Peter Pauling: Cambridge Struggles, 1954-1956

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Julia and Peter Pauling, 1956.

[The life of Peter Pauling, Part 6 of 9]

The year 1954 was a tumultuous one for Peter Pauling. For one, Jim Watson had left for Caltech, and Peter lamented that his absence was felt, as he was “a positive force, albeit a bit conceited” when it came to social dynamics in the lab. At the same time, Peter’s sister Linda was preparing to move to Cambridge, where her father hoped that Peter might help her to find lab work assisting with crystal structure determinations. (Linda was quite interested in mathematics.) His sister’s imminent arrival excited in Peter visions of European exploration, and especially of skiing.

But while Peter dreamed, serious matters were afoot at the Cavendish Laboratory. Its director, Sir Lawrence Bragg, was planning to resign his Cambridge professorship to take a position as head of the Royal Institution in London. Meanwhile, the lab’s incoming director of physics, Nevill Mott, was widely known to be of the opinion that the unit’s increasing focus on biology needed to be redirected. John Kendrew was worried that the MRC unit that he and Max Perutz headed might be kicked out of the lab, or even the department, entirely.

This uncertainty both distracted Kendrew from Peter’s lack of progress on his myoglobin work, and, in retrospect, made Peter’s lack of enthusiasm for his topic all the more glaring. Indeed, while John Kendrew was worried about the future of their research, Peter was writing to his father that he was unconcerned about Mott’s approval. Rather, as was so often the case, Peter’s main preoccupation was his vehicle, this time a 1930 Mercedes Benz open touring car, described as “18 feet long and mostly engine,” that Peter was now cruising in for special occasions like the May Ball at Peterhouse. Peter’s older brother, Linus Jr., had forwarded him money to purchase the car, hoping that it would be affordable to rebuild the engine. When the cost of doing so turned out to double his investment in the vehicle, Linus Jr. thought it more expedient to simply let his younger brother have the car.

Linus Jr. and Peter formed a strong relationship during Peter’s years at Cambridge, a time period where Linus Jr. and his wife Anita made a habit of travelling around Europe during the summers. This closeness marked something of a renewal of the brothers’ relationship since they had seen little of one another during their more formative years, and as children had little in common. Now, cars in particular emerged as an area in which the two could share their exuberance. Linus Jr. reflected later that, on those trips abroad, he and his wife enjoyed Peter tagging along – his vitality, beaming smile, and friendly nature made him the life of any party.

But this was clearly only one side of Peter Pauling. Privately, he admitted to his mother that he often felt unsure of his path in life, and that he felt unable to meet the challenges of his PhD program. He often wondered whether or not he would be better off simply teaching chemistry, or helping to write his father’s textbooks. These bouts with gloom were contrasted by sudden and excited turns to sociability. Linus Jr. would later point out that their paternal grandmother – Linus Pauling’s mother, Belle – was possibly manic depressive, and was reported to have died in a mental hospital. This, he believed, was likely where Peter had inherited his own emotional instability, and it was during his stint in Cambridge that manic depressive symptoms started to manifest most clearly.


 

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The Paulings in Stockholm, December 1954. Credit: Svenskt Pressfoto.

Linus Pauling’s frustration with Peter’s hoax “Francis Crick letter” had faded by the time that the entire family met in Stockholm for the 1954 Nobel Prize ceremonies. It was there that Pauling was to receive his highest honor to date, the Nobel Prize for Chemistry, commemorating his work on the nature of the chemical bond. After a frustrating battle to receive government permission to leave the country – by then, Linus’ political activities were causing him problems with the Passport Office – the Pauling family flew to Copenhagen where they met Peter and Linda. By then, Linda had taken up residence in the basement room that her brother had just left at the “Golden Helix,” as the Crick home on Portugal Place was now known. Once arrived, she worked for a time as Francis and Odile Crick’s au pair.

Watson returned to the Cavendish in 1955 to find the MRC unit on the verge of being squeezed out by Nevill Mott. Finally registering this threat, Peter began to panic, writing to implore his father that he vocalize his positive impressions of the unit’s work and that he recommend that the group be allowed to continue their research there. At the same time, Peter applied for a post-doctoral fellowship grant from the National Science Foundation, hoping to solidify the standing of both himself and the group by bringing additional research money into the lab.

As it turned out, Peter’s maneuver worked: he received the grant, and this was no doubt a boon to his position at a crucial time. It did little to help him in his research, however. He continued to struggle with myoglobin and, increasingly, he placed his fading hopes squarely upon the idea that mercuric tetraiodide ion crystals might be a better candidate for the sorts of analysis that Kendrew and Perutz were beginning to doubt he could complete.


As the final year of Peter’s program dawned in fall 1955, the frequency of his drives about the grounds to impress the girls dropped to what Jim Watson considered a startlingly low level. Perhaps realizing the “do or die” position that he was in with respect to his research, Peter seemed to be redoubling his focus on finishing his degree.

During this same period, Peter had begun seeing a young woman by the name of Julia, who was a student at a nearby all-women’s school. Jim Watson, curious about the situation, queried several girls that he knew from the school, but most were silent, and Julia herself became conspicuously absent as the New Year drew closer.

Meanwhile, Peter’s father had been working to prepare his son for life after Cambridge, offering him an appointment in the Caltech Division of Chemistry and Chemical Engineering as a Research Fellow focusing on the crystalline structure of globular proteins, to be determined through the use of x-ray diffraction. Pauling wrote to his son

We have a real need here for someone who has had the sort of experience in taking x-ray photographs of crystals that you have obtained. I think our effort to determine the complete structure of a crystalline globular protein is going to be successful, and that you might like to be associated with the successful effort.

Peter did not respond immediately, taking about a week to think about the proposal. It may well be that he was simply overwhelmed by both the work to be done and the festivities to be had during his final months at Cambridge. Plus, it seemed that the job his father had offered likely would be waiting for him as soon as he had finished his program in England.


Few had seen much of Peter in the run-up to Jim Watson and Linda Pauling’s practical joke of a dinner party. In response to a rumor that Watson and Linda were seeing one another, the two decided in good fun to host a get-together, thus driving speculation into a frenzy by implying an impending announcement that, in fact, was never to come. Peter was invited and did show up, but much to the surprise of the hosts, he was not his usual grinning, charming self. Instead, he seemed sentimental and full of a solemn interest in the future of his friends at Cambridge. Watson and Linda later realized that, on this particular evening, Peter was wrestling with a weighty issue: he was soon to become a father.


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The Pauling family on Christmas Day, 1956. Peter and Julia sit at right.

A letter sent by Peter’s parents in early 1956 concluded with an expression of excitement: Linus and Ava Helen would be visiting soon and would look on with pride as they witnessed their son receiving his Cambridge Ph.D. In his response, Peter explained that this day, sadly, would never come. Though he felt that she was a “clever, delicate, and lovely girl,” Peter had not made Julia an “honest woman,” and for this he would be sent down from Cambridge and not be allowed to take a degree. Accordingly, this also meant that he would not qualify for the position that his father had offered him at Caltech.

When he learned of his situation, John Kendrew suggested that Peter might be able to transfer both the remainder of his fellowship with the National Science Foundation, and also the completion of his doctoral research, to the Royal Institution in London, where Sir Lawrence Bragg – his old program director at the Cavendish – was now director of the Davy-Faraday research lab. By then, however, Peter had decided to marry the mother of his child, and arrangements were quickly made by Linda Pauling for a quiet civil wedding that was out of the spotlight and not attended by Linus or Ava Helen.

Peter and Julia were married on March 13, 1956 at the Cambridge Register Office on Castle Hill. Peter’s bride was given away by her father, and with no family members other than Linda present, Peter’s sister acted as the sole adjudicator of the Pauling family’s approval of the union. Peter’s Cambridge advisor, John Kendrew, stood with him as his best man. Following the wedding, a reception was held at Kendrew’s home at Tennis Court Road, after which Peter put on his trademark grin and, with Julia, vanished in a new Porsche. Before the year was out, Linda Pauling, struggling financially and burdened by an expired work visa, returned to Pasadena.

Between 1957 and 1959, Kendrew and Perutz successfully modelled the molecular structure of myoglobin that Peter had been working on. In this, the Cavendish once more beat Caltech to the punch, as the position that Linus had offered to Peter was meant to contribute to a similar problem. Myoglobin was the first ever protein to have its atomic structure determined, and Kendrew and Perutz shared the Nobel Prize in chemistry for this achievement in 1962.

Peter Pauling at Cambridge, 1953-1954

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Peter Pauling, 1954.

[The life of Peter Pauling, part 5 of 9]

In the first months of 1953, with his office mates scrambling to determine the molecular structure of DNA before his own father could beat them to it, Peter Pauling was mostly concerned with the English weather. He had been at Cambridge University since the fall of 1952 when he began his PhD program in physics at the university’s Cavendish Laboratory, and in that time he judged that he had seen a mere two full days of sun and was now officially fed up.

His father, by contrast, was mostly concerned with finishing his most recent edition of The Nature of the Chemical Bond, for which he had often solicited Peter as a source to provide example problems and solutions prior to his departure for England. As he was now beginning his graduate research, however, Peter was too busy to provide much assistance for this edition.

Instead, he was mostly occupying himself with a muscle camera developed by Hugh E. Huxley, a molecular biologist studying the physiology of muscle with Max Perutz’ Medical Research Council (MRC) Unit of Molecular Biology at Cambridge. Taking pictures of fibrous and globular proteins – beginning with insulin and tropomyosin – Peter applied the Cochran-Crick theory, with the goal of determining the helical structure of these protein molecules. This inquiry was, in principle, made possible by Linus Pauling’s work from less than a decade prior.

Since 1947, when the MRC unit was founded by Sir Lawrence Bragg, John Kendrew and Max Perutz had endeavored to use x-ray crystallography to determine the molecular structure of hemoglobin in sheep. By the time that Peter arrived at Cambridge, however, hemoglobin had proven to be an untenable object of study, and Kendrew’s focus had shifted to myoglobin. Whereas hemoglobin is found mostly in the blood, myoglobin is generally found only in muscle tissue. Both are proteins that carry oxygen to cells. Problematically, myoglobin is one fourth the size of hemoglobin, and too small for the era’s techniques of x-ray analysis.

To solve this issue, sperm whale myoglobin was used in hopes that the molecular details of the larger, oxygen-rich proteins of a diving mammal would be more observable with the tools then available. “Stranded whales are the property of the Queen,” Peter explained to his father as he discussed this work, “but we have an agreement with her to get a piece of meat if one comes ashore.” Nonetheless, though availed of samples from beached whales in the United Kingdom and from countries as far afield as Peru, Kendrew could not render the x-ray diffraction patterns with complete certainty.


 

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Sperm whale myoglobin image created by John Kendrew.

In 1953, Perutz realized that by comparing the diffraction patterns of natural whale myoglobin crystals to crystals soaked in heavy metal solutions – a procedure called multiple isomorphous replacement – the positions of the atoms in myoglobin could be more accurately determined. Accordingly, Peter was tasked with making countless measurements in support of this effort.

Peter wrote to his father often over the next two years as he struggled to complete this project, which was the focus of his PhD. In particular, Peter asked for advice on how one might best get heavy metal atoms onto myoglobin, detailing his attempts to use everything from saltwater to telluric acid, which was used to produce salts rich in metallic contents, such as the element Tellurium.

Indeed, Peter’s work proceeded slowly, not least of all because of his knack for keeping things entertaining. Shortly after Watson and Crick’s discovery of DNA, for example, he fabricated a letter of invitation from his father, Linus Pauling, to Francis Crick, requesting Crick’s presence at an upcoming conference on proteins at Caltech. “Professor Corey and I want you to speak as much as possible during the meeting,” the impostor Pauling said to Crick in the fake letter, even urging him to consider lecturing at Caltech as a visiting professor. Linus Pauling had appeared to sign the letter himself, his signature skillfully forged. The letter proved so convincing that Crick actually replied, accepting the invitation to speak at the conference.

Before long, it became apparent that the entire communication was, in fact, a practical joke. Lawrence Bragg, the director of the Cavendish Laboratory, where Crick himself worked, was scheduled to speak at the proteins conference in the same time slot that the fake letter had proposed for Crick. Were it not for this, the deception might have gone even farther, since upon seeing his son’s forgery Linus himself was almost convinced that he had written the letter and had simply forgotten about it amidst the relentless pace of his schedule.

Ever a stickler for the details, however, Pauling noticed a grammatical error in the document that he would never have made. From there, he deduced the letter as having been authored by his mischievous son. For this transgression, Linus subtracted a five-pound fine from the $125.00 check that he sent to Peter each month.

Peter Pauling: Leaving Home, 1945-1952

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The Pauling family in 1946. From left: Peter, Ava Helen, Linus, Crellin, Linda and Linus Jr.

[The life story of Peter Pauling, part 2 of 9]

In April 1945, while German forces were surrendering to the Allies in Europe, Peter Pauling was completing his education at Flintridge Prep and moving on to McKinley Junior High, where he would enter the 10th grade. He continued to do well in most subjects, with the exception of a few poor marks in Latin. Now fourteen years of age, Peter went outside of the Pauling family home in Pasadena one day to discover a message painted on their garage door; it read: “AMERICANS DIE BUT WE LOVE JAPS. JAPS WORK HERE, PAULING.” Peter quickly called for his parents, who surmised that the hate message had been written by misguided individuals angered by Ava Helen’s work with the American Civil Liberties Union to prevent the internment of many Japanese-American citizens during the war.

Within the year, Linus Jr., now twenty-one years old, had returned home from his time in the Army Air Corps. He promptly came into possession of a 1932 Ford V8 roadster that had belonged to the Mt. Wilson astronomer Ted Dunham, Jr. The car would become something of an heirloom of burgeoning adulthood for the Pauling boys, passing to Peter when Linus Jr. went off to medical school, and then again to Crellin when Peter finished college in California and went off to Cambridge.

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Peter Pauling sitting in the frame of a converted 1932 Model-B Ford, 1947.

In 1947, Linus and Ava Helen returned from a scientific congress in Scandinavia to find their three youngest children growing somewhat depressed by, and resentful of, their frequent long absences. Knowing that they were about to spend six months in England, where Linus would lecture as a visiting professor at Oxford, the Paulings decided it best to take the entire family abroad with them. They traveled by train to New York City in December, where they then boarded The Queen Mary and crossed the Atlantic.

The voyage would prove to be an extraordinary missed opportunity for Linus. Onboard was Erwin Chagraff, who was excited to talk with Pauling about his discovery that DNA nucleotide base pairs obeyed a set rule – a 1:1 ratio of adenine to thymine and cytosine to guanine. As Crellin Pauling later recounted

Chargaff had a reputation as a, well how do you put it politely, as a difficult personality. And what Daddy said to me was that he found Chargaff so unpleasant to be trapped on the Queen Mary with, that he dismissed his work.

In doing so, Pauling overlooked the importance of a critical piece of knowledge that would help lead Watson and Crick to the discovery of the structure of DNA – a discovery with which both Linus Pauling and his son Peter would be intimately involved.


 

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The Paulings at sea, 1948. Peter stands at right.

After the family returned from England,  Peter made the fateful decision to follow in his father’s footsteps, enrolling at Caltech as an undergraduate and assuring his father that his “chief purpose in life” was to be a physicist. Unlike the elder Pauling, however, Peter gravitated almost immediately to those new freedoms that a young man no longer under his parents’ roof might be expected to find suddenly and inescapably important: cars, girls, and parties.

With respect to the former, Peter wrote to his father from Caltech, asking whether or not Linus might be interested in helping to pay for a new engine for the roadster. Peter had already been putting some work into the car since it had passed from Linus Jr.’s hands into his own. Now off at college and free to pursue his own interests, he was eager to get under the hood.

Peter likewise wrote to his mother asking her for advice on different perfumes, listing the names of four different girls, all of whom were apparently familiar to Ava Helen, and asking which scents she thought that each would prefer (he then added a fifth young lady to the list as an afterthought).

While Peter was at Caltech, the Pauling home in Pasadena became something of a social hotspot for young, aspiring scientists, many of them graduate students and postdocs who coveted the opportunity to hobnob with the great Linus Pauling. By right of birth and strength of personality, Peter emerged as both gatekeeper and VIP at such events, and he thrived in this atmosphere. In his biography of Pauling’s life, Force of Nature, author Thomas Hager paints a scene of pilgrims making their way up into the hills on warm afternoons for, “a beer, a dip in the pool, some jokes with Peter, and a chance to flirt with tall, slim, blond, teenaged Linda Pauling.”

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Peter Pauling, ca. late 1940s.

Peter, now nineteen and cruising the streets of Pasadena at night in the modified “hand me down” roadster, was the life of many of these parties. His undergraduate years were accordingly marked by the ecstasies, despairs, and calamities – including a long and somewhat severe case of infectious mononucleosis – familiar to many college students. His father, observing from the middle distance, sent him a stern letter during this period, noting that he had opened some mail at the house intended for his son and that it was from the Bank of America, alerting Peter that his account was overdrawn by 50 cents. Pauling then advised his son, in great detail, as to how he should best manage his finances to avoid such a problem in the future.

Though they lived in the same city and worked at the same institution, Peter corresponded often with his father, expressing relatively little concern about his finances and far more with the prospect of being called up for the draft. In June 1950, North Korea, aided by the Soviet Union, invaded South Korea, where United States troops had been stationed since the ousting of Japanese occupation at the close of the Second World War. As hostilities in the Korean peninsula ramped up, Peter grew increasingly fearful of being called upon to serve.

The elder Pauling advised that his son request a deferment as a student of physics, which Peter sought and successfully attained. Part of Peter’s later motivation to spend some of his time as an undergraduate in London likewise emerged from his desire to avoid the draft for as long as possible. Peter felt that his enrollment as a student overseas would at least prolong his recruitment, whereas, if he remained at Caltech, he might he pulled in any day and waste his final undergraduate months in military training.


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Peter Pauling with his parents, 1949.

Meanwhile, in the summer of 1951, Peter was involved in a serious car accident. The Pasadena Star News reported that, “While driving his father’s expensive 1949 sedan, Peter J. Pauling, 20, son of Linus Pauling, world-famed Caltech physicist, was injured in a spectacular traffic crash at Fair Oaks Avenue and Washington street.” The police report indicated that the Pauling car had been sideswiped by a Harry L. Nottingham, a 30-year old welder, at 2:11 AM.

The police jailed Nottingham overnight on a drunk driving charge, and Peter was treated at the emergency hospital for mild injuries to his head that had been sustained when his car flipped onto its roof after the impact. The accident happened less than a month before Peter was to leave California to spend his summer at a laboratory in Woods Hole, Massachusetts. His eventual departure back east left his parents quite literally picking up the pieces in his absence, as Peter had requested that they keep what remained of the vehicle to see what he could salvage.

His father later wrote to Peter while he was at Woods Hole, explaining that, even with compensation paid out by insurance and the drunk driver involved, the family would still, after legal fees, “come out a little bit in the hole from your use of the Lincoln that night.” Peter responded through his mother, writing “Please tell Daddy that I am sorry I ruined his car,” and asking that she remind him that, of the cars he could have wrecked that night, at least he chose the one that offered a barrier between his head and the road. The old Ford roadster was, after all, a convertible.


 

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Crellin, Linda, and Peter Pauling, 1952.

Peter’s stint at Woods Hole was both formative and crucial to his next steps. While there, he studied ion movement in nerves using sodium and potassium tracers in squid axons.  At the same time, Peter began seriously considering what institution to go to for graduate school, looking at Cambridge, among others. Fortuitously, John Kendrew, of Cambridge’s Cavendish Lab, was serving as a lecturer at Woods Hole and, unbeknownst to Peter, was recruiting for his protein structure research group.

Years later, Peter would recount that when Kendrew told Peter’s Woods Hole boss, David Nachmanson, that he had recruited him, Nachmanson replied, “What? That sex maniac?” Kendrew reportedly replied, “What does that matter?” In typical good humor, Peter offered that Kendrew had replied in this manner because he knew that being a “sex maniac” was an advantage at Cambridge. He later confessed, however, that his reputation was not well earned, admitting that he was likely “the most unsuccessful Don Juan in Woods Hole.”

While in Massachusetts, Peter was, in fact, pretty clearly agonizing over how to resolve his relationship with his college girlfriend, who remained in Pasadena. In his correspondence, Peter sometimes indicates a deep affection for his sweetheart, and at other times reveals significant doubt about any chance of a shared future.

It is entirely possible that the hot and cold nature of Peter’s feelings towards this woman were merely a reflection of a young man’s whimsies. It might also be argued that this was an early sign of a lifelong struggle with manic-depression that would come to plague Peter by the later stages of his graduate career at Cambridge. In any case, Peter’s beau was equally unsure. At times she seemed to favor the appraisal of her father, a high-ranking scientific adviser to the American military who was stationed in Europe. The father believed that marriage would prematurely end his daughter’s own academic ambitions and that, more broadly, Peter was bad news.

However, by the following summer of 1952 – just before Peter left for Cambridge – she had warmed to her boyfriend again. It was a summer of exploration; the two crossed the nation prior to the beginning of graduate school for Peter, travelling together to New York, Washington D.C., Princeton, and Long Island. Their romance seemed to burn brightly, if briefly, as Peter’s life in America drew to a close.

In the last few months before leaving the states, Peter and Crellin visited Hawaii, staying with their older brother Linus Jr, who lived there. Meanwhile, Linus and Ava Helen were engaged in world travels of their own, making lengthy stops in France and England. Peter wondered aloud if he would get the chance to see his parents upon his brief return to Pasadena, or if, instead, he would be gathering his belongings from an empty house, departing with the well wishes of Linda and Crellin, and setting out alone for Montreal, where he would board a ship to cross the Atlantic.

The exact circumstances of Peter’s bon voyage from southern California are unknown, but by September 1952, Peter was on his way to a new life in England.

 

Pauling and Perutz: The Later Years

[Concluding our series on Max Perutz, in commemoration of the Perutz centenary.]

In 1957, Max Perutz and Linus Pauling wrote to each other again on a topic that was new to their correspondence. This time Pauling asked Perutz to sign his petition to stop nuclear weapons tests, a request to which Perutz agreed.

Signature of Max Perutz added to the United Nations Bomb Test Petition, 1957.

Signature of Max Perutz added to the United Nations Bomb Test Petition, 1957.

As the decade moved forward, the discovery of the double helical structure of DNA attracted ever more attention to the work of James Watson and Francis Crick. In May 1958, Perutz asked Pauling to sign a certificate nominating his colleagues Crick and John Kendrew to the Royal Society. Pauling agreed, though stipulated that Kendrew’s name be placed first on the nomination, as he expected that Crick would get more support. As with Pauling’s bomb test petition a year earlier, Perutz agreed.

At the beginning of 1960, William Lawrence Bragg wrote to Pauling about nominating Perutz, along with Kendrew, for the 1961 Nobel Prize in Physics. Pauling was hesitant about the nomination, thinking it was still early, as their work on hemoglobin structure had only recently been published. Pauling also felt that Dorothy Hodgkin should be included for her work in protein crystallography. Bragg thought this a good idea and included Hodgkin in his nomination.

By March, Bragg’s nominations had gone through and Pauling was asked to supply his opinion. After spending some time thinking about the matter, Pauling wrote to the Nobel Committee that he thought that Robert B. Corey, who worked in Pauling’s lab, should be nominated along with Perutz and Kendrew for the Nobel Prize in Chemistry instead. Pauling felt that if Perutz and Kendrew were included in the award, Corey should be awarded half, with the other half being split between Perutz and Kendrew. Pauling also sent a letter to the Nobel Committee for Physics, indicating that he thought that Hodgkin, Perutz, and Kendrew should be nominated for the chemistry prize. Pauling sent a copy of this letter to Bragg as well.

Pauling’s letter to the Nobel Committee, March 15, 1960. pg. 1.

Pg. 2

In July, Bragg replied to Pauling that he was in a “quandary” about Corey, as he was “convinced that” Corey’s work “does not rank in the same category with that which Mrs. Hodgkin or Perutz and Kendrew have done.” Perutz and Kendrew’s efforts, he explained, had theoretical implications directly supporting Pauling’s own work, whereas Corey’s research was not that “different from other careful analyses of organic compounds.” Once everything was sorted out, Perutz and Kendrew were awarded the Nobel Prize for Chemistry in 1962 (the same year that Watson and Crick, along with Maurice Wilkins, won in Physiology/Medicine, and Pauling, though belated for a year, won the Nobel Peace Prize) and Hodgkin received the Nobel Prize for Chemistry in 1964. Robert Corey never was awarded a Nobel Prize.


Linus Pauling, Max Delbrück and Max Perutz at the American Chemical Society centennial meeting, New York. April 6, 1976.

Perutz and Pauling corresponded very little during the 1960s, with Perutz writing only to ask for Pauling’s signature, once for a photograph that would be displayed in his lab and a second time for a letter to Italian President Antonio Segri in support of scientists Domenico Marotta and Giordano Giacomello, who were under fire for suspected misuse of funds.

In 1971 Perutz read an interview with Pauling in the New Scientist which compelled him to engage Pauling on scientific questions once again. Perutz was surprised to have read that Pauling had tried to solve the structure of alpha keratin as early as 1937 and that his failure to do so led him to study amino acids. Perutz wrote that had he known this in 1950, he, Bragg and Kendrew might not have pursued their own inquiry into alpha keratin. Pauling responded that he thought his efforts had been well-known as he and Corey had made mention of them in several papers at the time. Pauling explained that he had difficulties with alpha keratin up until 1950, when he finally was able to show that the alpha helix best described its structure. Perutz replied that he was aware of Pauling and Corey’s work and the alpha helix, but was surprised that Pauling’s early failure to construct a model led him to a more systematic and fruitful line of research.

Perutz also wondered whether Pauling had seen his article in the previous New Scientist, which reflected on Pauling and Charles Coryell’s discovery of the effect of oxygenation on the magnetic qualities of hemoglobin. Perutz saw this as providing “the key to the understanding of the mechanism of haem-haem [heme-heme] interactions in haemoglobin.” Pauling responded that he had not seen Perutz’s article but would look for it, and also sent Perutz a 1951 paper on the topic. Perutz took it upon himself to send Pauling his own article from the New Scientist.

A few years later, in 1976, Perutz again headed to southern California to attend a celebration for Pauling’s 75th birthday, at which he nervously gave the after dinner speech to a gathering of 250 guests. Before going to the event in Santa Barbara, Perutz stopped in Riverside and visited the young university there, which impressed him. Perutz wrote to his family back in Cambridge that he wished that “Oxbridge college architects would come here to learn – but probably they wouldn’t notice the difference between their clumsy buildings and these graceful constructions.”

Perutz also visited the Paulings’ home outside Pasadena, which elicited more architectural comments. Perutz described to his family how the Pauling house was shaped like an amide group, “the wings being set at the exact angles of the chemical bonds that allowed him to predict the structure of the α-helix.” Perutz asked Pauling, perhaps tongue in cheek as he thought the design somewhat conceited, “why he missed the accompanying change in radius of the iron atom.” Pauling replied that he had not thought of it.

Bertrand Russell and Linus Pauling, London England. 1953.

In preparation for his speech, Perutz also took some time to read No More War! which he concluded was as relevant in 1976 as when it was first published in 1958. Perutz saw Pauling’s faith in human reason as reminiscent of Bertrand Russell’s. Indeed, the many similarities between the two were striking to Perutz, and he included many of them in his talk, “except for their common vanity which I discreetly omitted.” In a personal conversation, Perutz asked Pauling about his relationship with Russell which, as it turned out, was mostly concerned with their mutual actions against nuclear weapons. Perutz was somewhat disappointed that “they hardly touched upon the fundamental outlook which I believe they shared.”


Perutz and Pauling were again out of touch for several years until April 1987, when Pauling traveled to London to give a lecture at Imperial College as part of a centenary conference in honor of Erwin Schrödinger. Pauling’s contribution discussed his own work on antigen-antibody complexes during the 1930s and 1940s, during which he shared a drawing that he had made at the time. Perutz was in attendance and noticed how similar Pauling’s drawing was to then-recent models of the structure that had been borne out of contemporary x-ray crystallography. Perutz sent Pauling some slides so that he could judge the similarities for himself.

Flyer for Pauling's 90th birthday tribute, California Institute of Technology, February 28, 1991.

Flyer for Pauling’s 90th birthday tribute, California Institute of Technology, February 28, 1991.

The final time that Pauling and Perutz met in person was for Pauling’s ninetieth birthday celebration in 1991. Perutz, again, experienced stage fright as he gave his speech. But he was encouraged afterwards, especially after receiving a compliment from Francis Crick who, according to Perutz, was “not in the habit of paying compliments.” Perutz told his family that the nonagenarian Pauling “stole the show” by giving one speech at 9:00 AM on early work in crystallography and then another speech at 10:00 PM on his early years at Caltech. Perutz found it enviable that Pauling stood for both lectures and was still getting around very well, though he held on to the arm of those with whom he walked. Without coordinating, Perutz and Pauling also found a point of agreement in their talks, noting that current crystallographers were “so busy determining structures at the double” that they “have no time to think about them.” This rush often caused them to miss the most important aspects of the newly uncovered structures.

Just as Perutz first encountered Pauling through one of his books, The Nature of the Chemical Bond, so too would Pauling’s last encounter with Perutz be through a book, Perutz’s Is Science Necessary? Pauling received the volume in 1991 as a gift from his friends and colleagues Emile and Jane Zuckerkandl. Pauling’s limited marginalia reveal his interest in the text’s discussions of cancer and aging research. Aged 90 and facing his own cancer diagnosis, Pauling was particularly drawn to Perutz’s review of François Jacob’s The Possible and the Actual which sought, but did not find, a “death mechanism” in spawning salmon. Pauling likewise highlighted the book’s suggestion that “like other scientific fantasies…the Fountain of Youth probably does not belong to the world of the possible.” And Pauling made note of particular individuals that he had known well, like John D. Bernal and David Harker. Pauling deciphered the latter’s identity from Perutz’s less-than-favorable anonymous portrayal.

Pauling also noted spots where Perutz wrote about him. While most of these references were positive and focused on topics like Pauling’s influence on Watson and Crick and his breakthroughs on protein structure, one in particular was not. Perhaps less cryptic than the reference to Harker, Perutz described how “one great American chemist now believes that massive doses of vitamin C prolong the lives of cancer patients,” following it with “even more dangerous are physicians who believe in cancer cures.”

While critical, Perutz really meant the “great” in his comment and he continued to repeat it elsewhere. After Pauling passed away in August 1994, Perutz told his sister Lotte that “many feel that he [Pauling] was the greatest chemist of this century” while also being “instrumental in the protests that led to Kennedy and Macmillan’s conclusion of Atmospheric Test ban.”  He reiterated this idea in the paragraph that concluded his obituary of Pauling, published in the October 1994 issue of Structural Biology.

Pauling’s fundamental contributions to chemistry cover a tremendous range, and their influence on generations of young chemists was enormous.  In the years between 1930 and 1940 he helped to transform chemistry from a largely phenomenological subject to one based firmly on structure and quantum mechanical principles.  In later years the valence bond and resonance theories which formed the theoretical backbone of Paulings work were supplemented by R. S. Mullikens’ molecular orbital theory, which provided a deeper understanding of chemical bonding….Nevertheless resonance and hybridization have remained part of the everyday vocabulary of chemists and are still used, for example, to explain the planarity of the peptide bond.  Many of us regard Pauling as the greatest chemist of the century.

Perutz’s Hemoglobin Breakthroughs and Later Work

Perutz with his hemoglobin molecule, 1959. Image credit: Life Sciences Foundation.

Perutz with his hemoglobin molecule, 1959. Image credit: Life Sciences Foundation.

[Part II of our survey of the life of Max Perutz, this time focusing on the years 1941-2002. Published in commemoration of the Perutz centenary, May 2014.]

Knowing that his parents were safe from Nazi persecution and able to return to the United States, circumstances began improving for Max Perutz. The Rockefeller Foundation reactivated his grant, allowing him to support himself while stateside as well as his parents in Cambridge, England. Perutz’s father was also able to find work as a laser operator during the war and afterwards qualified for a pension.

In September 1941, Perutz met Gisela Peiser, who was an accountant at the Society for the Protection of Science and Learning, an organization that assisted Jewish and other academic refugees fleeing from the Nazis. After a quick courtship, they were married the following March and, in December 1944, welcomed their daughter Vivien into the world. That same year, Perutz also found himself back in good stead with the British government and recruited to research ice strength for potential ice stations in the North Atlantic. The research did not work out, so Perutz returned to his work on hemoglobin at Cambridge. The next few years were spent trying to put together a secure source of income for him and his growing family. In the interim, he took out more loans and found a temporary fellowship.

Meanwhile, Perutz’s health continued to suffer. As his chronic gastrointestinal attacks became more unbearable, interfering with his daily activities more and more, Perutz began to seek out help. Most doctors he saw told him it was a psychological problem, but eventually one doctor recognized that the symptoms could be treated by a mixture of atropine and codeine. The remedy helped enough for Perutz to live more or less undisturbed by the problem for several years, though eventually that would change.


Perutz and John Kendrew, 1962. Image credit: Nobel Foundation.

Perutz and John Kendrew, 1962. Image credit: Nobel Foundation.

In 1947, the war now completed, Perutz, along with John Kendrew, was appointed to head the new Research Unit for the Study of the Molecular Structure of Biological Systems (Perutz later shortened the unit’s name to Molecular Biology Research) at the recently established Medical Research Council. Situated at the Cavendish Laboratory in the physics department, the group expanded on Perutz’s earlier application of x-ray crystallography to biological materials. Perutz, in this new administrative role, described his lab management as one where he would “leave people free to do what they wanted…if they were good scientists.”

One of the several student researchers that came through the lab was Francis Crick, who started work in 1949. Perutz had Crick look at the validity of his hemoglobin model, which was the culmination of roughly six years of research. Crick applied his mathematical training to show that the model was “nonsense.” Perutz accepted Crick’s assessment and later reflected that only in England at that time could a student be so critical of their principal investigator. Crick was eventually drawn away from hemoglobin research by James Watson, who came to the lab in 1951 to work under Kendrew on molecular structure, but his impact on the development of Perutz’s hemoglobin structure was long-lived.

Throughout the late 1940s, Perutz also continued his work on glaciers in the Alps and helped found the Glacier Physics Committee in 1947. Though he had trouble recruiting able assistants who could also ski (the first two broke their legs), the work gave Perutz and his family the opportunity to spend summers in the mountains. Perutz’s research led him to conclude that glaciers flowed faster at the surface than at the bottom.

Perutz’s digestive attacks began increasing in intensity in the early 1950s to the point where, in 1954, he was hospitalized for ten days. While there, doctors looked for possible causes but came up empty and could only prescribe bismuth, with little effect. What did help, for reasons Perutz did not understand, was visiting the Alps, and so he arranged for a trip after being released from the hospital. Unfortunately the attacks resumed as soon as he returned to Cambridge, pushing Perutz to his limits – he considered resignation and even contemplated suicide. In desperate straits, he arranged for another trip to the Alps that spring but, once there, continued to get worse and, as an added complication, came down with scurvy.

When he returned, Perutz sought out other doctors who might be able to help, eventually visiting Werner Jacobson, who was also at Cambridge. Jacobson thought Perutz’s symptoms sounded like those of Celiac disease. He suggested that his patient stop eating wheat, or more specifically gluten, which immediately improved Perutz’s condition. Whenever the symptoms appeared again, as they did in the early 1960s, Perutz could trace them back to gluten; he eventually stopped eating any form of bread, since even gluten-free flour contained small amounts of gluten that negatively affected his health.


Perutz in lecture. Image credit: Nature.

Perutz in lecture. Image credit: Nature.

Perutz’s improved physical condition coincided with the final years of his triumphant work on a determination of the structure of hemoglobin. After working out a solution to interpret x-ray diffraction photos of proteins three-dimensionally, Perutz came upon the structure in September 1959, submitting his findings to Nature before heading to the Alps to ski over the winter break. By the time he returned, he was famous.  It was quickly and widely acknowledged that his work comprised a major breakthrough for both chemistry and biology.  As Hugh E. Huxley wrote, in 2002

He was the first person to find out how to determine protein structure by X-ray crystallography, after many years of patient struggle, and he applied the technique to solve the structure of haemoglobin, the oxygen-carrying protein in blood….The results showed that it was possible to see, in the atomic detail necessary to understand mechanisms, the structure of the macromolecules that carry out many of the functions of a living cell. Such knowledge is basic to the revolution that has swept through biology in the past 50 years, and to modern medicine and biotechnology.

By Fall 1962 there were rumors that Perutz would be awarded the Nobel Prize for chemistry. As October arrived, he began receiving calls from the press, but did not quite trust them. As the calls continued, Perutz received a telegram and thought, along with the rest of the lab, that it may be from the Nobel committee. Alas, the message was only from Nature asking how many reprints of his article Perutz wanted. That afternoon however, Perutz received another telegram, the one he had been waiting for. The lab celebrated with a champagne party as Perutz and Kendrew had been awarded the Nobel Prize for Chemistry, and Watson and Crick, along with Maurice Wilkins, would receive the Nobel Prize in Physiology and Medicine.

Perutz continued to work on the hemoglobin structure after his rise to fame, next turning to the question of how the structure changed with the uptake of oxygen. His Nobel lecture described this continued research on the four subunits within hemoglobin that changed their structure as oxygen was taken up; the first description of how proteins changed in structure.

In the years that followed, Perutz focused more on why this change occurred. Aided by automated x-ray diffraction machines and able assistants, Perutz’s lab was able to turn out more measurements than ever before. But the measurements, as Perutz later related, did not make any sense. After one of his research assistants completed his postdoc, Perutz looked closer at his results and realized that the new x-ray instruments had not been calibrated correctly.

In 1967, with all the bugs fixed, Perutz and his team put together the first atomic model of hemoglobin, but Perutz’s questions about why the structure changed still were not answered. By 1970, the lab was able to construct an oxygen-free model, allowing Perutz to compare it with the oxygenated model. As Perutz later described “there came this dramatic moment when between them, the models revealed the whole mechanism.” What he was able to see was how a slight movement of the iron atom triggered a change in the whole molecule. Thus, Perutz felt he was able to explain “all the physiological functions of hemoglobin on the basis of its structure.” The results were published in Nature.

Within the field, objections to Perutz’s explanation were numerous and he spent much of the next two decades refuting criticisms and refining his own explanation. At the same time, his celebrity also rose among scientists as he was increasingly invited to give lectures all over Europe and North America. By 1975 Perutz’s fame outside of scientific circles had grown such that Queen Elizabeth II invited him to visit with her at Buckingham Palace. Afterwards, Perutz expressed his regrets to the Queen’s secretary that “she had made me talk away like an excited little boy about my own doings and that I never asked her anything about hers.” Nonetheless, Perutz did hope that the Queen would enjoy his gift, the autobiography of Charlie Chaplin.


Max Perutz with his hemoglobin model. Image credit: BBC.

Max Perutz with his hemoglobin model. Image credit: BBC.

By 1980 Perutz had begun to reach out to broader audiences more intentionally. Shortly after retiring from the chair of the Laboratory of Molecular Biology, Perutz wrote a memoir of his time there. This, in turn, inspired him to compile an account of his experiences during World War II and submit it to the New Yorker. Penned in 1980 but not published until 1985, “Enemy Alien” helped bring Perutz greater levels of fame, as he received more letters after its publication than he did congratulations for his Nobel Prize.

An Italian pharmaceutical company also approached Perutz in 1980 to give a lecture on the social implications of molecular biology. According to a 2001 interview, Perutz told the company that “molecular biology has no social implications,” but that he could talk about “science as a whole.” This spurred him to take more of an interest in broader scientific questions, ultimately leading him to adopt controversial stances combatting criticism of the Green Revolution, DDT use and nuclear power, among other issues in the headlines. It also evolved into an interest in philosophy – Karl Popper’s Open Society and its Enemies proved particularly impactful. By 1989, Perutz expanded his popular lectures into a book of essays, Is Science Necessary? which included writings that he had also done for the New York Review of Books as well as “Enemy Alien.”

While continuing to write for the New York Review of Books up to the end of his life, Perutz also pursued new research on proteins and hemoglobin, taking a particular interest in neurodegenerative diseases like Parkinson’s and Alzheimer’s. In 2001, right before he passed away, Perutz was still at the lab seven to eight hours a day (including lunch and tea), preparing a publication for the Proceedings of the National Academy of Sciences on the common structure of insoluble protein deposits in neurodegenerative diseases. He passed away at the age of 87, unable to reconcile his initial structure with x-ray diffraction photos which showed contradicting features that Perutz concluded arose from three different structures. The results were published in 2002, after Perutz had died, in two separate articles.