Perutz, Max (1914-2002)

English crystallographer, molecular biologist, and bio-chemist

Max Perutz transformed a fascination of geological processes and crystal structure into one of the fundamental techniques upon which modern molecular biology was founded. Ultimately, Perutz pioneered the use of x-ray crystallography to determine the atomic structure of proteins by combining two lines of scientific investigation—the physiology of hemoglobin and the physics of x-ray crystallography. His efforts resulted in his sharing the 1962 Nobel Prize in chemistry with his colleague, biochemist John Kendrew. A passionate mountaineer and skier, Perutz also applied his expertise in x-ray crystallography to the study of glacier structure and flow.

Perutz's work in deciphering the diffraction patterns of protein crystals opened the door for molecular biologists to study the structure and function of enzymes—specific proteins that are the catalysts for biochemical reactions in cells. Known for his impeccable laboratory skills, Perutz produced the best early pictures of protein crystals and used this ability to determine the structure of hemoglobin and the molecular mechanism by which it transports oxygen from the lungs to tissue.

Perutz was born in Vienna, Austria, on May 19, 1914. His parents were Hugo Perutz, a textile manufacturer, and Adele Goldschmidt Perutz. In 1932, Perutz entered the University of Vienna, where he studied organic chemistry. In 1936, Perutz landed a position as research student in the Cambridge laboratory of Desmond Bernal, who was pioneering the use of x-ray crystallography in the field of biology. Perutz, however, was disappointed again when he was assigned to research minerals while Bernal closely guarded his crystallography work, discussing it only with a few colleagues and never with students.

Perutz's received excellent training in the promising field of x-ray crystallography, albeit in the classical mode of mineral crystallography.

In the early 1930s, crystallography had been successfully used only in determining the structures of simple crystals of metals, minerals, and salts. However, proteins such as hemoglobin are thousands of times more complex in atomic structure. Physicists William Bragg and Lawrence Bragg, the only father and son to share a Nobel Prize, were pioneers of xray crystallography. Focusing on minerals, the Braggs found that as x rays pass through crystals, they are buffeted by atoms and emerge as groups of weaker beams which, when photographed, produce a discernible pattern of spots. The Braggs discovered that these spots were a manifestation of Fourier synthesis, a method developed in the nineteenth century by French physicist Jean Baptiste Fourier to represent regular signals as a series of sine waves. These waves reflect the distribution of atoms in the crystal.

The Braggs successfully determined the amplitude of the waves but were unable to determine their phases, which would provide more detailed information about crystal structure. Although amplitude was sufficient to guide scientists through a series of trial and error experiments for studying simple crystals, proteins were much too complex to be studied with such a haphazard and time consuming approach.

Initial attempts at applying x-ray crystallography to the study of proteins failed, and scientists soon began to wonder whether proteins in fact produce x-ray diffraction patterns. However, in 1934, Desmond Bernal and chemist Dorothy Crowfoot Hodgkin at the Cavendish laboratory in Cambridge discovered that by keeping protein crystals wet, specifically with the liquid from which they precipitated, they could be made to give sharply defined x-ray diffraction patterns. Still, it would take 23 years before scientists could construct the first model of a protein molecule.

Perutz and his family, like many other Europeans in the 1930s, tended to underestimate the seriousness of the growing Nazi regime in Germany. While Perutz himself was safe in England as Germany began to invade its neighboring countries, his parents fled from Vienna to Prague in 1938. That same summer, they again fled to Switzerland from Czechoslovakia, which would soon face the onslaught of the approaching German army. Perutz was shaken by his new classification as a refugee and the clear indication by some people that he might not be welcome in England any longer. He also realized that his father's financial support would certainly dwindle and die out.

As a result, in order to vacation in Switzerland in the summer of 1938, Perutz sought a travel grant to apply his expertise in crystallography to the study of glacier structures and flow. His research on glaciers involved crystallographic studies of snow transforming into ice, and he eventually became the first to measure the velocity distributions of a glacier, proving that glaciers flow faster at the surface and slower at the glacier's bed.

Finally, in 1940, the same year Perutz received his Ph.D., his work was put to an abrupt halt by the German invasions of Holland and Belgium. Growing increasingly wary of foreigners, the British government arrested all enemy aliens, including Perutz. Transported from camp to camp, Perutz ended up near Quebec, Canada, where many other scientists and intellectuals were imprisoned, including physicists Herman Bondi and Tom Gold. Always active, Perutz began a camp university, employing the resident academicians to teach courses in their specialties. It didn't take the British government long, however, to realize that they were wasting valuable intellectual resources and, by 1941, Perutz followed many of his colleagues back to his home in England and resumed his work with crystals.

Perutz, however, wanted to contribute to the war effort. After repeated requests, he was assigned to work on the mysterious and improbable task of developing an aircraft carrier made of ice. The goal of this project was to tow the carrier to the middle of the Atlantic Ocean, where it would serve as a stopping post for aircrafts flying from the United States to Great Britain. Although supported both by then British Prime Minister Winston Churchill and the chief of the British Royal Navy, Lord Louis Mountbatten, the ill-fated project was terminated upon the discovery that the amount of steel needed to construct and support the ice carrier would cost more than constructing it entirely of steel.

Perutz married Gisela Clara Peiser in 1942; the couple later had a son and a daughter. After the war, in 1945, Perutz was finally able to devote himself entirely to the study of hemoglobin crystals. He returned to Cambridge, and was soon joined by John Kendrew. In 1946 Perutz and Kendrew founded the Medical Research Council Unit for Molecular Biology, and Perutz became its director. Many advances in molecular biology would take place there, including the discovery of the structure of deoxyribonucleic acid (DNA).

Over the next years, Perutz refined the x-ray crystallography technology. Often bogged down by tedious mathematical calculations, the development of computers hastened the process tremendously.

By 1957, Kendrew had delineated the first protein structure through crystallography, again working with myoglobin. In 1962, Perutz and Kendrew were awarded the Nobel Prize in chemistry for their codiscoveries in x-ray crystallography and the structures of hemoglobin and myoglobin, respectively. The same year, Perutz left his post as director of the Unit for Molecular Biology and became chair of its laboratory.

Perutz was a Fellow of the Royal Society. He died on February 6, 2002.

See also Atomic theory; Crystals and crystallography