The Singular Moral Compass of Otto Krayer

On June 15, 1933, Otto Krayer sat down to write the most important letter of his professional career. The thirty-three-year-old clinical scientist had just been offered the chair of pharmacology and toxicology at the Medical Academy of Düsseldorf, and everyone expected Krayer to accept the appointment. He declined. “I will abstain from winning a position that corresponds to my inclinations and abilities,” he wrote^a, “rather than make a decision contrary to my conviction or, by remaining inauspiciously silent, further an opinion about me that is not in accordance with the facts” (1).

Krayer saw the removal of the Jewish incumbent chairman, Philipp Ellinger, to be an injustice that he explicitly challenged. “Under these circumstances, assuming such a position as the one in Düsseldorf would impose a great mental burden on me,” he explained. Krayer was the sole scientist to decline the “call” (as it is said in German) to a chaired position that, in accordance with Nazi law, could no longer be occupied by a Jew.

Krayer’s moral stand, so carefully and thoughtfully considered, enraged the German authorities. The sanctions they imposed, banning him from teaching or even using university libraries, effectively ended his promising academic career in Germany. Contemporaries of Krayer who faced similar censorship were driven to become vocal political dissidents (2). Otto Krayer, on the other hand, did not enter into external, political discourse, and chose rather to leave his homeland in order to pursue his interests in pharmacology. He went on to lead a highly productive professional life, in the sphere of science, that was always guided by an uncompromising moral compass.

Otto Hermann Krayer was born October 22, 1899, in the village of Köndringen, on the edge of the Black Forest and Rhine valley in southern Germany. During Otto’s formative years, his father, Hermann, ran an inn and a butcher shop; he also farmed. The Krayers were churchgoing Protestants, and Otto, the eldest son, learned important lessons in honesty and responsibility from his parents. Before and after school, the boy dutifully performed his chores in the fields, barnyard, and home.

Young Otto’s intellectual talents were recognized by the local schoolmaster and by the family’s minister, who persuaded the Krayers to continue their son’s education. Otto attended the six-year middle school at Emmendingen and then studied three more years for his university entrance exams; however, World War I interrupted his studies. When he turned eighteen, in 1917, Otto was drafted into the German infantry and saw action on the Western Front.

While convalescing from a combat wound, Otto finished his university entrance requirements. In the autumn of 1919, he finally enrolled as a medical student at the University of Freiburg. Many activities that Otto would pursue for the rest of his life, both professionally and personally, began during his years at Freiburg. He took long walks through the countryside, in the foothills of the Black Forest, taking careful note of all the native plants and flowers. His interest in botany and knowledge of plants evolved into his primary line of research, which focused on the medicinal value of plants (4).

An accomplished amateur skier, Otto loved to ski the slopes from the heights of the Black Forest to the outskirts of Freiburg, often accompanied by a classmate, Erna Ruth Philipp. Throughout his life, he maintained a vigorous lifestyle; skiing, in particular, transformed his normally reserved personality into that of a jolly and uninhibited child (1).

While he was a student at Freiburg, Krayer was drawn to Paul Trendelenburg, a pharmacology professor whose personality and lectures proved inspirational. After completing his formal coursework and passing his medical examinations in 1924, Krayer spent half of 1925 working in Trendelenburg’s department and the other half fulfilling his internship requirements in internal medicine. He received his MD degree in 1926, successfully defending his research dissertation on apocodeine, an opiate alkaloid closely related to apomorphine. After graduation, he continued his pharmacology research as Trendelenburg’s assistant.

Trendelenburg’s research focused on endocrinology, and Krayer’s initial studies concerned the relationship between thyroid function and the autonomic nervous system. Explorations of the adrenal medullary hormone epinephrine—along with a fortuitous trip to Stockholm in 1926 to attend the International Physiology Congress—turned Krayer’s interests to the cardiovascular system. In Stockholm, Krayer met leading contemporary cardiovascular physiologists and pharmacologists, including E.H. Starling, J.H. Burn, and G. Liljestrand (1).

As a medical student, Krayer had been intrigued by gross anatomy and found great satisfaction in exploring the biological relationship between form and function. This interest led naturally to his mastery of the dog heart–lung preparation as a research tool (1). In the heart–lung preparation, the heart and lungs remain in situ, but the entire output of the left ventricle (except for the coronary circulation) is routed through an external circuit. The experimenter maintains control of peripheral resistance, and the height of a blood reservoir determines the pressure at which the right atrium fills. A respiration pump provides oxygenation. In the 1920s, the dog heart–lung preparation was a state-of-the-art research method, and Krayer became one of its most prolific and preeminent practitioners (4).

In 1927, Krayer followed his mentor to the University of Berlin, where Trendelenburg had accepted the chair of pharmacology. Young Dr Krayer rapidly advanced from assistant to senior assistant to Privatdozent, the latter position entitling him to teaching privileges. When Trendelenburg became seriously ill in 1930, Krayer assumed full responsibility for the department. Trendelenburg died the following year, and Krayer was made acting department head.

Krayer performed brilliantly. He adeptly handled Trendelenburg’s administrative responsibilities, which included a heavy teaching load, personal participation in over 500 medical student oral examinations per year, and oversight of construction for a new building to house the department. He also assisted the courts by providing forensic toxicology analyses.

Officially, Krayer could not succeed Trendelenburg. According to the unwritten but rigidly followed rules of academic promotion in Germany at the time, chairmanship at a top-tier university such as Berlin could only be filled by someone who was already the incumbent of another chair. Nevertheless, the visibility of the interim position gave Krayer substantial recognition, and he expected to be offered a chair in his own right at another university (4).

When Professor Heubner, the chair at Göttingen, relocated to Berlin as Trendelenburg’s permanent replacement in 1932, he appointed Krayer Professor Extraordinarius of Pharmacology and Toxicology. Relieved of administrative obligations, Professor Krayer was able to turn his attention again to scientific research. His expert surgical technique and elegant experiments led to several major scientific discoveries.

In 1921, Otto Loewi had first demonstrated chemical neurotransmission using isolated frog hearts. By the early 1930s, evidence was accumulating that Loewi’s Vagus-Stoff was acetylcholine. Collaborating with W. Feldberg of the physiology department at Berlin in 1933, Krayer published a now classic paper that first demonstrated the existence of a neurotransmitter in an intact mammal. Krayer and Feldberg used the dog heart–lung preparation to show that an “acetylcholine-like substance” was released into the coronary circulation after electrical stimulation of the vagus nerve (5).

Each of Krayer’s experiments required dozens of dogs, and in the course of his long career he must have sacrificed thousands of dogs in the name of science and medical education. Today, the use of animals in research is a hotly contested ethical issue. Intriguingly, despite Krayer’s unbending sense of human values, he saw no moral dilemma in being personally responsible for the deaths of so many dogs. In an era characterized by high infant mortality, few vaccines, and no antibiotics, the desire to ease human suffering justified animal experimentation. Indeed, several times in his career Krayer redirected his research efforts to investigate clinical problems brought to his attention by attending physicians. He sought, for example, to understand the unexpected heart failure that had been reported in patients treated with reserpine, and he investigated the therapeutic efficacy of veratrum alkaloids that had been reported to lower blood pressure in eclampsia patients (1).

Krayer was the sole scientist to decline...a chaired position that, in accordance with Nazi law, could no longer be occupied by a Jew.

In April of 1933, Krayer took a leave of absence from Berlin to pursue collaborative experiments, using the heart–lung preparation, in the physiology department of the University of Göttingen. It was during his time in Göttingen that the Department of Education of the State of Prussia invited Krayer to take the chair of pharmacology left vacant in Düsseldorf upon Philipp Ellinger’s dismissal from the Nazi-regulated university system.

Like so many others in Germany at that time, Krayer could have taken the post and kept his opinions about Ellinger’s treatment to himself. After all, the Jewish Ellinger would never be reinstated, and if Krayer did not take the position, someone else would (2); there was ample precedent for such rationalization among German academics of the time. Alternatively, Krayer could have declined the post by offering some politically correct excuse. Instead, Krayer confronted this injustice head-on.

Krayer had never met Philipp Ellinger and knew little about him. Nevertheless, his candid letter declining the position contained no ambiguities and offered no compromises: “I feel the exclusion of Jewish scientists to be an injustice, the necessity of which I cannot understand, since it has been justified by reasons that lie outside the domain of science…. The work to which I have heretofore dedicated all my strength, with the goal of applying my scientific knowledge and research expertise to effective university teaching, means so much to me that I could not compromise it with the least bit of dishonesty” (2).

Krayer knew the price of his refusal would be high. The rules of academic promotions in Germany at the time mandated that any chair offered to a non-incumbent must be accepted. A second offer simply would not be made (4). The response from the Prussian Minister for Science, Art, and National Education was accordingly harsh: “I herewith forbid you, effective immediately, from entering any government academic institution, and from using any State libraries or scientific facilities” (1).

Such censorship would be devastating for any young scientist, and it struck Krayer at a particularly vulnerable time. He had inherited two literary projects from Trendelenburg: updating the second edition of a textbook on the principles of therapeutics and finishing Volume 2 of Trendelenburg’s treatise on hormones. Krayer had supervised publication of the textbook shortly after Trendelenburg’s death in 1931, but completing Die Hormone proved to be more difficult. He was still drafting Volume 2 when the censorship was imposed.

Returning to Berlin, Krayer defiantly continued his literary obligation to Trendelenburg. He relied on private literary sources and the generosity of friends (including Dr Erna Ruth Philipp), who brought books and journals from libraries for his use. As Krayer worked on the hormone treatise during the summer and fall of 1933, he also evaluated his professional future. Among the offers he received was a Rockefeller Foundation fellowship at University College, London. Having received a one-year leave of absence from the German authorities to study abroad, Krayer submitted the proofs of Die Hormone to Springer-Verlag on December 31, 1933, and left Germany for London. He did not return to Germany until 1948.

After temporary positions at University College London and the American University in Beirut, Krayer was offered an appointment in the pharmacology department at Harvard University, in 1936, where, shortly after arriving, he took yet another moral stand against Nazi policy. The 1935 Nobel Peace Prize had been awarded retrospectively to German writer and journalist Carl von Ossietzky. The Nazi regime had incarcerated Ossietzky for his outspoken pacifism and for exposing clandestine German rearmament. In response to the Nobel committee’s recognition of Ossietzky, Hitler issued a decree forbidding Germans to accept any Nobel Prize. Subsequently, at the next regular meeting of the German Chemical Society, Society President Professor Stock publicly supported Hitler’s decree and condemned the Nobel Committee for slighting the German State. Krayer promptly withdrew his membership from the German Chemical Society, explaining, “I do not find sufficient basis for your interpretation, and I am not of the opinion that the scientific Nobel prizes have lost any of their value or significance by the honoring of Carl von Ossietzky” (1).

As with Philipp Ellinger, Krayer had never met Carl von Ossietzky and only knew about him through his writings. Nevertheless, Krayer’s conscience would not allow him to be associated with a scientific organization that condemned a person whose only apparent fault was to disagree with the prevailing political party. In defending Ossietzky to Professor Stock, Krayer’s words could well be applied to himself: “A man [that is, Ossietzky] who is not motivated by the lust for power and fame but who is forced to speak by the persuasion of the rightness of his beliefs, and who fights unafraid for that persuasion with the force of his arguments” (1).

In 1939, Krayer came to the aid of Rafael Mendez, a Spanish political refugee. Trained as a pharmacologist, Mendez had served the Spanish Republic as a financial attaché, responsible for procuring military hardware, and as undersecretary of the interior in charge of information and internal security. After the Spanish Republic was overthrown by Francisco Franco, Mendez served as the Spanish consul in southern France directing the mass emigration of defeated loyalists. In the US, Mendez was considered a political pariah, and American universities and pharmaceutical companies refused to employ him. Although Krayer had only met Mendez briefly years before, he did not hesitate in appointing Mendez as instructor and research associate at Harvard. “Krayer took care of me as a loving father,” Mendez later recalled (1). Mendez went on to become a distinguished cardiologist in Mexico.

During World War II, the US considered Otto Krayer an “enemy alien,” and his travel was restricted to a twenty-five-mile radius around Boston. Focusing on education during the war years, Krayer systematically built Harvard’s laboratory-based pharmacology curriculum (1). The roots of Krayer’s deep commitment to teaching can be traced to his early days at Freiburg, where he was responsible for preparing lecture demonstrations for the students. Krayer strongly believed in the importance of practical laboratory work for medical students and introduced a small, elective experimental laboratory course at Freiburg—a radical innovation at the time. Similarly, his pharmacology program at Harvard became a model emulated by many other medical schools throughout the US (3).

When travel restrictions were lifted in 1946, Krayer enthusiastically participated in war relief efforts. He accompanied Harvard cardiologist Paul Dudley White on a medical mission to Czechoslovakia that was sponsored by the Unitarian Service Committee. In Central Europe, Krayer witnessed the ravages of war: starving people, demolished universities, and wrecked research institutes. Through discussions with his university counterparts, he became aware of similar devastation to the German university system.

When he returned to Harvard, Krayer founded the Committee to Help German University Scientists. Over the next two years, this group provided material and moral assistance to the German academic community. In 1948, Krayer headed a medical mission to Germany that was organized by the Unitarian Service Committee and supported by the US State Department and US occupation authorities. The mission visited universities in Frankfurt, Berlin, Göttingen, Munich, Tübingen, Freiburg and Heidelberg. In his subsequent mission report, Krayer made a series of recommendations as to the resurrection of Germany’s university system. These initiatives included study tours abroad for professors who had not been active Nazis, fellowships for younger scientists, reconstruction of libraries, equipment and supplies for selected institutions, blood banks and plasma fractionation laboratories, and production facilities for antibiotics.

“I do not find sufficient basis for your interpretation, and I am not of the opinion that the scientific Nobel prizes have lost any of their value or significance...”

Krayer’s report also reveals his deeply held humanitarian convictions: “The greatest accomplishment of the mission seems to me to be that for the first time since cultural and political ties between Germany and the rest of the democratic western world were ruptured, ten to fifteen years ago, a large group of university members not connected with government and not having political motives have met with their counterparts in German universities on a basis of equality in the scientific field and with the aim and good will to establish friendly relations.…[We] have shown the German colleagues that the possibility exists of ending their isolation from the rest of the world” (1).

Although Krayer and his long-time assistant Erna Ruth Philipp had married in 1939, they had no children of their own. But the personal interest that they took in Otto’s students was profound. Their red brick house in West Newton became a gathering place for generations of his medical students and young scientists. Each summer the entire pharmacology department—faculty, graduate students, and technicians—were treated to a swim party and picnic, with all food and trimmings supplied by the Krayers (Victor H. Cohn, personal communication). The lobster and steak cooked on the beach during those outings left deep, lasting impressions on the young staff.

Students remember Professor Krayer as a clear lecturer and a no-nonsense laboratory mentor. Although he carried himself with great natural dignity, Krayer was approachable and showed a paternal concern for their problems. As Peter Dews, a young faculty member who observed Krayer’s influence, put it, “He never discarded a human being. Anyone who had ever been associated with the department had a permanent claim to his concern” (4).

A man with tremendous self-control, Krayer never raised his voice, but students clearly knew when he was displeased (4). He inspired excellence, and with few exceptions, his graduate students responded by performing better than they thought they could. Many went on to chair departments of pharmacology, and countless others became outstanding pharmacologists in academic and research institutes around the world. Through them, Krayer’s influence on the field of pharmacology has been seldom paralleled.

Although Professor Krayer quickly established himself as a popular teacher at Harvard, his unyielding principles compelled him to consider other posts at least twice. His European manner, excessive formality, stern demeanor, and moody temperament had not endeared him to the medical school administration. Consequently, he failed in his initial attempts to win the financial support and administrative commitment needed to build a pharmacology department according to his vision. In 1939, after only two years at Harvard, he began making plans to accept a position in China. In an extraordinary move, all of the medical students in Krayer’s pharmacology course and many from the previous year’s medical class presented the medical school dean with a petition asking Krayer to stay (4). Instead of leaving, Krayer was granted tenure and made head of the department.

Again, by 1947, recurring tensions between Krayer and the medical school administration reached the breaking point. Krayer’s blunt honesty and tendency to speak the brazen truth rankled fellow members of university committees. Krayer considered a position in Basel, Switzerland, and this time both Dean C. S. Burwell and Harvard President James Conant urged him to leave. The Swiss post was awarded to an internal candidate, and Krayer managed to outlast Burwell and Conant, both of whom retired soon afterward.

In 1951, George Packer Berry, the incoming dean, forged a close professional relationship with Krayer. Over the next fifteen years, the two men joined forces to build laboratory facilities and to attract a steady stream of high-caliber students, junior faculty, and visiting scientists. By 1966, the year Krayer retired after thirty years at Harvard, Krayer’s department ranked at the top of the American Council on Education’s list of pharmacology departments in the US.

A year earlier, the Academic Council of the Medical Academy of Düsseldorf invited Krayer to become an honorary member. The council wished to recognize him for his integrity in refusing the Düsseldorf chair in 1933, his tireless efforts in support of German science during and after the war, and his scientific contributions. Although flattered by the scientific recognition, Krayer respectfully declined the academy’s invitation. To Krayer, ethical behavior was not a contest; he would not accept an award for it (2).

Krayer remained active after his retirement, serving as a visiting professor at Howard University, Stanford University, University of Arizona, and Technical University of Munich. He died in Tucson on March 18, 1982, from prostate cancer. For his contributions to science, Krayer was elected to the National Academy of Science. The American Society for Pharmacology and Experimental Therapeutics recognizes distinguished, mature investigators with the Otto Krayer Award in Pharmacology, and the University of Freiburg’s science building is named for him.

Throughout his life, in all that he did, Otto Krayer remained true to his internal moral sensibilities. He didn’t wear his convictions on his sleeve; he carried them in his heart. His conscience didn’t compel him to convert others to his own moral stance, but to those who knew him, he set uncompromising standards in research, in education, and in ethical behavior. Ulrich Trendelenburg, the son of Krayer’s mentor, noted, “He set [for my coworkers] something that is very rare nowadays—an example” (3).

• © American Society for Pharmacology and Experimental Theraputics 2005