Peter Pauling and the Discovery of the Double Helix, 1952-1953

1954i.57-peter-600w

Peter Pauling, 1954.

[The life of Peter Pauling: Part 4 of 9]

With Winter break coming fast and Linus Pauling having apparently solved the structure of DNA, Jim Watson and Francis Crick extinguished any hope of modeling their own structure. Eager to take advantage of a few days off, their Cavendish office mate, Peter Pauling, headed for the continent in the company of a friend whom he described as “a mad Rhodes scholar” who had “wooed” him with his “insane plan” for exploring Europe.

On this trip, which was indeed ambitious, Peter visited Munich, Vienna, Linz, Brussels, Frankfurt, and Bavaria, hitchhiking his way from location to location. Crossing Germany, Peter saw neighborhoods still littered with the rubble of the Second World War, alongside industrious people struggling to rebuild. His mode of travel, he confessed to his mother in a letter, had seemed a better idea when its low cost was his only consideration. In person, however, spending several hours standing in or walking through the snow had a way of changing one’s priorities.

Nonetheless, the whole escapade proved a romantic adventure for the young Peter Pauling. He spent Christmas Eve in a gas house belonging to the director of an iron company somewhere in Leoben, Austria. Resting there and watching the snow fall, he wrote again to his mother:

I look out the window to the lovely white mountains. It is grand. Considering the possibilities, Christmas and your birthday [Ava Helen was born on December 24, 1903] could hardly have been spent in a nicer place. Considering impossibilities, I can think of places where I would much prefer to be. Sometimes it is sad to grow up.


 

[Triple Helix animation and narration created by Cold Springs Harbor Laboratory]

With the arrival of the new year, the Cavendish researchers put their skis away, shook the snow from their coats, and resumed their work.  It wasn’t long into the term before Peter learned, from two letters received in February, that his father was, in fact, having difficulty with some of the van der Waals distances hypothesized to be near the center of his DNA model. In response – and almost as an afterthought – Peter casually asked his father for a manuscript of the DNA proposal, mentioning that his coworkers in Max Perutz’ unit would like to give it a read. Upon receiving the paper, Peter promptly revealed to Watson and Crick that the Pauling-Corey model was a triple helix, a concept similar to one that Watson and Crick had developed themselves – and rejected – back in 1951.

This moment was a major turning point for Watson and Crick, who only then realized that they still had a chance to discover the structure before Linus Pauling. That said, what followed may not have been quite the race as it was made out to be after the fact. At least, Peter Pauling did not see it that way, and the casual manner in which his father interacted with him (and with others at the Cavendish) seems also to belie such a dramatization.


 

[Jim Watson recalls learning of the Pauling-Corey triple helical model. Video created by Cold Springs Harbor Laboratory.]

Near the end of February 1953, while wishing his father a happy birthday, Peter noted that his office still felt that Linus’ structure required sodium to be located somewhere near the oxygens, whose negative charges would have to cancel out to hold the molecule together. “We agree that everything is a little tight,” he said, referring to the small atomic distances between Pauling’s three polynucleotide chains with phosphate groups in the middle.

As communicated in an earlier letter to his son, Linus Pauling had already identified these structural arrangements as a weakness of the model, and he was in the midst of attempting to correct the issue. Peter confided to his father that, at that time, the Cambridge office had nothing better to offer. He added simply that “We were all excited about the nucleic acid structure,” and concluded with his many thanks for the paper.

In response, Linus Pauling asked for updates on any progress that Watson and Crick were making with their own model, and casually requested that Peter also remind Watson that he should arrive for a scheduled protein conference at Caltech by September 20th. Peter clarified only that the Cavendish group had successfully built the Pauling-Corey model and that Watson and Crick had then discarded it, becoming very involved in their own efforts and “losing objectivity.” It would be up to them, Peter said, to communicate the details of their structure. Shortly thereafter, Watson and Crick sent a letter to Linus Pauling, outlining their structure and including the short article that they had submitted for publication in Nature.


sci9.001.5-600w

Crystallographic photo of Sodium Thymonucleate, Type B. “Photo 51.” Taken by Rosalind Franklin, May 1952.

It has been well-established that Pauling and Corey made basic errors in their own modeling  of the structure of DNA. But in March 1953, having no knowledge of the x-ray crystallographic photographs of DNA that had been taken by Rosalind Franklin at Kings College, Pauling felt bewildered by the certainty with which Watson and Crick had rejected his triple helical model. Upon learning its details, Pauling agreed that the double helix model was at least as likely, and he considered it to be a beautiful molecular structure, but he could not understand why his own structure was being ruled out entirely.

At the heart of his confusion lay the fact that he did not believe that any x-ray evidence existed that proved that the phosphate groups might somehow be located on the outside, rather than in the core, of the DNA molecule. Pauling did not believe that this evidence existed because he hadn’t seen it yet; crucially, Watson and Crick had. Indeed, from the point of their realization that Pauling had modeled the structure incorrectly, Watson and Crick worked fervently to once again convince Maurice Wilkins to provide them with Rosalind Franklin’s data.

(On one occasion, they met with Wilkins for lunch at the Crick home, where Peter could often be found for brunch on the weekends. On certain of these earlier brunch occasions, while in the home’s basement dining room, Watson and Crick discussed the feasibility of redoubling their efforts to model DNA while Peter, casually eating biscuits and sipping tea at the table, offered that if they didn’t do it soon, his father would take another shot at it. After the embarrassment of a failed attempt, he assured them, Linus Pauling was a strong bet to get it right the second time around.)

Within a month’s time, and with Rosalind Franklin having left his lab, Wilkins finally consented to providing Watson and Crick with all of the relevant data that he had requested. This proved to be the final piece that the duo needed in building their correct structural model of DNA.


1953i.6

Pauling en route to Europe, 1953.

While all of this went on, Linus himself was seemingly unconcerned by any “race” for the structure of DNA. In fact, the only racing on his mind was a jaunt across Western Europe in a new sports car.

While Watson and Crick frantically worked to unravel the secrets of DNA before Linus Pauling beat them to it, Linus Pauling himself was debating the virtues of British, German, and Italian motor vehicles. Preparing for multiple trips overseas and in the market for some new wheels, Pauling’s plan was to select a car while in Europe during the Spring for the Solvay Conference, and then to actually pick it up in August, when he and Ava Helen would return to Europe for the International Congress of Pure and Applied Chemistry in Stockholm and Uppsala. The couple would then tour the continent in style before returning to the United States on a Scandinavian freighter and driving across the country from either New York or New Orleans to their California home.

While Peter advised his father that a Jaguar Mark VII was absolutely the best buy of the season, Linus expressed a preference for the slightly more modest convertible Sunbeam-Talbot. Peter countered with the possibility of an Austin A-40 Sports 4-Seater, and Linus finally agreed to have Peter look into purchasing the car on his behalf and scheduling a delivery of sorts. Seeing that his father was finally taking the bait, Peter attempted to spring a trap: “Might you be in need of a chauffeur, mechanic, linguist, travelling companion, navigator, break repairer, tire changer, witty conversationalist etc. on your trip next summer?” he wondered. “I know just the fellow. Good friend of mine.”


 

dnamodel-piece-600w

A segment of the original Watson and Crick DNA model. 1953.

As the end of March rolled around and the Solvay Conference approached, Linus Pauling alerted his son to the fact that he had not made hotel reservations or, really, any plans for his visit to Cambridge. This responsibility he delegated wholly to Peter, who was somewhat distracted at the time, writing to his father about the blue sky and sun that had finally begun to break up the English winter gloom, and announcing with pride that he had gone to two balls in one week, getting along quite well with the Scandinavian girls. “As a sensible young American, I stand out in this town of pansy Englishmen,” he declared with impunity.

When Linus finally arrived at Cambridge in April, however, he found his son’s sensibilities to be somewhat lacking. Peter had in fact not made the requested hotel reservations, and while campus accommodations were fine for the son, they were not so wonderful for the elder Pauling. Watson later joked that, “the presence of foreign girls at breakfast did not compensate for the lack of hot water in his room.”

When the moment of truth finally came, Peter and his father strode into the Cavendish offices to see the model that Watson and Crick had constructed. Upon inspection, Linus reiterated the interpretation that he had given to his son earlier: the structure was certainly possible, but to be certain, Pauling would first need to see the quantitative measurements that Wilkins had provided. By way of response, Watson and Crick produced “Photo 51,” Rosalind Franklin’s now-famous image that enabled crucial measurements concerning the structure of the B-form of DNA.

Presented with this evidence, Linus Pauling quickly conceded that Watson and Crick had solved the problem. Later that night, the Paulings, together with Watson, had dinner with the Cricks at their home at Portugal Place to celebrate. To quote Watson, each “drank their share of burgundy.”


 

So was it a race? And if so, what was Peter Pauling’s role? Was he a double agent or an informant? Or merely an unwitting accomplice, ignorant of the full implications of his actions?

In trying to answer these questions, it is important to emphasize that, for Peter, the “race for DNA” had never been a race at all. His father, he believed, was only interested in the nucleic acids as an interesting chemical compound. Linus Pauling clearly didn’t attack the structure with the same tenacity as Watson, in particular, who regarded the genetic material as the holy grail of biology, the secret of life. As Peter would write two decades later in New Scientist 

The only person who could conceivably have been racing was Jim Watson. Maurice Wilkins has never raced anyone anywhere. Francis Crick likes to pitch his brains against difficult problems… For Jim, however…the gene was the only thing in life worth bothering about and the structure of DNA was the only real problem worth solving.

In 1966, Jim Watson, then in the process of writing his book on the discovery of DNA, The Double Helix, sent Peter Pauling an early draft. His concern, he explained, was that he accurately portray Peter’s role in the entire affair; that, and he didn’t want Peter to sue him for defamation.

Peter laughed and told his old office mate that he thought it was a very good book; certainly very exciting. However, he pointed out that Watson should ask Linus Pauling for an agreement not to sue him, too. After all, Peter said, “He has more experience than I do.”

Advertisements

A Feminist and an Educator

Ava Helen Pauling at home, 1977.

[Part 3 of 3; “The Atomic Awakening of Ava Helen Pauling,” by Ingrid Ockert]

Ava Helen the Educator

As a public speaker, Ava Helen sought to both educate and empower her audience. She deftly wove scientific facts, sociological theories, and inspirational prose into an entertaining speech. A survey of the speeches which remain in the Pauling Papers at Oregon State University offer a glimpse of the scientific topics which Ava Helen covered; a range which included ecology, chemistry, physics, and biology. Most of her speeches were focused on the dangers of radiation and many would have fit well into the National Committee on Atomic Information’s collection of educational atomic literature. In one such speech, “High Energy Radiation and the Human Race,” Ava Helen discussed the history of radioactivity. Drawing on then-current studies, she clearly explained how radiation affects the human body. “High Energy Radiation,” like all of her speeches, was tailored to a female audience. Throughout the speech, Ava Helen beseeched fellow mothers to think about the health of their own children:

[Scientists] from the Atomic Energy Commission estimated the total genetic hazards of carbon-14 produced by the explosion of atomic bombs…their estimates are 500,000 children with gross physical and mental defect, 1,900,000 still born and childhood deaths, and 4,500,000 embryonic & nonnatal deaths.

Ava Helen utilized hard statistics and emotional appeals to connect the women in her audience to the dangers of atomic weapons. Her desire to educate women on radiation dangers extended beyond the lectern. Ava Helen, like many women who were allied with the NCAI, also promoted scientific education by creating public informational displays on atomic energy and arranging showings of scientific educational films. She distributed literature, such as pamphlets and booklets, on the dangers of nuclear weapons. Only two educational pamphlets on the dangers of atomic warfare survive in Ava Helen’s personal papers.

As Ava Helen’s reputation as a dynamic lecturer grew, she started to speak to her audiences on more general scientific topics. She became interested in the environment in the 1970s and gave speeches on water pollution and habitat loss. She asked audiences members to consider how their actions affected the quality of local drinking water. She also appeared on radio stations and gave short speeches on various scientific topics. Only one transcript of these broadcasts survives – on the science of making bread.

Ava Helen the Feminist

Ava Helen wanted to both educate and empower her audiences. She paired the democratic vision of the atomic scientists with the egalitarian beliefs of the feminists. Ava Helen earnestly believed that social equality for women was key to creating world peace. “I believe that we can only make real progress towards a better world if men and women work together,” she told an audience in the early 1960s. The peace movement had successfully united intelligent and motivated women towards a common goal. Ava Helen recognized the potential strength of the women’s peace movement and wanted to see that energy channeled toward women’s liberation.

Ava Helen at a women’s group meeting, ca. 1950s.

Ava Helen had certainly witnessed gender discrimination throughout her life. She had especially seen it within in the academic community. In a private interview in the 1970s, she confided her fury regarding the treatment of Rosalyn Franklin, who greatly contributed to the discovery of DNA. “If only women’s lib had come along a few years earlier,” she lamented. “If ever there was a woman who was mistreated, it was Rosalind Franklin…. She didn’t get the notice that she should have gotten for her work on DNA. She died.”

Ava Helen could personally empathize with Franklin. Both women had been denied the highest public honor for their contributions to society, a Nobel Prize. Linus Pauling received the Nobel Peace Prize in 1963, which both delighted and disappointed the Paulings. Although Linus certainly deserved credit for galvanizing the scientific community towards peace, Ava Helen had worked within the peace movement for at least as long. She was thrilled for him, but they were both saddened that the prize hadn’t been awarded jointly. Publicly, Linus gave Ava Helen full credit. As he accepted the Nobel, Linus told the crowd, “In the fight for peace and against oppression, [Ava Helen] has been my constant and courageous companion and coworker.” Still, the entire incident highlighted Ava Helen’s growing frustration with the accepted status of women.

Ava Helen was especially appalled by the lack of social progress in the United States. She angrily observed in a 1964 speech

Discrimination against women is still very real and nowhere more than here in the United States, which lags woefully behind the more advanced Western Nations and indeed in many respects behind the socialist countries.

Determined to rally the spirit of American women, Ava Helen traveled nationally to colleges, churches, and women’s clubs to spread the word.

Ava Helen loudly urged the women in her audience to stand up for themselves. “Women have equal capacity with men in brain power, talents, and capabilities,” Ava Helen proclaimed in a 1964 talk. “Indeed, in the matter of courage, sensitivity, and fearlessness, they may be superior.” Ava Helen especially wanted her female colleagues to pursue careers and to advocate for equal pay. She applauded President Kennedy’s 1961 Commission on the Status of Employed Women, which revealed discrimination across virtually all work fields. Ava Helen encouraged women to pursue non-traditional careers in medicine and science. “In every field of human endeavor… writing, science, engineering, woman has shown that she has ability,” Ava Helen told her audience. She famously suggested that the first scientists were women. She eagerly cited studies showing the equal intellectual abilities of boys and girls. She celebrated the appearance of women scientists, like Rachel Carson. In a speech given at a medical conference in the 1970s, Ava Helen applauded the appearance of women-run women’s health clinics. Like her suffragette mother before her, Ava Helen actively promoted equality between men and women.

Conclusion

“No woman wants to be put up on a pedestal, where she can be easily ignored and neglected,” remarked Ava Helen during one of her speeches. “She wants to be taking and doing her part in the affairs of the world with her feet on the ground and sharing in and contributing to the life around her.”

Ava Helen speaking at the Quilapayun Concert in Tribute to Victor Jara, Eugene, Oregon, 1979.

Despite her earlier misgivings about a woman’s role in life, Ava Helen leapt onto the world stage and become a political player. By the late 1970s, almost half a century after she had been a starry-eyed student in Germany, Ava Helen had finally become a respected public citizen within the international peace community. During the Cold War, Ava Helen had transformed from a frustrated suburban hausfrau into a confident public speaker. She became a dynamic player in two social revolutions that dared Americans to challenge their previously accepted conceptions about the roles of scientists and women. Although Ava Helen eventually accepted her own role as a non-scientist, she encouraged other women to pursue their own scientific careers. She became a role model for other women within her own community, who were interested in pursuing lives outside of domestic circles. Although Ava Helen modestly downplayed her own abilities, her insightful speeches won the admiration of American women. When a newspaper reporter asked Ava Helen what it was like to live with a genius, a friend of the Paulings piped up, “Ask Linus. He’s been living with Ava for years.”

Letters to Peter

Linus and Peter Pauling at Warwick Castle, England. 1948.

Linus and Peter Pauling at Warwick Castle, England. 1948.

“You know how children are threatened ‘You had better be good or the bad ogre will come get you.’ Well, for more than a year, Francis and others have been saying to the nucleic acid people at King’s ‘You had better work hard or Pauling will get interested in nucleic acids.’”

Peter Pauling. Letter to Linus Pauling, January 13, 1953.

Normally, when Linus Pauling became interested in something, he would dive headlong into it. Hours and hours of his time, over weekdays and weekends, would be committed to research in pursuit of fleshing out every last useful detail. This arduous process is best illustrated by his work on the nature of the chemical bond, work which would later win him a Nobel Prize in Chemistry.

Pauling’s experience with DNA, however, was not an example of this typical approach.

First, it should be noted that Pauling did not have years to spend working on DNA. Its importance was fully realized in the summer of 1952, less than a year before Watson and Crick elucidated its structure, and although Pauling actually began studying nucleic acids as early as 1933, he wasn’t able, or willing, to spend a significant amount of time on a molecule that was perceived to be relatively unimportant.

Even after learning of the importance of DNA, Pauling still didn’t make time for it. As emphasized in earlier posts on Linus Pauling and DNA, Pauling remained very much preoccupied with his work on the nature of proteins.

An examination of Pauling’s correspondence with his son Peter – a man uniquely positioned in the middle of the DNA story – reveals that other matters, many of them trivial, also took precedence over Pauling’s pursuit of the structure of DNA.

In the fall of 1952, Peter Pauling, an aspiring crystallographer and the second oldest of the four Pauling children, began his graduate studies at the University of Cambridge. Coincidentally, James Watson and Francis Crick were also at Cambridge at this time, and not long after his arrival, Peter had met them, become an office-mate, and was spending off-hours time with the duo.

Because Linus Pauling and the Watson-Crick tandem were both attempting to solve the structure of DNA, Peter’s arrival at Cambridge gave his father an excellent opportunity to keep tabs on the work being done by his competitors in England. A close examination of the voluminous father-son correspondence from this era suggests, however, that DNA was far from a pressing topic in Pasadena.

Also, as to your curtains: will you check the dimensions and let us know. You say in your letter two windows 6’ 6” high, 50” and 37” wide respectively, in other words four curtains each 48” wide. Mama thinks that you probably mean four curtains each 36” wide. It would be hard to get the wider material.

Also, would you write us as to the exact points between which the vertical dimensions are measured. What is the distance from, say, the top of the window frame (or some other exactly specified locus) to the floor, and also to the bottom of the window frame? Mama thinks that probably the curtains should reach all the way to the floor, but in any case they should extend from the top of the window frame to the bottom of the window frame (if you have window frames), or from a point a little below the opening at the bottom. She suggests that one of your old curtains might serve for one of the windows, and that she would then have to make only a pair for the larger window.

I sympathize with you about the bed. I remember sleeping on a bed which had a two by four across under my ear; it was not very comfortable.

-Linus Pauling, letter to Peter Pauling, October 22, 1952.

Linus first wrote to Peter in England on October 22, 1952. By this time, the elder Pauling was well aware of the importance of DNA, but had not yet devised a structure. Watson and Crick, on the other hand, had developed a structure for DNA a year earlier. Although their model turned out to be incorrect, the two men continued their work with nucleic acids. Clearly, for Watson and Crick, DNA was becoming extremely important. For Pauling this did not appear to be the case – although Watson and Crick were both mentioned in this first letter, DNA was not.

As it turns out, other subjects – including, but not limited to, curtains for Peter’s new apartment, recent travels and upcoming travel plans, finances, and, of course, cars – were much more prevalent than was DNA in the Paulings’ early correspondence.

As time went on, nucleic acids naturally became a slightly larger topic, though never did they assume center stage. Take, for example, this letter sent from Linus to Peter on February 4, 1953. By the time of its authoring, Linus Pauling had completely developed his structure, and had also sent off his manuscript for publication, a development which merited one paragraph worth of description. The rest of the letter is used to discuss, in great detail, Pauling’s plans to travel to England and also his keen interest in purchasing a new Riley from the U.K.-based International Motors. (Being something of a family obsession, cars were a very popular subject in many of the letters between Linus and Peter.)

In another letter from Pauling to Peter written on March 10, 1953, DNA plays a much larger role. This time, about half of the three-page document is dedicated to discussing various aspects DNA; the remainder focuses on travel plans and automobiles.

Peter Pauling, December 1954.

Peter Pauling, December 1954.

The other letters follow this same trend. Clearly, Linus and Peter’s lengthy discussions on subjects such as cars, traveling, curtains, and other aspects of science suggest that Pauling wasn’t interested in DNA on the level of certain other scientific pursuits.

Another interesting aspect of the correspondence between Linus and Peter Pauling is the opportunity that it provides for tracking the evolution of the consensus response to Pauling’s structure.

As might be expected, Peter’s reaction stayed upbeat throughout all of their letters. However, as time progressed, it is clear that Peter became less-confident that his father had solved DNA. For example, in a few of the earlier letters, Peter mentions that Watson and Crick earlier devised and discarded a structure similar to the Pauling-Corey triple helix, but that the opinion at the Cavendish Laboratory is that Pauling’s structure is a good one, albeit “pretty tight.”

From that point on though, Peter begins talking less about Pauling’s structure, and more about work being done by Watson, Crick, and Rosalind Franklin. One might deduce that, although Peter didn’t specifically issue a disagreement with his father’s structure, he did develop a certain degree of skepticism as time progressed. Peter also does not often mention other opinions of his father’s structure, most likely because, upon further examination, it was not well-received by the English contingent.

Peter Pauling Discusses His Father’s Strengths and Personality

For more information on DNA, please visit the Race for DNA website. For more information on Linus Pauling, check out the Linus Pauling Online portal.

Chargaff’s Rules

Erwin Chargaff, 1930.

Erwin Chargaff, 1930.

“We have created a mechanism that makes it practically impossible for a real genius to appear. In my own field the biochemist Fritz Lipmann or the much-maligned Linus Pauling were very talented people. But generally, geniuses everywhere seem to have died out by 1914. Today, most are mediocrities blown up by the winds of the time.”

-Erwin Chargaff, 1985.

Erwin Chargaff, (1905-2002) a biochemist born in Austria, became interested in DNA earlier than most. In the 1930s, while he was working with the bacteria Rickettsi, he became aware of nucleic acids, and decided to educate himself about them.

In 1944, after Oswald Avery published his paper detailing the transforming principle of the Pneumococcus bacteria, Chargaff decided to devote his laboratory almost entirely to the chemistry of nucleic acids. Experimenting with these delicate substances was not an easy task, but eventually a chromatographic technique was developed that would allow for the separation and analysis of the base rings in DNA. This work would later lead to the development of Chargaff’s Rules, the topic of today’s post.

The guanine-cytosine base pair.

The guanine-cytosine base pair.

DNA has two main structural components – a backbone made up of sugar and phosphate groups, and a series of bases found in the middle of the molecule. There are four different bases found in DNA: Adenine (A), Cytosine (C), Guanine (G), and Thymine (T). These four bases can be divided into two categories, pyrimidines and purines. The pyrimidine bases, Cytosine and Thymine, contain only one ring, while the purine bases, Guanine and Adenine, contain two rings. In the DNA structure, the bases pair complementarily, meaning that a purine base will bind with a pyrimidine base. More specifically, Adenine binds with Thymine and Cytosine binds with Guanine.

The adenine-thymine base pair.

The adenine-thymine base pair.

Although this information is now considered fundamental biology, it wasn’t fully understood until after Watson and Crick discovered the structure of DNA in 1953. However, Chargaff’s research in the late 1940s had suggested that the four bases paired in the manner described above.

When Chargaff first decided to devote his laboratory to nucleic acids, he allowed a postdoctoral student named Ernst Vischer to choose his research program from a list of suggested topics. Vischer decided to analyze the purines and pyrimidines in nucleic acids, and went to work developing the chromatographic technique so crucial to isolating the bases. Although his technique was rather crude, it did the trick and Vischer achieved great success. The results of the base analysis showed that the amounts of Adenine and Thymine were about equal, and also that the amounts of Guanine and Cytosine were about equal. Eventually, Chargaff came to the conclusion that in a single molecule of DNA, Guanine/Cytosine = Adenine/Thymine = 1. This concept would later become known as Chargaff’s Rules.

Chargaff’s Rules were officially announced in a lecture delivered in June of 1949 and were first published in May of 1950. However, Linus Pauling had heard about the ratios much earlier – straight from Chargaff in late 1947, while traveling to England for his six-month stay as a professor at Oxford University. Pauling, who considered the trip by ship across the Atlantic Ocean with his family to be a vacation, did not pay attention to what Chargaff told him.

Crellin Pauling, the youngest child of Linus and Ava Helen Pauling, mentioned the remarkable background to the incident in a speech given during a symposium to celebrate Pauling’s life that was held here at Oregon State University in 1995.

Crellin Pauling on “The DNA Story: A Missed Opportunity.”

[Click here to view the rest of Crellin’s talk]

Over time Chargaff mentioned his work to individuals beyond Pauling. In the spring of 1952, Chargaff met James Watson and Francis Crick.  A prickly character, it is clear that Chargaff didn’t think much of the duo. In his truly remarkable autobiography Heraclitean Fire: Sketches from a Life before Nature, Chargaff calls Watson and Crick “a variety act” and further describes them as:

One 35 years old (Crick), with the looks of a fading racing tout. . .an incessant falsetto, with occasional nuggets gleaming in the turbid stream of prattle. The other (Watson), quite undeveloped. . .a grin, more sly than sheepish. . .a gawky young figure.

He further notes that:

I never met two men who knew so little and aspired to so much. They told me they wanted to construct a helix, a polynucleotide to rival Pauling’s helix. They talked so much about ‘pitch’ that I remember I wrote it down afterwards, ‘Two pitchmen in search of a helix.’

[More samples from Chargaff’s acid pen are available here]

Regardless of what he thought of them, Chargaff still mentioned his work to Watson and Crick. The information, although published almost two years earlier, seemed to be new to the pair.

Though Chargaff himself didn’t speculate much on his rules, and Pauling completely ignored them, they did prove to be extremely useful to Watson and Crick. With this new knowledge, the feedback they had received from Rosalind Franklin and Maurice Wilkins, and data obtained through their own research, Watson and Crick were soon able to correctly deduce the structure of DNA.

For more information on DNA, please visit the Race for DNA website, or check out the other posts in the DNA series. For more information on Linus Pauling, visit the Linus Pauling Online portal.

The X-Ray Crystallography that Propelled the Race for DNA: Astbury’s Pictures vs. Franklin’s Photo 51

Rosalind Franklin, March 1956

Rosalind Franklin, March 1956

During their so-called race to discover the structure of DNA, Linus Pauling and the unlikely pair of James Watson and Francis Crick utilized remarkably similar approaches in attempting to solve the riddle of the genetic material. In fact, one of the main tactics used by Watson and Crick was to approach the problem in the same manner that they assumed Pauling would. Although Pauling and Watson and Crick did, at one point, come up with nearly identical, yet incorrect, structures, it was Watson and Crick who would eventually solve DNA. Why then, if the pair were thinking like Pauling, were they able to beat him to the structure?

Although there were a variety of reasons behind Watson and Crick’s success, a good portion of it can be attributed to the relative superiority of resources available to them. Watson and Crick obviously had each other to keep themselves in check, but they also benefited from other voices of criticism such as Rosalind Franklin, Maurice Wilkins, and later Jerry Donohue. Linus Pauling also shared his ideas with his colleagues, but none of them were very familiar with DNA, and therefore couldn’t offer much feedback. (And they were largely ignored even when they did offer criticisms of Pauling’s structure.)

Another vital resource available to Watson and Crick was an excellent X-ray crystallography pattern, the famous photo 51, taken by Rosalind Franklin. Although, in all likelihood, Pauling could have also viewed Franklin’s photographs had he tried, he settled on using blurry patterns published by William T. Astbury several years before Franklin’s superior images. These X-ray photographs are the main topic of today’s post. In particular, the factors accounting for the difference in quality between Franklin’s and Astbury’s patterns will be discussed. Before delving into this subject, however, a brief overview of X-ray crystallography is necessary.

William T. Astbury, ca. 1950s.

William T. Astbury, ca. 1950s.

X-ray crystallography, also sometimes known as X-ray diffraction, is used to determine the arrangement of atoms within a crystalline molecule. It is a rather complicated procedure, and the photos taken in the process can be interpreted only by a person with significant training. The steps to obtaining these photos are as follows.

First, an adequate crystal must be obtained. This is a very difficult step because the crystal must be large enough to observe and also sufficiently uniform. If it does not meet these specifications, errors – such as blurriness – will occur, often rendering the resulting crystallographic patterns useless, at least for purposes of determining atomic arrangement.

After an adequate crystalline specimen is obtained, a beam of X-rays is shined through it. When the beam strikes the electron clouds of the atoms in the crystal, it is scattered. These scattered beams can then be observed on a screen placed behind the crystal. Based on the angles and intensities of the scattered beams, a crystallographer can create a three dimensional picture of the electron density of the crystal.

Finally, from the electron density information, the mean positions of the atoms within a crystal can be determined, and the structure of the molecule can be considered “solved.” That said, just one image is not nearly enough to determine the structure of an entire crystal. Therefore, the crystal must be rotated stepwise through angles up to and even slightly beyond 180 degrees, depending on the specimen. Patterns are required at each step, and complete data sets may contain hundreds of photos.

Clearly, because the process of X-ray crystallography is so cumbersome, there are many opportunities for mistakes that may have led to the poor quality of Astbury’s photographs. However, Astbury’s techniques seem to have been excellent. He was a very experienced crystallographer, and had achieved great success in his earlier work with X-ray diffraction on substances such as keratin.

As it turns out, Astbury’s photos were of poor quality because of the DNA sample he was using. In the early 1950s, Rosalind Franklin had discovered that DNA came in two forms – a dry condensed form and a wet extended form. Astbury’s DNA sample was well prepared from calf thymus, but it contained a mixture of the two forms. This turned out to be the major reason why Astbury’s photographs were so blurry

Astbury's images, 1947. Plate 2.

Astbury's images, 1947. Plate 2.

It is important to note that, even if Astbury had known he was using a poor crystalline sample of DNA, he probably still wouldn’t have been able to compete with the quality of Franklin’s photos. In 1950, three years after Astbury’s images were published, Maurice Wilkins developed a way to obtain much better X-ray patterns of DNA through the use of a solution of sodium thymonucleate. This solution is highly viscous, and Wilkins found that thin strands could be drawn out by gently dipping a glass stirring rod into a sample and slowly pulling it out. These thin strands were pure DNA, and Wilkins was able to get excellent X-ray patterns from them.

Before long, Wilkins had also acquired better equipment and had also hired Rosalind Franklin to run it. Franklin, essentially working independently, used the same basic technique developed by Wilkins. She did, however, add several of her own smaller experimental refinements, which made the photographs even better. Eventually, she developed photo 51, which would later be shown to Watson and Crick. The rest, as they say, is history.

Rosalind Franklin and William Astbury were both excellent crystallographers, but Franklin’s experience with DNA gave her a clear advantage when working with the molecule. Her brilliant X-ray patterns would later prove to be a major determining factor in the “race for DNA”. For more information on DNA, please visit the Race for DNA website. For much more on Linus Pauling, check out the Linus Pauling Online portal.

The Watson and Crick Structure of DNA

Francis Crick and James Watson, walking along the the Backs, Cambridge, England. 1953.

Today, our series on models of DNA is concluded with a discussion of the correct structure determined by James Watson and Francis Crick. Although they made an unlikely pair, the two men succeeded where one of the era’s leading scientists – Linus Pauling – failed, and in the process they unraveled the secrets of what may be the most important molecule in human history.

In the fall of 1951, James Watson was studying microbial metabolism and nucleic acid biochemistry as a postdoctoral fellow in Europe. It didn’t take long for him to tire of these subjects and to begin looking for more inspiring research. He became interested in DNA upon seeing some x-ray photos developed by Maurice Wilkins. He then tried to talk his way into Wilkins’ lab at King’s College, but was denied and ended up studying protein x-ray diffraction in the Cavendish Laboratory at Cambridge University. Here he was assigned space in an office to be shared with an older graduate student named Francis Crick, a crystallographer. At the time, Crick was studying under Max Perutz, and was also becoming bored with his research. Watson and Crick hit it off immediately and before long, Watson’s interest in DNA had worn off on Crick. Although neither of them were experts in structural chemistry, they decided to attempt to solve the structure of DNA. As Watson put it, their planned method of attack would be to “imitate Linus Pauling and beat him at his own game.”

The pair’s first attempt at the structure in the fall of 1951 was very quick, and also unsuccessful. Interestingly, however, it was quite similar to Linus Pauling and Robert Corey‘s own attempt about a year later. Watson and Crick came up with a three stranded helix, with the base rings located on the outside of the molecule and the phosphate groups found on the inside. This left them with the problem of fitting so many negatively charged phosphates into the core without the molecule blowing itself apart. In order to solve this problem, they turned to Pauling’s own The Nature of the Chemical Bond. They were looking for positive ions that would fit into the core of DNA, therefore canceling the negative charge. They found magnesium and calcium to be possibilities, but there was no significant evidence that these ions were in DNA. However, there was no evidence against it either, so they ran with the idea.

Watson and Crick assumed – as would Pauling in his later attempt – that the finer details would fall into place. Overjoyed at solving DNA so quickly, they invited Wilkins and his assistant, Rosalind Franklin, to have a look at their structure. Expecting praise, they were undoubtedly surprised when Franklin verbally destroyed their work. She told them that any positive ions found in the core would be surrounded by water, which would render them neutral and unable to cancel out the negative phosphate charges. She also noted that DNA soaks up a large amount of water, which indicates that the phosphate groups are on the outside of the molecule. All in all, Franklin had no positive feedback for Watson and Crick.  And she was, at it turned out, correct. After the visit, Watson and Crick attempted to persuade Wilkins and Franklin to collaborate with them on another attempt at the structure of DNA, but their offer was declined.

Diagram of the double-helix structure of DNA. August 1968.

When Sir William Lawrence Bragg, the head of the Cavendish laboratory, heard about Watson and Crick’s failure, he quickly sent them back to other projects. Almost a year passed with Watson and Crick accomplishing no significant work on DNA. Although they weren’t building models, DNA was still at the front of their minds and they were gathering information at every opportunity. In the fall of 1952, Peter Pauling, the second eldest of Linus and Ava Helen Pauling’s four children, arrived at Cambridge to work as a graduate student. Jerry Donohue, another colleague of Pauling’s from Caltech, also arrived at the same time and was assigned to share an office with Watson and Crick. As a result, Peter also fell in with the group. Therefore, as the quest for DNA progressed, Linus Pauling was provided with a general idea of Watson and Crick’s work with DNA through contact with Peter. However, the opposite also proved true.

When Pauling and Corey submitted their manuscript on the structure of DNA in the last few days of 1952, Peter passed on to Watson and Crick the news that his father had solved DNA. Although the two men were crestfallen by this information, they decided to soldier on with their own program of research, figuring that if they published something at the same time Pauling that did, they might at least be able to share some of the credit.

Around this time, the pair added an important piece of information that they had learned from Erwin Chargaff, a biochemist. He had told them that the four different base rings in DNA appeared to be found in pairs. That is, one base ring is found in the same relative amounts as another. This first correlation constitutes one pair, and the remaining two bases make up the other pair. Interestingly enough, Chargaff had also told Pauling this same thing in 1947. However, Pauling had found him to be annoying and, as a result, disregarded his tip. Chargaff’s information did, however, prove to be crucial for Watson and Crick, who were slowly piecing together the basics of the DNA structure.

When Watson and Crick finally received Pauling’s manuscript via Peter in early-February 1953, they were surprised – not to mention elated – to see a structure very similar to their own first attempt. Bragg, a long time competitor of Pauling’s, was so pleased to see Pauling’s unsatisfactory work that he allowed Watson and Crick to return to DNA full time. The pair wasted no time, and had soon spread the news about Pauling’s model to all of Cambridge. Watson even told Wilkins about the manuscript, and was rewarded with the permission to view Franklin’s most recent DNA x-ray patterns. These beautifully-clear photos immediately confirmed Watson’s suspicion that DNA was a helix, adding yet another piece of important information.

Based on all of the information that they had gathered, Watson and Crick began rapidly building models. One model, which Watson called “a very pretty model,” contained the wrong structures for two base rings. Fortunately, Donohue, who was an excellent structural chemist, set them right. After his correction, Watson and Crick noticed that hydrogen bonds would form naturally between the base pairs. This explained Chargaff’s findings, and also showed the potential for replication of the molecule. The rest of the model came together quickly, and Watson and Crick began to write up their structure.

Eventually, Linus Pauling began to catch wind of the recent work that Watson and Crick had been doing with DNA. His first actual glimpse of their work came in March 1953 when Watson sent a letter to Max Delbrück, a colleague of Pauling’s, that included a brief description and rough sketches of the structure. Although Watson had asked Delbrück not to show the letter to Pauling, Delbrück could not resist. Pauling marveled at the simplicity and functionality of the structure, but still retained confidence in his own structure. Only a few days later, Pauling received an advance copy of the Watson and Crick manuscript, but he was still not convinced they had solved DNA. In April, Pauling finally traveled to England, and only after seeing the model in person and comparing it to Franklin’s DNA photographs was he certain that Watson and Crick had solved the structure of DNA.

On April 25, 1953, Watson and Crick’s article, “A Structure for DNA” was published in Nature. James Watson, Francis Crick, and Maurice Wilkins would go on to share the Nobel Prize in Physiology or Medicine for 1962 “for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material.” Unfortunately, Rosalind Franklin died of cancer at age 37 and, for many years, was given only minor credit for her considerable contributions related to the discovery of the DNA structure.

For more information on Watson and Crick and DNA, please visit the website Linus Pauling and the Race for DNA: A Documentary History. For more information on Linus Pauling and his research, visit the Linus Pauling Online Portal.

The Pauling-Corey Structure of DNA

Today, the structure of DNA series is continued with the model proposed by Linus Pauling and Robert Corey in 1953. As a result of insufficient data and an overloaded research schedule, Pauling’s structure turned out to be incorrect. However, it is interesting to see the ways in which one of the world’s leading scientists went wrong with his approach to the structure of this hugely-important molecule.

Linus Pauling played around with nucleic acids as early as 1933 when he hypothesized a structure for guanine, a base ring. In the summer of 1951, he again became interested in DNA when he heard that Maurice Wilkins at King’s College had developed a few good photographs of nucleic acids. Unfortunately for Pauling, Wilkins was unwilling to share his research. In November of that same year, a structure of nucleic acids was proposed and then published by Edward Ronwin. Pauling could tell almost immediately that Ronwin’s structure wasn’t correct, but it did contain a few good ideas that got him thinking about other possible structures. Pauling hypothesized that DNA was likely helical in shape, with the large base groups facing out and the phosphate groups stacked in the core. At this juncture, however, Pauling was again distracted by other research and let the project drop.

Until 1953 nucleic acids weren’t considered to be very important. At the time, proteins, rather than DNA, were considered by most scientists to be the carriers of genetic material. Partly because of this, Pauling’s attention was focused on proteins, not DNA. In May of 1952, Pauling was scheduled to attend a special meeting of the Royal Society where he would address questions pertaining to his protein structures. This trip would also give him an opportunity to discuss DNA with Rosalind Franklin, who was Maurice Wilkins’ assistant. She had recently developed an especially clear photograph of DNA which likely would have saved Pauling from making some key mistakes when determining the structure of DNA.

As a result of his very-public anti-war and anti-nuclear activities, Pauling’s initial request for a passport was denied, though he was granted a limited passport only ten weeks later. However, when Pauling arrived in England, he did not visit King’s College. He was preoccupied with his protein research and he assumed that Wilkins still wouldn’t be willing to share his data.

Soon after his visit to England, Pauling was granted a full passport and traveled to France. Here he was informed, through an experiment performed by Alfred Hershey and Martha Chase, that DNA was in fact the genetic master molecule. Upon learning this, Pauling decided that he would solve the structure of DNA. However, when he returned to California, he continued to work primarily with proteins. It wasn’t until November 25, 1952 that Linus Pauling would make a serious attempt at the structure of DNA.

Unfortunately, when Pauling did decide to put in some time with DNA, he still had insufficient data to correctly deduce its structure. Using only a few blurry x-ray patterns done by William Astbury in the 1930s and a photograph published by Astbury in 1947, Pauling decided that DNA was indeed a three-chain helix with the bases facing outward and the phosphates in the core.

Astbury's 1947 photographs of DNA.

Astbury's 1947 photographs of DNA.

However, it was immediately clear that making room for so many phosphates in the center of the molecule would be quite a task. Pauling spent a great deal of time manipulating his model, and eventually produced a satisfactory representation. He then asked Robert Corey, his chief assistant at Caltech, to perform detailed calculations on the proposed atomic positions. Corey’s calculations proved that, despite Pauling’s efforts, there still wasn’t enough room for all of the atoms. Pauling, refusing to consider the possibility that his structure was incorrect, resorted to further manipulation. (In fact, Pauling refused to concede even after a colleague pointed out that there was no room for sodium ions in the core of his model, a feature that is essential in the creation of sodium salts of DNA.) Convinced that the finer details would later fall into place, Pauling and Corey spent the last week of the year writing up their structure, and on the last day of 1952, they submitted “A Proposed Structure for the Nucleic Acids” to the Proceedings of the National Academy of Sciences.

Diagram of the Pauling-Corey structure for DNA, as published in PNAS.

Diagram of the Pauling-Corey structure for DNA, as published in PNAS.

The paper was uncharacteristic of Pauling. Instead of his usual confidence, he stated that the structure was “promising” but also “extraordinarily tight.” Pauling likewise noted that the model accounted only “moderately well” for the x-ray data, and that the atomic positions were “probably capable of further refinement.” As it turned out, Pauling wasn’t seeking perfection with his structure. In reality, he wanted to be the first to publish a roughly correct structure of DNA. Rather than having the final say, he wanted the first.

Once the article was published in February of 1953, it became more and more apparent that Pauling’s structure wasn’t even roughly correct. By this time, Pauling had already moved on to other projects, and was surprised at the fact that his paper was received so poorly. Once he caught wind of the talk surrounding his structure, he decided to return to the topic of DNA. Despite the negative reaction, Pauling still believed that his structure was essentially right. However, he soon received better nucleotide samples from Alex Todd, an organic chemist at Cambridge, and began a more rigorous approach to determining the structure of DNA.

Unfortunately, by this time it was too late. Upon the publication of Pauling’s unsatisfactory model, James Watson and Francis Crick were given the green light to pursue their own model of DNA. Before long, Pauling saw that the work they were doing was very promising. A few days after first seeing their structure, Pauling received an advance copy of the Watson and Crick manuscript. At this point, he still retained a fair amount of confidence in his own model, but acknowledged that there was now another possible model. In a letter to Watson and Crick written on March 27, 1953, Pauling noted

I think that it is fine that there are now two proposed structures for nucleic acid, and I am looking forward to finding out what the decision will be as to which is incorrect.

However, he had still not seen Rosalind Franklin’s data; Watson and Crick had. (Interestingly enough, Robert Corey had traveled to England in 1952 and viewed Franklin’s photographs. It is unknown whether or not he purposely failed to provide Pauling with the details of the images.)

This fact would soon change. In April of 1953, Pauling was to attend a conference on proteins in Belgium. On his way, he stopped in England to see the Watson and Crick model of DNA as well as Franklin’s photographs. After examining both, Pauling was finally convinced that his structure was wrong and that Watson and Crick had solved DNA.

Linus Pauling, although disappointed with the results, accepted his defeat graciously. He gave Watson and Crick full credit for their discovery and assisted them in tying up a few loose ends with their model. For Pauling, this event was a single failure in a sea of successes. In fact, the very next year, he would win the Nobel Prize in Chemistry – the first of his two Nobel Prizes. Despite his embarrassing mistakes, Pauling was to remain in good standing with the scientific community.

Please check back on Thursday for the conclusion of the DNA structure series – an examination of the correct structure deduced by Watson and Crick. For more information on DNA, please visit the website Linus Pauling and the Race for DNA. For more information on Linus Pauling, visit the Linus Pauling Online Portal.