Max Perutz

For more information on Max Ferdinand Perutz, visit Britannica.com.

Austrian–British biochemist (1914––)

While studying chemistry at the university in his native Vienna, Perutz became interested in x-ray diffraction techniques; after graduation he went to England to work on the x-ray diffraction of proteins with William L. Bragg at the Cavendish Laboratory, Cambridge. A meeting in Prague with the biochemist Felix Haurowitz in 1937 turned his attention to the blood protein hemoglobin and he received his PhD in 1940 for work in this field. Soon after, he was arrested as an alien and interned, first on the Isle of Man and then in Canada with Hermann Bondi and Klaus Fuchs. He was released and allowed to return to Britain in 1941. In the following year he joined the staff of Lord Mountbatten, examining various applications of science for the war effort.

After the war Perutz organized the setting up, in 1946, of the molecular biology laboratory in Cambridge, where he was soon joined by John Kendrew. After seven years' hard work Perutz was still far from his objective of working out the three-dimensional structure of hemoglobin, a molecule containing some 12,000 atoms. Then in 1953 he applied the heavy atom or isomorphous replacement technique to his work whereby heavy metal atoms, e.g., mercury or gold, are incorporated into the molecule under study. This alters the diffraction patterns, making it easier to compute the positions of atoms in the molecule. By 1959 he had shown hemoglobin to be composed of four chains, together making a tetrahedral structure, with four heme groups near the molecule's surface.

For this achievement Perutz received the 1962 Nobel Prize in chemistry, sharing it with Kendrew, who had worked out the structure of the muscle protein, myoglobin, using similar methods. In later work Perutz demonstrated that in oxygenated hemoglobin the four subunits are rearranged. This explained the change in structure noted by Haurowitz in 1938. Perutz also investigated the various mutated forms of hemoglobin characteristic of inherited blood diseases.

While indulging his hobby of mountaineering, Perutz made some notable contributions to the understanding of glaciers, particularly by his demonstration that the rate of flow is faster at the glacier surface than at the base.

Perutz continued as head of the Medical Research Council molecular biology unit at Cambridge until his retirement in 1979. He published a brief account of his early life and his views on science in his Is Science Necessary? (1989).

Max Perutz (born 1914) 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 Cowdery Kendrew.

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. A passionate mountaineer and skier, Perutz also applied his expertise in X-ray crystallography to the study of glacier structure and flow.

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. However, he found the university's adherence to classical organic chemistry outdated and backward. By 1926 scientists had determined that enzymes were proteins and had begun to focus on the catalytic effects of enzymes on the chemistry of cells, but Perutz's professors paid scant attention to this new realm of research. In 1934, while searching for a subject for his dissertation, Perutz attended a lecture on organic compounds, including vitamins, under investigation at Cambridge University in England. Anxious to continue his studies in an environment more attuned to recent advances in biochemical research, Perutz decided he wanted to study at Cambridge. His wish to leave Austria and study elsewhere was relatively unique in that day and age, when graduate students seldom had the financial means to study abroad. But Hugo Perutz's textile business provided his son with the initial funds he would need to survive in England on a meager student stipend.

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. Despite Perutz's disenchantment with his research assignments and the old, ill-lit, and dingy laboratories he worked in, he received excellent training in the promising field of X-ray crystallography, albeit in the classical mode of mineral crystallography. "Within a few weeks of arriving, " Perutz states in Horace Freeland Judson's Eighth Day of Creation: Makers of the Revolution in Biology, "I realized that Cambridge was where I wanted to spend the rest of my life."

During his summer vacation in Vienna in 1937, Perutz met with Felix Haurowitz, a protein specialist married to Perutz's cousin, to seek advice on the future direction of his studies. Haurowitz, who had been studying hemoglobin since the 1920s, convinced Perutz that this was an important protein whose structure needed to be solved because of the integral role it played in physiology. In addition to making blood red, hemoglobin red corpuscles greatly increase the amount of oxygen that blood can transport through the body. Hemoglobin also transports carbon dioxide back to the lungs for disposal.

Although new to the physical chemistry and crystallography of hemoglobin, Perutz returned to Cambridge and soon obtained crystals of horse hemoglobin from Gilbert Adair, a leading authority on hemoglobin. Since the main goal of X-ray crystallography at that time was to determine the structure of any protein, regardless of its relative importance in biological activity, Perutz also began to study crystals of the digestive enzyme chymotrypsin. But chymotrypsin crystals proved to be unsuitable for study by X-ray, and Perutz turned his full attention to hemoglobin, which has large crystal structures uniquely suited to X-ray crystallography. At that time, microscopic protein crystal structures were "grown" primarily through placing the proteins in a solution which was then evaporated or cooled below the saturation point. The crystal structures, in effect, are repetitive groups of cells that fit together to fill each space, with the cells representing characteristic groups of the molecules and atoms of the compound crystallized.

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 X-ray 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 twenty-three 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. "It was a very nice, very sunny day - a nasty day to be arrested, " Perutz recalls in The Eighth Day of Creation. 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 on March 28, 1942; the couple later had a son, Robin, and a daughter, Vivian. After the war, in 1945, Perutz was finally able to devote himself entirely to pondering the smeared spots that appeared on the X-ray film of hemoglobin crystals. He returned to Cambridge, and was soon joined by John Kendrew, then a doctoral student, who began to study myoglobin, an enzyme which stores oxygen in muscles. 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 and, in 1953, finally solved the difficult phase dilemma with a method known as isomorphous replacement. By adding atoms of mercury - which, like any heavy metal, is an excellent X-ray reflector - to each individual protein molecule, Perutz was able to change the light diffraction pattern. By comparing hemoglobin proteins with mercury attached at different places to hemoglobin without mercury, he found that he had reference points to measure phases of other hemoglobin spots. Although this discovery still required long and assiduous 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. Perutz followed two years later with a model of hemoglobin. Continuing to work on the model, Perutz and Hilary Muirhead showed that hemoglobin's reaction with oxygen involves a structural change among four subunits of the hemoglobin molecule. Specifically, the four polypeptide chains that form a tetrahedral structure of hemoglobin are rearranged in oxygenated hemoglobin. In addition to its importance to later research on the molecular mechanisms of respiratory transport by hemoglobin, this discovery led scientists to begin research on the structural changes enzymes may undergo in their interactions with various biological processes. 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.

The work of Perutz and Kendrew was the basis for growing understanding over the following decades of the mechanism of action of enzymes and other proteins. Specifically, Perutz's discovery of hemoglobin's structure led to a better understanding of hemoglobin's vital attribute of absorbing oxygen where it is plentiful and releasing it where it is scarce. Perutz also conducted research on hemoglobin from the blood of people with sickle-cell anemia and found that a change in the molecule's shape initiates the distortion of venous red cells into a sickle shape that reduces the cells' oxygen-carrying capacity.

In The Eighth Day of Creation, Judson remarks that Perutz was known to have a "glass thumb" for the difficult task of growing good crystals, and it was widely acknowledged that for many years Perutz produced the best images of crystal structures. In the book, published in 1979, Perutz's long-time colleague Kendrew remarks that little changed over the years, explaining, "If I had come into the lab thirty years ago, on a Saturday evening, Max would have been in a white coat mounting a crystal - just the same." Although Perutz retired in 1979, he continued to work as a professor for the MRC Lab of Molecular Biology at Cambridge and also served as a patron for the Cambridge University Scientific Society.

Further Reading

Cambridge University Scientific Society, 1997, "http://cygnus.csi.cam.ac.uk/CambUniv/Societies/cuss/patrons/patrons.htm, " July 22, 1997.

Judson, Horace Freeland, The Eighth Day of Creation: Makers of the Revolution in Biology, Simon & Schuster, 1979.

"X-rays Mark the Spots, " in The Economist, November 21, 1992, pp. 100-101.

Max Ferdinand Perutz
Born	May 19, 1914 Vienna, Austria
Died	February 6, 2002 (aged 87) Cambridge, England
Nationality	Austria
Fields	Molecular biology, Crystallography
Institutions	University of Cambridge
Alma mater	Peterhouse, Cambridge
Doctoral advisor	J.D. Bernal
Doctoral students	James D. Watson Francis Crick
Known for	Heme-containing proteins
Notable awards	Nobel Prize for Chemistry (1962)

Max Ferdinand Perutz, OM (May 19, 1914, Vienna, Austria – February 6, 2002, Cambridge, UK) was an Austrian-British molecular biologist, who was awarded the Nobel Prize for Chemistry in 1962, shared with John Kendrew for their studies of the structures of hemoglobin and globular proteins. At Cambridge he supervised the PhD work of Francis Crick and James Watson in the Cavendish Laboratory as they determined the structure of DNA in 1953.

Contents 1 The scientist 1.1 DNA structure and Rosalind Franklin 2 The author 3 The scientist-citizen 4 References 5 Books about Max Perutz 6 Books referring to Perutz 7 External links

The scientist

In 1936, after completing his first university degree at the University of Vienna, Perutz became a research student at the University of Cambridge's Cavendish Laboratory, in a crystallography research group under the direction of J.D. Bernal.

Perutz was affiliated with Peterhouse, Cambridge's oldest college, from his 1936 matriculation until his death. He was elected an Honorary Fellow in 1962, and was seen at least weekly in the College's halls until just before his death. He took a keen interest in the Junior Members, and was a regular and popular speaker at the Kelvin Club, the College's scientific society. Perutz's contributions to molecular biology in Cambridge are documented in The History of the University of Cambridge: Volume 4 (1870 to 1990) published by the Cambridge University Press in 1992.

During World War II, Perutz was part of Project Habakkuk, a secret project investigating the recently invented mixture of ice and woodpulp known as pykrete, in the hope of using it to build an aircraft carrier. He carried out early experiments on pykrete in a secret location underneath Smithfield Meat Market in the City of London.^[1][2][3]

Perutz established the Laboratory of Molecular Biology, Cambridge, England in 1962 and was its chairman until 1979. He remained active in research to the end of his life.

In 1953, Perutz showed that the diffracted X-rays from protein crystals could be phased by comparing the patterns from crystals of the protein with and without heavy atoms attached. In 1959, he employed this method to determine the molecular structure of the protein hemoglobin, which transports oxygen in the blood. This work resulting in his sharing with John Kendrew the 1962 Nobel Prize for Chemistry; on Saturday, October 20, 1962 the award of Nobel prizes to John Kendrew and Max Perutz, and to Crick, Watson, and Wilkins was satirised in a short sketch in the BBC TV programme That Was The Week That Was with the Nobel Prizes being referred to as 'The Alfred Nobel Peace Pools'.

Robin Perutz, the son of Max and Gisela Perutz, is a professor of chemistry at the University of York in England. Their daughter Vivien has edited a selection of Max's letters for publication by the Cold Spring Harbor Laboratory Press.

DNA structure and Rosalind Franklin

During the early 1950s, Perutz supervised James D. Watson and Francis Crick while they were determining the structure of deoxyribonucleic acid (DNA). Watson and Crick made use of unpublished X-ray diffraction images taken by Rosalind Franklin, shown at meetings and shared with them by Maurice Wilkins, and of Franklin's preliminary account of her detailed analysis of the X-ray images included in an unpublished 1952 progress report for the King's College laboratory of Sir John Randall. Randall and others eventually criticized the manner in which Perutz gave a copy of this report to Watson and Crick.

It is debatable whether Watson and Crick should have been granted access to Franklin's results without her knowledge or permission, and before she had a chance to publish a detailed analysis of the content of her unpublished progress report. It is also not clear how important the content of that report had been for Watson and Crick's modeling. In an effort to clarify this issue, Perutz later published the report, arguing that it included nothing that Franklin had not said in a talk she gave in late 1951 and that Watson attended. Perutz also added that the report was addressed to an MRC committee created in order to "establish contact between the different groups of people working for the Council". Randall's and Perutz's labs were both funded by the MRC.

The author

In his later years, Perutz was a regular reviewer/essayist for The New York Review of Books on biomedical subjects. Many of these essays are reprinted in his 1998 book I wish I had made you angry earlier.^[4] Perutz's flair for writing was a late development. His relative Leo Perutz, a distinguished writer, told Max when he was a boy that he would never be a writer. Thus Max highly cherished his having been awarded the Lewis Thomas Prize for Writing about Science in 1997.

The scientist-citizen

Within days of the September 11 attacks in 2001, Perutz 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."^[5]

References

1. ^ Gratzer, Walter (2002-03-05). "Max Perutz (1914–2002)". Current Biology 12 (5): R152–R154. doi:10.1016/S0960-9822(02)00727-3. http://download.current-biology.com/pdfs/0960-9822/PIIS0960982202007273.pdf. Retrieved 2008-01-12. 
2. ^ Ramaseshan, S (2002-03-10). "Max Perutz (1914–2002)". Current Science (Indian Academy of Sciences) 82: 586–590. doi:10.1016/S0960-9822(02)00727-3. http://hdl.handle.net/2289/728. Retrieved 2008-01-12. 
3. ^ Collins, Paul (2002). "The Floating Island". Cabinet Magazine 12 (7): R152. doi:10.1016/S0960-9822(02)00727-3. http://www.cabinetmagazine.org/issues/7/floatingisland.php. Retrieved 2008-01-12. 
4. ^ Max Ferdinand Perutz OM FRS - Nature Structural & Molecular Biology
5. ^ Max Perutz and the Secret of Life, By Georgina Ferry. 352 pp., illustrated. Cold Spring Harbor, NY, Cold Spring Harbor Laboratory Press, 2008 ISBN 978-0-87969-785-3. p283 in UK version

Books about Max Perutz

• Paterlini, Marta, 2006. Piccole Visioni: La Grande Storia di una Molecola. Codice Edizioni. ISBN 88-7578-052-8
• Ferry, Georgina, 2007. Max Perutz and the Secret of Life. Published in the UK by Chatto & Windus (ISBN 0-701-17695-4), and in the USA by the Cold Spring Harbor Laboratory Press.
• Jean Medawar and Pyke, David, 2000. Hitler's Gift - Scientists Who Fled Nazi Germany - Einstein, Max Perutz, Fritz Haber, Leo Szilard, Max von Laue, Max Planck & more. London: RCB. ISBN 1-860-66172-6

Books referring to Perutz

• Brown, Andrew, 2005. J. D. Bernal: The Sage of Science. Oxford University Press. ISBN 0-199-20565-5
• De Chadarevian, Soraya, 2002. Designs For Life: Molecular Biology After World War II. Cambridge Univ. Press. ISBN 0-521-57078-6
• Dickerson, Richard E., 2005. Present at the Flood: How Structural Molecular Biology Came About. Sinauer. ISBN 0-878-93168-6;
• John Finch; 'A Nobel Fellow On Every Floor', Medical Research Council 2008, 381 pp, ISBN 978-1840469-40-0; this book is all about the MRC Laboratory of Molecular Biology, Cambridge.
• Hager, Thomas, 1995. Force of Nature: The Life of Linus Pauling. Simon & Schuster. ISBN 0-684-80909-5
• Hunter, Graeme, 2004. Light Is A Messenger, the life and science of William Lawrence Bragg. Oxford Univ. Press. ISBN 0-19-852921-X.
• Krude, Torsten, ed., 2003. DNA Changing Science and Society. Cambridge Univ. Press. ISBN 0-521-82378-1). Being the Darwin Lectures for 2003, including one by Sir Aaron Klug on Rosalind Franklin's role in determining the structure of DNA.
• Brenda Maddox, 2003. Rosalind Franklin: The Dark Lady of DNA. ISBN 0-00-655211-0.
• Olby, Robert; 'Perutz, Max Ferdinand (1914-2002), Oxford Dictionary of National Biography, online edn, Oxford University Press, Jan 2008
• Matt Ridley, Francis Crick: Discoverer of the Genetic Code (Eminent Lives). HarperCollins Publishers. ISBN 0-06-082333-X.
• Sayre, Anne, 1975. Rosalind Franklin and DNA. New York: W.W. Norton and Company. ISBN 0-393-32044-8.
• James D. Watson, 1980 (1968). The Double Helix: A Personal Account of the Discovery of the Structure of DNA. Atheneum. ISBN 0-689-70602-2. Gunther S. Stent edited the 1980 Norton Critical Edition (ISBN 0-393-01245-X).
• Maurice Wilkins, 2003. The Third Man of the Double Helix: The Autobiography of Maurice Wilkins. ISBN 0-19-860665-6.

External links

Wikiquote has a collection of quotations related to: Max Perutz

• Fersht, Alan R., 2002, "Max Ferdinand Perutz OM FRS," Nature Structural Biology 9: 245-46.
• By his colleagues at the MRC Laboratory of Molecular Biology.
  • PhysicsWeb.
• Nobel website biography.
• Online video interview with Max Perutz, provided by the Vega Science Trust. (~40 mins.)
• Key Participants: Max Perutz - Linus Pauling and the Race for DNA: A Documentary History

v • d • e Nobel Laureates in Chemistry Edwin McMillan / Glenn T. Seaborg (1951) · Archer Martin / Richard Synge (1952) · Hermann Staudinger (1953) · Linus Pauling (1954) · Vincent du Vigneaud (1955) · Cyril Hinshelwood / Nikolay Semyonov (1956) · Alexander Todd (1957) · Frederick Sanger (1958) · Jaroslav Heyrovský (1959) · Willard Libby (1960) · Melvin Calvin (1961) · Max Perutz / John Kendrew (1962) · Karl Ziegler / Giulio Natta (1963) · Dorothy Hodgkin (1964) · Robert Woodward (1965) · Robert S. Mulliken (1966) · Manfred Eigen / Ronald Norrish / George Porter (1967) · Lars Onsager (1968) · Derek Barton / Odd Hassel (1969) · Luis Federico Leloir (1970) · Gerhard Herzberg (1971) · Christian B. Anfinsen / Stanford Moore / William Stein (1972) · E.O.Fischer / Geoffrey Wilkinson (1973) · Paul Flory (1974) · John Cornforth / Vladimir Prelog (1975) Complete roster · 1901–1925 · 1926–1950 · 1951–1975 · 1976–2000 · 2001–present

Persondata
NAME	Perutz, Max Ferdinand
ALTERNATIVE NAMES
SHORT DESCRIPTION	Molecular biology, Crystallography
DATE OF BIRTH	May 19, 1914
PLACE OF BIRTH	Vienna, Austria
DATE OF DEATH	2002-2-6
PLACE OF DEATH	Cambridge, England

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