The evolution of the discipline of pharmacology amid an era of global turbulence: The unique contributions of Otto Krayer (1899

Abstract

This article revisits the life and times of Otto Krayer, a gifted scientist, teacher and administrator. His unique contributions to the discipline of pharmacology and to the biomedical sciences are chronicled in the wake of the political upheaval that crippled German science during the 1930s. The anti-scientific attitude that pervaded Germany at the time led to the exile of Krayer and many other eminent scientists. Their fate is recounted, as well as the negative impact on science caused by a National Socialist regime that blatantly disregarded basic scientific principles. The threat of intolerance and unethical behaviour still remains a key obstacle to scientific creativity.

Keywords

Otto Krayer German Science Pharmacology Expatriats Nobelists

Introduction

It is often the most gifted scientists who make the most of the serendipitous events presented to us and so it was with Otto Krayer, a man who because of unanticipated events was put into position to reshape our concepts in biomedical research, particularly as they relate to pharmacology.

Because the career of Otto Krayer was caught up in the political turmoil of the first half of the 20th century, this story provides historical perspective by describing the era in which Krayer helped to solidify pharmacology as a true biomedical discipline. The text revisits a time when irrational forces threatened civilised society by prohibiting freedom of thought and stifling intellectual inquiry. With the advantages of hindsight, this story once again demonstrates that ultimately objectivity, integrity and fairness should always trump oppression, injustice and intolerance.

Early life and career

Born on 22 October 1899 in Köndringen, a small town near Freiburg in Germany, Otto Krayer was the eldest son of a village innkeeper.¹ Drafted into the German Army in 1917 at the age of 18, Krayer completed the requirements for entrance to the university while convalescing from war wounds and in the fall of 1919 he enrolled as a medical student at the University of Freiburg. After completing his internship in internal medicine and dissertation research on apocodeine in 1926,² Krayer’s developing interest in research prompted him to join the laboratory of Paul Trendelenberg (1884–1931). A year later, when Trendelenburg assumed the chair of pharmacology in Berlin, Krayer accompanied him. Krayer’s major responsibility in his new position involved teaching medical students about the effects of drugs on mammalian systems.

However, in 1928 Krayer found time to publish the first of two studies on the cardiovascular toxicity of the organic arsenical neosalvarsan. This work, which involved the use of the canine heart–lung preparation (HLP), became a foundation for most of Krayer’s future experiments and spawned a lifelong commitment to cardiovascular pharmacology.

In Berlin he rose through the academic ranks from Assistant to Oberassistent to Privatdozent. When Trendelenburg became chronically ill with tuberculosis, Krayer assumed greater administrative responsibilities. However, according to existing rules the chair of pharmacology in Berlin could only be occupied by the incumbent of another chair. Following the appointment of Wolfgang Heubner (1877–1957) to the chair in 1931, Krayer was promoted to a position equivalent to associate professor. His responsibilities included the teaching of a required course in pharmacology, an elective laboratory course and special elective courses on cardiovascular pharmacology and toxicology. He also supervised the planning of a new building for the Department of Pharmacology.

Krayer also inherited two literary projects left by Trendelenburg. The third edition of the textbook The Principles of Therapeutics was published in 1931 while the second volume of Die Hormone had to be postponed. In addition, an important experimental study with Wilhelm Feldberg, followed by collaboration with Hermann Rein at Gottingen, made it seem almost axiomatic that Krayer would be offered a position as head of a pharmacology department at some other university. However, future plans were altered by events surrounding the dismissal of the chair of pharmacology at Dusseldorf.

The Philipp Ellinger affair

In the spring of 1933, during the first year of Nazi rule Krayer was invited by the Department of Education to occupy the chair of pharmacology at Dusseldorf which had been vacated by the dismissal of Philipp Ellinger. Although unacquainted with Ellinger and a Protestant by birth, Krayer had the temerity to decline this attractive offer because Ellinger had been dismissed solely because he had been identified as a Jew. Krayer would not accept a position that had become available because of an arbitrary decision.

Krayer was fully aware that unwritten rules dictated that his decision would rule out the possibility of an offer of another chair. Despite responding to the Minister of Education’s response with a carefully worded letter,³ Krayer was suspended from his academic position and forbidden to enter university and state libraries and scientific facilities. However, in order to fulfil his obligation to Trendelenburg to complete Die Hormone, Krayer had colleagues provide him with books and journals from the libraries. A fellow medical student at Freiburg, Erna Ruth Philipp, who eventually became his wife, assisted him in this endeavour.⁴

Although the German government eventually reinstated Krayer in September 1933, he left Germany for London on the last day of 1933. While remaining in London for only a brief period, he developed further expertise in the HLP by collaborating with EB Verney (1894–1967) and another expatriate, Wilhelm Feldberg, to provide important evidence in support of the neurochemical basis of synaptic transmission.⁵

Before long, Krayer was invited to head the Department of Pharmacology at the American University in Beirut, Lebanon,⁶ a position that turned out to be a visiting professorship. Teaching pharmacology predominantly as a laboratory course, he inspired several students to enter careers in research. One such student was Alfred Farah who joined Krayer at Harvard and in 1953 was appointed department chair at the State University of New York at Syracuse. Later he became director of the Sterling-Winthrop Research Institute in Rensselaer, New York. An expert on renal function, Farah pioneered studies on the effect of diuretics on solute excretion.⁷

A fortunate turn of events occurred in 1936 when Krayer was asked to represent his university at Harvard’s tercentenary celebration. Coincidentally, during the fall of 1936 Walter Cannon (1871–1945), one of the world’s most renowned physiologists, had arranged for Krayer to receive a three-month appointment at Harvard as a lecturer in pharmacology. The belief that Krayer’s trip to the United States was more than a courtesy visit was supported by the fact that Harvard Medical School was then searching for a pharmacologist to replace the incumbent Reid Hunt (1870–1948).⁸

The years of emigration and expulsion (1933–1939)

The wrath that non-Aryan scientists, and pharmacologists in particular, had to endure was not limited to a few unfortunate individuals including Philipp Ellinger. Although anti-semitism had existed for centuries in Germany, when the National Socialists came to power it took on a new aspect that eclipsed anything that had gone before.⁹ It began in 1933 with the dismissal of scientists and scholars from universities who were of Jewish heritage or who expressed liberal views. Book burning by students presaged the loss of intellectual freedom. Despite their mistreatment, most German Jews did not envision themselves as Jews and eagerly integrated themselves into the culture of their country. In fact, they contributed extensively to the high level of scientific achievement for which Germany had been recognised internationally during the early part of the 20th century. However, the German scientific community seemed oblivious to the plague that was engulfing its people and even actively supported it.¹⁰

Although many pharmacologists, including Otto Krayer, emigrated in 1933, all emigration was subsequently banned in 1941. Persecution was then extended to the loss of all properties and financial resources, and even to incarceration and extermination in concentration camps. The few that were not exiled were marginalised by working as physicians to treat only Jewish patients or were employed in industry.

Ironically, the enforced exile of many German scientists proved to be an invaluable asset to those countries that provided a haven for them. Although the United States became a major source of asylum, the United Kingdom also served as a major destination for émigrés. In fact, the Golden age of British pharmacology was a direct result of the exodus from Germany of a number of very talented scientists.¹¹

The exile of scientists of non-Aryan descent

Entering the 1930s Germany clearly was the world leader in scientific achievement. Since the awarding of Nobel Prizes, German citizens had won 33, equivalent to one-third of those awarded. David Pyke described the enforced emigration as one of the most remarkable episodes in the history of man: ‘The story carries a powerful, even deadly message, on the danger of intolerance’.¹² Twenty scientists who were forcibly exiled eventually won Nobel Prizes and 50 became Fellows of the prestigious Royal Society. As a result, it was inevitable that Germany would lose its lofty position as the leader of the scientific world.

Wilhelm Feldberg (1900–1993)

One eminent Jewish scientist forced to leave Germany during the early stages of the purge was Wilhelm Feldberg.¹³ After receiving an offer from Sir Henry Dale (1875–1968) at the National Institute for Medical Research in Great Britain, Feldberg went on to publish 25 scientific papers between 1933 and 1936 which helped establish the concept of neurochemical synaptic transmission.¹⁴ The success of the collaboration was viewed as a reward for Dale because he secured positions for several of the exiled scientists from Germany.

Otto Loewi (1873–1961)

Another enforced exile, Otto Loewi, provided the definitive experiments proving the chemical nature of synaptic transmission and in 1936 he shared the Nobel Prize with Sir Henry Dale.¹⁵ Loewi’s loyalty to Germany and its culture failed to prevent his enforced exile as a non-Aryan.

Otto Loewi was born of Jewish parentage in 1873 and grew up in an era when scientific thought was not stifled by government intervention. As chair of pharmacology at the University of Graz, he misguidedly believed he would not be persecuted because of his religious background but in 1938 Loewi and two sons were imprisoned. They were finally freed when Henry Dale and Walter Cannon threatened to terminate all interactions of British and American scientists with German colleagues.¹⁶ However, Loewi was forced to transfer the monetary award for winning the Nobel Prize to a German bank run by the government and was also divested of his personal property.

For the next few years Loewi travelled to Belgium, the United Kingdom and then the United States, when Walter Cannon invited him to Harvard. Loewi was eventually offered a professorship at New York University and he spent winters in New York and summers at the Marine Biological Laboratory in Woods Hole. So, despite being a patriotic German, Loewi’s ethnic origin proved to be the major factor that determined where he would spend the latter portion of his life.

Edith Bulbring (1903–1990)

Although educated as a clinician, Bulbring began her career as an unpaid pharmacologist in the laboratory of Paul Trendelenburg, the mentor of Otto Krayer. After Trendelenburg died in 1931, she continued to pursue her interest in research by studying infectious diseases at Virchow Hospital but because of the non-Aryan lineage of her maternal grandparents she was arbitrarily discharged from her position in 1933.¹⁷

Unlike Loewi, Bulbring recognised the extreme danger of remaining in her homeland and she made an easy escape while on vacation in England. Again, Sir Henry Dale came to her rescue by sending her to Joshua Harold Burn (1892–1981) who had begun working at the Pharmacological Laboratory of the Pharmaceutical Society. Bulbring accompanied Burn when he assumed the chair of pharmacology at Oxford in 1937. At the time, Burn’s laboratory had a superb reputation as a centre for pharmacological research in the United Kingdom and was the site where the Nobelist John Vane (1927–2004) developed his lifelong interest in pharmacology.¹⁸

However, Bulbring’s interest in smooth muscle began in the late 1940s after spending a year at Johns Hopkins on a Rockefeller Fellowship. Her major contributions were made in the field of smooth muscle electrophysiology which earned her a promotion to professor at Oxford in 1967. At the time of her death Edith Bulbring was arguably the most influential smooth muscle physiologist in the world. But perhaps as important as her research accomplishments, Edith Bulbring, like Otto Krayer, helped to train many scientists who went on to develop their own major research programs. In honour of her achievements, Edith Bulbring was elected as Fellow of the Royal Society in 1958.

Heinz Otto Schild (1906–1984)

Another notable scientist who ultimately profited from the purge was Hans Otto Schild who came from Munich in 1937 to the Department of Pharmacology at University College, London. Schild pioneered the development of analytical pharmacology which compares pharmacological data with quantitative models and is employed to categorise drugs according to class and predict their mechanisms of action. The principles of analytical pharmacology continue to impact on drug discovery into the 21st century. Another of Schild’s most outstanding contributions was his development of the ‘Schild plot’, a now standard mathematical method for analysing the efficacy of a pharmacologic antagonist.¹⁹

Hans Kosterlitz (1903–1996)

Another scientist sent into forced exile was Hans Kosterlitz who left Berlin in 1934 for Aberdeen, Scotland. Kosterlitz intended to work with JJR MacLeod who had returned home from Toronto following his co-discovery of insulin in collaboration with Frederick Banting and Charles Best. After MacLeod died, Kosterlitz eventually became head of the Department of Pharmacology at the age of 68. After he was forced to retire at 70, Kosterlitz continued his study of narcotic analgesics and opioid receptors and in 1975, together with John Hughes, he identified in brain the endogenous derivatives of morphine called encephalins. The discovery of opioid peptides as the body’s endogenous pain killers represents one of the great scientific achievements of the last half of the 20th century.²⁰

One cannot complete this brief survey without taking note of the fact that Hans Krebs (1900–1981), Ernst Chain (1906–1979) and Sir Bernard Katz (1911–2003) were three Jewish scientists who also left Germany and later won Nobel Prizes.²¹ Krebs won the Nobel Prize in 1953 jointly with Fritz Lipmann (1899–1986), another German refugee, who settled in the United States, while Chain was awarded the Nobel Prize for his contribution to the discovery of penicillin. Sir Bernard Katz won the Nobel Prize in 1970 for his work on the chemical nature of synaptic transmission. So, British and American science profited greatly from the valuable human resources that Germany had so foolishly relinquished.

Fritz Haber (1868–1934)

At the other end of the spectrum, a glaring example of a German scientist who chose patriotism over religion was the chemist Fritz Haber.²² In 1918 Haber won the Nobel Prize for developing the Haber–Bosch process which involves the catalytic formation of ammonia and is responsible for feeding much of the world’s population. However, this chemical reaction also proved very deleterious to mankind because it led Haber to oversee the production of chlorine and other deadly gases.

Being an ardently patriotic German, Haber personally assisted in the release of war gases during World War I, despite its proscription by the Hague Convention. During the 1920s scientists working at Haber’s institute developed the cyanide gas Zyklon B. Originally used as an insecticide, this lethal weapon was employed subsequently at concentration camps to eradicate millions of so-called political prisoners during the 1940s. As a result, Haber had a profound influence on the German war effort by orchestrating two eras of gas warfare.²³

Although a convert to Catholicism, Haber had been born into a Jewish family and so he was forced to dissolve his institute. Subsequently he resigned his post at the Kaiser Wilhelm Institute in 1933 to become director of the Department of Physical Chemistry in Rehovot, Israel. However, Haber was never able to reconnect to his heritage; he died in Basel, Switzerland, in 1934. To honour Haber’s scientific contributions, in 1981 the Fritz Haber Center for Molecular Dynamics Research at the Hebrew University in Jerusalem was established to encourage research cooperation between Israel and Germany. The private collection of Fritz Haber is also included among the libraries of the Weizmann Institute.²⁴

Stances taken by non-Jewish scientists

Max Planck (1858–1947)

Unlike the stand taken by Otto Krayer, most non-Jewish scientists remaining in Germany not only failed to express their disfavour with the National Socialist Government but they also abandoned their basic principles in which science is viewed with impartiality and objectivity, and independently. The most notable exception was Max Planck, the so-called godfather of German science and the recipient of the Nobel Prize in 1919.²⁵

Unlike Albert Einstein’s sharply critical pronouncements about the political and racial policies of the National Socialists, Planck’s criticisms were more muted and directed toward preserving German science as he knew it. He even met with Hitler in a futile attempt to persuade him to curtail his actions against Jewish scientists. However, because of a resolute loyalty to his country, Planck did not leave Germany even after he was forced to dismiss the Jewish scientists working in his institute. But his escalating aversion to governmental policies eventually caused Planck to resign his position as president of the Kaiser Wilhelm Society in 1938. After World War II, when the institution was renamed the Max Planck Institute, he was appointed its head. However, Planck died shortly thereafter in 1947.

Marthe Vogt (1903–2003)

A few, including Marthe Vogt, were strident in expressing their anti-government views.²⁶ Born and educated in Germany, Vogt found the political situation to be intolerable and left Germany in 1935 for England. A Rockefeller Fellowship awardee, Vogt first worked with Henry Dale in London and then with EB Verney in Cambridge. During the first half of her fellowship, Vogt contributed to a classical study on chemical transmission with Dale and Feldberg in 1936²⁷ and went on to publish a series of papers with Verney on various aspects of hypertension. She employed a portion of these data to write up her thesis for the doctoral degree in pharmacology in 1938.

Though not of Jewish heritage, Vogt had utter disdain for the Nazi regime and had no intention of returning to Germany. However, when World War II broke out she was threatened with internment as an enemy alien by the British. Strong support from Henry Dale, EB Verney, Wilhelm Feldberg and Edith Bulbring enabled Vogt to avoid internment and ultimately she became naturalised in 1947. During World War II she worked as a staff member at the Pharmacological Laboratories of the Pharmaceutical Society in London. In January 1947 Vogt moved to the Pharmacology Department at Edinburgh and in 1960 she became director of the Pharmacological Unit at the Institute of Animal Physiology at Babraham. Recognised as one of the leading neuroscientists of her time, particularly for her contributions to our understanding of the role of neurotransmitters in the brain, Vogt was elected a Fellow of the Royal Society in 1952. While officially retiring in 1968, she continued to carry out research into the 1990s.

Gerhard Domagk (1895–1964)

The story of Gerhard Domagk and his Nobel Prize-winning accomplishments in the development of the sulpha drugs exemplifies how an effort to advance science was not obstructed by the Fascists. IG Farben, one of the world’s largest chemical firms, hired Gerhard Domagk in 1927 to demonstrate anti-bacterial activity in azo dyes.²⁸ To accomplish this task, Domagk developed an ingenious assay to test anti-bacterial activity in mice. In 1932 the chemists finally synthesised the red dye Prontosil which Domagk found to be very effective in treating mice and rabbits infected with beta hemolytic streptococci. Prontosil eventually attained worldwide acceptance when President Franklin Roosevelt’s son was treated effectively for tonsillitis.

The subsequent finding that the active ingredient in Prontosil was sulphanilamide spawned the synthesis of many sulphanilamide derivatives. Although Domagk was awarded the Nobel Prize in 1939, he was forbidden by his government to accept it because of the controversy created by the journalist and Nobelist Carl von Ossietzky for his anti-government stance.²⁹ This edict only delayed the formal presentation of the Noble Prize to Domagk until 1947. Because he was pursuing investigations that would aid Germany in any potential war it might wage, Domagk was allowed to usher in the golden age of chemotherapy.

The early years at Harvard

Amid the political turmoil in Germany, the career of Otto Krayer, now an expatriate, continued to unfold. Shortly after returning to Beirut from Boston, Krayer received a formal invitation from Harvard to assume the chair of pharmacology. The incumbent Reid Hunt had come to Harvard in 1913 from the United States Public Health Service with an excellent reputation and the anticipation that a new era in pharmacology at Harvard would begin. The major portion of Hunt’s work on choline derivatives and the thyroid gland had been completed before his arrival in Boston, although this work continued at Harvard.⁸

Hunt was particularly noted for his earlier work on choline derivatives in which he demonstrated that choline, isolated from adrenal glands, produced a fall in blood pressure. Although later he found that a chemical analogue of choline, acetylcholine, possessed a depressor action several orders of magnitude greater than choline, Hunt was never able to relate any physiologic relevance to his findings. As a result, the key experiment that would establish the concept of chemical neurotransmission and the role of acetylcholine was held in abeyance for several years until Otto Loewi performed his classical experiment on the frog heart.

History has generally been harsh on those scientists who reach the precipice of a major discovery but are unable to interpret their experimental findings correctly. Thus, although a member of the National Academy and a pioneer in pharmacology in the United States, Reid Hunt is perceived as a rather vague figure in the annals of science. So when Hunt retired from the chair of pharmacology at Harvard in 1936, the mantle was passed to Otto Krayer who orchestrated a unique and illustrious era in pharmacology.

Krayer’s appointment included the title of associate professor for five years (without tenure) as well as acting head of the Department of Pharmacology. One explanation for the unusual appointment resides in the fact that in 1936 pharmacology was still viewed as a second tier biomedical discipline. At the time, the Department of Pharmacology at Harvard was composed of only one other faculty member, encumbered with antiquated facilities and equipment and endowed with a very limited budget. Becoming disillusioned with his lack of support, Krayer became receptive to an offer from the University at Peiping (now Beijing) to occupy the chair of pharmacology. However, after becoming aware of Krayer’s intention, the entire medical class of 1941, as well as many in the class of 1940 who had been taught pharmacology the previous year, sent a letter to Krayer expressing their admiration and gratitude for his efforts on their behalf.³⁰

The letter prompted Krayer to reconsider his plans. This decision was solidified by the fact that Krayer was awarded tenure and appointed head of department although he was not promoted to full professor. The sense of security provided by the awarding of tenure prompted Krayer to marry Erna Ruth Philipp and to relocate from the student dormitory (Vanderbilt Hall) and move to the suburbs of West Newton.

Productive years at Harvard

Following 7 December 1941 and with the United States at war, Krayer was considered an enemy alien and was prohibited therefore from travelling beyond a 25-mile radius of Boston so he turned his attention to teaching while at the same time laying the foundation for developing a strong department. With the help of colleagues including Douglas Riggs, George Acheson, Sydney Ellis, Gordon Moe and Alfred Farah, Krayer systematically built a laboratory-based pharmacology curriculum for the teaching of medical students.

Fortunately for Krayer, Dean Burwell retired in 1949 and George Packer Berry (1898–1986) was appointed to succeed him. Recognising an obvious injustice, Dean Berry promoted Krayer to full professor after 14 years as associate professor. Krayer and Dean Berry then went on to form a close professional relationship and over the next 15 years they mounted a campaign to develop a Department of Pharmacology that was considered the strongest in the United States.

Krayer believed the aim of pharmacological investigation was to elucidate the mechanisms involved in drug action rather than merely making phenomenological observations. This approach was facilitated by the fact that the discipline of pharmacology had begun to make considerable progress in understanding pathophysiological mechanisms and therefore in developing more selective and effective medications.

Also, at this time important centres for pharmacological research sprang up throughout the United States. These departments were headed by legendary luminaries in pharmacology including Oliver Lowry of Washington University, Fred Shideman of the University of Minnesota, Thomas Maren of the University of Florida, Arnold Welch of Yale University, Alfred Gilman of Albert Einstein College of Medicine, Louis Goodman of the University of Utah, Maurice Seevers of the University of Michigan, George Koelle of the University of Pennsylvania and Brian Hoffman of Columbia University, to name just a few. These were truly the golden years of pharmacology as a discipline.

During the 1950s and 1960s the Pharmacology Department at Harvard received visiting scientists, junior faculty and students with diverse scientific and ethnic backgrounds.³¹ Krayer had a unique ability for recognising quality in his colleagues and the criteria he employed for selecting associates included intellectual ability, dedication to work and character. Many of these individuals went on to become distinguished members of the community of pharmacologists and their names are familiar to those who were trained during the 1950s, 1960s and 1970s. They included Lewis Aronow, John Blinks, Peter Dews, Sydney Ellis, Alfred Farah, Werner Flacke, William Fleming, Louis Harris, Jan Koch-Weser, Salomon Langer, Jean Marshall, Gordon Moe, Charles Rutledge, Douglas Riggs and Edward Carr. Krayer also inspired several medical students to become pharmacologists, including Avram Goldstein, George Acheson and Norman Weiner. While Krayer certainly profited from the skilled scientists who frequented his department, in return he offered them strong leadership and guidance and an unwavering disregard for his own interests.

The canine HLP became a key experimental model for assessing the primary action of drugs in situ, devoid of any external and/or reflex effects. It was technically a very difficult preparation to master and only a few pharmacologists and physiologists were able to utilise it successfully. Krayer himself made important contributions to cardiovascular pharmacology by using this preparation to demonstrate the anti-cardioaccelerator effect of veratrum alkaloids and the peripheral catecholamine-depleting action of reserpine. In addition, this preparation provided a most valuable educational tool for teaching medical and graduate students about the mechanisms of action of drugs.

In order better to understand drug action from diverse perspectives, Krayer’s broad vision of science also prompted him to encourage new lines of experimentation. For example, in 1953 Krayer recruited Peter Dews (1922–2012), a pharmacologist interested in the behavioural effects of drugs. With the recruitment of Roger Kelleher and Bill Morse, Dews built a laboratory of psychobiology within Krayer’s department and later in the Department of Psychiatry.³² With Krayer’s support, Dews not only established himself as a leader in the field of behavioural pharmacology but his work also brought about the emergence of behavioural pharmacology as a scientific discipline under the general umbrella of pharmacology.

In addition, a group of neurophysiologists headed by Stephen Kuffler (1913–1980) also joined the department when Krayer made available a large amount of space that had been allocated originally for the Department of Pharmacology. The individuals who Kuffler brought with him included two 1981 Nobel Laureates, Torsten Wiesel and David Hubel.³³ The School of Medicine as a whole profited from Kuffler’s recruitment when ultimately he formed the first Department of Neurobiology in the United States.

Mention should also be made of the arrival from Oxford of Ullrich Trendelenburg (1922–2006) to Harvard in 1957. The junior Trendelenburg, the son of Krayer’s mentor, shared the same ideals and goals as Krayer and established himself as a key figure in the department’s research and teaching activities. In 1968 Trendelenburg returned to Germany to chair the Department of Pharmacology at Wurzburg.³⁴

Because of his close relationship with Dean Berry, Krayer also played an increasing role in the activities of the School of Medicine. However, as the years passed Krayer began to find that his department was being dismantled by the departure of faculty for prestigious positions elsewhere. Then, when Dean Berry retired in 1965, the department was left without a key advocate and, as Krayer’s retirement drew near, protracted discussions about the future of pharmacology delayed the search for Krayer’s successor. On 31 August, having reached the mandatory age, Krayer retired to his home in West Newton and for the next five years did not return even once to Harvard.

After his retirement Krayer was given the title of Special Consultant to the Dean. However, Dean Ebert never sought his advice and after six months the post was summarily abolished. Krayer and his wife began to travel and in September 1971 they settled in Tucson, Arizona. The winters were spent in Tucson where Krayer had an appointment as visiting professor at the University of Arizona School of Medicine, and the summers were spent in Germany teaching at the Technical University of Munich.

The post-war years

The anti-intellectual views that many German scientists harboured during the regime of the National Socialists continued to alienate colleagues worldwide when World War II finally came to an end. But, perhaps most important, because scientists in Germany during the 1930s and 1940s were unable to view their discipline in an objective and impartial manner, they suffered a dramatic regression in the quality of their work.

Despite the unfair treatment that he had received from his scientific colleagues in 1933, Krayer still volunteered to help rebuild Germany’s infrastructure. For this undertaking, a series of missions to Europe was formed under the auspices of the World Health Organisation. Initially, in 1946 Krayer joined a Mission to Czechoslovakia headed by the famed cardiologist Paul Dudley White (1886–1973). In 1948 Krayer returned to Germany under similar auspices to serve as chairman of a medical mission composed of 15 scientists from a variety of biomedical disciplines.³⁵ Not only were provisions supplied but advancements in medical care and pharmacotherapy were provided by members of the distinguished committee. Because of his broad knowledge of the German medical profession and its scientific heritage, Krayer performed an invaluable service to German medicine and science by resuming professional relations with scientific colleagues who had summarily abandoned the scientific establishment.

The post-Krayer years at Harvard

By 1966, the year in which he retired, Krayer's department ranked at the top of the American Council on Education’s list of pharmacology departments in the United States. However, the future of the Department of Pharmacology received an additional setback when the internal candidate, Irving Goldberg (1926–2012), was appointed to succeed Krayer.³⁶ While Goldberg authored a significant number of publications on the molcular mechanisms of anti-tumour agents, he did little to maintain the lofty status that the department had enjoyed previously and he never earned the acclaim received by his predecessor. So, as time passed it became apparent that the Krayer era of transcendence would be only a fleeting one.

After Goldberg resigned his post in 1987, a decision was made to merge the Departments of Pharmacology and Biological Chemistry at Harvard Medical School to form the Department of Biological Chemistry and Molecular Pharmacology. The Medical School supported the merger because it was thought to provide pharmacologists with broader training.³⁷

In just a few years the Department of Pharmacology had transformed from one that was arguably the finest in the United States to one that was no longer a distinct academic discipline.

But Harvard did not deny Krayer his proper place in the annals of renowned professors. An Otto Krayer Lectureship was established in 1974 at the Medical School. Harvard also established the Otto Krayer Professorship of Pharmacology. A more general acknowledgment of his achievements came in 1964 when Otto Krayer was elected to the National Academy of Sciences.

In 1980, after nine years of travelling between Tucson and Munich, Krayer’s health began to deteriorate from prostatic cancer, exacerbated by a blood dyscrasia. Finally, on 18 March 1982 Otto Krayer passed away at his home. At the end of his life Krayer was able to look back upon years of unmitigated success in one of academia’s most prestigious institutions where his true abilities were allowed to flourish. Otto Krayer always seemed to be where he was needed, ready to participate in the eternal struggle for progress and righteousness.

The legacy

Because of his unbridled efforts to help others, the legacy of Otto Krayer resonated for many years after his passing. As noted by Ullrich Trendelenburg, Krayer’s career encompassed the three components of researcher, teacher and administrator (leader), although they overlapped.³⁸ While the name of Otto Krayer is closely associated with administration and teaching, it also deserves to be tightly linked to research. Krayer considered mediocrity in research to be unacceptable yet he did not attempt to convert others to his views. He stressed the importance of utilising only pure compounds in pharmacologic studies and he disdained the use of high drug concentrations in a test tube in order to explain major effects in vivo. Krayer’s obdurate refusal to draw conclusions not supported by experimental data and an unwillingness to publish questionable experiments reflected his thorough evaluation of every aspect of a study. Although Krayer was always ready to discuss his research findings, he was reluctant to promote his own work or to engage in petty squabbles about awarding credit for one’s scientific contributions.

Although the scientists of today now utilise more modern methods of biochemistry, molecular biology and electrophysiology to address questions related to physiologic mechanisms, the values and concepts that Krayer left behind will endure as a legacy of excellence and dedication. He will not only be viewed as a memorable figure in the pantheon of scientific immortals but will continue to stand as a prime example of how one person was able to impact positively the scientific world, despite the profound negativity that engulfed the era in which he lived.

Footnotes

Acknowledgement

The author would like to thank Dr. Charles O. Rutledge, former Dean of the School of Pharmacy, Nursing, and Health Sciences at Purdue University, who provided critical and expert analysis of the manuscript.

Author biography

Ronald Rubin is Professor Emeritus and Former Chair at the Department of Pharmacology and Toxicology of the School of Medicine at the University at Buffalo of the State University of New York. His interests have been in the history of medicine and cell signalling, and he has published extensively in these areas.

References

A portion of this overview is based on detailed accounts of Krayer’s life and career in: Goldstein A. Otto Krayer 1899–1982. Biographical Memoirs of the National Academy of Sciences 1987; 57: 150–225.

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Anderson

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References to this work can be found in Goldstein A. Biographical Memoirs of the National Academy of Sciences 1987; 57: 215–216.

Goldstein A. Biographical Memoirs of the National Academy of Sciences 1987; 57: 189–191.

Department History; pharmacology; SUNY Upstate Medical University http://www.upstate.edu (accessed 24 May 2013).

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A comprehensive overview of the fate of non-Aryan pharmacologists is provided in Loffelholz K. The persecution of pharmacologists in Nazi Germany and Austria. Naunyn Schmiedeberg’s Archives of Pharmacology 2011; 383: 217–225. Additional information on this topic may also be found in Medawar J and Pyke D. Hitlter’s gift: The true story of the scientists expelled by the Nazi regime. New York: Arcade Publishing Inc., 2000.

10.

A comprehensive treatment of this topic is provided by Deichmann U. Biologists under Hitler. Harvard University Press: Cambridge Massachusetts, 1996, pp.10–58.

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A complete list of scientists, postdoctoral fellows and graduate students who were trained by or collaborated with Otto Krayer is provided in Goldstein A. Biographical Memoirs of the National Academy of Sciences 1987; 57: 204–206.

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In 2009 a publication by the Harvard Medical School lauded the assimilation of pharmacology with biological chemistry by noting that ‘The evolution of the program from that of a small department [sic. pharmacology] to one with myriad interdepartmental interactions resulted in a broader intellectual and experimental base for training in pharmacological sciences …’ http://www.hms.harvard.edu/dms/bbs/PharmSci/About.html (accessed 19 July 2012).

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Trendelenburg U. Remembrances. Otto Krayer. Life Sciences 1978; 22: 1113–1114. Otto Krayer’s papers can be found in the Francis A Countway Library of Medicine, Center for the History of Medicine at the Harvard University Medical Library; http://oasis.lib.harvard.edu/oasis/deliver/∼med00150 (accessed 13 July 2012). Updates of Collections in the Countway Library have also recently become available which encompass the Otto Krayer papers, 1917–1982 (inclusive), 1946–1968 (bulk) and the Records of the Department of Pharmacology, 1938–1974 (inclusive). These updates are listed under posts tagged: Paul Dudley White, https://cms.www.countway.harvard.edu/wp/?tag=paul-dudley-white (accessed 23 December 2012).

The evolution of the discipline of pharmacology amid an era of global turbulence: The unique contributions of Otto Krayer (1899–1982)