Max Perutz

Max Perutz
Born	Max Ferdinand Perutz 19 May 1914
Birthplace	Vienna, Austria-Hungary
Died	6 February 2002 Cambridge, England
Nationality	British (Austrian-born)
Occupation	Molecular biologist, crystallographer
Known for	Determining the three-dimensional structure of haemoglobin
Education	PhD, University of Cambridge
Spouse(s)	Gisela Clara Peiser (m. 1942)
Children	2
Awards	Nobel Prize in Chemistry (1962), Royal Medal (1971), Copley Medal (1979)

Max Ferdinand Perutz (19 May 1914 – 6 February 2002) was an Austrian-born British molecular biologist who devoted more than two decades to unravelling the three-dimensional structure of haemoglobin, the protein in red blood cells responsible for transporting oxygen throughout the body. For this achievement he shared the 1962 Nobel Prize in Chemistry with John Kendrew, who had determined the structure of the related protein myoglobin. Perutz's work demonstrated that X-ray crystallography could be applied to large, biologically significant molecules — an insight that transformed the study of life at the molecular level and laid the groundwork for the modern discipline of structural biology. Born in Vienna and educated in part at the University of Vienna, Perutz emigrated to England in 1936 to pursue research at the University of Cambridge, where he would spend the remainder of his career. He founded and served as chairman of the Medical Research Council (MRC) Laboratory of Molecular Biology in Cambridge, an institution that became one of the most productive research laboratories in the world, with fourteen of its scientists eventually receiving Nobel Prizes. In addition to the Nobel Prize, Perutz received numerous honours over the course of his career, including the Royal Medal of the Royal Society in 1971 and the Copley Medal in 1979. He was also recognised as a gifted science writer whose essays made complex biological topics accessible to general audiences.

Early Life

Max Ferdinand Perutz was born on 19 May 1914 in Vienna, then the capital of Austria-Hungary, into a prosperous Jewish textile manufacturing family. His parents were Hugo Perutz and Adele Goldschmidt, and the family had roots in the Austro-Hungarian business community. Growing up in Vienna during the interwar period, Perutz was exposed to the city's rich intellectual and cultural traditions. He developed an early interest in chemistry, partly influenced by his secondary school education, which provided a strong grounding in the natural sciences.

Perutz's family had originally hoped he would follow them into the textile business, but his fascination with science drew him toward an academic career. He began his university studies at the University of Vienna, where he studied chemistry. During this period, he became increasingly interested in the emerging field of X-ray crystallography — the technique of using X-ray diffraction patterns to determine the arrangement of atoms within crystals — which was beginning to be applied to problems in chemistry and biology.

The rise of Nazism in the 1930s had a profound effect on Perutz's life. Although his family had converted from Judaism, the political situation in Austria became increasingly dangerous for people of Jewish descent. In 1936, Perutz left Austria to pursue graduate studies at the University of Cambridge in England, a move that would prove permanent. After the annexation of Austria by Nazi Germany in 1938 (the Anschluss), his parents lost most of their assets and eventually fled to Switzerland. Perutz's status as a refugee shaped his early years in Britain and gave urgency to his efforts to establish himself in the scientific community.

Education

Perutz began his undergraduate education at the University of Vienna, where he studied chemistry in the early 1930s. In 1936, he moved to the University of Cambridge in England to undertake graduate research at the Cavendish Laboratory. He worked under the supervision of J. D. Bernal (John Desmond Bernal), a pioneering X-ray crystallographer who was among the first scientists to apply X-ray diffraction techniques to biological molecules. Bernal's influence was formative; it was in his laboratory that Perutz first encountered the idea of using X-ray methods to study the structures of proteins, a pursuit that would define his career.

Perutz completed his PhD at the University of Cambridge. His doctoral thesis focused on the X-ray crystallography of haemoglobin, a topic that he would continue to investigate for the next several decades. The choice of haemoglobin as a research subject was partly inspired by a suggestion from the Czech biochemist Felix Haurowitz, a family friend. Haemoglobin was already known to undergo a structural change when it bound oxygen, making it a compelling target for crystallographic study.

Career

Early Research and Wartime Interruption

Perutz began his X-ray crystallographic studies of haemoglobin at the Cavendish Laboratory in Cambridge in the late 1930s. He obtained crystals of horse haemoglobin and began collecting X-ray diffraction data, but the technical challenges were immense. Haemoglobin is a large protein containing thousands of atoms, and the methods available at the time had only been used successfully to solve the structures of much smaller molecules.

The outbreak of the Second World War disrupted Perutz's research. In 1940, as an Austrian national living in Britain, Perutz was classified as an "enemy alien" by the British government and was interned. He was transported to Canada along with other internees, spending several months in an internment camp before being released and allowed to return to Cambridge. During the war, Perutz was briefly involved in a secret military project codenamed Project Habakkuk, which explored the feasibility of constructing aircraft carriers from a frozen mixture of water and wood pulp known as pykrete. While this project was ultimately abandoned, Perutz's expertise in ice crystallography contributed to its early stages.

After the war, Perutz returned full-time to his haemoglobin research. In 1947, with the support of the Medical Research Council, he established a small research unit at the Cavendish Laboratory dedicated to the study of the molecular structure of biological systems. This unit, initially consisting of Perutz and John Kendrew, would grow over the following years and eventually evolve into one of the most influential scientific institutions of the twentieth century.

The Phase Problem and the Isomorphous Replacement Method

The central technical challenge facing Perutz was known as the "phase problem." X-ray diffraction patterns record the intensity of scattered X-rays but lose information about their phase — the timing relationship between different scattered waves. Without phase information, it is impossible to reconstruct the three-dimensional electron density map of a crystal. For small molecules, various mathematical techniques could solve this problem, but these methods did not scale to macromolecules like proteins.

Perutz's breakthrough came in 1953 when he demonstrated that the method of isomorphous replacement could be applied to protein crystals. The technique involved introducing heavy atoms (such as mercury) into specific sites within the protein crystal without otherwise altering its structure. By comparing the diffraction patterns of the native crystal and the heavy-atom derivative, it became possible to determine the phases and thus to calculate the electron density map.

This methodological advance was of enormous significance. It proved that the three-dimensional structures of proteins — molecules containing tens of thousands of atoms — could, in principle, be determined by X-ray crystallography. John Kendrew applied the same approach to myoglobin, a smaller and simpler relative of haemoglobin, and produced the first three-dimensional structure of a protein in 1958. Perutz followed with the structure of haemoglobin at low resolution in 1960, later refining it to higher resolution. These achievements opened an entirely new era in the understanding of biological molecules at the atomic level.

The Structure of Haemoglobin

Haemoglobin is a tetrameric protein, composed of four polypeptide chains (two alpha chains and two beta chains), each carrying a haem group that can bind one molecule of oxygen. Perutz's structural studies revealed how these four subunits are arranged in three-dimensional space and how the protein undergoes conformational changes upon binding and releasing oxygen — a phenomenon known as cooperativity. The haemoglobin molecule shifts between two distinct structural states, the "tense" (T) state (with lower oxygen affinity) and the "relaxed" (R) state (with higher oxygen affinity), a mechanism that allows for efficient oxygen transport in the blood.

Perutz spent decades refining and extending his understanding of haemoglobin's structure-function relationship. He proposed a stereochemical mechanism for cooperativity, explaining how the binding of oxygen at one haem group transmits structural changes to distant subunits, thereby increasing their affinity for oxygen. This model had direct implications for understanding haemoglobin disorders such as sickle cell disease, in which a single amino acid mutation in the beta chain causes the protein to polymerize under low-oxygen conditions.

The structural determination of haemoglobin represented not only a technical triumph but also a conceptual one: it demonstrated that the function of a protein is intimately connected to its three-dimensional structure and that understanding disease at the molecular level requires knowledge of protein architecture.

Founding the MRC Laboratory of Molecular Biology

In 1962, the Medical Research Council's small unit that Perutz had led since 1947 was formally reconstituted as the MRC Laboratory of Molecular Biology (LMB), housed in a new building on the outskirts of Cambridge. Perutz served as the first chairman of the LMB from 1962 to 1979, during which time the laboratory became a world-leading centre for research in molecular biology and structural biology.

Under Perutz's leadership, the LMB fostered an unusually collaborative and informal research culture. Scientists from diverse disciplines — physics, chemistry, biology, and medicine — worked in close proximity and shared ideas freely. This environment proved extraordinarily productive. Among the scientists who worked at the LMB or its predecessor unit, fourteen went on to receive Nobel Prizes. These included Francis Crick and James Watson for their discovery of the double-helix structure of DNA, Frederick Sanger for his work on protein and nucleic acid sequencing, Aaron Klug for his contributions to electron microscopy, and Sydney Brenner for his studies of the genetics of the nematode Caenorhabditis elegans.

Perutz was credited with creating an administrative style that minimised bureaucracy and maximised scientific freedom. He believed that the best research was driven by curiosity rather than by directives, and he resisted efforts to impose top-down management on the laboratory. This philosophy attracted talented scientists from around the world and contributed to the LMB's sustained record of discovery.

Later Career and Scientific Writing

After stepping down as chairman of the LMB in 1979, Perutz continued his research on haemoglobin and protein structure. He remained scientifically active into his later years, publishing papers and refining his understanding of how haemoglobin's structure relates to its biological function. He also extended his interests to the study of other protein-related diseases, exploring the structural basis of conditions such as Huntington's disease and other disorders caused by expanded polyglutamine repeats.

Perutz was also recognised as an accomplished science writer. He published several books and numerous essays aimed at making the principles of molecular biology accessible to general readers. His book Protein Structure: New Approaches to Disease and Therapy (1992) synthesised decades of research on the relationship between protein structure and human disease. His collection of essays, Is Science Necessary? and other writings demonstrated a literary sensibility unusual among scientists of his generation. He contributed book reviews and essays to publications such as The New York Review of Books and The London Review of Books, covering topics ranging from the history of science to the social responsibility of scientists.

Personal Life

Perutz married Gisela Clara Peiser in 1942. Gisela was a medical photographer whom he met in Cambridge. The couple had two children: a daughter, Vivien, and a son, Robin. The Perutz family settled in Cambridge, where Max remained based for the entirety of his professional life.

Despite his background as a refugee from Nazi-occupied Austria, Perutz rarely spoke publicly about the personal hardships of his wartime experiences, preferring to focus his public statements on scientific matters. He maintained a reputation for personal warmth, modesty, and a strong sense of fairness. Colleagues recalled his deep commitment to fostering the careers of younger scientists and his belief in the value of basic research pursued for its own sake.

Perutz held British citizenship for most of his adult life, having become a naturalised British subject after his arrival in England as a young refugee. He was a member of the European Molecular Biology Organization (EMBO).

Max Perutz died on 6 February 2002 in Cambridge, England, at the age of 87.

Recognition

Perutz received numerous awards and honours throughout his career. The most prominent was the 1962 Nobel Prize in Chemistry, which he shared with John Kendrew for their studies of the structures of globular proteins — haemoglobin in Perutz's case, myoglobin in Kendrew's. The Nobel committee recognised that their work had demonstrated the feasibility of determining protein structures by X-ray crystallography, opening a new field of scientific investigation.

In addition to the Nobel Prize, Perutz was awarded the Royal Medal of the Royal Society in 1971 and the Copley Medal, the Royal Society's highest honour, in 1979. He was elected a Fellow of the Royal Society (FRS) and received honorary degrees from several universities. He was appointed a Companion of Honour (CH) by Queen Elizabeth II in 1975 and later received the Order of Merit (OM) in 1988, one of the highest personal honours in the British system, limited to 24 living members at any time.

The MRC Laboratory of Molecular Biology continues to honour Perutz's legacy through the annual Max Perutz Lecture, at which a distinguished scientist presents their research. The 2026 lecture was given by Dirk Görlich on the topic of "Transport through nuclear pores." Buildings have also been named in Perutz's honour at various institutions, including the Max Perutz Building at Liverpool John Moores University.

Legacy

Max Perutz's determination of the three-dimensional structure of haemoglobin stands as one of the foundational achievements of molecular biology. By demonstrating that X-ray crystallography could be applied to large, complex proteins, Perutz and John Kendrew established the field of structural biology, which has since yielded the structures of tens of thousands of proteins and nucleic acids and has become central to modern drug design and biomedical research.

The methodological innovation of isomorphous replacement, which Perutz developed to solve the phase problem for protein crystals, remained the principal technique for determining new protein structures for several decades after its introduction. Although newer methods — including anomalous scattering and cryo-electron microscopy — have since expanded the structural biologist's toolkit, the conceptual framework established by Perutz's work continues to underpin the field.

As the founding chairman of the MRC Laboratory of Molecular Biology, Perutz shaped an institutional culture that proved remarkably productive. The LMB's record of scientific achievement — including multiple Nobel Prizes and fundamental contributions to understanding the molecular basis of life — is frequently attributed in part to the collaborative, curiosity-driven research environment that Perutz cultivated. His belief that great science emerges from freedom, small-scale organization, and the interaction of researchers from different disciplines has influenced the design and management of research institutions worldwide.

Perutz's biography, Max Perutz and the Secret of Life by Georgina Ferry, published in 2007, brought wider public attention to his life and contributions. His own scientific essays and books remain valued for their clarity and literary quality, and his legacy as both a researcher and a communicator of science continues to be celebrated in the scientific community.

A biographical memoir written by colleagues noted that Perutz combined extraordinary scientific persistence with a humane vision of science's role in society. His career, spanning more than six decades, encompassed not only landmark discoveries but also a sustained commitment to the values of intellectual freedom, mentorship, and the public understanding of science.