Book Review

Max Perutz and the Secret of Life

N Engl J Med 2008; 358:2652-2653June 12, 2008

Article

Max Perutz and the Secret of Life
By Georgina Ferry. 352 pp., illustrated. Cold Spring Harbor, NY, Cold Spring Harbor Laboratory Press, 2008. $39. ISBN: 978-0-87969-785-3

Biographies that are most apt to appeal to physicians offer a coherent and accurate account of the subject's contributions to medicine, along with insights into his or her character and personality. Georgina Ferry amply fulfills these criteria in her account of the life of Max Perutz, the Nobel laureate who worked out the structure of hemoglobin and the chemical basis of its physiological properties. Her lively narrative draws us into the world of high-powered science, with its triumphs, frustrations, and foibles. Although Ferry met Perutz only once, near the end of his life, she treats him with comfortable informality in her narrative, calling him Max — as did all his colleagues, senior and junior, near and distant.

Perutz went from Vienna to the Cavendish Laboratory at the University of Cambridge, England, in 1936 to pursue a doctoral degree with two pioneering x-ray crystallographers, John Desmond Bernal and William Lawrence Bragg. His audacious decision to work on hemoglobin was met with skepticism and condescension. At the time, the most complex organic molecule whose structure had been solved by x-ray analysis was the dye phthalocyanine, which is about 1/200th the size of hemoglobin.

Max Perutz in His Laboratory at the University of Cambridge, November 1962.

Ferry has written an engrossing account of the challenges and setbacks that Perutz faced. At first fortune smiled on him. His hemoglobin crystals yielded diffraction patterns that Dorothy Crowfoot Hodgkin called “the most beautiful protein x-ray photographs yet seen.” Hodgkin would win the Nobel Prize in Chemistry in 1964, 2 years after Perutz won his. Unfortunately, Perutz's work was interrupted when, at the outbreak of World War II, he was declared an enemy alien and banished to Canada. After his return to the Cavendish Laboratory, progress was agonizingly slow. His eureka moment came in 1953, when he used heavy-metal atom replacements to orient the position of oxyhemoglobin molecules within the crystal. That year was an annus mirabilis both for the Cambridge laboratory and for England and its former colonies. During the same year, James Watson and Francis Crick discovered the double helix, Queen Elizabeth II was crowned, and Sir Edmund Hillary conquered Mount Everest.

Perutz's feat, the cornerstone of structural biology, earned him (with John Kendrew) the Nobel Prize in Chemistry in 1962. However, he knew that he was still at the beginning of a career-long quest to understand the workings of hemoglobin. He went on to determine the structure of deoxyhemoglobin and found that the differences between the oxy and deoxy isoforms explained the physiological properties of hemoglobin at the atomic level. Ferry's accounts of the controversies that delayed the acceptance of some of Perutz's boldest conclusions are frank and entertaining. She stresses the high premium that he placed on the medical applications of his discoveries. During a span of three decades, he was actively involved in research on sickle cells and the challenge of developing drugs that might inhibit or interrupt polymerization of sickle hemoglobin. Late in his career, Perutz immersed himself in attempts to understand how self-associating proteins could be crucial in the pathogenesis of Alzheimer's disease and Huntington's disease.

Ferry's biography provides a revealing glimpse into Perutz's persona and idiosyncrasies. He was disarmingly modest and readily acknowledged the importance of luck and location. He was unstintingly generous in acknowledging his debt to his mentors and collaborators. Most of all, he was deeply appreciative of the opportunity to spend his career in Cambridge. He was enormously proud of the Medical Research Council Laboratory of Molecular Biology, which he founded in 1959 and directed for more than 20 years. His collegial and unobtrusive approach to administration allowed the flowering of one of the world's most distinguished molecular biology laboratories. Perutz rejoiced in associations with colleagues of luminous intellect, such as Francis Crick, Sidney Brenner, and Aaron Klug. In scientific discourse Perutz thought slowly and deeply — so much so that he was sometimes teased by his colleagues. Happily, he had the self-confidence to deal with Crick's admonition: “Explain it so that even Max can understand it.”

Ferry portrays Perutz's passions for mountain climbing, music, art, and creative writing, as well as his strong humanitarian impulses. Within days after September 11, 2001, he wrote to British Prime Minister Tony Blair, appealing to him not to respond with military force: “I am alarmed by the American cries for vengeance and concerned that President Bush's retaliation will lead to the death of thousands more innocent people, driving us into a world of escalating terror and counter-terror. I do hope that you can use your restraining influence to prevent this happening.”

H. Franklin Bunn, M.D.
Harvard Medical School, Boston, MA 02115
hfbunn@rics.bwh.harvard.edu