent cornerstone of modern research ethics.
During the time of the Nuremberg military trials, the United States military investigated similarly cruel experiments by the Japanese infamous Unit 731 in China before and during the Second World War, 1932-1945, primarily bacteriological and chemical warfare experiments [4;5;6]. The United States seemed to be interested in the results of those experiments, including methods and bacteria used, protocols and results. In return for an amnesty and total immunity from any further prosecution Dr. Ishii, the infamous head of Unit 731, wrote an extensive account of his two decades of biological warfare experiments. Other experimenters produced thousands of slides and summaries of field tests, including a 600-page report on warfare experiments involving natural and artificial plague [4;5;17]. The US State-War-Navy Coordinating Committee stated that these materials were 'of great value in confirming, supplementing and complementing several phases of US research in biological warfare, and may suggest new fields for future research'. The material and the 'business' dealings with the Japanese were kept secret. Nobody ever was prosecuted for those experiments, neither by Japanese nor by the victorious US authorities.
Open questions, still unanswered today, are abundant: Why were German and Japanese physicians treated differently by the United States and the military? Did the US have access to the results of the German experiments without having to grant immunity first, or were the Japanese experiments 'better' or more 'valueable' in design or results? What kind of research were the US involved in, to which the Japanese protocols were 'of great value in confirming, supplementing and complementing several phases of US research in biological warfare'  ? The American Medical Association published her first guidelines on human experimentation in 1945; the Helsinki Declaration of 1964 was adopted in 1966. Finally, 74 years after the Prussian Instructions, the US Department of Health Education, and Welfare published guidelines for the 'Protection of Human Subjects'  in 1974.
The Continuing Challenge To National And Cross-National Bioethics
While the Nuremberg trials made headlines all over the globe, particularly in Europe and the United States, the negotiations with the Japanese were conducted in secret and kept secret. The only early source of information about the Japanese atrocities was a 1950 publication out of Moscow, which correctly described few of the horrendously cruel Japanese experiments, but was thought to be associated with propaganda at the beginning of the Cold War . Also, Chinese local newspapers reported about tens of thousands of humans and animals of plague in Harbin province at the end and after the end of Japanese occupation in China . It is still unknown why the United States not long after 1960 returned the Japanese files to Japan after having paid the high price of complacency and pardoning unpardonable crimes and cruelties against innocent people.
The publication of Beecher's book on human experimentation in the US  documented the very limited influence the Nuremberg Code and the publicity around it had and how little those trials on the attitude of many people in medical research. The report on radiation experiments  seems to underline a low impact of national or international guidelines and of the various revisions of the Helsinki Declaration [6:165; 9]. In December 1990 the US Food and Drug Administration published regulation permitting that the requirement for obtaining informed consent from human subjects prior to the use of experimental drug or vaccine could be waived for military personnel participating in the Desert Storm battle. The US Department of Defense had requested such a waiver [2:346-352] based on the argument, that 'military combat is different'. We now know that if not the vaccines but their combination was not tested prior to inoculation, resulting in diseases of yet undetermined or not publicly admitted and described nature. But the courts in 1990 refused to intervene for the protection of soldiers from unapproved drug in voicing 'the primary purpose of administering the drugs is military, not scientific. The Department of Defense's decision to use unapproved drugs is precisely the type of military decision that the courts have repeatedly refused to second-guess' [2:216].
In general, the ethics of human experimentation has been left behind the progress of medical research. Anecdotal narratives tell that pharmaceutical companies or their subcontractors perform pilot studies without regulatory oversight or subject information or consent in countries with little or no regulatory structure prior to starting official clinical research procedures in more strictly regulated countries in which they seek approval. Often Western-style informed consent forms are used in cultures where tribal, familial or individual decision making is different from the West, thus making the formal process of obtaining consent a cynical mockery of the original concept. The US government returned essential material, which very likely could have documented crimes against humanity by Japanese physicians. The Japanese government which previously called for those experiments now harbors the experimenters and makes those files inaccessible. Both sides still protect prospective war criminals and suppress access to the evidence and facts of what really happened to those fellow humans who were unfortunate enough to be the victims of those crimes.
Recently, the 'Washington Post' reported that lawyers of the Johns Hopkins affiliated Kennedy Krieger Institute in Baltimore argued that 'researchers have no legal obligations to those in their research studies'. While two lower courts had thrown out the complaints of parents, whose children were involved in hazardous lead exposure experiments and who claimed that they had not been adequately informed of the health risk involved, the Appeals Judge rejected the arguments of the two lower courts; the lawsuit will now go forwards. The 'Washington Post' in second-guessing the Appeal Court judge's decision chose the headline 'The judge went too far' .
The lessons learned from the hypocritical complacency of governments with criminal human experimentation, even negotiating for its share of the results of those experiments and for keeping documents and evidence out of the public eye and scrutiny, are multifold. They are particularly cumbersome, as attitudes associated with such a behavior do not seem to have subsided much. Elsewhere I have suggested that the outdated soft-paternalistic principle of informed consent be replaced by an informed contract model outlining not only issues of information and compliance of probandi or patient but delineating rights and obligations of all parties involved: sponsors, physicians, patient, probandi and their families [13;14;15].
To break the vicious cycle of unacceptable attitudes and to replace rules written on paper by moral and medical resolve and ethics the most important suggestion, however, was and still is the one made in article 14 of the Reich Regulations 1931: 'In academic teaching, already, every opportunity should be used to stress the special duties of a physician undertaking New Therapy and Human Experimentation' [9:106]. The rules for ethically responsible human research were all written on paper in Germany in 1900 and again in 1931. The Nazi doctors choose to look the other way. In their company are those who associate themselves one way or the other with those or similar crimes against fellow humans in using them as guinea pigs. Medical ethics education, good role models and an educated public might be more effective in changing attitudes and in preventing harm from most vulnerable individuals and populations, where laws and regulations have failed.
1. Alexander L (1976) Ethics of Human experimentation. Psychiatric Journal of the University of Ottawa 1:40-46.
2. Annas GJ, Grodin MA (1992) The Nazi Doctors and the Nuremberg Code. New York NY: Oxford U Press.
3. Beecher H (1970) Research and the Individual Human Subject. Boston: Litte Brown.
4. Chen YF (1997) Japanese death factories and the American cover-up. Cambridge Quarterly of Healthcare Ethics 6:240-242
5. Harris S (1995) Factories of Death: Japanese Biological Warfare 1932-1945 and the American Cover-Up. New York: Routledge.
6. Kimura R (1997) Verbrechen gegen die Menschlichkeit. Ethik und Medizin, Troehler U, Reiter-Theil S eds, Goettingen: Wallstein, 161-170.
7. NN (2001) Editorial: The judge went too far. The Washington Post, Oct 12.
8. Preussisches Ministerium fuer Religion, Unterricht und Medizin (1900) Instruktionen fuer die Direktoren der Krankenanstalten und andere medizinische Einrichtungen. Centralblatt der gesamten Unterrichtsverwaltung in Preussen 2000, 188-189 [Engl. transl.: Annas GJ, Grodin MA (1992) The Nazi Doctors and the Nuremberg Code. New York NY: Oxford U Press, 127}.
9. Sass HM (1983) Reichsrundschreiben 1931: Pre-Nuremberg regulations concerning new therapy and human experimentation. J Med Philos 8:99-111 [reprint of German original and English translation].
10.Sass HM (1988) Comparative models and goals for the regulation of human research. The Use of Human Beings in Research, eds Spicker SS, Alon I, de Vries A, Engelhardt HT. Boston: Kluwer, 47-89.
11. Sass HM (1989) Ethics of Drug Research and Drug Development Arzneim.Forsch./Drug Res. 39 (II) 8a:1041-1047
12. Sass HM (1997) The Nuremberg Code, German law, and prominent thinkers. JAMA 277(9):709.
13. Sass HM (2000) Ethica Decision Making in Committee. Convivium Revista de Filosofia 13:148-165.
14. Sass HM (2001) A 'contract model' for genetic research and health care for individuals and families. Eubios J Asian and Intern Bioethics 11(5):130-132.
15. Sass HM (2001) Brauchen wir neue klinisch-ethische Modelle in der medizinischen Forschung? Wien Klin Wochenschr 113/22:863-866.
16. Soviet Union, NN (1950) Documents on trial against the former Military Personnel prosecuted for the Preparation and Use of bacteriological Warefare Weapon. Moscov: Foreign Books Publishing Press.
17. United States Navy (1947) Naval Aspects of Biological Warfare; Appendix XIII: Biological Warfare in Japan. Washington DC: The National Archive [classified publication at that time; only later made public].
18. United States. Military Tribunal 1, Case 1 (1949) United States versus Karl Brand et al.. Washington DC: US Governmental Printing Office [vol. I, 1004pp; vol. II,352pp].
19. United States. Department of Health, Education, and Welfare (1974) Protection of Human Subjects. Federal Register 39:18914ff.
20. United States. Advisory Committee on Human Radiation Experiments (1995) Report. New York: The Free Press.