First do no harm†
Authors: Adrian Reuben
Journal: Hepatology (2005)

At first thought, there would appear to be little or no obvious connection between Landmarks in Hepatology and the essay recently published in the New England Journal of Medicine by 1986 Nobel Peace Prize Laureate Elie Wiesel.1 In 40 articles published over the past 4 years, the Landmarks series has not only documented the background of numerous discoveries in hepatology that have resulted from observation and experimentation, but it has also celebrated the physicians and investigators who brought us these new hepatological insights, investigations, and therapies. The Landmarks essays have been embellished with play on words and other attempts at humor, biography, history, politics, and the arts, and have presented for the readership abstruse facts and historical trivia to enhance the appreciation and enjoyment of the science and clinical innovation of hepatology. In contrast, Professor Wiesel's essay reminded us of one of the saddest eras in medical experimentation that serves as an archetype for inhumanity perpetrated by physicians, often but not always in the name of science, on hapless human subjects who had no choice but to participate in the most cruel and brutal experiments. It goes without saying that there was no semblance of informed consent. Wiesel refers, of course, to the medical experiments carried out by Nazi physicians and their henchmen and lackeys during the Dark Age known as the Third Reich. Out of this sordid experience, portrayed in the accounts of survivors and eyewitnesses, historical documents, and in the testimonies of those physicians who faced the Nuremberg Tribunal, ethical rules for experimentation on patients and volunteers were codified2 (Fig. 1). Surely, however, there is no connection between the celebration of hepatological discovery and the perversion of Nazi medical brutality—but there is. And because there is we have the opportunity, justification, and, in fact, the duty to confront the memory of these events so as to reinforce our vigilance and determination to uphold the highest ethical standards in hepatology and, indeed, in all of medicine, be it experimental science or routine clinical practice. This connection between discovery in hepatology and cruel experimentation was personified by one of the most prestigious and prodigious investigators in liver disease in the 1920s and 1930s; namely, Hans Eppinger. Observant and perceptive readers of Landmarks in Hepatology will surely have noticed that until now there has been no mention of Hans Eppinger nor any reference to his many contributions in the field. This purposeful exclusion came about, rightly or wrongly, because I felt unable to honor this physician-scientist for his early discoveries, knowing full well about his later utterly ethically unacceptable activities as a medical leader, physician-scientist, and human being. This month's article will therefore redress the balance with respect to both components of that man's extraordinary career, which ended ignominiously in self-destruction. My decision to revisit those tragic events was not taken lightly; it is also in full keeping with the commitment expressed in the first paragraph of the very first article in this series,3 which promised enlightenment in order to avoid repetition of past mistakes. Whereas it is hard to believe that anything as terrible as occurred under the auspices of Nazi medicine could happen now or in the future, we can never be reminded too often of the needs for obtaining true informed consent, for full disclosure in explaining the likely outcome of our actions as physicians, and of partnering with rather than patronizing our patients and study volunteers. Physicians have an abiding responsibility toward their patients and experimental subjects, whose rights must be protected and championed even when the good of the community, of the state, and of humankind appears to be at stake. It is timely to address this issue now in the closing days of the year that simultaneously commemorated the 60th anniversary of the liberation of the Nazi extermination camps at the end of the Second World War and saw the wide distribution and acclaim of the movie Hotel Rwanda, which poignantly and painfully chronicled a recent modern genocide so graphically. We have yet to learn the full extent of physician participation and complicity in the abuse and torture of detainees at Abu Ghraib.4, 5 To paraphrase Elie Wiesel in his interview with Professor Georg Klein6 on December 10, 2004, in connection with the Nobel Peace Prize that he was awarded for his work on genocide and for his message of peace, atonement, and human dignity, "It was not hatred that perished at Auschwitz….only the victims died." Hans Eppinger was born in Prague in 1879 supposedly into a part-Jewish family of so-called "Privileged Jews"7-10 who, thus entitled by the Emperor, enjoyed social, civil, and professional liberties that were out of reach to their less favored co-religionists. It may appear paradoxical that Eppinger was also apparently accredited years later as an "Official Aryan" by the National Socialist authorities, a designation that was clearly linked to his joining the Nationalsozialistische Deutsche Arbeiter-Partei (NSDAP); i.e., the National Socialist German Workers' Party, nicknamed the Nazi Party. Yet it was not uncommon that exemptions to the 1935 Nuremberg Racial Laws were granted to certain Mischlinge; i.e., Jewish half-breeds, and incongruously many Deutschblütigkeitserklärüngen (Certificates of German Blood) were actually signed by Adolf Hitler himself, thereby officially classifying the recipients as Aryans when such outright hypocrisy suited the Führer and his kind.11 An astounding number of these Mischlinge were promoted to high rank in the German Armed Forces, and some even prospered politically.11 It should be noted, however, that the truth about Eppinger's ethnicity is still not known, and more discovery about it is needed. In 1902, more than 30 years before these grotesque events transpired, Eppinger was awarded his Doctorate in Medicine in Graz, where 20 years earlier his father, Hans Eppinger senior, had been appointed Professor of Pathological Anatomy. After staying for a few years, Eppinger moved to the famed Allgemeine Krankenhaus (General Hospital) in Vienna, where he rose to become First Assistant in the First Medical Clinic, which was headed by the internationally acclaimed cardiologist Karel Frederik Wenckebach. Later, when he was a full Professor of Medicine, Eppinger accepted the position of Chair of Medicine in Freiburg im Breisgau, after turning down offers from Strassburg, Halle, Königsberg, Leipzig, Frankfurt, and even Berlin. He left for Cologne in 1930, but it was there that in April 1933—ironically, probably because of his part-Jewish heritage—he fell foul of the Brown Shirts, Hitler's Sturmabteilung (SA or Storm Division). He hurriedly returned to Vienna to head the First Clinic but, importantly, because of his tussle with the German Reich, this appointment was permitted only after the intervention of Kurt von Schuschnigg, the Austrian Education Minister, who was to succeed Engelbert Dollfuss as Chancellor when the latter was assassinated in July 1934. Eppinger's professional interests and expertise ran the gamut of internal medicine and pathology, and he published extensively on topics as diverse as bundle branch block, diaphragmatic defects, cardiac asthma, circulatory dysfunction, nephrosis, hemolytic anemia, the inflammatory reaction, parathyroid disease, and many more besides.7 He was a fanatical and overzealous experimenter and at the same time a much sought-after clinical consultant for monarchs, heads of state, and other notables, including Josef Stalin and the Dowager Queen Marie of Rumania. It was rumored that he had also attended Adolf Hitler, but this possibility was dismissed by the late Fritz Redlich (1910-2004) in his biography of the German dictator,12 on the grounds that Hitler did not like famous and overbearing academic physicians and was pathologically as secretive about his health as he was over other details of his personal life and history. By coincidence, Redlich, who was Chair of Psychiatry (1950-1967) and Dean of the Medial School (1967-1972) at Yale University, had been a medical student and resident in Vienna when Eppinger was Chair of Medicine, before he emigrated to the United States in 1938. There are several associations between Eppinger and modern hepatology. First, of course, was his fascination with liver disease, in which he undertook many studies. Arguably his most important—one could say "Landmark"—contribution was in helping to dispel the myth that jaundice in hepatitis, so-called "catarrhal jaundice," is due to biliary obstruction caused by ascending duodenal inflammation, swelling of the ostium of the bile duct, and mucus biliary plugging, as Gabriel Andral and his many followers maintained.13, 14 Eppinger reasoned instead that toxins absorbed from the intestines injured the endothelium in the liver ("capillaritis"), causing intralobular edema and allowing serum to escape from the blood and deposit in the space of Disse.15 Eppinger's monograph on liver pathology and therapy, in which this hypothesis of "serous hepatitis" is also discussed,16 was, in its time, the handbook or bible for anyone interested in liver disease. The second link between Eppinger and modern hepatology was his mentorship of and complex relationship with the late Hans Popper (1903-1988), the undisputed father of hepatology in the latter part of the 20th Century.8-10, 17 Hans Popper worked in Eppinger's laboratory both in Vienna as a medical student and later in Freiburg in 1928.9, 10 When Eppinger returned to Vienna in 1933, he persuaded Popper to transfer from the Institute of Pathology to the First Medical Clinic as an Assistant Physician. Next, Eppinger appointed Popper and Hans Kaunitz (who, like Popper, was Jewish) to supervise a new ward that he opened. During all of his activities, Eppinger's brilliance and achievements were indelibly stained by defects of personality and character, which were well recognized by all who knew him and of him. Notwithstanding Popper's admiration for him as a scientist and his profound debt to him as a mentor and supporter, these flaws alone were grave enough to mar Eppinger as a role model for young scientists and physicians. As John Cornwell points out in the opening of his book on Hitler's scientists,18 quoting François Rabelais,19 "Science without conscience is the ruin of the soul" — Science sans conscience n'est que ruine de l'âme — a warning that might have been written with Eppinger in mind. Eppinger had no scruples10; he stole case histories from other physicians and had to be supervised while watching operations in case he stole instruments as well. He was banned from the University library after being caught cutting pages out of books and bound journals. He stole gallbladders from Wenckebach's laboratory and later, using these specimens without due acknowledgment, he published the phenomenon of gallbladder edema in patients who died of beriberi. Eppinger's callous handling of his patients was no less dishonorable or overt. In his autobiography, the esteemed German theologian Helmut Thielicke described the cruel, dangerous, and demeaning treatment he received from Eppinger, whose advice he had sought for severe tetany following inadvertent parathyroid injury.20 Otto Fleming, who had been a medical student in the 1930s in Vienna and who later was a general practitioner in south Yorkshire, UK, recalled how he and all his fellow students were shocked by Eppinger's brutality when he reduced a patient to tears by explaining to those present in the lecture theater that this man with nephritis was in the "final act of the tragedy" of his disease.21 Apparently even those in NSDAP circles in Vienna complained about, among other criticisms, Eppinger's brutality to his patients and his reckless driving.22 Werner Creutzfeldt, Professor Emeritus and former Chair of Medicine at the University of Göttingen for 28 years, recalled Hans Popper inferring that Eppinger had a hole in his brain where other people have a conscience. Creutzfeldt also related to me that even almost a score of years after Eppinger's departure from Freiburg, senior nurses still in practice there vividly remembered Eppinger's heartless attitude towards his patients, a contrast to the warmth of their nostalgia for Siegfried Thannhauser, who succeeded him briefly. There is no doubt that Eppinger was an ardent Nazi, as Redlich described him,12 and played a key role in the dastardly Sea Water Experiments in the Dachau concentration camp.22-24 However, these signature activities in his curriculum vitae are either glossed over euphemistically or omitted completely from the many available, albeit brief, biographical accounts of Eppinger's life.7-10, 25, 26 Eppinger was dismissed from his position in the University of Vienna after the war, in June 1945, because he had been a member of the then-illegal Nazi Party in Austria before the Anschluss; i.e., the annexation of Austria by Germany.27 He had also been a clandestine member of the nationalistic Deutschen Klub, to which he had paid dues since November 1937.22 He stood idly by when 153 of the 197 medical faculty in Vienna were sacked within weeks of the Anschluss, mostly for being Jewish.28 Eppinger may not have been driven by extreme racist views per se—after all, he had appointed several Jews like Popper and Kaunitz to high positions in his Clinic. Rather, Eppinger fervently believed that the goals of the Third Reich offered the best future for Germans everywhere. Whether this was the main philosophy of so many other physicians, who it must be remembered represented the highest enrollment (45%) in the NSDAP of any professional group,29 is far from clear. Also, by joining forces with the NSDAP he sought to further his own megalomania for research opportunities and material support. Whatever his motivation, Eppinger did abet the militantly prejudiced, recently appointed Dean, Eduard Pernkopf, in ruthlessly promoting the Nazi medical ethos in the Vienna school. Hans Eppinger even celebrated the first anniversary of the "cleansing" of the faculty by authoring an upbeat newspaper article in the Neues Wiener Tagblatt, in which he declared, "Now that all disease (my italics) has been eradicated, the Viennese School of Medicine can in future dedicate itself to its great task without inhibition."28 Pernkopf, incidentally, rose to become the Rector of the University in 1943; after spending 2 years imprisoned by the Allies after the war, he was free to complete his notorious "Atlas of Topographical and Applied Human Anatomy," for which the bodies of almost 1,400 people executed by the Gestapo, mostly for "political" reasons, served as artists' models.30 To Eppinger, who threw in his lot wholeheartedly with the philosophy, doctrines, policies, and hierarchy of the Third Reich, it was but a small step to invest his medical research expertise in the planning and conduct of human studies for the benefit of the German military effort. Although Eppinger's other activities have not yet been exhaustively researched, there has been no evidence presented thus far that he also participated medically in the sickening racial hygiene work that aimed to perfect techniques of mass extermination and sterilization, nor in studies that sought to document and preserve the anatomical characteristics of inferior racial groups, those people referred to as Untermenschen, or "subhumans," considered to have Lebensunwertes Leben, i.e., lives unworthy to be lived, and other individuals, such as the enfeebled, retarded, and those with neurological or physical defects. Neither did he seem to engage in futile sadistic experiments, such as excruciatingly painful attempts at muscle, bone, and even whole limb transplantation. In this context, it is chilling to point out that numerous German physicians had already played key practical roles in forcible sterilizations (some 300,000 to 400,000 victims) and in legalized killings, mostly by gassing and cremation, of individuals with mental or physical handicaps. Therein was the prototype for the extermination process of the Final Solution of the Jews, which physicians made feasible.31 Space does not permit an analysis of the reasons why German physicians flocked to join the Nazi party, the SA, and the dreaded Schutzstaffel (SS or Protective Squadron), and were capable of perpetrating atrocities using their medical skills. Potential explanations, such as the early suppression of resistance, indifference, the so-called "medicalization" of racism, and economic opportunism have been thoughtfully discussed elsewhere.32-37 The question of how to sustain downed airmen and shipwrecked sailors and submariners in the sea for long periods of time vexed the Allied and Axis military commands alike. The answer appeared to lie in making seawater potable, and studies were performed to this end on both sides of the military conflict. To resolve a dispute at the German Air Ministry over the relative merits of disguising the taste of seawater with an additive (the so-called Berka method, which some already thought was deleterious) versus true desalination with an expensive, inconvenient process, Eppinger and Wolfgang Heubner (an eminent pharmacologist from Berlin) insisted that a controlled trial be conducted to compare the feeding of seawater (plain, Berka-treated, and desalinated) with that of fresh water or complete water deprivation for up to 12 days, to give the best chance of observing whether permanent health impairment and even death may be suffered by the test subjects. Eppinger also recommended that his recently promoted protégé in Vienna, Dr. Wilhelm Beiglböck, conduct the study, which had to be done at the Dachau concentration camp because the usual type of volunteers at the medical school were unavailable so late in the war. The monstrous experiments were soon performed in the summer of 1944, but the pitiful descriptions of suffering, including the endurance of a liver biopsy without anesthesia, do not bear reproducing here, except to mention that the experimental subjects deprived of water would lick mopped floors and other damp objects in crazed attempts to obtain some moisture.24 The transcripts of Beiglböck's trial and exhibits, including letters between Oskar Schröder, the Chief of the Medical Service of the Luftwaffe, and Heinrich Himmler, Reich Minister of the Interior and Reich Leader of the SS, make it clear that Eppinger was no mere accomplice but was instead a key protagonist.24 Among the defenses offered on Beiglböck's behalf was the claim that there was no legal definition of crimes against humanity. Other specious defenses submitted during the course of the entire Doctors Trial included the inevitable lame excuses that the physicians were only following the orders of their superiors or the directives of the State; the precedent that the Allies and other had performed criminal experiments too; the justification that the victims were going to die anyway; and the plea that there were no established codes or guidelines for human experimentation that they could follow. The defendants also argued that to treat them as war criminals would seriously harm the reputation of medical research, and shamefully it seems that their argument resonated among some of the political and scientific leaders on the Allied side.38, 39 Although it is true that reprehensible human experiments have been conducted in almost every country, even long after the Nuremberg Code was established,40-42 none have matched the magnitude, sadism, and State-sponsored human degrading policies of the Third Reich. One act of criminality does not exonerate another. Also, whether or not the aphorism Primum non nocere, "First do no harm," originated with Hippocrates43 or Galen, Thomas Sydenham or the American surgeon Lewis A. Stimson,44 this physicianly responsibility has been expressed in all cultures over the centuries. Also, the Hippocratic Oath45 certainly was recognized in Germany, where specific norms for human experimentation also had been established before 1900.46 During his trial, Beiglböck's fraudulent attempt to tamper with his notebooks was discovered, and despite his denial that there had been any of the fatalities that others had witnessed, and notwithstanding Eppinger's sworn affidavit to that effect on his behalf,22 Beiglböck was convicted to 15 years of imprisonment. Of the 19 other physicians and 3 administrators indicted in the Doctors Trial, 16 were found guilty, 7 of whom were sentenced to death by hanging, 5 to life imprisonment, 2 to imprisonment for 25 years, and 1 to 10 years; 7 were acquitted.47 Eppinger was not prosecuted but he was summoned to appear before the Tribunal. However, on the night of September 25, 1946, one month before the indictment of the defendants was filed, he took poison and committed suicide.38 Were it not for the extraordinary events that occurred almost 40 years later, the dark side of Hans Eppinger may well have remained buried with him. However, in the late 1960s Herbert Falk, the benign and kindly managing director of the Falk Pharma GmbH pharmaceutical company that he established in Freiburg in 1960 and the generous benefactor of many workshops and symposia in liver research that fostered international fellowship, collegiality, and collaboration, decided to sponsor a prize for outstanding achievement and leadership in liver studies. Naturally, he turned to his close friend, Hans Popper, the father of hepatology of the age, for advice on a suitable eponym for the award, and Popper suggested the name of Eppinger. Werner Creutzfeldt, for one, was aghast at the recommendation, having heard in the 1950s of Eppinger's amorality, unscrupulousness, and ruthlessness from none other than Hans Popper himself, and so he cautioned Popper against the proposal. But Popper was adamant on account of his reverence for Eppinger as a liver scientist and his unstinting gratitude to him.48 After all, when Popper fled Vienna in 1938, under the nose of the Gestapo, among the possessions he took with him were his old Haitinger fluorescence microscope, his scientific papers, his mother's porcelein collection, and a signed photograph of Eppinger10 that he later kept next to that of his own father,48 For the record it must be stated that it was exceedingly unlikely and unthinkable that Popper knew of Eppinger's role in Dachau, and Herbert Falk certainly did not, as he implicitly trusted his dear friend for advice. The fact must be faced, however, that Popper's judgment was faulty. At the very least, he should have investigated his old mentor more carefully, knowing well of his considerable moral flaws, right-wing views, and the fact that he had stayed on in Vienna in the medical school even when its faculty had been decimated by racism. The Eppinger Prize, which Popper likened to a Nobel Prize of Hepatology, was awarded first to Thomas Starzl in 1970, but neither he nor subsequent illustrious recipients were likely to have had any certainty as to what Eppinger's name truly represented. In the early 1980s, Howard Spiro, Professor of Medicine at Yale University and Director of the Program for Humanities in Medicine at the Yale University School of Medicine, somewhat belatedly heard of the prize's eponym and connected it with the Eppinger whose obituary he had read as a medical student and about whom he had later read in the Doctors of Infamy.24, 48, 49 The case was taken up by the Simon Wiesenthal Center, and Eppinger's name eventually was removed from the award, but only after the story broke publicly on the front page of the New York Times on Sunday, November 11, 1984. The New York Times article caused great consternation to delegates who were attending the annual meeting of the American Association for the Study of Liver Diseases in Chicago that very weekend. Armed with few verifiable facts at that time, opinions were charged and fiercely divided between those who demanded withdrawal of the prize and those who were angered and thought that Spiro's revelation was divisive. The affair sullied the last years of Hans Popper's life, especially as he was cognizant of his earlier lapse of judgment, but he showed no rancor over the exposure of the truth. As he told me once while on a visit to Yale, he knew that when he agreed to work for Eppinger in 1933 he had "made a pact with the devil." Approximately 8 years later, the Working Group for Planetary System Nomenclature unanimously voted for the same reasons to drop the name of Eppinger from a moon crater that had received its official designation by the International Astronomical Union in 1976 on the 30th anniversary of its namesake's death. These latter events—the third and, we hope, the last association between Hans Eppinger and modern hepatology—bring us full circle to the dilemma posed at the beginning of this article; namely, how to reconcile scientific achievement with the moral flaws of the scientist, especially when these shortcomings are directly related to the conduct of the science itself and human welfare and life are involved. In essence, this quandary can be considered under the rubric of "Forbidden Knowledge," which often refers to scientific data from studies that were unethical, or worse. Some, like Vivien Spitz, the youngest court reporter at Nuremberg, who recently published her experience there,51 feel that no data acquired from unethical heinous experiments should ever be used, by anybody. Some take comfort in the likelihood that experiments conducted by such rogue physician-scientists are likely to be flawed scientifically, as well as being morally repugnant.52 Moreover, there was evidence that even in Dachau the data were tampered with.53 Unfortunately, this is not a dependable approach, since some measures and investigations, like the Nazi antitobacco campaign and search for the link between smoking and cancer,54 were sound, even though they were based on the same racial hygiene principles that led to sterilization and extermination. Others have argued that if the benefit of the research is of such sufficient magnitude that it saves more lives than were lost acquiring the data, and the data could not or would not have been obtained in any other way without entailing such human suffering, then perhaps we should acknowledge and use the data and at the same time express the highest censorship and opprobrium to the investigator each time the data are discussed. This carries the real risk, however, of conferring scientific martyrdom on the victims, and by making them our retrospective guinea pigs we make ourselves their retrospective torturers.55 To walk between these two extremes is too difficult a path to tread. As Henry Beecher considered, although useful information might be lost by ignoring such data the moral loss to medicine would be greater for publishing it.49 This concept was put to the test in the 1980s when the Editor of the New England Journal of Medicine refused to publish the results of Nazi hypothermia studies that were thought to be useful in potentially life-saving research.55 In the case of citing Eppinger, the decision is an easier one. Acknowledgment of his earlier work is clearly justified if it can be shown to have been scientifically and ethically sound, yet at the same time and at each opportunity one should censor him severely and explicitly for the evil he did and one should never permit his name to be used as an inspiration for achievement or as a role model. The more searching question posed by Wiesel, however, and one that is both more important and arguably more difficult to answer, is why so many physicians throughout the world and in so many ages have "crossed the line," especially given their advantage of education and a supposed commitment to healing. Yet for all that, Wiesel still remains confident in us as a profession. "Am I naïve in believing that medicine is still a noble profession," he asks, "upholding the highest ethical principles? For the ill, doctors still stand for life. And for us all, hope."1 We cannot afford to disappoint him. Note added in proof: Following submission of this article, the author was made aware (courtesy of Professor Michael Thaler) that there was no evidence that Eppinger had any Jewish heritage. It was a rumor that Eppinger's maternal grandmother, Aloysia Solomon, was Jewish. A search of genealogical records from the mid-18th Century onwards revealed Catholic ancestors on both sides. Register of Births, Jewish Communities of Prague, 1870-1900, Central State Archives, Doc. 8573/10-91; Marriage Records, Main Archive of the City of Prague, 1735-1900. Docs AMP-4272-4/91. The author acknowledges, with gratitude and humility, conversations by telephone and e-mail with Ms. Vivien Spitz and Rabbi Dame Julia Neuberger, and with Professors Werner Creutzfeldt (Göttingen), Alan Hofmann (San Diego), Jean Lindenmann (Zurich), Mary Faith Marshall (Minneapolis), Bryan Mark Rigg (Dallas), Howard Spiro (New Haven), Paul Weindling (Oxford), and Elie Wiesel (Boston). The author also thanks the Editor, Dr. Andres Blei, for his support and courage in permitting the publication of this essay in HEPATOLOGY. Whereas the opinions, recollections, and experiences of these distinguished thinkers helped the author find his way through a morass of troublesome literature and documents, the opinions set forth here are solely his own.