Max Perutz and the Secret of Life

  • Georgina Ferry
Chatto & Windus/Cold Spring Harbor Laboratory Press: 2007. 304 pp. £25/$39 0879697857 0701176954 | ISBN: 0-879-69785-7

I have a problem with the title of this book, but it's almost my only quibble with this marvelous biography of one of the least known of the twentieth century's great scientists. By no measure could Max Perutz be said to have discovered the secret of life — a claim that might be defended for Gregor Mendel, or Charles Darwin and Alfred Russel Wallace, or James Watson and Francis Crick. The mechanism of oxygen's reversible binding to haemoglobin, which Perutz elucidated in 1970 after more than 25 years of work, doesn't even apply to most living organisms (and oxygen is deadly to most anaerobes). That said, Perutz did many extraordinary things, including winning the Nobel Prize in Chemistry in 1962 for solving haemoglobin's three-dimensional structure.

Perutz the showman: Max continued to captivate audiences well into his eighties. Credit: PERUTZ FAMILY

It is hard to write a biography of someone only recently deceased (Perutz died in 2002). The biographer must accurately portray someone who was known personally to many readers, yet at the same time expose previously hidden aspects of his or her character. Georgina Ferry achieved both in her biography of Dorothy Crowfoot Hodgkin, and now she has done it again in her engrossing account of the life and work of Max Perutz.

Perutz, whom I knew well for 30 years, can't have been an ideal subject. No scandal colours his career; his personal life was stable and happy; his accomplishments were clear in terms of priority; he made a number of significant mistakes; his major discoveries are not easily understood by the layperson; and he lacked the forceful manner of a Crick or Bernal. But as the father of protein crystallography — arguably one of the greatest scientific advances of the last century — and the founder of the Medical Research Council (MRC) Laboratory of Molecular Biology in Cambridge, UK, his influence was enormous.

Ferry succeeds in bringing what could, in lesser hands, be considered a somewhat drab character sharply to life. As an Austrian Jew born during the First World War, Perutz left for Cambridge in 1936, where he joined the laboratory of one of the larger-than-life figures of modern science, John Desmond Bernal. Together with Dorothy Hodgkin, Bernal had, just two years earlier, taken the first X-ray diffraction photograph of a single crystal of a protein molecule, the digestive enzyme pepsin. This showed that, in principle, the extraordinary power of crystallography could reveal the atomic details of even large biological molecules. Undeterred by the scale of his task, Perutz ventured to use crystallography to unravel how haemoglobin could bind oxygen tightly enough to transport it around the bloodstream, yet release it when and where it was needed.

I doubt whether most people, even today, understand how pioneering this was. Determining the three-dimensional structure of proteins was a goal of Nobel-prize potential for several powerful research groups of that time, but none particularly cared what the protein was. Only Perutz had a greater aim. He wanted to understand the function of haemoglobin, which meant solving all the problems presented by this large, flexible protein. What would he have made of the recent International Structural Genomics Initiative, I wonder, which aims to turn out massive numbers of protein crystal structures without regard to biological or biochemical function?

Perutz's greatest achievement was demonstrating that the method of 'isomorphous replacement', previously used to solve the structures of small organic compounds, could be used to crack the 'phase problem' in protein crystallography. This is the problem of how to deduce a wave's phase component in diffraction patterns. This method made it possible to sum up the scattered X-ray waves in proper registration with each other and therefore to reconstruct the molecule's structure. It opened the way to solving the structure of any large crystalline molecule. Ferry explains the many false starts, and embarrassing errors, that led up to that moment, while allowing the reader to feel the frustrations and joys along the way. It's as good an account of a scientific breakthrough as you will find.

Haemoglobin's structure followed. More than a decade later, Perutz showed that it was the minute movement of the iron atom into the plane of the haem group upon binding oxygen that triggered the shape change from the deoxygenated form of the protein. He once spent an hour explaining the new mechanism to me when I was a graduate student (even though he had just published it and must have talked about it many times before), as enthusiastically as a child with a new toy.

Perutz's sometimes child-like character is the surprise in Ferry's biography. Apparently, he had a desire to be praised for his discoveries, which sometimes manifested as petulance and led to ruthlessness towards competitors. But he was equally ready to confess his blunders, which endeared him to many younger scientists. Fragile health, combined with an acute sense of his failures, may have explained his reserve, particularly around the boisterous young molecular biologists at Cambridge. Ferry avoids the pop-psychology that permeates so many modern biographies, while offering insight into Perutz's temperament and behaviour.

For Ferry, one of Perutz's finest achievements was the creation in 1962 of the MRC Laboratory for Molecular Biology, which has produced an astounding number of Nobel laureates and Fellows of the Royal Society. She devotes an entire chapter to its history and to Perutz's unique, hands-off style of managing it. His skill in identifying and nurturing talent at a time when molecular biology was just starting out is one of the things that makes Perutz a central figure in modern scientific history.

Ferry doesn't end the book with Perutz's death from Merkel cell carcinoma, just days after submitting his manuscripts on the structure of the protein aggregates in Huntington's disease. Instead, she follows it with a chapter about his avocation as a writer of popular essays about science and society. This is a masterstroke, because his wise and witty writings present Perutz to us at his most candid, and so the chapter sums up the book, and the man, very nicely.

Ferry has mined gold in the lives of two of the founders of structural biology; I can't wait to see whom she tackles next. Frederick Sanger, one of only four people to win two Nobel prizes? Or how about William H. Bragg or Max von Laue?