THE FALL AND RISE OF RESEARCH ETHICS

The year 1998 marks the 60th anniversary of a series of events that took place in Austria that, among other disastrous consequences, turned a university that had been a beacon of medical and scientific scholarship into an arm of Nazi propaganda and genocide. In March of 1938, more than half of the medical faculty senior staff of the University of Vienna–the Jews and other "undesirables"–were expelled, concomitant with the annexation of Austria into the Third Reich.

Wolfgang Schütz

Ten years ago, on the 50th anniversary of the annexation and the expulsion, there was silence in Austria, Wolfgang Schütz, dean of the medical faculty of the University of Vienna, told an NIH audience earlier this year. But today, he said, his country, his university, and the medical profession are bent on remembering. They are investigating the university’s history between 1938 and 1945 and beyond, and the university calendar is dotted with commemorative assemblies.

"We are constantly evoking the memory of all these events because the medical profession must ever be vigilant to the challenges they represent. It is incumbent upon the medical profession to recognize its role in the Holocaust," Schütz avowed at an NIH symposium on "Medical Research Ethics at the End of the 20th Century: What Have We Learned?"

The symposium was sponsored by NIH, the United States Holocaust Memorial Museum, the New York Academy of Medicine, and the Austrian Embassy. The NIH coordinating committee included Robert Nussenblatt, NEI scientific director; Pablo Gejman, head of molecular investigation in the NIMH Clinical Neurogenetics Branch; Michael Gottesman, deputy director for intramural research; Ezekiel Emanuel, director of the Department of Clinical Bioethics; and Alan Sandler, head of the Office of Human Subjects Research who coordinates the institutional review boards (IRB) for NIH clinical protocols.

The symposium addressed the complicity of German and Austrian physicians in the Third Reich’s "ethnic cleansing" crusade and the postwar efforts by a horrified world citizenry to establish codes of ethics to prevent future medical atrocities–including, on an international level, the Nuremberg and Helsinki codes; nationally in the United States, the IRB network and commissions for the protection of human subjects of biomedical research; and, on the NIH campus, the Clinical Bioethics Department and Ethical Grand Rounds.

"Our intent," Nussenblatt said later in an interview, "was not to dwell on the past but to use the historical framework to show why controls are necessary, to reflect on the philosophy of medicine, the ethical focus–especially important now with the rejuvenation of clinical research on campus. We wanted a positive message–to reconfirm clinical research in an ethical context."

The symposium was nearly two years in the organizing. The seeds were planted when Nussenblatt and Gejman attended a lecture series at the Holocaust Museum on Nazi medicine and there met Karl Holubar, a professor of dermatology and head of the Institute for the History of Medicine at the University of Vienna–and one of the driving forces behind the university’s investigation into the activities of its medical community during the Holocaust.

Another impetus for the meeting–and an issue NIH had to address–was that the NIH library houses the Pernkopf Atlas, a meticulously detailed, vividly drawn tome of human anatomy for decades viewed as a masterwork of medical art and now the subject of intensive investigation at its place of origin, the University of Vienna. Eduard Pernkopf, an anatomy professor at the university, was a dedicated Austrian Nazi who became dean of the medical faculty in 1938 and rector of the university in 1943. The suspicion is that the subjects for his depictions were shipped to him from prisons and concentration camps.

After much discussion, Nussenblatt said, it was decided that the Pernkopf Atlas would remain available in the NIH library, with a proviso accompanying the computer reference and the work itself regarding Pernkopf’s history and the questionable source of his drawings. A similar information sheet accompanies copies of the atlas at the University of Vienna, pending the outcome of the investigation, to be released later this year.

Theresa Magone

But when Teresa Magone, now a visiting fellow at the NEI Clinical Branch, had her anatomy training during her first two years of medical school at the University of Vienna Medical Faculty in the early 1990s, the unadorned Pernkopf Atlas was the text. "I am shocked that I could go through school and not be informed of this," she said during the symposium question-and-answer period. It was only after she came to NIH in 1995, where she interned for three months in the Clinical Center’s bioethics program and attended the Holocaust Museum lecture series, that she learned "the whole Pernkopf story" from Nussenblatt, she said in an interview.

Responding to Magone during the NIH symposium, Schütz assured her that the Pernkopf inquiry is "only the beginning of a more detailed investigation." He and other speakers–Austrian, German, and American–were unflinching in their discussions of potential and actual perversions of medical ethics.

Looking back and forward: (top row, left to right): Michael Gottesman, NIH; Wolfgang Schütz, University of Vienna, Robert Proctor, Penn State University; Michael Wunder, Protestant Foundation of Alstrersdorf, Germany; Karl Holubar, University of Vienna; Robert Nussenblatt, NIH; (bottom row, left to right): Barbara Mishkin, Hogan and Hartson; James Childress, National Bioethics Advisory Commission; William Seidelman, University of Toronto; Pablo Gejman, NIH

Schütz faulted the Austrian medical hierarchy for the fact that "after the reich collapse, most of those with a Nazi past remained in office. Pernkopf finished his notorious atlas and co-authored a work on euthanasia of retarded children and adults. . . . A progression of past Nazis held their places in Vienna’s universities."

But his nation and his profession have slowly come to grips with the past: In the 1980s, he said, an IRB-equivalent system was developed in his country, and courses in medical ethics and the history of medicine emerged. In 1991, the country as a whole took responsibility for its support of the annexation, and in 1997 the Pernkopf Commission was officially constituted to investigate the connection between the atlas and the death camps.

Robert Nussenblatt   "It was an introspective day for NIH, it gave us the opportunity to understand what a duty and honor it is to be a physician."

Jeremiah Barondess, president of the New York Academy of Medicine and professor emeritus of clinical medicine at Cornell Medical College in New York, pointed to the Tuskegee syphilis study as an example of "problematic research in this country, too." He observed that the United States had also had its proponents of eugenics and involuntary sterilization.

Barondess advised his audience to recognize that the majority of German physicians embraced National Socialism and responded with alacrity to the state’s call to help "prevent the disabled from overwhelming the abled. . . .[They] performed selections in concentration camps, experimented on the nonconsenting and nonwilling, and reported their results in medical journals on race hygiene." He asked U.S. physicians to consider the implications of any differences now in treatment in this country among different races and classes. He cautioned that yet another hierarchy based on genotype lies waiting in the wings.

Robert Proctor, professor of the history of science at Penn State University, in University Park, Penna., cautioned against "demonizing" Nazi physicians, lest "we forfeit our ability to understand how this can happen."

With a series of cartoons and posters published in Germany in the 1930s, Proctor illustrated the advanced understanding and public policy of the German public health establishment with regard to cancer prevention and the dangers of cigarettes, alcohol, and environmental carcinogens. Smoking was banned in factories and damned as a major cause of lung cancer and angina. Asbestos was targeted as the culprit in mesothelioma and lung cancer.

Amends: Karl Holubar (left), director of the Institute for the History of Medicine at the University of Vienna, apologizes for his country's past to Czech physician and researcher Tomas Radil, professor of psychiatry at Charles University, Prague, who as a boy survived Auschwitz. The dia logue unfolded as the NIH symposium ended, with Radil requesting: "I want someone to tell me and the tens of thousands of us who are still here: 'We are sorry.' No one has yet." Holubar came forth and responded: "We do repent. We are sorry" -upon which Radil observed: "Yes, those who are sorry are always those who did nothing wrong."	Posters warned pregnant women not to drink alcohol or smoke; the world’s first brochure on the need for breast self-exam appeared in Germany in 1936; other posters admonished Germans to eat whole-grain bread and to pay as much attention to their colons as their cars and get themselves screened for cancer once a year. There were also numerous depictions of Jews and other non-Aryans as diseased races. "The ordered, hygienic state [was the] ethic of Nazi medical practice," Proctor said. Symposium proceedings will be published in the Journal of Clinical Ethics. A videotape of the symposium is on-line at http://www2.cc.nih.gov/nih/symposium/. There is a link to the required software -- RealPlayer 5 -- at the site.	Michael Gottesman   "We are balancing the inherently moral content of what we do as clinical researchers at NIH with the autonomy and rights of the patients."
	Science: Then and Now Twin studies at Auschwitz, said William Seidelman, professor of family and community medicine at the University of Toronto, were peer reviewed and approved at the Kaiser Wilhelm Institute. (A twin study example: One twin was injected with typhoid and the other killed when the first one died; their organs were then compared.) Tracking the fall of what had been the "finest" medical community in the world, Seidelman asked his colleagues: "Are we less susceptible to seduction? Are we guileless in fighting for grants? Are we ever contemptuous or intolerant of patients who are incontinent, unwashed, insane, incurable?" Among issues to ponder today, he advised, are the relationship of the physician to the state, the inherent conflict between individual and population health, the role of the physician in determining which genetic characteristics are desirable and undesirable, the selection of patients for therapy and the denial of therapy, physician-assisted suicide and euthanasia, science as a vehicle for social change, and the individual physician conscience in the face of institutional brutality.

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Ethics Grand Rounds at NIH Ethics Grand Rounds are now a feature of clinical research at NIH. Four to six times a year, the ethical questions and decisions arising from an actual Clinical Center case will be open for public view and review, according to Ezekiel Emanuel, director of the Department of Clinical Bioethics. The whole idea of Ethics Grand Rounds is "not to criticize or point fingers or be ethics police, but to engage in serious discussion about real cases," Emanuel said in opening remarks at an Ethics Grand Rounds held in May to review a case emanating from the NIMH geriatric psychiatry branch involving informed consent from a cognitively impaired research subject to participate in an Alzheimer’s disease study. The issues that arose were whether the woman herself was competent to give consent or to designate a proxy and whether the chosen individual was acceptable as a proxy. Decisions had been made with the help of an NIH bioethics consultant. At Grand Rounds, the facts of the case and rationale for decisionmaking were presented; an independent review was offered by invited discussant Paul Applebaum, director of the law and psychiatry program at the University of Massachusetts Medical School in Worcester. The issue of informed consent involving mentally impaired patients was also on the agenda at the last meeting of the NIH Advisory Committee to the Director (ACD). NIMH director Steve Hyman summarized recommendations that emerged from a workshop to devise additional IRB safeguards to protect vulnerable individuals involved in human research. Among them were ensuring that at least one IRB member be qualified to represent the subjects of the research under review, that patient advocates be voting members of the IRB, and that an individual’s capacity to consent be based on appreciation of the risks and benefits–an understanding that risks and benefits are not abstractions but actual possibilities in that person’s life. The consensus at the workshop and at the ACD meeting: It would be in everyone’s worst interest not to study such disorders as Alzheimer’s disease, manic-depression, and alcoholism as a result of unachievability of perfection in informed-consent criteria.

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