Perutz, Max Ferdinand

Citation metadata

Date: 2008
Complete Dictionary of Scientific Biography
Publisher: Charles Scribner's Sons
Document Type: Biography
Pages: 6
Content Level: (Level 5)

Document controls

Main content

Full Text: 
Page 79


(b. Vienna, Austria, 19 May 1914; d. Cambridge, United Kingdom, 6 February 2002),

x-ray crystallography, molecular biology, hemoglobin.

Perutz dedicated a large part of his long scientific career to unraveling the molecular structure and function of hemoglobin, the protein of red blood cells. In this work he made pioneering use of x-ray crystallography. He was a co-recipient of the 1962 Nobel Prize for Chemistry and the founder and first chairman of the Medical Research Council Laboratory of Molecular Biology in Cambridge, which produced a string of Nobel Prize winners.

Education and Early Career Born into an affluent Viennese family of textile industrialists, Perutz soon resolved not to step into the family business and instead pursue a career in science. He studied chemistry in his hometown. In 1936, after graduation, he joined John Desmond Bernal’s Crystallographic Department at the Cavendish laboratory in Cambridge following an introduction by his teacher Hermann Mark. Perutz had to learn x-ray crystallography from scratch by working on some silicate mineral fragments. Yet from the beginning his aspiration was to work on biological material.

A few years before Perutz joined the laboratory, Bernal, together with Dorothy Crowfoot (later Hodgkin), had obtained the first sharp x-ray diffraction images of a protein using crystals in their mother liquid instead of the usual dry crystals. In principle, this observation opened the way to the determination of the atomic structure of proteins. Proteins were considered to hold the key to all life processes, including inheritance; knowing their structure promised to provide clues to their function. Yet by the time Perutz joined the laboratory, Bernal, a key exponent of the scientific Left, was increasingly taken up with political activities connected to the rising threat of a Fascist war. When he moved to London in 1938 to take up a chair at Birkbeck College, Perutz stayed on at the Cavendish. By that time he had settled on a diffraction analysis of hemoglobin as the topic for his PhD thesis. The suggestion had come from the Prague biochemist Felix Haurowitz whom Perutz had asked for advice. Haurowitz had observed that hemoglobin showed a change in crystal form under the microscope when moving from the oxygenated to the deoxygenated form. Gilbert Adair from the Physiology Department in Cambridge supplied the first crystals.

Fortunately for Perutz, Bernal’s departure coincided with Lawrence Bragg’s appointment as Ernest Rutherford’s successor to the Cavendish Chair in Cambridge. Bragg became excited at the prospect of extending the method he himself had first applied to propose a structure for common salt some twenty-five years before, to the fantastically complex structure of proteins. When later in 1938 Adolf Hitler annexed Austria and Perutz became an émigré, Bragg obtained a grant from the Rockefeller Foundation that supported Perutz until the end of the war. It also enabled Perutz to have his Jewish parents, Hugo and Adele Perutz, come to Britain and thus escape deportation.

Perutz was to dedicate most of his scientific career to the study of the structure and function of the hemoglobin molecule, but he had certainly not anticipated this at the time. The original aims were rather modest, although the hopes to achieve a significant result ran high. To prepare and mount the hemoglobin crystals, determine the dimensions and hydration of the crystals, and study the effects of denaturation was enough to acquire a PhD. Perutz’s dissertation also included the discussion of a two-dimensional vector analysis (also known as Patterson analysis) of a hemoglobin derivative calculated by Dennis Riley of Dorothy Hodgkin’s group in Oxford.

Comparison with Hodgkin’s Patterson analysis of insulin led Perutz to confirm that protein molecules were composed of small subunits, arranged in a regular manner. This was a common assumption at the time. It also led crystallographers to believe that the knowledge of the structure of one protein would provide decisive clues for the structure of all proteins. Although these expectations proved wrong, they provided the motivation for researchers including

Max Ferdinand Perutz. AP IMAGES. Max Ferdinand Perutz. AP IMAGES.

Page 80  |  Top of Article

Perutz to approach the problem; without those expectations they might have been discouraged.

Internment and Secret War Work Perutz submitted his doctoral dissertation on the structure of hemoglobin in the spring of 1940. A few months later, with mounting fears of a German invasion, he was rounded up with other “enemy aliens.” After prolonged stays in various remote parts of Britain, twelve hundred internees including Perutz were herded on a large troopship that eventually brought them to an internment camp in Canada (while still at sea they learned that another troopship crammed with internees had been sunk by a German U-boat; more than six hundred of the fifteen hundred people on board lost their lives). The humiliating and uncomfortable conditions did not lead to complete despair. With his freshly gained PhD Perutz found himself the doyen of the camp’s scholars and set out to organize a camp university. The staff included several future fellows of the Royal Society, among them the mathematician and cosmologist Hermann Bondi, who was to become chief scientific adviser to the Ministry of Defence, the astronomer Thomas Gold; and Klaus Fuchs, who was to join the Manhattan Project and became an “atom spy,” a role to which he was led not as a German but as a communist.

Unknown to Perutz, in the meantime his British colleagues were agitating for his and other internees’ release. He was offered the choice to return to England or take up a professorship at the New School for Social Research in New York, organized as part of a rescue campaign by the Rockefeller Foundation for its grantees. Undeterred by the perils of the transatlantic passage, Perutz opted to return to England. The whole adventure had lasted about eight months.

Perutz resumed his research at the Cavendish, but before long was called to participate at a secret wartime project code-named Habakkuk. The plan, conceived by the maverick Geoffrey Pyke, scientific advisor of General Mountbatten, chief of Combined Operations, consisted in building an airplane base made of reinforced ice in the Atlantic. Perutz, who before the war had combined his (lifelong) passion for the mountains and for science by participating in a scientific expedition to the Alps to study the crystalline structure of ice in glaciers, was called to the project as an expert. Working for several months in a cold room at minus 20 degrees Celsius beneath Smithfield Market in London (the rooms were normally used for meat storage), Perutz and his team managed to develop a mixture of ice and wood pulp as strong as concrete; the reinforced ice became known as pykrete.

Page 81  |  Top of Article

After a successful demonstration of the qualities of pykrete to Franklin Roosevelt and Winston Churchill at their meeting in Quebec in August 1943, Habakkuk gained top priority. The British team was ordered to continue work in Washington. For the overseas mission Perutz was rapidly naturalized and received a British passport. Yet by the time he reached America, Mountbatten had been ordered to Southeast Asia. Having lost its strongest supporter, Habakkuk slid down the priority list and eventually was abandoned. A further reason for the demise of the project was that the rapidly increasing range of aircraft made artificial landing strips in the Atlantic superfluous.

In January 1944, Perutz once more returned to his research in the Cavendish. Later he gave a detailed and humorous account of his wartime experience as enemy alien and as scientist on a secret wartime project. “Enemy Alien” first appeared in the New Yorker in August 1985 and established his fame as a writer. It has since been reprinted several times.

Structure and Function of Hemoglobin In the last years of the war, Perutz’s work on the structure of hemoglobin was the only piece of pure research still pursued in the Cavendish. Blood and its products, however, were intensively studied in other laboratories because of their relevance to wartime medicine, and Perutz was part of an active network of Cambridge researchers working on different aspects of hemoglobin. The informal group was held together by the physiologist Joseph Barcroft, a pioneer in the field and an inspired teacher.

After the war, John Kendrew, a physical chemist who had occupied high offices in operational research during the war and, while on a common mission in Ceylon, had been convinced by Bernal of the promises of protein crystallography, joined Perutz to do a PhD. (Although working closely with Perutz, Kendrew was officially supervised by William T. Taylor, head of the crystallography division at the Cavendish; like most professional crystallographers Taylor regarded protein crystallography as a hopeless undertaking, but still accepted the formal agreement.) Kendrew first embarked on a comparative analysis of fetal and adult hemoglobin, but later switched to the simpler protein myoglobin, the oxygen carrier in muscle.

Although Perutz now had a collaborator, his own future was still uncertain. With the end of the war, the Rockefeller grant had run out. Bragg had obtained a two-year Imperial Chemical Industries fellowship for Perutz, but his aim to secure a university post for his protégé looked increasingly bleak. At this critical juncture, the Cambridge parasitologist and biochemist David Keilin, a strong supporter of Perutz’s work, suggested to Bragg to apply to the Medical Research Council (MRC) for funding. The successful application led to the establishment of the MRC Unit for the Study of Molecular Structure of Biological Systems with Perutz as its director. Among the first recruits were Hugh Huxley, Francis Crick, James Watson (who joined as a visitor) and, somewhat later, Sydney Brenner.

In 1949 Perutz published a paper in which he proposed the “pill box” or “hat-box” model of hemoglobin. It featured the polypeptide chains running in parallel bundles. Crick, although still a newcomer in the field, forcefully criticized the model and the assumption of a regular arrangement on which it was based. Crick’s attack produced some turmoil, but Perutz recognized the force of his argument. He developed a strong respect for Crick’s sharp judgment and, on several occasions, defended him against the grudge of the Cavendish head who resented his irreverent behavior.

The turning point in Perutz’s endeavor to unravel the structure of the complex hemoglobin model came in 1953, when he found a solution to the so-called phase problem. To derive the structure of a molecule from its diffraction pattern both the intensity as well as the phase of each spot were required. Yet while the intensities could be directly measured on the diffraction pictures (up to the mid-1950s this was done by eye), the phases had to be established by other methods. To circumvent the phase problem, Perutz and his colleagues used the Patterson function. It allowed them to calculate the distances between atoms on the basis of the intensities alone, but it left ample space for interpretation regarding the actual position of the atoms in space. The infamous hat-box model still relied on that method.

Perutz now managed to attach a heavy atom (mercury) to the hemoglobin molecule. From the difference produced in the diffraction pattern he was able to deduce the phase of the reflections. The method had been known since the 1930s, but it had only been used for small molecules. Although the suggestion to apply the method to proteins dated from the same period, its applicability had not been proved. The problem consisted, firstly, in finding a heavy metal compound that could be attached to a specific site without altering the arrangement of the other atoms in the molecule and, secondly, in estimating with sufficient accuracy the overall changes in intensity produced by the heavy atoms. In Bragg’s judgment, Perutz’s skill in this last respect was “probably unique” at the time (Bragg, 1965, p. 12). To this day, the isomorphous replacement method is considered the key method to determine the crystal structure of proteins.

Kendrew, working on the smaller myoglobin molecule, was the first to take full advantage of the new method. In 1958, he presented the first model ever of a globular protein derived by direct structure determination. The model showed the general outline of the

Page 82  |  Top of Article

Max Perutz Max Perutz. Max Perutz (left) with fellow Nobel Prize winner Paul Kendrew, 1962. © HULTON-DEUTSCH COLLECTION/CORBIS.

molecule; a second model at atomic resolution followed two years later. In the same year Perutz presented the first model of hemoglobin at 5.5 Ångstrøm. Its four subunits proved to be closely related to the myoglobin molecule. The white-and-black disk model built of thermosetting plastic is still widely reproduced.

The determination of any of these protein structures could not have been contemplated without the use of ever more powerful electronic computers. Perutz initially distrusted the new calculating devices and resisted resorting to the experimental digital computers developed at the nearby Mathematical Laboratory. Eventually he came around to recognize their usefulness, but he freely admitted that he was always hopeless at computing. He never made use of the machine himself and rather left this part of the work to the younger people in his group.

Perutz and Kendrew shared the 1962 Nobel Prize for Chemistry for their work on the structure of proteins.

However, for Perutz the challenge posed by hemoglobin continued. He realized that to understand the oxygen-binding function of hemoglobin, including its cooperative effect, he needed an atomic model of both the oxygenated and deoxygenated forms of hemoglobin. This immense task involved measuring several hundred thousand reflections, stretching even the patience of a crystallographer. Perutz and his collaborators completed it in 1970, well thirty-three years after Perutz had taken the first x-ray picture of the molecule. Close examination of the two models led Perutz and his colleagues to propose a cooperative mechanism that saw the different parts of the model clicking back and forth between the two forms. The proposed mechanism included relative movement of the four subunits as well as conformational change of the subunits when oxygen was bound. It beautifully illustrated, and refined, the mechanism of conformational change (or allostery) postulated by the French biochemist Jacques Page 83  |  Top of ArticleMonod a few years earlier. For his argument, intended to explain regulatory functions in enzymes, Monod had used hemoglobin as a model. As a result, and to Perutz’s delight, hemoglobin was elevated to the status of an “honorary enzyme.”

Another important resource for Perutz’s work was the extensive clinical and biochemical knowledge of abnormal hemoglobins gathered by Hermann Lehmann, professor of clinical biochemistry at Cambridge. By building the known amino acid substitutions into the hemoglobin model, clinical symptoms could be explained in molecular terms; at the same time the functional knowledge of the clinic provided decisive clues for deriving the working mechanism of the molecule. The two researchers published a paper (1968) announcing the new field of molecular pathology. Perutz was deeply satisfied that his research was becoming medically important. Although details of Perutz’s proposed mechanism of the hemoglobin model were contested, the model as a whole stood the test of time.

Laboratory of Molecular Biology Besides remaining deeply committed to work at the bench, Perutz was an effective institute builder. Throughout the 1950s the MRC Unit at the Cavendish under his direction grew in size and importance. Apart from the protein work that was attracting more researchers, Watson’s arrival in 1951 stirred Crick into a collaboration on the structure of DNA that led to the proposal of the complementary double helical structure of the molecule in 1953. Although only time would confer on it the iconic place it later gained, the DNA model was regarded early on as an important achievement that confirmed the power of structure-function analysis.

Watson’s later account of the discovery in the bestselling The Double Helix (1968) put Perutz in the awkward position of appearing as the person who passed on decisive data gained by the London crystallographer Rosalind Franklin contained in a report on her unit’s work to an MRC committee of which he was a member. In a letter to Science Perutz made clear that the report was not confidential and the data had been presented at talks before, although he acknowledged that as a matter of courtesy he should have asked the London unit for permission. Watson responded by apologizing for having misrepresented the incident.

The double-helix work gave rise to further research in the Cambridge unit on the mechanism by which DNA is translated into proteins. With the work and the number of researchers it attracted expanding, the unit outgrew its place in the physics laboratory. At this critical juncture Perutz, joining forces with the Cambridge protein biochemist Fred Sanger, applied to the MRC for a new Laboratory of Molecular Biology (known as the LMB). The laboratory opened on the outskirts of Cambridge in 1962. Perutz became its first chair and for seventeen years light-handedly guided the institution, which quickly established itself as a key center of the burgeoning new field of molecular biology. The memorandum written to argue for the new laboratory became the basis for a series of lectures and finally a book on Proteins and Nucleic Acids: Structure and Function (1962), which Perutz liked to regard as the first textbook of the new discipline.

Perutz’s approach in leading the laboratory consisted in keeping administration and formal paperwork at a minimum. Asked for the recipe for a successful laboratory such as the LMB, Perutz’s usual answer was that the key lay in picking good people and helping them get what they needed to develop their work and for the rest let them follow their own interests. He also believed that seeing the leading people of a lab doing work at the bench helped boost working morale.

Despite disliking committee work, Perutz agreed to act as first chair of the European Molecular Biology Organization, founded in 1963. The main aim of the organization, formed by molecular biologists, was to fund a European fellowship, training, and travel program. However, Perutz remained critical of the plan to found a European molecular biology laboratory, which he thought would become too much a bureaucratic structure and would divert capable people away from existing laboratories. At times Perutz was disappointed that he missed out on a university career, but in later years he increasingly saw the advantages of being able to dedicate all his time to research and to building up the LMB.

Active Retirement Perutz retired as chair of the LMB in 1979, but his research work continued. Initially hemoglobin remained at the heart of the problems he tackled. One project concerned the adaptation of hemoglobin in different species. Another, in the end unsuccessful, project aimed at identifying drugs that would improve the solubility of sickle cell hemoglobin. However, the work on ligand binding to hemoglobin led to other clinical investigations. Aged eighty, Perutz for the first time strayed away from hemoglobin and, with several collaborators, started a series of original studies on glutamine repeats in proteins connected to neurodegenerative conditions such as Huntington disease. They showed that proteins carrying the repeats form aggregates that lead to neural cell death. In a paper published shortly before his death, Perutz and his coauthor linked the onset of Huntington’s disease to the length of the glutamine repeat.

In his later years Perutz became a regular contributor to the London Review of Books and the New York Review of Books. Scientific biographies fascinated him most. He also wrote autobiographical pieces and personal vignettes of Page 84  |  Top of Articlescientists he knew, and engaged with political and moral issues, including the organization and freedom of science, population politics, food production, nuclear energy, and human rights. Many of these topics he addressed in public speeches. In all his writings he emphasized the passionate and heroic aspects of scientific research as well as the humanizing influence of science in society. His essays were collected in two volumes, Is Science Necessary? (1989) and I Wish I’d Made You Angry Earlier(1998), edited by himself. In 1997 he was awarded the Lewis Thomas Prize of the Rockefeller University, which honors the scientist as poet.

This was the last in a long series of awards and honors. He was elected a fellow of the Royal Society in 1954 and received the Royal Medal of the Royal Society in 1971 and the Copley Medal of the Royal Society in 1979. He was made a Companion of the British Empire in 1963 and a Companion of Honour in 1975, and was appointed to the Order of Merit in 1988. Among others he was a member of the U.S. National Academy of Sciences and a foreign member of the Pontifical Academy of Sciences.

He married Gisela Peiser in 1942 and had a daughter (Vivien) and a son (Robin). He died of cancer.


The memoir of the Royal Society (see below) includes a full bibliography.


The Crystal Structure of Methaemoglobin. PhD diss., University of Cambridge, 1940.

“Recent Developments in the X-Ray Study of Haemoglobin.” In Haemoglobin: A Symposium Based on a Conference Held at Cambridge in June 1948 in Memory of Sir Joseph Barcroft, edited by Francis J. Roughton and John C. Kendrew London: Butterworths Scientific Publications, 1949.

With Michael G. Rossmann, Ann F. Cullis, Hilary Muirhead, et al. “Structure of Haemoglobin: A Three-Dimensional Fourier Synthesis at 5.5 Å. Resolution, Obtained by X-Ray Analysis.” Nature 185 (1960): 416–422.

Proteins and Nucleic Acids: Structure and Function. Amsterdam: Elsevier, 1962.

With Hermann Lehmann. “Molecular Pathology of Human Haemoglobin.” Nature 219 (1968): 402–409.

With Maurice H. F. Wilkins and James D. Watson. “DNA Helix.” Science 164 (1969): 1537–1539.

“Stereochemistry of Cooperative Effects in Haemoglobin.” Nature 228 (1970): 726–739.

Haemoglobin: Mr Max Perutz Interviewed by Mr H. Judson, 13 November 1987. Video interview. Biochemical Society. Available from .

Is Science Necessary? Essays on Science and Scientists. New York: E.P. Dutton, 1989. Includes the autobiographical essay “Enemy Alien.”

Science Is No Quiet Life. Videotape of a lecture on his scientific career held at the Kelvin Club in Peterhouse, Cambridge, 12 November 1996. Available from Peterhouse College.

Science Is Not a Quiet Life: Unravelling the Atomic Mechanism of Haemoglobin. London: Imperial College Press, 1997. A collection of all Perutz’s major scientific papers, with introduction.

I Wish I’d Made You Angry Earlier: Essays on Science, Scientists, and Humanity. Cold Spring Harbor, NY: Cold Spring Harbor Press, 1998. A collection of his major reviews.

“Interview with Max Perutz: Discoverer of the Structure of Haemoglobin.” Vega Science Trust interviews with Max Perutz, 2001. Video excerpts available from .

With Alan H. Windle. “Cause of Neural Death in Neurodegenerative Disease Attributable to Expansion of Glutamine Repeats.” Nature 412 (2001): 143–144.


Blow, David M. “Max Ferdinand Perutz OM CH CBE 19 May 1914–6 February 2002.” Biographical Memoirs of Fellows of the Royal Society 50 (2004): 227–256. Includes a microfiche with a full bibliography of Max Perutz’s publications. A photocopy is available from the Royal Society Library.

Bragg, William Lawrence. “First Stages in the X-Ray Analysis of Proteins.” Reports on Progress in Physics 28 (1965): 1–16.

Ferry, Georgina. Max Perutz and the Secret of Life. London: Chatto & Windus, 2007.

Kendrew, John C., Gerhard Bodo, Howard M. Dintzis, et al. “A Three-Dimensional Model of the Myoglobin Molecule Obtained by X-Ray Analysis.” Nature 181 (1958): 662–666.

———, Richard E. Dickerson, Bror E. Strandberg, et al. “Structure of Myoglobin: A Three-Dimensional Fourier Synthesis at 2 Å. Resolution.” Nature 185 (1960): 422–427.

Olby, Robert. “Perutz, Max Ferdinand (1914–2002).” In Oxford Dictionary of National Biography. Online ed., edited by Lawrence Goldman. Oxford: Oxford University Press, 2006. Available from .

Watson, James D. The Double Helix: A Personal Account of the Discovery of the Structure of DNA. New York: Atheneum, 1968.

———, and Francis H. C. Crick. “Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid.” Nature 171 (1953): 737–738.

Soraya de Chadarevian

Source Citation

Source Citation   

Gale Document Number: GALE|CX2830906001