Biography

Peter Dennis Mitchell (1920-1992), biochemist. Peter Dennis Mitchell was born in Mitcham in Surrey on 29 September 1920. He was educated at Queen's College, Taunton, 1932-1938 and in 1939 he gained admittance to Jesus College, Cambridge. He obtained a Third Class in Part I of the Natural Sciences Tripos and after specialising in biochemistry in Part II he gained an Upper Second Honours Degree. In 1942 Mitchell accepted a research post in the Department of Biochemistry at Cambridge at the invitation of J.F. Danielli. His first research concerned the development of a glycoside of BAL (British Anti-Lewisite) to treat skin lesions resulting from use of the chemical warfare agent, lewisite. This secret war work was published in 1946 and 1947 but was considered an unsuitable basis for a doctoral thesis. In 1945 Mitchell began research towards his Ph.D and following Danielli's move to London became a research student of E.F. Gale, Director of the Sub-Department of Microbial Biochemistry, in the Cambridge Biochemical Department. It was during this period that he was first introduced to Jennifer Moyle who acted as his research associate from 1948 until her retirement in 1983, apart from a short period between 1952 and 1955 when she was an assistant to Malcolm Dixon at Cambridge. While at Cambridge Mitchell also consulted David Keilin who had a strong influence on him scientifically. Mitchell's doctoral thesis 'Nucleic acid synthesis and the bactericidal action of penicillin' was initially rejected in 1950 but was passed early in the following year after resubmission. In 1950 Mitchell became Demonstrator in the Biochemistry Department at Cambridge where from 1951 to 1953 he designed and carried out experiments on the exchange and uptake of inorganic phosphate and arsenate through the osmotic barrier of Micrococcus pyogenes. In 1955 Mitchell moved from Cambridge to the University of Edinburgh, where he accepted Professor Michael Swann's invitation to set up a biochemical research unit in the Zoology Department. Mitchell in turn asked Jennifer Moyle to join him which she did. It was at Edinburgh University that the chemiosmotic theory of oxidative phosphorylation was developed by Mitchell. He first used the term 'chemiosmotic' in a lecture read to a Biochemical Society Symposium in February 1957 and in 1961 he set out the principal features of his hypothesis in a paper for 'Nature', entitled 'Coupling of phosphorylation to electron and hydrogen transfer by a chemiosmotic type of mechanism'. At this time Mitchell was appointed as a Senior Lecturer and in the following year (1962) he became a Reader. Severe gastric ulcers in 1962 led Mitchell to take a long leave of absence from Edinburgh in order to recuperate in a holiday cottage, Glynn Mill, at the entrance to Glynn House, near Bodmin, Cornwall. He had already purchased Glynn House with a view to restoring it, just as he had bought a manse in Temple, ten miles south of Edinburgh and used his building skills to renovate it several years earlier. It was only after Mitchell's illness that he decided to establish a research institute at Glynn House. Jennifer Moyle agreed to act as co-founder and Mitchell left Edinburgh in 1963. Between 1963 and 1965 he withdrew from scientific research. By the autumn of 1964 Glynn House had been completely reconstructed and restored at a cost of £70,000, paid for by Mitchell himself. The Institute was provided with an endowment of £240,000 by Peter Mitchell and his brother, Christopher, who transferred their shares in Wimpey and Co. to Glynn Research Limited. This charitable company administered the Institute until its name was changed to the Glynn Research Foundation Limited in 1985. From 1964 to 1986 Mitchell held the post of Director of Research at the Glynn Research Institute. The chemiosmotic hypothesis he had advocated during his years at Edinburgh University did not gain immediate acceptance but he continued to support it. In 1965 Mitchell, Moyle and a technician, Roy Mitchell (later research associate), began work, planning and carrying out the experimental research required to test the hypothesis. This was an extension of the experiments with mitochondria and bacteria which Mitchell and Moyle had carried out at the University of Edinburgh. Mitchell spent a considerable amount of time on theoretical work, while Moyle and the other members of the research group did much of the experimental work. In 1966 the first 'grey book' was produced (so called because of the cover's colour) entitled 'Chemiosmotic Coupling in Oxidative and Photosynthetic Phosphorylation'. A second 'grey book', 'Chemiosmotic Coupling and Energy Transduction' followed in 1968. Both were published by Glynn Research Limited and the ideas they contained remained fundamentally unaltered by Mitchell until 1975. From the beginning scientists were invited to stay briefly at Glynn House so that informal, private discussion could take place. Robert Crane made the first visit, to be followed by over 150 other scientists during the ensuing twenty years. By 1970 a large amount of evidence had been accumulated which supported the chemiosmotic hypothesis and Mitchell's work continued to examine its application for the next twenty years. The early 1970s saw criticism of his linear loop model for the respiratory chain. Mitchell's own concerns about this model led to a major breakthrough on 20 May 1975, when he came up with the concept of the Q cycle. Although the Q cycle faced opposition from various quarters, by the mid-1980s the weight of evidence stood in its favour. Throughout the 1980s Mitchell continued to apply his chemiosmotic theory to experimental evidence, using it for example to examine the model of the ATPase mechanism and the functioning of cytochrome oxidase. Mitchell was a prominent figure in the scientific debate as to whether cytochrome oxidase acts as a proton pump. He arranged a conference at Glynn on this subject on 22-24 March 1983 in the form of an 'octavian discussion', at which no more than eight of the twenty participants sat at the table at any one time. By 1985 the controversial issue was resolved. Mitchell changed his views, accepting that cytochrome oxidase has a proton pumping function, and proceeded to propose mechanisms for cytochrome oxidase. In 1987 Mitchell became Chairman and Honorary Director of The Glynn Research Institute, with Dr Peter Rich given the position of Director of Molecular Research. Much of the last decade of Mitchell's life was devoted to fund raising for the Institute to prevent its closure. Mitchell died on 10 April 1992. Mitchell had numerous interests besides scientific research and the restoration of buildings of historical interest. He was elected as a member of the Economic Research Council in 1975 and his interest in economic matters is further reflected by a number of letters he wrote to the Financial Times as well as his open letter in 1982 to Sir Jeremy Morse, Chairman of the Committee of London Clearing Bankers. Mitchell was interested in communication problems between individuals in civilised societies and sought to promote studies of human communication at Glynn alongside the molecular research. Mitchell's other interests included the minting of his own silver coins. Peter Mitchell was accorded many honours for his contributions to biochemistry, starting with the Ciba Medal from the Biochemical Society in 1973. He was elected to the Fellowship of the Royal Society in 1974 (Copley Medal, 1981, Croonian Lecturer, 1987) and made an Honorary Member of the US National Academy of Sciences in 1977. He was awarded the Nobel Prize for Chemistry in 1978 'for his contribution to the understanding of biological energy transfer through the formulation of the chemiosmotic theory'. He was elected Honorary Fellow of Jesus College, Cambridge, in 1980. Mitchell's main contribution to biochemistry was his chemiosmotic theory. In a document drawn up for the Central Office of Information in 1989 (see A.10) he wrote about the theory in the following way: 'Dr Mitchell's theory explains the main mechanism by which the energy of electron-transfer, associated with light absorption or oxidation, is made available in the living cells of plants, animals and microbes. He first proposed it as a hypothesis in 1961, challenging the prevailing view that energy-supplying actions, such as absorption of sunlight in a plant or oxidation of chemicals in an animal, were coupled to the synthesis of the universal energy-storage substance adenosine triphosphate (ATP) through a series of unstable chemical intermediaries. He suggested instead that the electron-transfer process, associated with light absorption or oxidation, generated proticity (the protonic analogue of electricity) in modules of molecular dimensions plugged through a membrane, and that the proticity drove the production of ATP in other modules plugged through the same membrane.'

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