CALVIN, MELVIN

(b. St. Paul, Minnesota, 8 April 1911;

d. Berkeley, California, 8 January 1997), chemistry, photosynthesis, origin of life, cancer, molecular basis of learning.

Calvin is remembered above all for his work in photo-synthesis, research that won him the Nobel Prize in Chemistry in 1961. During the latter part of the 1940s, and throughout the following decade, he led and inspired an outstanding group of researchers in unraveling a mechanism that had been a mystery for centuries. Not only was his scientific understanding outstanding, so was his leadership. Under his guidance, what was probably the first of the large integrated, modern research units in the biological sciences flourished unsurpassed for more than fifteen years.

Early Days . Born to Elias and Rose (née Hervitz) Calvin, immigrant parents from East Europe, Melvin Calvin began to show an interest in science even in his tender years. As a child, he collected rocks, watched birds, and mused about the nature and composition of the many products he saw in his parents’ grocery store. It led inevitably to a lifelong dedication to chemistry.

The family moved to Detroit, where Melvin attended the Central High School before going on to take a degree in chemistry at Michigan College of Science and Technology. There followed a PhD at the University of Minnesota, where he worked with George Glockler on the electron affinity of halogens (initially iodine and later also bromine and chlorine) from space-charge effects.

Leaving Minnesota with his doctorate, Calvin used his own savings to supplement a postdoctoral fellowship from the National Research Council to work for two years with Michael Polány, as Rockefeller Fellow during the 1935–1937 period, at the University of Manchester. His research topic was the interactions between quantum mechanical theory and chemical experimentation, starting with platinum-hydrogen activation systems.

Move to Berkeley . While Calvin was still in Manchester, Joel Hildebrand of the Chemistry Department in Berkeley paid a passing visit there and met Calvin. With a glowing recommendation from Polányi, Calvin was invited to join the Berkeley faculty, where he remained for the next sixty years. Calvin’s innate talent and experience were the sources of his inspiration, competence, and confidence; he was soon to benefit from being in the right place at the right time, and good luck followed in due course.

For Calvin, the period in Manchester was part of becoming a mature scientist: He gained from the experience of living outside his native country and, as a postdoctoral fellow, was recognized as one of them by his fellow scientists. He was drawn into studies on the activation of hydrogen by phthalocyanine and copper, becoming familiar with pigment chemistry and light absorption. Ten years later that experience was to prove invaluable, providing him the opportunity to embark upon what emerged as his life’s great contributions to biological chemistry. But in 1937, he joined the Berkeley faculty as an assistant professor with an interest in chelate chemistry; in the war that followed just a few years later, he used his knowledge and skills as a participant in the Manhattan Project. In 1942, he married Genevieve Jemtegaard, a junior probation officer.

The Beginning of the Photosynthesis Studies . Calvin’s big chance came in the autumn of 1945; to understand its significance it is necessary to go back to the history of photosynthesis and the level of understanding before Word War II. It had been known for two centuries that

sunlight allows green plants to fix atmospheric carbon dioxide into all the organic compounds needed for the plants to grow and reproduce. What was not known was how it was done. There were theories—including a suggestion that the fixation of carbon dioxide first formed formaldehyde, which was then supposed to polymerize into sugars. But the basis for that idea was simply that the empirical formula for formaldehyde (CH₂ O) multiplied six times gave the equally empirical formula for a hexose sugar (C₆ H₁₂ O₆); there was no experimental evidence and, indeed, plants fail to produce sugar when supplied with formaldehyde and are actually poisoned by it.

The problem, of course, was that, once inside the plant, the carbon atoms that had originated in the carbon dioxide could not be distinguished from those already there; where had the carbon dioxide carbons gone? Hope for resolution came with the discovery in the early 1930s of the first radioisotope of carbon,¹¹ C.

By virtue of its radioactivity,¹¹ CO₂ supplied to plants would allow the incoming carbon to be located in whatever compound(s) in which it might become incorporated. The limitation was the way carbon-11 is produced (in the cyclotron, compounds containing nitrogen-14 are bombarded with protons; each impacted nitrogen atom captures a proton and then emits an (-particle to yield an atom of carbon-11) and its short half-life of only twenty minutes. Early attempts to use it, by Sam Ruben and Martin Kamen (joined later by Andrew Benson), took place in prewar Berkeley, but the experimental difficulties were immense; experiments had to be completed within two or three hours of manufacturing the nuclide.

Those studies were undertaken in the Radiation Laboratory of the University of California at Berkeley—just yards away from Calvin’s office. Ernest Lawrence, director of the laboratory and inventor of the cyclotron used to produce the carbon-11, reasoned from his knowledge of nuclear physics that a longer-lived isotope (¹⁴ C) should exist. It was indeed discovered in 1940 but no more than minute amounts were available, and all further developments ceased when the United States entered the war in December 1941. Everybody involved had more important things to do, and by the time the war ended the original team was no longer in place.

ORL and the Bio-Organic Chemistry Group . But Lawrence had not forgotten. The Manhattan Project generated sizable quantities of carbon-14, to which Lawrence, as director of the Radiation Laboratory (the contractor for the Manhattan Project), had access. The story has it that one day in the autumn of 1945 Lawrence and Calvin were walking back to their offices after lunch in the faculty club. Lawrence suggested to Calvin that he might like to make use of the newly available carbon-14 to do two things: develop its chemistry and synthesize compounds for medical research, and use it to resolve the age-old photosynthesis puzzle: the pathway of carbon from carbon dioxide to sugars, proteins, and all the other compounds in green plants. Lawrence would supply the funding, the carbon-14, and a building, an old two-story wooden structure that had been the original home of his cyclotron and known as “ORL—the Old Radiation Lab.” It was to become world-famous among plant biochemists. The Bio-Organic Chemistry Group was born.

As the prime experimental tool, Calvin’s group decided to use the green microalga Chlorella rather than the leaves of a higher plant; as a chemist, Calvin was much happier using a suspension of a unicellular organism that could be dispensed in a pipette than trying to get uniform samples of leaves.

The basic experiment was to shine a bright light onto a suspension of the algal cells in the famous “lollipop,” a thin vessel (so that light reached all the cells uniformly) into which, at the start of the experiment, was injected a solution containing¹⁴ CO₂ in the form of NaH¹⁴ CO₃. At precise times thereafter, from seconds to minutes, the

stopcock at the base of the vessel was opened to allow some of the suspension to fall into a flask of boiling ethanol, instantly killing the alga and stopping all biochemical reactions. The location of the carbon-14 in products could then be determined by appropriate analysis.

In the early days analysis depended on ion-exchange resins, a slow and tedious procedure. Nevertheless, it did allow the identification of the first compound to incorporate carbon from carbon dioxide; it turned out to be the 3-carbon sugar acid phosphate, 3-phosphoglyceric acid, thereafter known around the world as PGA. In short-term experiments, the carbon-14 was found almost entirely in the terminal carboxyl carbon, strongly suggesting that carbon dioxide had been added in some way to a 2-carbon receptor. The next problem was to identify it.

If the research had relied permanently on ion-exchange chromatography, the path of carbon in photo-synthesis might never have been elucidated. Fortunately, in 1944, the technique of paper chromatography had been developed in Britain by Archer J. P. Martin, Raphael Consden, and Richard L. M. Synge. By 1948, word of this new and powerful technique had reached the Botany Department in Berkeley, from whence it was brought to Calvin’s laboratory by a graduate student, William H. Stepka.

Resolving the Photosynthesis Puzzle . Paper chromatography revolutionized the group’s analytical procedures; using a wide panoply of classical and novel analytical procedures combined with chromatography, a whole range of compounds incorporating carbon-14 from labeled bicarbonate were identified (always in minute chemical quantities), revealed, and made accessible by virtue of their¹⁴ C labeling. Each large paper chromatogram was placed against a sheet of x-ray film and sealed in a lightproof envelope; in the course of days or weeks, the radioactive emissions produced a latent image on the film which, when developed, gave the exact location, size, and shape of each “spot” of a labeled compound; such “radioauto-grams” were the mainstay of the path-of-carbon research. It took years to identify all the radioactive spots, but in time that was done and maps were produced of how

compounds of interest migrated in the chromatographic system, which everybody in the lab used.

The kinetic relationships between these compounds were explored: How fast and in which order did these substances acquire carbon-14? Degradation methods were developed allowing the accumulation of radiocarbon to be measured within the individual atoms of the product molecules.

It eventually became clear that carbon dioxide was converted into hexoses by a reversal of glycolysis (breakdown of sugar into carbon dioxide and water, releasing energy), the reducing power necessary to drive the process deriving from the capture of sunlight by the energy-conversion mechanism of chloroplasts. But identifying the 2-carbon acceptor with which carbon dioxide combined was much more difficult; in short-term labeling experiments this acceptor would not itself be labeled so there was no obvious way of identifying it.

Clues ultimately came from the kinetics of the intramolecular distribution of carbon-14 within many of the compounds already shown to be products of carbon dioxide fixation. As it gradually became clear that the biochemistry of carbon fixation was a cyclic process, Calvin and his colleagues moved towards the idea of a 5-carbon acceptor, which, in accepting one molecule of carbon dioxide, would be split into two molecules of PGA, each identical with the other except for its radioactive labeling pattern.

In two classic experiments in 1954 and 1955, Peter Massini from Switzerland and Alex Wilson, a New Zealander, showed that when the light was switched off and then on again, or the carbon dioxide concentration suddenly reduced, the kinetic behavior of compounds in the putative cycle was consistent with the operation of a cyclic pathway. By the late 1950s, the mystery of the path of carbon in photosynthesis had essentially been solved except for some details. A detailed understanding of the enzymology, particularly of the primary fixation reaction, came later from work in a variety of laboratories.

Calvin and the group’s interest in photosynthesis was by no means confined to metabolic pathways; many pioneering experiments were conducted to characterize the primary photochemical events. The laboratory was one of the first two to apply the new method of electron para-magnetic resonance to photosynthetic systems, which showed there were two kinds of organic free radicals produced as a result of light absorption, one of which appeared to be either a one-electron reduced or oxidized chlorophyll species. Pursuit of such studies eventually led to the assignment of one of these signals to a pair of chlorophyll molecules which served as the primary electron donor in photosystem I, while the second was assigned to an oxidized tyrosine side chain in the protein of photosystem II.

This most exciting period of discovery yielded a famous series of twenty-three papers (the last in 1958) under the title “The Path of Carbon in Photosynthesis.” ORL became the mecca for biochemists, biophysicists, and plant physiologists from around the world; graduate students (mostly, but not exclusively, from the United States) came for two or three years to carry out their thesis work, while postdoctoral visitors from around the world spent a year or two before going back home and spreading the word. In 1961, Calvin himself was awarded the Nobel Prize in Chemistry, in just and proper recognition of a remarkable achievement in inspiring his colleagues to achieve the success in which all of them shared.

As he himself recognized, he was but one of many scientists who had contributed. Foremost among them were Andrew A. Benson and James A. Bassham. Benson had for a time been part of the prewar¹¹ C effort; at the war’s end he was no longer in Berkeley, and Calvin invited him back to take charge of the photosynthesis subgroup. For ten years they did it together before Benson left to become independent at another university. Thereafter, Bassham, who had joined the group as a graduate student after service in the U.S. Navy, became the de facto leader of the photosynthesis laboratory activities, with his publications world famous. He stayed for the whole of his working life.

Isotopic carbon and related activities were run by Bert M. Tolbert until he left for Colorado in 1958. Just as in the Benson/Bassham exchange, he was succeeded by Richard M. Lemmon, who had also joined as a graduate student some years earlier. Lemmon’s specialty was hot atom recoil chemistry, and he, too, remained a member of the group until retirement.

After ORL . Inevitably, after the excitement of the path of carbon, the character of the Bio-Organic Chemistry Group changed. ORL itself was demolished in 1959 as part of a new chemistry development; all that remained was a plaque, although for many years Calvin kept the old door in his office. The Bio-Organic Chemistry Group was temporarily relocated several hundred yards away in the Life Sciences Building, with uncertainty about their ultimate home. Indeed, the two parts, photosynthesis and isotope work, had never been together under one roof; the latter had occupied space in the Donner Laboratory, itself a distance from ORL.

Calvin had plans for a new building. ORL was notable for its comparative lack of internal subdivisions. The researchers in the large labs were constantly talking to one another as they went about their work, while in the center of the main laboratory stood a large white table on which the radioautograms were scrutinized, compared, and discussed. A map of the relevant compounds hung on the wall above the table. That table was the social and scientific nerve center of the group; it was where people constantly met for coffee and discussion. Not infrequently, such discussions would generate new ideas for experiments and inevitably another avenue of inquiry had been established.

It was very important that a new building had enough space to accommodate the whole group and also retained in some way the open structure. As funding became available, a three-story circular building was designed with half of the two upper floors open spaces without walls. The building, originally called the Laboratory of Chemical Biodynamics (LCB) and later Melvin Calvin Laboratory, was opened with some ceremony in November 1963. While the new building was modern, and with facilities that made the lovingly remembered ORL seem in some ways old-fashioned if not primitive, the ambience was never quite recreated.

There were a number of reasons. At the founding of the group in 1945, Calvin himself was thirty-four years old and his associates ten years younger. Some of them were still there in the 1960s and 1970s, experienced and respected scientists in their forties and fifties, each with their own research teams. Moreover, the group as a whole never again had that unity of purpose it possessed during the path-of-carbon years, and Calvin was not able to provide that same sort of leadership. Gradually, fragmentation began.

Calvin himself acquired a number of interests. He never entirely abandoned either the biochemical or the physical chemical aspects of photosynthesis, but his involvement was greatly diluted by his other activities. In the following twenty years, they encompassed the chemical origins of life, the biochemistry of learning, control of protein synthesis, cancer, moon rock analysis, novel synthetic biomembrane models for plant photosystems, and the use of certain plant oils as potential vehicle fuels. A number of these developed into discrete research activities, often accompanied by the recruitment of a scientist of some seniority and experience and with Calvin’s continuing involvement and encouragement.

In addition, Calvin was at various times a consultant for Dow, Upjohn, and Diamond Shamrock as well as some start-ups, and was a member at one time of the Dow main board. During the late 1950s and early 1960s he was chairman of the National Academy of Sciences Committee on Science and Public Policy.

Furthermore, after Calvin was awarded the Nobel Prize, President Kennedy appointed him to his Science Advisory Committee. Calvin, whose life hitherto had been devoted almost totally to science and scientific discovery, suddenly found a whole new world of politics, social significance, and the rest. For him, of course, that was a new voyage of discovery, undertaken with his customary enthusiasm.

Inevitably, he found himself more and more stretched among his many concerns. Once upon a time, in the early days, he was constantly in the lab. As Andy Benson wrote:

Melvin usually finished his lectures, office and committee work about 5:30 p.m. and stopped in at the lab with his usual question, “What’s new?.” Though we had just started the experiment for the day, we usually had some answer. But, the next morning when Melvin came in at 8 or before; he was an early riser; there was the first cheery question, “Well, what’s new?” There was no letup. I had to keep some tidbits in reserve so that there was always something interesting to report. When important chromatograms were exposed on X-ray film we used two sheets, one to develop too early, to appease Melvin’s insatiable curiosity, and one for proper documentation. (Communication to the author, 9 September 1998)

From an early date in its history, the group would meet collectively for a seminar round a long table at 8 a.m. on Friday mornings. When they first started, Calvin (who always sat at the front, on the right-hand side facing the speaker) would look round the room, point a finger at a colleague and say, “You tell us what you’ve been doing.” No sooner was the poor unfortunate so selected halfway through his opening sentence than Calvin asked the first of many, many questions. The graduate students were petrified but dared not absent themselves. So it became the practice at the Thursday management lunch of the more senior group members to nominate the speaker for the next morning. At least that gave the victim time to collect his thoughts and arrange his material, and many a student worked nonstop through the night to do so. It was only after twenty years or so that a schedule encompassing several months was drawn up.

Calvin was perceived as being fierce in his questioning; he was not unkind or rude but certainly determined to have an answer. It was in practice an excellent training for his colleagues, some of whom adopted similar styles when later they left for academic positions elsewhere and formed their own groups.

The Friday morning seminars continued throughout Calvin’s directorship of the group, but his own involvement in the details of lab activities and results declined markedly. There was much too much of it, and he was busy on too many fronts, both inside and outside the lab. Towards the end, his immediate students had something of a thin time: The fire and imagination were undiminished but even for Calvin the day was only twenty-four hours long.

The Outstanding Scientist . Calvin was a superb lecturer, particularly in his earlier days when he felt able to get away with total informality. Hitching himself onto the front of the lecturer’s bench or table, he would speak without notes, both he and his listeners carried away by enthusiasm for the topic. He seemed to have no concept of time and would suddenly pull himself up short, realizing he had overrun and would hastily try to bring his presentation to an orderly end.

When awarded the Nobel Prize, he was shocked to learn that protocol demanded him to give his acceptance lecture in exactly forty minutes. So, perhaps for the first time in his life, he wrote out his lecture and got his colleagues to edit and time it for him. His wife, following his text, sat next to the projectionist in order to indicate when the next slide was to be shown, thus saving Calvin the trouble of saying so and giving him a few extra precious seconds.

Those who knew Calvin and worked with him will never forget the experience. He was the most stimulating colleague one could imagine, ready to entertain any idea backed up with reason and sense. He read science voraciously; challenging him on any issue was no easy matter because he knew where the evidence had been published. But he was not averse to floating proposals that themselves were flimsily based and took being shot down with good grace—provided the ammunition was itself reliable.

Calvin retired as director in 1980 but continued to occupy an office and some laboratory space in the chemistry department. He had suffered a severe heart attack in 1949 from which he recovered completely, but after his wife died in 1987, he became rather depressed and gradually grew more frail. He died on 8 January 1997 after suffering a fall, survived by his daughters Elin and Karole, and his son Noel.

BIBLIOGRAPHY

WORKS BY CALVIN

With Gerald E. K. Branch. The Theory of Organic Chemistry. New York: Prentice-Hall, 1941.

With Charles Heidelberger, James C. Reid, Bert M. Tolbert, and Peter E. Yankwich. Isotopic Carbon: Techniques in Its Measurement and Chemical Manipulation. New York: John Wiley, 1949.

With Arthur E. Martell. The Chemistry of Metal Chelate Compounds. New York: Prentice-Hall, 1952.

With James A. Bassham. The Path of Carbon in Photosynthesis. Englewood Cliffs, NJ: Prentice-Hall, 1957.

The Path of Carbon in Photosynthesis. Nobel Lectures, Chemistry 1942–1962, Elsevier Publishing Company, Amsterdam, < >1964. Also available at http://nobelprize.org/nobel_prizes/chemistry/laureates/1961/calvin-lecture.html.

Chemical Evolution: Molecular Evolution towards the Origins of Living Systems on Earth and Elsewhere. Oxford: Clarendon Press, 1969.

“Melvin Calvin: Chemistry and Chemical Biodynamics at Berkeley, 1937–1980.” Archived in the History of Science and Technology Program, The Bancroft Library, University of California at Berkeley, 1984.

Following the Trail of Light: A Scientific Odyssey. Washington, DC: American Chemical Society, 1992. This book contains a bibliography listing many of Calvin’s papers.

OTHER SOURCES

Moses, Vivian. “Professor Melvin Calvin” (obituary). The Times (London), 16 January 1997.

———. “Melvin Calvin (1911–1997).” Nature 385, 13 February, 1997.

———. “Melvin Calvin (1911–1997).” Advances in Carbohydrate Chemistry and Biology 55 (1999), 14–21.

Moses, Vivian, and Sheila Moses, eds. The Bio-Organic Chemistry Group, University of California (1945–63): Interviews for an Oral History. 1998. Recordings and transcripts archived in the Bancroft Library, University of California at Berkeley, at the Chemical Heritage Foundation, Philadelphia, and in the British Library, London.

Seaborg, Glenn T., and Andrew A. Benson. “Melvin Calvin.” Biographical Memoirs, vol. 75. Washington, DC: National Academy of Sciences, 1998. Also available at http://www.nap.edu/books/0309062950/html/96.html.

Zallen, Doris T. “Redrawing the Boundaries of Molecular Biology: The Case of Photosynthesis.” Journal of the History of Biology 26 (1993), 65–87. Not much on Calvin, but good for background reading.

Vivian Moses