From Nuclear Science to Bacterial Cytochromes: the Work of Martin D. Kamen

Structural Bases for Function in Cytochromes c. An Interpretation of Comparative X-ray and Biochemical Data (Salemme, F. R., Kraut, J., and Kamen, M. D. (1973) J. Biol. Chem. 248, 7701–7716) Martin David Kamen (1913–2002) was born in Toronto, Canada, but grew up in Chicago. He enrolled at the University of Chicago in 1930, intending to study English. However, the Great Depression took a toll on his family''s finances, and his father suggested he switch his major to chemistry in order to make a living after graduating. By his junior year, Kamen was hooked on chemistry. He graduated in 1933 with honors in physical chemistry, working with William Draper Harkins to determine ammonia gas emission spectra excited by electrodeless discharge. He remained in Harkins'' lab for graduate school, earning his doctorate in physical chemistry in 1936 for an article on neutron scattering (1) that was accepted as his dissertation.Open in a separate windowMartin D. KamenBecause economic conditions were still bleak, Kamen followed the suggestion of one of his mentors, David Gans, and applied for a research post with Nobel laureate Ernest O. Lawrence, who had developed the cyclotron at the radiation laboratory in Berkeley, California. Kamen used his savings to move to Berkeley and worked at the laboratory without pay for 6 months before Lawrence offered him a staff position as a chemist. In addition to troubleshooting the cyclotrons and preparing samples of radioisotopes, Kamen performed numerous photosynthetic studies with Samuel Ruben, using carbon-11. Because carbon-11 had a half-life of only 21 min, Lawrence assigned Kamen and Ruben the task of finding carbon-14. The pair succeeded by bombarding graphite in the cyclotron, producing carbon-14, which had a 5730-year half-life (2).Kamen and Ruben planned to use their discovery to create a company that would construct and operate several cyclotrons dedicated to carbon-14 production and expand on the laboratory''s radioisotope program. However, the war intervened, and all non-war-related research at Berkeley was halted. Kamen was assigned to head a program studying the separation of uranium isotopes for the Manhattan Project. But, unexpectedly in 1944, he was declared a security risk and dismissed from the lab. A few years later, Kamen was called before the House Un-American Activities Committee, being wrongly linked to an espionage ring working for the USSR. Subsequently, the State Department refused to issue Kamen a passport, and the Chicago Tribune named him as a suspected spy. During the next decade, he fought recurring rumors and accusations that he had leaked atomic bomb secrets. Eventually, he won a libel suit against the Chicago Tribune, and the State Department reinstated his passport.In 1945, Kamen moved to the Mallinckrodt Institute of Radiology at the Washington University School of Medicine where he supervised cyclotron production of radioisotopes for medical research. His own research interests gradually shifted away from nuclear physics and radiochemistry to biochemistry, and he began several collaborations involving the use of radioisotopic tracers in biological and biomedical research.Kamen also initiated a series of experiments using carbon-14 to study photosynthesis in bacteria. This resulted in a number of important discoveries, including hydrogen photoevolution (3) and nitrogen fixation (4) in Rhodospirillum rubrum. While working with the bacteria, Kamen and Leo Vernon discovered that R. rubrum contained a c-type cytochrome (5), which they later named “cytochrome c₂.”Twenty years after it was discovered, the structure of cytochrome c₂ was solved (6). By comparing this structure with the recently solved structure of eukaryotic mitochondrial cytochrome c (7), Kamen and his colleagues were able to deduce information about the structural, functional, and evolutionary relationships in the cytochromes c. This is the subject of the Journal of Biological Chemistry (JBC) Classic reprinted here.Despite the fact that both eukaryotic cytochrome c and cytochrome c₂ serve analogous functions in their respective physiological electron transport chains, i.e. they both transport electrons to the terminal and most oxidizing electron carrier of each system, Kamen was able to find several differences between the molecules. For example, he noted that cytochrome c₂ has a more positive electrochemical potential and does not exhibit the large oxidation state-dependent conformational change characteristic of mitochondrial cytochrome c. Open in a separate windowKamen continued to study other bacterial cytochromes, showing that at least 12 subgroups of the cytochromes c exist. This resulted in new perspectives on potential variations in structure and function of the heme group in relation to protein.In 1957 Kamen moved to Brandeis University to help establish the graduate department of biochemistry, and in 1961 he joined the University of California, San Diego chemistry department to help found their new campus. He remained there until 1975, when he became director of the Chemical-Biological Development Laboratory at the University of Southern California. Kamen continued to teach into his eighties, being one of six faculty members of the Oregon Institute of Science and Medicine.Kamen received numerous awards and honors for his contributions to science, including the American Chemical Society''s Award for Applications of Nuclear Chemistry (1963), the American Society of Plant Physiologists'' Charles F. Kettering Research Award (1968), the American Society of Biological Chemists'' Merck Award (1982), the John Scott Medal of the City of Philadelphia (1988), the World Cultural Council''s Einstein Award (1990), and the U.S. Department of Energy''s Enrico Fermi Award (1996). He was a member of the National Academy of Sciences, the American Academy of Arts and Sciences, and the American Philosophical Society. ¹