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Max Perutz was one of a handful of pioneers who began something that has become so familiar to us: Molecular Biology.

Born in Vienna, he came to Cambridge in 1936 to join the lab of the legendary Communist thinker J.D. Bernal. There he began to explore the structure of proteins. In 1940, he was interned and deported to Canada as an enemy alien, only to be brought back and set to work on a bizarre top-secret war project. In 1947, he founded the small research group at the LMB in Cambridge in which Francis Crick and James Watson discovered the structure of DNA. His own twenty-two year quest to reveal the structure of hemoglobin was rewarded with a Nobel Prize in 1962 and launched a new era of medicine.

Beyond intellectual brilliance, Max Perutz stands out as an ambassador for science and human rights and as an inspiration for young scientists.


Max aged about two,
with his Bavarian nanny Cilly Jetzfellner

Childhood

Max Ferdinand Perutz was born in Vienna on May 19th, 1914. Both his parents, Hugo Perutz and Dely Goldschmidt, came from families of textile manufacturers who had made their fortune in the 19th century by the introduction of mechanical spinning and weaving into the Austrian monarchy.


Pupil at the Theresianum, aged fifteen

Teenage Years

Max Perutz was first educated at the Theresianum, a grammar school derived from an officers’ academy from the days of the Empress Maria Theresia.

Many years later he said:“I owe my first step to popularity to scarlet fever which I caught when I was fourteen. To disinfect the classroom, my schoolmates got three days off, for which they thanked me solemnly in a letter signed by the entire class”.


Relaxing with friends Fritz Eirich and Pussy Gatzenburg in a mountain hut, 1931

Friends

At sixteen, Max won the cup for his school in the skiing competition of the Vienna High Schools, and as a result of that victory his standing at school was transformed.

“For the first time in my life I was treated with a certain degree of respect. From then on our gym teacher always gave me top marks, but they happened to be the only ones in my otherwise mediocre school reports”.


Students in the organic chemistry laboratory of the University of Vienna, 1935.

University

Max was supposed to study law in preparation for entering the family business. A good schoolmaster at the Theresianum kindled his interest in chemistry, and he made this the subject of his studies at university (can you spot him in the picture?).

Although largely disappointed with the way in which the subject was taught, he acquired a special interest in organic biochemistry and heard about the work of the Nobel Prizewinner (and discoverer of vitamins) Sir Gowland Hopkins at Cambridge.

His teacher, Herman Mark, visited Cambridge and had planned to pave the way for Perutz to join Hopkins’ group. But Mark met J. D. Bernal, who said that he would take Perutz as his student.


One of Max’s many stunning mountain photographs,
taken on a trip in the swiss alps, 1938

Mountains

Mountains played an important part in Max Perutz’s life. He had a great passion for mountaineering and skiing. Barely a year passed without a visit to Austria or Switzerland. He also lead courses in alpine skiing for his friends.


Max Perutz with a polarizing microscope examining thin sections
of glacier ice in a cave in the Alps, 1938

Ice Crystals

From his early twenties Perutz had a deep interest in glaciers. How do glaciers flow? Does this occur like honey flowing out of a tilted container, or is there some other mechanism? More or less as a hobby, Perutz, examined this problem and proposed that they behave like a ductile metal (such as aluminum when it is rolled into a sheet), a story to be published in Nature in 1953. In honor of his contributions to glaciology, a glacier in the Antarctic was named after him (Perutz Glacier (67°36′S 66°33′W) on the west coast of Graham Land).


Max Perutz with his three-year-old daughter Vivien
during the 1948 Jungfraujoch expedition.

Passion


Patterson Map of Hemoglobin

Maps

In 1946 Max Perutz was joined in Cambridge by John Kendrew, who set out to work on myoglobin, the much smaller one-chain cousin of hemoglobin. Both spent several years collecting huge amounts of data and using the intensities of the reflections to calculate contour maps (Patterson maps), hoping that these would allow them to determine the hemoglobin structure.

The approach failed. Provoked and inspired by a graduate student (Francis Crick), Perutz decided to attack the so-called phase problem from a different angle.


Return visit to the Swiss alps, 1951

Laboratory


Diffraction photograph of oxyhemoglobin and the famous hemoglobin model.

Protein Crystals

The breakthrough came in 1953, when Perutz and Kendrew managed to soak a heavy atom (mercury) into the hemoglobin molecule. From the difference produced in the diffraction pattern Perutz was able to deduce the phase of the reflections. To this day, the isomorphous replacement method is considered the key method to determine the crystal structure of proteins.


Perutz with his first high-resolution model of hemoglobin

Details

Max Perutz completed the low-resolution 5.5 Å map of hemoglobin in 1959 and a high-resolution 2.8 Å map in 1968. For being the first to successfully identify the structures of complex proteins, Perutz and Kendrew were rewarded with the Nobel Prize for Chemistry in 1962.


Cartoon drawn by Max Perutz’s colleague Kyoshi Nagai, illustrating the shift between tense (T) and relaxed (R) states of hemoglobin.

Mechanism

For Max Perutz the challenge continued. To understand the oxygen-binding function of hemoglobin, he needed an atomic model of both the oxygenated and deoxygenated forms of hemoglobin. This required measuring several hundred thousand reflections.

Perutz and his collaborators completed it in 1970, about thirty-three years after he had taken the first x-ray picture of the molecule. He proposed a cooperative mechanism with the different parts of the model swinging back and forth between the two forms. It beautifully illustrated, and refined, the mechanism of conformational change (or allostery) postulated by the French biochemist Jacques Monod.


After he retired as Chairman, Max Perutz kept an office at the LMB in Cambridge, the wall hung with portraits of his scientific heroes.

Reflections

Approaching his eightieth birthday, Max Perutz took an interest in Huntington disease, a neurodegenerative disorder caused by abnormal expansions of glutamine repeats in the mutant protein (later called huntingtin).

He proposed that proteins with long runs of glutamine residues would form aggregates harmful to the cell. Max Perutz led by example and carried out his own experiments at the bench well into his eighties.

When asked in a BBC radio interview what luxury he would take on a remote island, 87-year old Max Perutz answered:


Georgina Ferry has written a superb biography: “Max Perutz and the Secret of Life”.
“I wish I ‘d made you angry earlier” contains a great selection of his essays on science, scientists and humanity.

Interested to learn more about Max Perutz?

I am indebted to Georgina Ferry (Oxford) for valuable advice on Max Perutz and permission to use excerpts from her biography. Many thanks to Vivien Perutz (Cambridge) for allowing us to reprint pictures that are owned by the Perutz family. Kyoshi Nagai (Cambridge) has kindly contributed the cartoon.

Alwin Köhler

Acknowledgements