Peter D. Mitchell

Peter D. Mitchell: The Man Who Was Right Alone

In 1961 Peter Mitchell proposed that cells make ATP by pumping protons across a membrane and letting them fall back through it. The idea was so foreign to the prevailing biochemistry that most of the field simply refused it. Two years later, worn down by institutional opposition and ill health, he resigned his university post, restored a derelict Cornish manor house, and built his own laboratory inside it. Seventeen years after that, the Nobel Prize in Chemistry.

Mitcham

Peter Dennis Mitchell was born on 29 September 1920 in Mitcham, Surrey, the son of Christopher Gibbs Mitchell, a civil servant, and Kate Beatrice Dorothy Taplin. His uncle was Sir Godfrey Mitchell, chairman of the construction firm George Wimpey — a family connection to serious money that would matter later, when Mitchell needed to fund science nobody else would.

He was educated at Queen's College, Taunton, and then at Jesus College, Cambridge, where he read the Natural Sciences Tripos and specialised in biochemistry.

Cambridge and Penicillin

In 1942 Mitchell took a research post in the Department of Biochemistry at Cambridge. His doctorate came slowly — he was awarded it in 1951, for work on the mode of action of penicillin, which is to say on how a molecule acts at a bacterial membrane. Membranes would remain his subject for the rest of his life.

In 1955 Professor Michael Swann invited him to Edinburgh to establish a Chemical Biology Unit in the Department of Zoology. He was promoted to Senior Lecturer in 1961 and Reader in 1962. In 1963 he resigned.

The Chemiosmotic Hypothesis

The idea he published in *Nature* in 1961 addressed the largest unanswered question in biochemistry. Everyone knew ATP was the energy currency of the cell. Nobody knew how cells actually made it. The reigning assumption was that some high-energy chemical intermediate must couple the oxidation of food to the synthesis of ATP — and laboratories across the world were hunting for that intermediate, without success.

Mitchell said there was no such intermediate. The coupling, he argued, was not chemical but spatial. Respiration pumps protons across a membrane, building an electrochemical gradient — a difference in both concentration and voltage between one side and the other. That gradient is the stored energy. ATP is made when protons flow back down it through a specific enzyme in the membrane.

This was an offensive proposal in two ways. It relocated the problem from soluble chemistry into membrane structure, which most biochemists of the era regarded as an inert container rather than a machine. And it was advanced largely on theoretical grounds by a man with a modest publication record.

Glynn House

Having left Edinburgh in 1963, Mitchell spent two years supervising the restoration of Glynn House at Cardinham in Cornwall. In the same period he founded Glynn Research Ltd with Jennifer Moyle, his long-time collaborator, to pursue fundamental biological research on his own terms and at his own expense.

It is the most literal case in modern science of a researcher building his own institution because the existing ones would not house him. From Glynn he elaborated the theory, publishing the major development in *Biological Reviews* in 1966 and going on to theoretical work on electron transport chains and the Q cycle, the proton-shuttling mechanism inside the respiratory chain.

Vindication

The evidence accumulated against the sceptics. André Jagendorf's experiments on chloroplasts showed that an artificially imposed pH difference across a membrane — a proton gradient and nothing else — could drive ATP synthesis. Then ATP synthase was identified: the membrane enzyme that Mitchell's scheme required, functioning as a channel through which returning protons drive the production of ATP.

The Royal Society elected him a Fellow in 1974. The Rosenstiel Award came in 1976. In 1978 he received the Nobel Prize in Chemistry — unshared — "for his contribution to the understanding of biological energy transfer through the formulation of the chemiosmotic theory." The Sir Hans Krebs Medal followed the same year, and the Royal Society's Copley Medal in 1981. He died on 10 April 1992.

Why Mitchell Matters

Chemiosmosis is now taught as fact in every introductory biology course, which obscures how radical it was. Mitchell explained the central energetic transaction of life — how mitochondria and chloroplasts convert food and sunlight into usable energy — and he explained it correctly while nearly everyone qualified to judge thought he was wrong.

The manner of it is as instructive as the content. He was proved right from a private laboratory in a restored Cornish house, funded outside the grant system, working with one principal collaborator. Consensus, his career demonstrates, is a description of what a field currently believes, not a measure of what is true.