BUTENANDT, ADOLF FRIEDRICH JOHANN

(b. Bremerhaven, Germany, 24 March 1903;d. Munich, Germany, 18 January 1995)

biochemistry, biotechnology, National Socialism.

A successful figure in twentieth century science, Butenandt was a Nobel Prize winner, director of the most important biochemical research institute in pre- and post-war Germany, and was twice elected President of the Max Planck Gesellschaft in the 1960s. As a biochemist, he deciphered the chemical structure of steroid hormones of major importance, and was instrumental in the transition from chemical physiology to molecular biology. He was also a lifelong collaborator with the pharmaceutical industry, contributing to the transformation of steroids into powerful drugs. Contemporary scholars have viewed his trajectory as a typical example of the complex relationship prominent German scientists maintained with the Nazi regime in order to advance their careers and expertise.

Gifted (Bio)Chemist. Born in 1903 into the family of a local entrepreneur, Adolf Butenandt was the first among his kin to enter the academic world. Having completed a university curriculum in biology and chemistry, he joined the laboratory of the organic chemist Adolf Windaus in Göttingen to prepare his dissertation. The topic offered to him had been selected during one of Windaus’s regular trips to the Swiss pharmaceutical firm Hoffmann-La Roche: Butenandt was to study a white powder prepared at Hoffmann’s laboratory that contained rotenone, a poison found in fish and insects. Butenandt completed his mission in less than one year, describing rotenone’s molecular composition and molecular structure. Yet this was mere training in organic chemistry; the real challenge was launched when Windaus followed another industrial proposal, this time from the Berlin-based Schering AG: Butenandt was to work on the purification of the ovarian hormone, a biological entity whose isolation was already under way in several highly regarded laboratories.

The follicular hormone was not a purified chemical entity but a biological preparation. The raw material Butenandt received from Schering was an oily extract of placentas. To label it a female hormone was a pragmatic operation, based on physiological testing. Biological assays played an essential role in the development of hormone research during the first half of the twentieth century. They performed many functions, such as enabling the standardization of extracts, the concentration of active principles, as well as the quantification of their effects. In the case of the female hormone, the physiological change taken as a marker of its presence was the growth and differentiation of the mouse uterus. Imported from the United States, the procedure was implemented in Göttingen by Erika von Ziegner. She later married Butenandt, ultimately leaving biological research to take care of a rapidly growing family (the couple had seven children, five daughters and two sons).

In spite of its biological complexity and multiple effects, the female hormone was relatively easy to purify with organic solvents, giving Butenandt a crystallized powder sharing many features with cholesterol in fairly short order. Cholesterol was under close scrutiny in Windaus’s laboratory, and was also the subject of a chemical controversy concerning its exact formula and structure. With his hormone, oestron, Butenandt extended Windaus’s previous results in favor of a four-ring structure, which would later become typical of derivatives of cheolesterol and steroid in general. The general acceptance of this scheme brought Butenandt international recognition. In 1932, he was invited to join the committee for the standardization of hormones set up by the League of Nations.

Given the visibility of his work on oestron, Butenandt did not remain long as the assistant of Windaus. Soon after he defended his habilitation thesis in 1932, he was offered a professorship in the so-called free city of Danzig (present-day Gdansk in Poland). Although he did not enjoy the same financial and material resources as in Göttingen, Butenandt gathered a group whose main aim was to exploit the same strategy of purification and structural analysis with other hormones. In 1936, the group moved to Berlin where Butenandt had been called to become director of the Kaiser Wilhelm Institute for Biochemistry (KWIB). The sex steroids remained at the center of research activities. A male hormone, androsterone (which later became a metabolite of testosterone), was isolated; the physiological test then selected involved inducing the growth of a crest in castrated chickens. A third major steroid described by Butenandt in parallel with several other biochemists was the hormone of the corpus luteum (progesterone), obtained from pig ovaries and tested in rabbits.

Butenandt’s way of analyzing the hormones was standard practice in organic chemistry at the time. He made extensive use of differential solubility in organic solvents as well as of reactions that led to changes of the steroid core structure, like the replacement of hydrogen by brome or chlorin atoms. The importance of his contribution to the isolation and characterization of the sex steroids, for which he was granted the Nobel Prize for chemistry in 1939, was not only in this application of chemical methods to natural substances of major physiological importance, but also in a structural approach to biological phenomena. This is best illustrated by Butenandt’s vision of the polarity between male and female bodies. One remarkable achievement of the work done in Butenandt’s laboratory was the combination of the then-emerging notion of a molecular continuum linking all sex steroids (with either male or female effects) with the prevailing approach of a reproductive biology stressing the incommensurability between the two sexes. During the 1930s, organic chemistry provided Butenandt’s group with a whole range of molecules showing strong or weak male or female properties, as well as a few examples of “hermaphrodite” steroids. Considering the structural proximities between androsterone, testosterone, oestron, progesterone, and their derivatives, Butenandt’s interpretation of their biosynthesis was based on two principles. Firstly, he was convinced that the laboratory reactions used to change the chemical groups attached to the core structure of the steroids had their counterpart in the cells of the sex glands. Secondly, he thought that the diverse sex steroids could be organized in natural biosynthetic series, such that the modification of peculiar lateral groups could be correlated with the acquisition of male or female potency, respectively (or, put another way, with the progressive acquisition of a unique sexual identity by the molecules).

Industrial Scientist. Butenandt called his female hormone Progynon, which was actually the brand name Schering had given to its commercial preparation made out of pregnant women’s urine. Butenandt’s choice was a vivid testimony to his debt to the pharmaceutical company, specifically for the biological material and the very basic possibility of conducting his research. Although Schering is often invisible in accounts of Butenandt’s research, it was a key partner until the end of World War II. In exchange for its material support, the firm obtained the

structure of the sex hormones and their purification protocols. These were patented, giving Schering exclusive intellectual property rights as well as considerable advances in the development of analogs and marketable derivates. As compensation, Butenandt obtained a significant percentage of the sales. Until the end of the war, these pharmaceutical revenues doubled the budget of the Institute.

The scientific consequences of this relationship were far from negligible. The question of steroid synthesis reveals the blurred boundary between industrial and laboratory practices that characterized biochemistry at the KWIB. In 1936, Butenandt reviewed and discussed the origins of the properties of the three families of natural and artificial sex steroids. He then proposed a unified scheme in which estrogens, progesterone, and male hormones could all be derived from cholesterol. Many of the intermediate molecules had been semi-synthesized at the bench, using natural steroids as starting material. The criteria ordering the reactions were simplicity of the reaction path, structural homology between products and substrates, and yield at the bench. This economy of natural synthesis was the very same economy governing Schering’s inquiries into the artificial production of such molecules out of cholesterol. In fact, many molecules the KWIB scientists used and eventually introduced in the natural pathways for steroid biosynthesis had first been elaborated by Schering’s chemists in their attempts to obtain more potent or cheaper derivatives of the natural sex hormones. Governed by the same chemical order, the cell and the plant could be viewed as two sides of the same coin.

The emphasis Butenandt and Schering’s scientists placed on the development of pathways and protocols was rooted in their shared interest for new steroids. It was also rooted in the political economy of the drug industry. In Germany, as in many European countries, drugs could not be patented until the 1960s. In practice, however, pharmaceutical companies protected production processes. The invention of processes thus became an essential part of the production and valorization of biochemical knowledge. During the 1930s, Butenandt’s protocols thus eased the scaling up of Schering’s hormone production, which in turn permitted wider uses. This dynamic deeply transformed reproductive medicine, resulting in new treatments—for female sterility, for male impotence—and more contested procedures like the medical handling of menopause.

Fellow Traveler of National Socialism. When Butenandt moved to Danzig to take his post, Adolf Hitler and the National Socialist party had seized power. The young professor was not an activist, but at the same time was far from non-political. During his Göttingen years Butenandt had become a member of a student fraternity opposed to the Versailles Treaty and the Weimar Republic. Butenandt hoped for a new order in Germany, although, in contrast to the National Socialists (Nazis), he did not look for a violent uprising. He did not join the Nazi Party in 1933, but rather later in 1936 in the context of intense negotiations about the succession of Carl Neuberg as head of the KWIB. Neuberg was forced into retirement because of his Jewish background. Butenandt was approached as a possible successor, but soon learned that his appointment was in jeopardy because of a report of “political unreliability” from the University of Göttingen. The application for membership in the Nazi Party was in effect a nomination passport. The move was not, however, purely opportunistic: as was the case for so many Germans, Butenandt’s “move toward Hitler” was the product of an authoritarian culture, as well as an effect of what many Germans then considered the early international “successes” of the regime.

Butenandt did not become an active member of the Nazi elite but still came into close contact with the state power centers. He was not a public advocate of race research and race policy, but shared the basic prejudices against Jews that were commonplace at the time, and expressed these in private. Butenandt’s vision of his duties toward the Reich was deeply imprinted by the traditions of the academic elite. His doubts about the Nazi revolution did not originate in the difficulties of the late war years, but surfaced somewhat earlier when he was denied the right to accept his Nobel Prize. After Carl von Ossietsky was granted the Nobel Peace Prize in 1935, the Nazi government had forbidden all German scientists to accept Nobel awards. In 1939, after three German scientists (Richard Kuhn for chemistry in 1938, Butenandt and Gerhard Domagk respectively for chemistry and physiology) were distinguished, Butenandt had hoped this policy would be softened. Although this event ruined the possibility of trust and ideological engagement, it did not annihilate opportunities for alliance, as Butenandt’s relentless self-mobilization demonstrated.

In 1947 Butenandt was called to testify during the Nuremberg doctors’ trial to answer questions about the work some of his collaborators had undertaken for the Luftwaffe. These links between the KWIB, forced medical experimentation, and race research have been much discussed in the recent historiography. Archives are incomplete and will remain incomplete. That said, enough is available to conclude that the connection was loose but real. Butenandt’s institute became a major center of war-related research (Kriegswichtige). The label was widespread; it says little about the military relevance of the work, but testifies to the negotiations and agreements that were a precondition of funding.

The diversification of KWIB activities during the war was remarkable. Butenandt was not a passive director upon whom the military or health administration could simply impose research topics. He was instead an active and pragmatic source of ideas and proposals. By the end of the war, he was leading two dozen different projects, including research on viruses, hormones and cancer, blood cell formation, steroid synthesis, insect physiology, and antibacterial therapies. Some projects extended work begun during the war. Investigations on the carcinogenic power of steroids, for instance, started in 1936 after laboratory studies of mice demonstrated that estrogens could induce the formation of tumors, and continued after the question of medical uses of estrogens had been made more acute with the marketing of diethylstilbestrol (DES), a synthetic analog that was much cheaper than the existing “natural” preparations. During the war, in conjunction with Schering and its medical mode of practice, the KWIB biochemists completed systematic testing in mice to assess the carcinogenicity of sex steroids. In 1949 they concluded that DES as well as the biological hormones were safe if used in physiological dosage and under medical surveillance. Modeling did not solve all problems. The DES question surfaced again in the 1970s in a much more dramatic way, with thousands of cases of genital cancers in the daughters of women who had taken the drug to prevent spontaneous abortion.

Given Butenandt’s strong industrial connections, it is not surprising that the majority of the KWIB war-related projects focused on the isolation, purification, and putative synthesis of biological agents. The skills developed with the study of sex steroids were thus incorporated in collaborative projects with Schering and (to a lesser extent) with IG Farben. War-time biopharmaceutical research at the KWIB targeted vitamins, a liver factor against anemia, a factor involved in resistance to tuberculosis, a hormone stimulating the formation of blood cells, penicillin and antibacterial secretions of molds, and plant viruses. The interest of these agents was rooted in far-reaching promises of use in military medicine. For instance, the work on the blood hormone (which would in time become erythropoietin) was sold to the Luftwaffe by Butenandt with the promise of increasing pilot resistance to low pressure, as well as being a potential agent in the etiology of epilepsy (insufficient intake of oxygen was considered a crisis factor).

Available records do not document any direct contribution by Butenandt to the development of biological weapons, although the preparation of highly purified viruses could be used both ways, on the one hand to develop protection systems (vaccines or biological protection of crops) and on the other to develop new arms. Nevertheless, a few projects did focus not only on the quest for new drugs, new food, or industrial ersatz but tied in with the criminal aspects of biomedical research in National-Socialist Germany. The putative connection of Butenandt’s Dahlem institute to Auschwitz is the most typical example of this sort of gray zone: It linked on the one hand the world of basic laboratory experimentation and on the other hand the murderous technological world of the camps. The Kaiser Wilhelm Institute for Anthropology, Human Heredity and Eugenics played a critical role in the National Socialist system of research. After 1942 and under the leadership of Otmar von Verschuer, the institute included Josef Mengele, Auschwitz’s chief physician, among its personnel. Conducting his own studies in the camp, Mengele simultaneously provided the Dahlem’s institutes with human research material. Blood samples collected in Auschwitz under unknown conditions were for instance used to develop a biochemical system of race identification based on specific blood “enzymes” thought to be involved in resistance to foreign proteins. Butenandt did not invent the race-oriented project, but—following a request from Verschuer—provided technical assistance via one of his collaborators (Günther Hillmann), laboratory space, and tools. From Mengele to Verschuer to Hillman to Butenandt, the chain transferred samples and results. It also “purified” the inquiries. The existence of such mediations made it possible for Butenandt to speak about inheritance without any hints of racial policies, and to be aware of Verschuer’s racial science without knowing too much about the camps. As a final testimony of his confidence and friendship, Butenandt remained loyal to von Verschuer. In the early 1950s, after the later’s links to Auschwitz had become public knowledge, Butenandt helped von Verschuer resume an academic career.

Godfather of Molecular Biology. Butenandt does not belong to the long list of early “molecular biologists” the history has retained. Given his research topics during and after the war—gene physiological action, virus structure, hormonal control of the metabolism—one could in fact argue for quite the opposite. This absence is to some extent artificial, an effect of the emphasis the historiography of molecular biology has given to molecular genetics.

However, the relationship of Butenandt’s work to molecular biology was ambiguous.

On the one hand, the difference between his biochemistry and what would become molecular biology is obvious. It is best exemplified with his involvement in physiological genetics. In 1935, shortly before the move to Berlin-Dahlem, Alfred Kühn approached Butenandt asking for his help. Having found a mutation in the flour mite Ephesia that produced red instead of black eyes, Kühn thought that the mutants lacked a hormonal darkening factor. To follow the effects of the mutation, Kühn developed a system based on the transplantation of glandular tissues in mutant organisms. By the time he contacted Butenandt, he needed a biochemist to purify the active substance. Issues and techniques were in all respects similar to the work then being done by Boris Ephrussi and George Beadle on Drosophila, in Paris and Pasadena respectively. The contribution of Butenandt—or, more accurately, of his collaborator Ulrich Westphal—was preparing and testing candidate fractions. Given the size of Ephesia, the biochemist’s skills, and the KWIB assay culture, the German teams won the race to identify the darkening factor. It proved to be kynurenin, a compound close to the amino acid tryptophan. In the United States, the study led to the “one gene, one enzyme” hypothesis, some version of which had been formulated by Kühn during the war. On the biochemist’s side, however, the pursuit of gene action was transformed into a more biochemical analysis of pigment synthesis. The project was relocated within the KWIB and became the responsibility of another Butenandt student, Peter Karlson. After the war Karlson continued various studies of insect hormones. Silkworms were collected en masse to analyze the synthesis of eye pigments, the substances involved in sex attraction and the factors controlling metamorphosis. The ability to induce metamorphosis was tested in larvae from Calliphora. A ligature in the middle of the body isolated the head from the posterior segments of the body, thus forced to remain in a juvenile state. After inoculation, active substances would induce the formation of a pupa in the posterior half. In the 1950s, new methods of analysis including liquid chromatography and electrophoresis were introduced, facilitating the isolation of the metamorphosis hormone. Ecdysone, as it was named, was crystallized in 1954. During the following decade, Butenandt’s collaborators’ studies of its effects, for instance the control of chromosomal puffs in Drosophila, radically changed our understanding of cell differentiation and development, linking hormonal regulation and gene activity.

At the same time, the virus studies conducted during and after the war suggest that Butenandt and his KWIB have to be placed on the molecular biology landscape.

In the 1930s, molecular biology was about genes and macromolecules rather than information, focusing on the uses of a new palette of physicochemical instruments including the ultracentrifuge, electrophoresis, and electron microscopy. The Rockefeller Foundation played an important role in this instrumental program. One of few German biologists invited by the Rockefeller Foundation to travel to the United States after 1933, Butenandt was well aware of these developments and rapidly followed up on them. In 1937, three directors of Kaiser Wilhelm Gesellschaft (KWG) institutes located in Dahlem, Kühn, Butenandt, and Fritz von Wettstein, discussed the creation of a common virus initiative. The idea was to work on the isolation, structure, and properties of viruses like the tobacco mosaic virus (TMV) that Wendell Stanley had recently crystallized. Industrial partners (IG Farben and Schering) and the KWG founded the project, which grew to the status of a full-fledged virus station in 1941 before being reincorporated within Butenandt’s institute after the war. As with the laboratory output of the Rockefeller Foundation’s 1930s investments in “molecular biology,” the KWG viruses were products of the ultracentrifuge. The ultracentrifuge could be used both to prepare pure (eventually crystallized) viruses and to analyze their physical characteristics (weight, size). It was a perfect boundary-object, which linked the biological and the technical, botany and biochemistry, agriculture and medicine. Wartime research encompassed cancer and potato-virus studies as well as contributions to a decade-long discussion about the respective roles of proteins and nucleic acids in the control of TMV specificity and infectivity, a discussion that played a significant role in the identification of DNA as genetic material. After the war, the uses of the ultracentrifuge became ever more fundamental. Butenandt’s former collaborators used TMV to pave their way into the second molecular biology, using studies of the plant virus to bring DNA structure and genetic information transfer to the fore. In 1954, on the basis of this work, they obtained the creation of an independent institute for virus research from the Max Planck Society, the postwar heir of the Kaiser Wilhelm Gesellschaft.

Reorganizer of German Biology. During the summer of 1944, Butenandt started to relocate his institute to Tübingen, well away from the dangers of a frequently bombed Berlin. When the Allies seized Tübingen, Butenandt was on a United States watch list because of his presumed participation in biological weapons research. However, the pressing need for German partners as well as a mounting cold war made Butenandt’s case less and less suspicious. By 1947, he had been cleared of all accusations concerning his Nazi Party membership or his institutional successes. Moreover, having established new industrial connections and remained as the director of a major institute, he became a central figure in the reorganization of German science in general, and in the transition from the Kaiser Wilhelm Gesellschaft to the Max Planck Society in particular.

During the first postwar decade, Butenandt participated in the many decisions regarding the nominations of professors or the displacement, reorganization, and creation of laboratories making up the new West German biological landscape. His ideological role was no less minor. Butenandt contributed to a discourse of moral responsibility and denial of culpability, one that focused squarely on the value of pure science. Building on selective memories, he presented the KWG laboratories as centers of resistance against a Nazi dictatorship viewed as inherently hostile to science in light of the expulsion of good researchers and mandated technological work. Basing the reconstruction on this imagined tradition of fundamental research was all the more timely, as it echoed trends toward a massive governmental support of basic science then ascendant in the United States.

During the 1960s, while leading the Max Planck Institute for Biochemistry in Munich, Butenandt was a very active president of the Max Planck Society. Benefiting from large governmental funding for science, his presidency gave occasion for the development of a more fundamental and more molecular German biology, with the creation of institutes in molecular genetics and in biophysical chemistry. Butenandt advanced the collaboration between the Max Planck Gesellschaft institutes and German universities, but his reaction to the late 1960s student revolt was largely hostile. Although he accepted some “co-management” within the institutes (their reform gave the scientific collaborators new representation and protection), he viewed the Max Planck Society as a home for the defense of a productive and elite science against misplaced calls for the democratization of universities and the students’ attacks against the generation of those who knew nothing and did nothing.

Adolf Butenandt died in 1995. His successful and problematic career blended biology, politics, and industry. As such he was a typical twentieth-century scientist.

BIBLIOGRAPHY

WORK BY BUTENANDT

Das Werk eines Lebens, 4 vols. Göttingen: Vandenhoeck & Rupprecht, 1981. Comprehensive collection of articles.

OTHER SOURCES

Brandt, Christina. Metapher und Experiment: Von der Virusforschung zum genetischen Code. Göttingen: Wallstein, 2004. Investigates the postwar development of virus research and the path toward molecular biology.

Ebbinghaus, Angelika, and Karl-Heinz Roth. “Von der Rockefeller Foundation zur Kaiser-Wilhelm/Max-Planck-Gesellschaft: Adolf Butenandt als Biochemiker und Wissenschaftspolitiker des 20. Jahrhunderts.” Zeitschrift für Geschichtswissenschaft 50 (2002): 389–418. Critical biography.

Gaudillière, Jean-Paul. “Better Prepared than Synthesized: Adolf Butenandt, Schering AG, and the Transformation of Sex Steroids into Drugs.” Studies in History and Philosophy of the Biological and the Biomedical Sciences 36 (2005): 612–644. Analyzes the connection with industry.

Gausemeier, Bernd. Natürliche Ordnungen und politische Allianzen:Biologische und biochemischen Forschung an Kaiser-Wilhelm-Instituten, 1933-1945. Göttingen: Wallstein, 2005. Discusses Butenandt’s research practices.

Karlson, Peter. Adolf Butenandt: Biochemiker, Hormonforscher Wissenschaftpoliker. Stuttgart: Wissenschaftliche Verlaggesellschaft, 1990. Important but rather apologetic biography by former student. Includes a list of Butenandt’s numerous publications.

Neubauer, Alfred. Bittere Nobelpreise. Berlin: Books on Demand, 2005. Analyzes refusal of the 1939 Nobel Prize.

Rheinberger, Hans-Jörg. “Virusforschung an den Kaiser-Wilhelm-Instituten für Biologie und Biochemie, 1937–1945.” In Epistemologie des Konkreten, Frankfurt: Surkhamp, 2006.

Sachse, Carola, ed. Die Verbindung nach Auschwitz Biowissenschaften und Menschenversuche am Kaiser-Wilhelm Instituten. Göttingen: Wallstein, 2003. Addresses the connection to Auschwitz.

Schieder, Wolfgang, and Achim Trunk, eds. Adolf Butenandt und die Kaiser-Wilhelm-Gesellschaft,Wissenschaft, Industrie und Politik im Dritten Reich. Göttingen: Walstein, 2004. Collection of studies of Butenandt’s career; discusses the relation to Auschwitz.

Walker, Mark, and Carola Sachse, eds. Politics and Science in Wartime: Comparative International Perspectives on the Kaiser Wilhelm Institutes. Chicago: University of Chicago Press, 2004. An evaluation of the war-time mobilization of the Kaiser-Wilhelm institutes.

Jean-Paul Gaudillière