Stephenson, Marjory

views updated May 23 2018

STEPHENSON, MARJORY

(b. Burwell, near Cambridge, England, 24 January 1885; d. Cambridge, 12 December 1948)

microbiology, biochemistry.

Marjory Stephenson figures in the history of science in several ways: most important, she was one of the half dozen or so people who, between the two world wars, created the new specialty of bacterial biochemistry. In so doing, she contributed to the distinctive and influential style of practice of F. G. Hopkins’ school of biochemistry at Cambridge. Her papers on adaptive enzymes in the 1930’s became, in the decade after her death, one of the growth points of molecular genetics. She was one of the first women to receive a D.Sc. from Cambridge, her alma mater, and with Kathleen Lonsdale was one of the first two women to be made fellows of the Royal Society (in 1945). She never married.

Stephenson was the youngest (by almost nine years) of four children born to Robert and Elizabeth Rogers Stephenson, comfortably well-to-do, public-minded, and progressive farmers and horse breeders in the fenlands of Cambridgeshire. Robert Stephenson was active in county politics and was instrumental in marshaling local support for the creation of a school of agriculture at Cambridge University. For this he received an honorary M.A. in 1903, the year that Marjory entered Newnham College, Cambridge. There she read part I of the natural science tripos in chemistry, physiology, and zoology, taking her degree (second class) in 1906. She would have liked to go on to medical school but lack of funds obliged her to earn her living by teaching.

Stephenson spent five not very happy years teaching at the Gloucester County Training College in Domestic Science and the Kings College of Household Science in London. Nutrition and dietetics were not an uncommon career choice for women scientists at the time (the more elite academic disciplines were virtually closed to them). For most it was an occupation that offered little chance for doing science, but for a few nutrition was an entry into the developing profession of physiological chemistry. Stephenson was one of the lucky ones. In 1911 her talents caught the eye of the nutritional biochemist R. H. A. Plimmer, who offered her a job in his laboratory at University College, London. There she assisted Plimmer in advanced teaching and in his researches on lipid metabolism and metabolic disease. In 1913 a Beit Memorial Fellowship for Medical Research gave Stephenson a measure of independence, but the outbreak of war in 1914 interrupted her career. In the British Red Cross from 1914 to 1918, she put her knowledge of nutrition and diet to practical use in France and Greece.

Resuming her fellowship in 1919, Stephenson moved to the very center of British biochemistry, joining F. G. Hopkins’ group at Cambridge. Hopkins’ prewar paper on essential amino acids had made him the most visible exponent of research on “vitamines.” Stephenson went there hoping to move from the metabolism of fats into the emerging field of fat-soluble vitamins. She was disappointed: her own research (on the possible role of vitamin A deficiency in keratomalacia) got nowhere, and Hopkins, unable to compete with better-organized and -funded research teams in London, lost interest in vitamins and threw himself into the chemistry of biological oxidation. It was in these circumstances that Stephenson turned to the decidedly more risky and less fashionable field of bacterial biochemistry.

In fact, she happened to be at the right place at the right time. Hopkins had long had a keen interest in the biochemistry of microorganisms. He envisioned “general” biochemistry much as comparative physiologists envisioned their discipline—as encompassing every kind of organism from bacteria to man. (Probably it was a strategy to keep the nascent discipline of biochemistry from being co-opted by the medical physiologists.) During the war, with funds from his friend and secretary of the Medical Research Council, Walter Fletcher, Hopkins arranged for a young chemist, Harold Raistrick, to begin a line of work on the chemistry of microbes. In 1921, however, Raistrick left to take a job in industry, just as a large endowment and a new laboratory were finally enabling Hopkins to realize his dream of a comparative biochemistry. Fletcher, who had his own (medical) reasons for developing bacterial biochemistry, was eager to provide support for a successor. Thus a strategic niche in Hopkins’ group became vacant just as Stephenson’s work on vitamins was coming to a dead end. She was never lacking in courage, and at that juncture she had little to lose.

Stephenson had carte blanche to develop bacterial biochemistry according to her own vision. The field had yet to be defined; space had been created for it before there was a body of certified knowledge to define it. Hopkins gave all his junior staff great freedom to develop their special fields, and Fletcher, while he hoped Stephenson would form strong connections with pathologists, shrank from pushing too hard. Stephenson’s distinctive style of practice is apparent from her first publications in 1922. Whereas Raistrick had been interested in the organic chemistry of fungal metabolites. Stephenson was interested in microbes as organisms with distinctive physiologies. Her early work built upon the classical researches of Pasteur, Max Rubner, and other biologists on material and energy metabolic balance. She was always fascinated by the evolutionary meaning of the extraordinary diversity of microbial metabolism. At the same time, Stephenson was deeply influenced by the more mainstream lines of biochemical work in enzymology and oxidation, which dominated Hopkins’ expanding school.

Between 1922 and 1940 Stephenson’s own work and that of her students alternated between mainline enzymology and a more biological approach. In the 1920’s, for example, she was greatly influenced by Juda Quastel, a young organic chemist with whom she worked on the inhibition by oxygen of the growth of anaerobic bacteria. But when Quastel delved into the chemical theory of biological oxidation, Stephenson turned to a more biological aspect of their problem, the adaptation of microbes to changes in their environment. Between about 1929 and 1935, she was preoccupied with the enzymology of a novel class of hydrogen-activating enzymes, and between 1938 and 1941 she put most of her own and her students’ efforts into the enzymology of amino acid deaminases. Yet in between, with her student John Yudkin, she did important work on the puzzling phenomenon of enzyme adaptation, with its rich implications for the big questions of biologists: physiological regulation, adaptation, and evolution.

Among biochemists, Stephenson is remembered best for her discovery of a new kind of enzyme. But her most distinctive contributions to the practice of bacterial chemistry are on the biological side. Most enzymologists saw cells as convenient bags of enzymes and preferred to work in cell-free systems; Stephenson always returned to the cell and devised experimental methods to assure herself that she was not dealing with chemical artifacts. With Margaret Whetham she perfected the “resting cell” technique of studying the chemical activities of heavy suspensions of nongrowing cells in minimal medium. She took pains to learn microbiologists’ techniques of isolating pure cultures and counting viable cells; she made it a standard part of every experiment to determine the proportions of viable and dead cells—to quiet biologists’ doubts that her “resting” cells were not resting but dead, and their chemical activities not normal physiology but chemical artifacts. Such techniques were a hallmark of Stephenson’s practice and enabled her to prove, among other things, that enzyme adaptation was the result not of selection but of a chemical change in the cell’s regulation of its physiology.

Stephenson’s alternation between biochemical and biological approaches to bacterial biochemistry mirrored the balance of interests within Hopkins’ school. Enzymology, oxidation, and intermediary metabolism were the prestigious mainstream fields, and chemists like Malcolm Dixon and Norman Pirie formed a powerful interest group, Hopkins himself talked like a chemist half the time, yet it was his broad biological outlook that gave his school its distinctive intellectual vigor. The biochemistry lectures and practicums, for example, were organized around organisms, not kinds of compounds, as was usual everywhere else. With Joseph Need ham, Margaret Whetham, and Robin Hill, Stephenson constituted a biological interest group that was able to resist pressures to bring the Cambridge style of biochemistry more into the chemical mainstream.

Stephenson’s work and career can be understood only as integral to the remarkable social organism of which she was a part. She gave concrete shape to an institutional and intellectual space that had been prized open between bacteriology and biochemistry by Hopkins and Fletcher. There were many ways it could have been done: as pure enzymology, organic chemistry, medical (or agricultural) applications, bacterial nutrition. Stephenson’s way was broader and more comprehensive; like Hopkins’ vision of a “general” biochemistry, Stephenson’s vision of a “general” microbiology was a blend of chemical technique and biological vision. She made use of the diverse resources of the Cambridge school and the Medical Research Council (MRC) network without being captured by any one of them. Enough of the political work of discipline building had been done to enable Stephenson to make effective use of her special gifts. Probably she could not have done what she did anywhere but at Cambridge. But someone with a better chance for a career in the mainstream probably would not have used those local resources so imaginatively.

In 1929 Walter Fletcher put Stephenson on the MRC’s regular payroll, as a full-time external research worker. Once again she inherited a niche created for Harold Raistrick, who had decided to return to academe, and whom Fletcher hoped to set up as director of an MRC-sponsored research unit in bacterial biochemistry. When Raistrick opted for a university chair in London, Fletcher offered Stephenson a regular position, with the prospect of support for her small group of student apprentices. It would not be a research unit, however: Fletcher, while he greatly admired and valued Stephenson’s achievements in her personal research, clearly did not see her as a manager of a team of full-time researchers. No doubt Fletcher did not expect women to be entrepreneurial. In any case, Stephenson’s style of leadership was essentially individual and informal; like Hopkins, she led by inspiring and setting an example.

Stephenson was a bench worker, and her enthusiasm for new lines of experiment never ran dry. Her list of publications is not long by modern standards, but there are no potboilers. She was never a good lecturer but was a generous and inspiring mentor. Her few students were unusually able. She had a deep sense of duty (a Stephenson family trait) and was active in college and professional matters, but never became a smooth operator of committees. Stephenson had a vivid and impetuous personality, and was known for occasional impulsive enthusiasms and outbursts. (She would take on, if provoked, even such strong personalities as Walter Fletcher.) She did not know how to tolerate pretension and sided instinctively with underdogs. It took her a long time—a lifetime, indeed—to develop her own capabilities, and she grew slowly but continually throughout her career.

The growing popularity of bacterial biochemistry in the 1940’s drew Stephenson into more formal organizing and managing. She was a vigorous and influential member of the MRC’s Committee on Chemical Microbiology, and after 1945 she devoted much of her time to organizing the MRC’s Research Unit in Chemical Microbiology at Cambridge. She helped found the Society for General Microbiology (1944) and served as its second president. She organized a summer school (1946) to meet the growing demand for workers in bacterial biochemistry. Stephenson took on the duties of an official university appointment (1947), as reader in the discipline she had helped to invent. Visitors to the Dunn Institute forty years later find her photograph in offices and the memory of her warm and vivid personality still fresh.

BIBLIOGRAPHY

I. Original Works. “Some Reactions of Resting Bacteria in Relation to Anaerobic Growth,” in Biochemical Journal, 19 (1925), 304–317, with Juda H. Quastel and Margaret D. Whetham; Bacterial Metabolism (London, 1930; 2nd ed., 1939; 3rd, ed., 1949); “Hydrogenase: A Bacterial Enzyme Activating Molecular Hydrogen. I . The Properties of the Enzyme,” in Biochemical Journal, 25 (1931), 205–214, with Leonard H. Strickland; “Galactozymase Considered as an Adaptive Enzyme,” ibid., 30 (1936), 506-514, with John Yudkin; and “The Economy of the Bacterial Cell,” in Joseph Needham and David Green, eds.. Perspectives in Biochemistry (Cambridge, 1937), 91–98.

Stephenson’s papers are in the archives of the Medical Research Council, London, and the archives of Cambridge University.

II. Secondary Literature. Robert E. Kohler, “Innovation in Normal Science: Bacterial Physiology,” in Isis, 76 (1985), 162–181; Muriel Robertson, “Marjory Stephenson 1885–1948,” in Obituary Notices of Fellows of the Royal Society, 6 (1949), 563–577, with full bibliography; and Donald D. Woods. “Marjory Stephenson, 1885–1948,” in Biochemical Joarnal, 46 (1950), 377–383.

Robert E. Kohler, Jr.

Stephenson, Marjory

views updated May 29 2018

STEPHENSON, MARJORY

(b. Burwell, near Cambridge, United Kingdom, 24 January 1885; d. Cambridge, 12 December 1948), microbiology, biochemistry. For the original article on Stephenson see DSB, vol. 18, Supplement II.

Stephenson belongs among the founders of new interdisciplinary fields known under various names— chemical microbiology, microbial biochemistry, or general microbiology, which are considered predecessors of molecular biology. Late twentieth- and early twenty-first century research into her life and work has highlighted her key position in forming the conceptual and methodical principles of these fields and her leadership, exceptional for a woman scholar of her time.

Archives disclose that Frederick Gowland Hopkins had followed with interest the career of the young Stephenson since 1913. That was a momentous year for Hopkins, when his interest in nutrition chemistry was at its peak and simultaneously he formulated his strategic program of “dynamic biochemistry,” which guided not only his Cambridge Biochemical Laboratory, but also biochemistry development in Europe in the forty years to come. Therefore, when Stephenson joined the Hopkins group in 1919, she did not take up her prewar nutrition research but, on the contrary, launched an entirely new field of “general” biochemistry corresponding to Hopkins’s vision. At Hopkins’s instigation, she turned her attention to bacterial metabolism, in which she became a leading specialist in the 1930s.

It is important to add a few details about Stephen-son’s institutional position in Cambridge. In 1924 Hopkins’s department became the Dunn Institute of Biochemistry, where Stephenson held her research appointment, which had been subsidized by the Medical Research Council (MRC) since 1922. She was appointed a permanent member of the MRC’s staff on 1 April 1929, but remained in her research post at the Dunn Institute in an independent position thanks to the MRC funding. Without ever being appointed its director, she eventually succeeded in putting into practice the MRC’s plan to establish in Cambridge a permanent research unit in bacterial chemistry. She stayed with the MRC and the Dunn Institute for the rest of her life.

The focus of Stephenson’s laboratory was investigation of various manifestations of metabolic activities in microorganisms, especially the actions of bacterial enzymes. Research into hydrogen-activating enzymes and identification of several new enzymes in the 1930s ensured her high reputation both in Britain and abroad. This applies even more to her monograph Bacterial Metabolism, published first in 1930 and then in two revised editions in 1939 and 1949. Written in a “lucid and forceful style” (Elsden and Pirie, 1949, p. 335), it became a reference work for several generations of biochemists and microbiologists all over the world.

For Stephenson, microorganisms represented not only research objects but also general models of the cell whose investigation provided for deeper understanding of cellular biochemistry and its organization. As early as 1930, in the preface to the first edition of her monograph, Stephenson stressed the importance of data

on the chemical activities of bacteria which may help us to gain an insight into the essential chemical processes accompanying the life of the organisms concerned.

She further stated that

it is time that an attempt should be made to arrange the scattered data in order to appraise our knowledge of bacteria as living organisms apart from their role as disease germs or the bearers of commercially important catalysts.

Her experiments demonstrating that bacterial enzymes behave similarly to enzymes in higher organisms and that metabolism in bacteria is governed by regularities analogous to those in higher organisms, contributed to the acceptance of the principle of unity in biochemistry in the 1930s.

These concepts also prompted her involvement with cellular metabolic adaptation phenomena. In 1930, Stephenson and Leonard Stickland discovered a new enzyme, formic hydrogenlyase, produced by various coliform organisms including Escherichia coli. Experiments performed in the years 1932 to 1936 with John Yudkin and Ernest F. Gale proved that this and several other enzymes are formed in E. coli and yeast as a “direct response of the enzymic composition of the cell to the constituents of the growth medium.”

It had been known long before Stephenson, that cultures of bacteria can adapt themselves to various nutrients in their growth medium. For instance, as early as 1900, F. Dienert reported that yeast that usually grows on glucose may acquire the ability to grow on galactose if this other sugar is present in the growth medium. Such adaptation to a new nutrient was usually accompanied by the production of a specific “adaptive” enzyme. In the first two decades of the twentieth century, various instances of such adaptive enzyme formation in multiplying cultures were investigated, but Stephenson and her collaborators were first to prove that also nongrowing bacterial cultures and individual cells are capable of fast adaptive formation of substrate-specific enzymes. Such observations enabled Stephenson and Yudkin to define in 1936 the enzymic type of adaptation as a “direct a response of the enzymic composition of the cell to the constituents of the growth medium,” independent of mutant formation or cell division, that “is definitely temporary and does not affect the heredity mechanism of the cell, which reverts to normal …when the organism is grown without the specific stimulus” (both quotes from Bacterial Metabolism, 1949, p. 296).

The first relevant so-called mass action theory of adaptive enzyme formation was advanced in the years 1936 to 1938 by Yudkin. He anticipated that the cells contain a small, sometimes immeasurable amount of the adaptive enzyme which normally is in equilibrium with its precursor. If substrate is added, the preexisting enzyme combines with the substrate and upsets the equilibrium. In consequence, more enzyme is formed until the equilibrium is restored.

Enzymatic adaptation (later known as enzymatic induction) was taken up by Jacques Monod in the 1940s to become a point of departure for the theories of cellular regulatory mechanisms and protein synthesis developed in the 1950s and 1960s.

From the 1930s on, Stephenson was an indisputable authority in her field and attracted many people to work with her. A list compiled from various sources names about sixty persons who cooperated with Stephenson in the years 1922–1948 (staff paid by MRC, graduate students, informal collaborators, local and foreign visitors), among them people who later became prominent scientists including two Nobel Prize winners, Hans Krebs and Peter Mitchell.

During World War II Stephenson coordinated teams of microbiologists, biochemists, and pathologists in fighting acute neonatal diarrhea in Britain. In the years 1941 to 1943 a group composed of specialists from the National Institute for Medical Research, the Royal College of Surgeons, the Lister Institute, and Cornell University participated under Stephenson’s guidance in exploring active immunization against gas gangrene. Other projects led by Stephenson investigated strategically important biotechnological production of organic compounds. Even this specialized wartime research led to discoveries of new bacterial enzymes and coenzymes. The invitation of Stephenson to become a member of the MRC’s Committee on Chemical Microbiology was the recognition of her efficient supervision of this interdisciplinary wartime network.

After the Nazis came to power in Germany, Stephenson assisted persecuted European scholars in finding adequate positions in Cambridge. A letter from Stephenson to the prominent German biochemist Otto Warburg written in early 1933 indicates that she was involved in the escape of the biochemist Krebs from Germany and his placement at the Biochemistry Department. Two refugee scholars from Czechoslovakia worked with Stephenson: Arnost Kleinzeller, who became a leading biochemist in postwar Czechoslovakia, and Heinrich Waelsch.

In 1945 Stephenson returned to her prewar research and organizing the Society for General Microbiology. In her plenary lecture, “Levels of Microbiological Investigation,” at the inaugural meeting of the Society for General Microbiology in 1945, Stephenson presented a strategic vision of general microbiology as a new field. She defined five equipotent levels of bacterial cultures at which interdisciplinary research in microbiology should be undertaken to arrive at a complex knowledge of the cell’s chemical activities.

Stephenson’s profile would not be complete without considering her experience as a woman playing an unusually important role in the scientific community of her time. Before and during World War II she belonged without question to the few women in the world who pioneered a new field of science and managed a research team. However, her position at the MRC was inconsistent with her indisputable scientific authority, competence, and leadership. On the one hand, MRC trusted her decisions and provided her with adequate salary and laboratory equipment; on the other she was faced with practices of undeclared discrimination: She was allowed and expected to do first-rate research but not to hold an executive appointment. The MRC’s plans of the 1920s to establish in Cambridge a permanent research unit in bacterial chemistry consisting of a director and a small team of researchers did not materialize in Stephenson’s lifetime; she was charged with the task without being assigned director. Most women in her position would have accepted reality, unlike Stephenson who from 1944 led a persistent campaign for the official acknowledgment of her “directorship” and recognition of the laboratory as an independent “Unit.” Her struggle reflected itself among other things in her annual reports to the MRC, submitted with the heading of a nonexistent “M.R.C. Research Unit for Microbiological Chemistry, The Biochemical Laboratory Cambridge” and Stephenson’s signature over the title “Director of the Unit.” Another issue that also became a permanent source of argument with the MRC’s authorities was Stephenson’s deliberate attempt to retain her scientific autonomy in choosing general topics to be investigated, compared with the MRC’s scheme of focusing on practical medical issues. Especially thanks to Stephenson’s wartime responsibilities, the MRC authorities eventually surrendered by tolerating Stephenson’s obstinate routine in using the terms Unit and Director, and her independence in research, but never recognized her status officially and did not give her sufficient technical assistance. In spite of that, Stephenson with her groundbreaking work and steadfast effort to crack the glass ceiling in a male-dominated field became a role model for other women scientists and as such was also remembered by her collaborators, among them Dorothy Needham.

In 1949, the Society for General Microbiology created the Marjory Stephenson Memorial Fund and agreed that the “most suitable memorial would be a Lecture, to be given at regular intervals … and to be known as the Marjory Stephenson Memorial Lecture.”

SUPPLEMENTARY BIBLIOGRAPHY

WORKS BY STEPHENSON

With Leonard H. Stickland. “Hydrogenlyases: Bacterial Enzymes Liberating Molecular Hydrogen.” Biochemical Journal 36 (1932): 712–724.

With Ernest Frederick Gale. “The Adaptability of Glucozymase and Galactozymase in Bacterium coli.” Biochemical Journal 31 (1937): 1311–1315.

“Enzyme Variation and Adaptation.” In Bacterial Metabolism. 3rd ed. London: Longmans Green, 1949.

OTHER SOURCES

Elsden, Sidney R., and Norman W. Pirie. “Marjory Stephenson 1885–1948.” Journal of General Microbiology3 (1949): 329–339.

Mason, Joan. “The Admission of the First Women to the Royal Society of London.” Notes and Records of the Royal Society46 (1992): 272–300.

———. “Marjory Stephenson 1885–1948.” In Cambridge Women: Twelve Portraits, edited by Edward Shils and Carmen Blacker. New York: Cambridge University Press, 1996.

Needham, Dorothy. “Dr. Marjory Stephenson, M.B.E., F.R.S.” Nature 163 (1949): 201–202.

———. “Women in Cambridge Biochemistry.” In Women Scientists: The Road to Liberation, edited by Derek Richter. London: Macmillan, 1982.

Strbánová, Sona. “Enzyme Adaptation—The Road to Its Understanding: Early Theoretical Explanation.” In Biology Integrating Scientific Fundamentals: Contributions to the History of Interrelations between Biology, Chemistry, and Physics from the 18th to the 20th Centuries, edited by Brigitte Hoppe. Algorismus 21. Munich: Institut für Geschichte der Naturwissenschaften, 1997.

———. “Marjory Stephenson and the Medical Research Council—A New Managing Role for a Woman Scholar.” In Women Scholars and Institutions: Proceedings of the International Conference, Prague, June 8–11, 2003, edited by Sona Strbánová, Ida H. Stamhuis, and Katerina Mojsejová.Studies in the History of Sciences and Humanities, vol. 13 A and 13 B. Prague: Research Centre for the History of Sciences and Humanities, 2004.

———. “Stephenson, Marjory.” In Lexikon der Bedeutenden Naturwissenschaftler, edited by Deter Hoffmann, Hubert Laitko, and Staffan Müller-Wille. Munich: Elsevier Spektrum Akademischer Verlag, 2004.

Sona Strbánová