Max Perutz

Austrian molecular biologist

• Born: May 19, 1914; Vienna, Austria
• Died: February 6, 2002; Cambridge, England

Max Perutz developed the procedure by which the atomic structure of proteins can be determined by the pattern of X-ray diffraction they produce. He later applied similar techniques of X-ray diffraction to explain the structure of hemoglobin.

Primary field: Biology

Specialties: Molecular biology; biochemistry

Early Life

Max Ferdinand Perutz was born May 19, 1914 in Vienna, the capital of what was then the Austro-Hungarian Empire. His father, Hugo Perutz, was a textile manufacturer of Czechoslovakian ancestry. His mother, Adele Goldschmidt Perutz, was Viennese. Her family was also in the textile business. Perutz was the youngest of their three children.

World War I and its aftereffects significantly disrupted the Perutz family. Two of Perutz’s uncles were killed in the war. His father served as a member of a mortar unit on the Italian front. Starvation was common after the war, and the Perutz family moved to Reichenau in order to exchange clothing for food. Textile products remained in significant demand after the war, allowing the Perutz family first to survive and then to become relatively prosperous. Anti-Semitism was widespread in Viennese society during this period, and consequently some members of the family, including Perutz, were baptized as Christians.

At age ten, Perutz enrolled at the Theresianum, an exclusive preparatory school established in 1746 for training the sons of the aristocracy. He was also educated by private tutors. The curriculum at the school changed during the eight years in which Perutz was enrolled. The school’s emphasis on Latin and Greek was replaced with French. The school continued to have strong mathematics and science programs, and Perutz developed a growing interest in chemistry during these years. He was strongly encouraged by his family to pursue law, but he convinced his parents to allow him to study chemistry instead.

Life’s Work

In 1932, Perutz enrolled at the University of Vienna to pursue a degree in chemistry. As a student, he found a course in organic biochemistry of particular interest. References to the work being carried out by biochemist and Nobel laureate Frederick Hopkins at Cambridge University in London inspired Perutz to pursue his doctoral work in London.

In September 1936, Perutz joined the Cavendish Laboratory at Cambridge, where he began working with Bernal on X-ray crystallography. Perutz became fascinated with crystallography, believing the key to understanding living matter lay in an understanding of protein. Although Perutz requested he be given a project analyzing biological material, he was instead given chips of silicate to analyze. To conduct the analysis, Perutz worked with an old X-ray apparatus. Another of Bernal’s associates instructed Perutz in the use of the instrument, while Bernal provided the interpretation of the data. Bernal and British chemist Dorothy Hodgkin demonstrated that X-ray diffraction patterns obtained when using crystals of protein could be applied in measurements of distance between atoms. Perutz theorized that the same principles could be used for atomic analysis of other larger molecules.

In the summer of 1937, Perutz travelled to Prague, where he met with a cousin who was married to biochemist Felix Haurowitz. Haurowitz had been studying horse hemoglobin (the molecule carrying oxygen in red blood cells) and showed Perutz how purple crystals of deoxyhemoglobin became scarlet-colored when exposed to oxygen. The demonstration peaked Perutz’s interest, and Haurowitz suggested that he contact the protein scientist Gilbert Adair at Cambridge in order to obtain his own crystalline samples of hemoglobin for analysis. In 1938, Bernal, Perutz, and a third scientist, Isidor Fankuchen, published a paper describing the X-ray diffraction pattern of hemoglobin.

In 1938, Austria and portions of Czechoslovakia were annexed to Germany by Nazi leader Adolf Hitler. Since the Perutz family was of Jewish ancestry, their businesses were appropriated by the Nazis, who had begun enforcing a strict anti-Semitic social policy. Although Perutz lost the funding for his work that was provided by his family, he was able to obtain a grant through the Rockefeller Foundation in New York, which allowed him to continue working as a research assistant to physicist Lawrence Bragg, a 1915 Nobel laureate who by 1938 had replaced Bernal as Cavendish Professor in Cambridge. In 1940, Perutz earned his PhD.

Following the beginning of the Second World War in September 1939, and the subsequent election of Winston Churchill as British prime minister the following year, Perutz was among 7,500 people of German or Austrian ancestry interned in England as “enemy aliens.” Perutz was subsequently exiled to Canada, though he was later allowed to return to Cambridge. Despite the treatment he received at the hands of the British government, Perutz participated in the Allied war effort, and was associated with Project Habakkuk. The project, proposed by scientist Geoffrey Pike, suggested using large ice flows in the Atlantic as floating aircraft carriers for Allied forces. Although the proposal never came to fruition, Perutz’s contribution included a study of crystal formations in glaciers.

Perutz married Gisela Peiser in 1942; they would have two children, one of whom, Robin Perutz, became a professor of chemistry.

Following the Allied victory in 1945, Perutz continued his X-ray diffraction studies. Bernal had departed from Cambridge prior to the beginning of the war, becoming Chair of Physics at Birkbeck College in London. Perutz had earlier shown Bragg his diffraction photographs of hemoglobin, and Bragg remained among the strongest supporters of Perutz’s research for the remainder of his tenure.

In 1946, biochemist and crystallographer John Kendrew joined the Cambridge laboratory as Perutz’s colleague. Kendrew was primarily involved in the study of myoglobin structure, a molecule found in muscle that functioned in a manner similar to hemoglobin; the diffraction principles for each were largely identical. The following year Perutz was appointed head of the Medical Research Council Unit for Molecular Biology (MRC), the position he held until 1962 when he became founder and chair of the MRC Laboratory of Molecular Biology. It was as the head of the MRC that Perutz oversaw the work of geneticists James Watson and Francis Crick in the early 1950s as they deciphered the structure of DNA.

One challenge Perutz faced in trying to decipher the X-ray diffraction patterns was that of phase variation, which prevented the superimposing of images necessary to understand the atomic pattern. Perutz solved the problem by 1954 through what he called isomorphous replacement, which was the attachment of heavy atoms to a structure that allowed for the determination of a reference point. Within five years both the structures of hemoglobin (by Perutz) and myoglobin (by Kendrew) had been determined. In 1962 they shared the Nobel Prize in Chemistry for their work.

Perutz’s later research focused on changes in hemoglobin structure that took place as a result of oxygen binding (oxyhemoglobin) and detachment of oxygen (deoxyhemoglobin). He applied this to the study of genetic diseases associated with hemoglobin. Perutz also studied Huntington’s disease, a genetic abnormality involving the degeneration of nerve cells in the brain. He had just completed a manuscript proposing a mechanism underlying the pathology of Huntington’s disease when he died on February 6, 2002.

Impact

Perutz’s analysis of hemoglobin represented the first time a protein structure was understood at the atomic level. He further applied this in his description of structural changes taking place in the binding or release of oxygen, as well as structural changes inherent in mutations of hemoglobin, opening a new field of molecular pathology. The result was an understanding of the mechanisms by which hemoglobin attaches to oxygen and subsequently releases the molecule into tissue, a linking of structure with function.

Other scientists quickly applied the isomorphous technique introduced by Perutz in their respective three-dimensional analyses of other proteins. In the years immediately following Perutz’s and Kendrew’s publications, the structures of lysozyme (an enzyme that hydrolyzes carbohydrates), the digestive enzyme a-chymotrypsin, carboxypeptidase B (a pancreatic enzyme that hydrolyzes protein), and ribonuclease A were all determined.

Bibliography

Brown, Andrew. J. D. Bernal: The Sage of Science. New York: Oxford UP, 2005. Print. Presents a biography of Bernal, Perutz’s mentor and colleague. Perutz was one of several students of Bernal’s to be awarded a Nobel Prize.

Ferry, Georgina. Max Perutz and the Secret of Life. Cold Spring Harbor: Cold Spring Harbor P, 2007. Print. Biography of Perutz. Discusses his ancestry and continues with both his personal life and scientific career. Includes a discussion of his significance as a mentor to other scientists.

Watson, James D. The Double Helix: A Personal Account of the Discovery of the Structure of DNA. New York: Touchstone, 2001. Print. Autobiography of one of the scientists who deciphered the structure of DNA. Perutz was head of the unit in the Medical Research Council that oversaw Watson and Francis Crick’s work at Cambridge.