Brains, flair and construction nous

Wandering in the Gardens of the Mind
April 30, 2004

Jon Turney recalls the leading light of an intractable branch of biochemistry.

The young theorist who commits all to a heterodox idea and is widely derided or misunderstood, but lives to see their version in all the textbooks, is one of the more compelling scientific narratives. Biology in the second half of the 20th century yielded two splendid examples. One was the American Lynn Margulis, with her insistence that symbiotic bacteria originally gave rise to the mitochondria now found as components of all complex cells. The other was an Englishman, Peter Mitchell, who figured out how mitochondria turn the energy extracted from respiration, the slow burning of foodstuffs by oxygen, into a form the cell can use where needed.

Mitchell, who died in 1992, remains less well known, even though he won a Nobel prize for chemistry in 1978. This is partly because he chose to pursue his science in a privately funded research institute, Glynn House, remote from casual visitors in England's west country. It was also, perhaps, because his ideas were harder to understand, both for laypeople and for biochemists outside the field. When some in my undergraduate biochemistry class complained that the lectures the local specialist gave on the topic in 1975 were hard to follow, we were cheerfully informed by the professor that we were not to worry because "no one understands the mitochondriacs".

It was true that the details, and the disputes about interpreting experiments, were confusing. But the basic ideas were simple enough. The mitochondrion does look like a little cell inside the cell - as Margulis maintained - a bag of stuff bound by a membrane, one furnished with complicated internal folds and creases. Somehow enzymes sitting inside these membranes simultaneously expedite the consumption of oxygen, which ends up combined with hydrogen as water, and the generation of the ubiquitous molecule adenosine triphosphate (ATP), usually termed the energy currency of the cell.

Regular biochemists, who had seen enormous success in unravelling the highways and byways of metabolism step by chemical step, were convinced that there must be short-lived "high-energy" chemical intermediates in-between oxygen and ATP. Their response to the repeated failure to identify them was to come up with more exotic candidates.

Mitchell's scheme abolished the high-energy intermediate. He proposed that the respiratory enzymes pumped protons across the membrane and the resulting proton gradient then drove ATP synthesis. Several things made acceptance of this notion a drawn-out process. Few others had considered the importance of compartmentalisation and spatial orientation of cellular reactions. It was hard to grasp exactly how the proton gradient was harnessed, as it would create a difference in acidity inside and outside the mitochondrion and an electrical potential difference across the membrane. The experiments needed to test the theory were hard to do. And a rival theory, invoking changes of shape in proteins as the energy store, appealed more to traditionalists.

John Prebble and Bruce Weber's very welcome biography describes in great detail the origins of Mitchell's insights and how, after lengthy and complex controversies, his theory, with some shape changes thrown in, came to dominate the field. It also reveals a remarkable, though highly strung, man who focused intensely on his science, but also revelled in art and music and found the energy to oversee a series of building restoration projects.

The most spectacular of these was Glynn House, which became Mitchell's home as well as his research institute after he left Edinburgh University in 1963, when pressure of work threatened his health. He already had the basic outlines of his chemi-osmotic theory, as it was called, so Mitchell and a tiny team, whose other most important member was his highly skilled research assistant for 30 years, Jennifer Moyle, set out to generate the results that would give it some credibility.

It is a satisfying story, though the biographers' style is workmanlike and resolutely undramatic. Their interest is mainly in the development of the science rather than Mitchell's idiosyncratic personal style. There are few concessions to lay readers, and non-biochemists will need to read the appendix summarising competing theories before tackling the main narrative.

The authors also relate a good deal of the history of Glynn and suggest that it offers a model for efficiently convivial "small science".

Unfortunately, the book also makes it clear that Glynn's undoubted success rested not just on its ownership by a scientist of the highest talent; also essential were his uncommon flair for rescuing ruined buildings and access to a substantial family fortune (from the Wimpey construction empire). You somehow doubt that this combination will recur. But all the more reason to savour the story of this unique institute and its remarkable guiding light.

Jon Turney is editorial director, Penguin Press, and was formerly in the department of science and technology studies, University College London.

Wandering in the Gardens of the Mind: Peter Mitchell and the Making of Glynn

Author - John Prebble and Bruce Weber
Publisher - Oxford University Press
Pages - 324
Price - £40.99
ISBN - 0 19 514266 7

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