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.

Linus Pauling baseball!

As the Phillies and Rays prepare for another rendition of the Fall Classic, we thought it appropriate to share with you one of our favorite pieces of video:  Linus Pauling playing beach baseball at a Caltech chemistry department picnic in 1938.

Author of more than 1,100 published articles and inarguably one of history’s great minds, Pauling’s knowledge of the strike zone was, evidently, a little less authoritative.  And while coaches around the world would surely appreciate Pauling’s hustle on the basepaths, one does fear for the safety of those enlisted to play third for any team opposing the two-time Nobel prizewinner.

The Linus Pauling baseball clip is just a small segment of “The Edward W. Hughes Tapes,” a series of home movies recorded by Hughes, for twenty-five years a colleague of Pauling’s at Caltech.  The Hughes tapes, which run to just under an hour, offer fascinating glimpses of Caltech social gatherings and Pasadena life over the course of five decades.  Along with Linus and Ava Helen Pauling, careful viewers will note the presence of multiple scientific luminaries in the films — Albert Szent-Györgyi, Dorothy Hodgkin, Jerry Donohue, James Watson and Francis Crick, to name a few.

It is worth noting that the tapes also include footage from additional baseball outings at later department picnics.  Pauling — whose general disinclination toward sports was covered here — doesn’t take part in these match-ups.  One who was a bit more interested in tossing it around the diamond was 1976 Nobel chemistry laureate William Lipscomb, who, in 1995, recounted that

[Pauling’s] illness from nephritis and his frequent trips meant that we did not see him very often, but he and his family did occasionally attend the Caltech Chemists games of (intermediate) baseball in the local league.

In a footnote, Lipscomb adds a few memorable details of his time roaming the outfield with The Chemists:

Seventy-five feet between bases, softball, but hardball rules and overhand pitching from 57.5 feet. I made the local newspaper for an unassisted triple play while playing center field.

Oregon State University, of course, has become something of a baseball powerhouse, given the Beavers’ back-to-back national championships in 2006 and 2007.  Our colleagues in the University Archives have created a terrific website documenting the evolution of this program through its centenary: Oregon State Baseball: 100 Years to a National Championship, 1907-2006.

Pauling the Educator

Linus Pauling in lecture, 1960s.

Linus Pauling in lecture, 1960s.

…[T]o awaken an interest in chemistry in students we mustn’t make the courses consist entirely of explanations, forgetting to mention what there is to be explained.”
– Linus Pauling. Letter to A. A. Noyes. November 18, 1930.

Linus Pauling began his teaching career in 1919, as an undergraduate sophomore, when Oregon Agricultural College offered him an assistant teaching position. After completing his graduate work at Caltech, Pauling dove into the role of educator as a fulltime professor.

Pauling believed that every student should approach chemistry with a sense of wonder and anticipation — he wanted his students to be excited and engaged. Pauling was not one to drone on in a hot classroom while his pupils dozed in their seats. Instead, he was always moving, gesturing and talking, a veritable flurry of activity at the front of the room. His lectures were filled with demonstrations, drawings, and models.

At a recent conference hosted by Oregon State University, one of the speakers, Nobel laureate Dr. Dudley Herschbach, told a story of Pauling’s in-class exploits. Dr. Herschbach explained,

“[T]here’s a classic [demonstration] always done in freshman chemistry – you have a bowl of water, you throw a chunk of sodium in, with some phenolphthalein so it changes colors as things go around and it reacts to produce a base. Well, Linus would do that, and then he’d get very excited about it and say “Isn’t this wonderful, it’s giving off hydrogen,” and all this, and then he’d say “What if we did it with gasoline!” He’d run down here, and all the students would be moving out of the way because the guy looks crazy because he’s so excited. He pours some gasoline in, steps back, and throws off the sodium chunk. Nothing happens. It was his way of making sure they appreciated one of the wonders of chemistry, that is, the business [of] how different things are.”

During his career at Caltech, Pauling’s freshman lectures became famous. While giving a presentation, if something caught his attention, he would explore the problem, following it through its different disciplines, tracing out theories and methods as he went. These seeming digressions often served to teach his students much more than any standard chemistry lecture could.

Indeed, Pauling was both interesting and entertaining, blessed with both an expansive knowledge base and a quick wit. Thomas Hager, a Pauling biographer, writes,

“Together with a spontaneity, vigor, and excitement, there was an ever-present sense of humor, and what a great many people have called ‘showmanship.’ Some have called one aspect of it ‘classroom calisthenics’ – leaps from the classroom floor to a sitting position on the lecture desk with legs dangling, or parallel bar exercises with one hand on the chalk tray and the other on the lecture podium, the body swinging back and forth while the lecture was going on at the same time.”

Despite his advanced abilities and deep understanding of multiple scientific disciplines, Pauling chose to spend much of his career teaching freshman chemistry. He was dedicated to bringing fresh minds into the field. By igniting a passion for the subject, or at least sparking an interest in young students, he knew he would be able to benefit both his pupils and the sciences.

Included among his students are:

Jerry Donohue – Aided James Watson and Francis Crick in their discover y of DNA’s structure.

Martin Karplus – Known for the creation of the Karplus equation.

Matthew Meselson – Responsible, in collaboration, for discovering how DNA replicates, recombines, and is repaired in cells.

E. Bright Wilson, Jr. – Notable advances in the fields of quantum mechanics and spectroscopy.

To learn more about Linus Pauling’s influence as an educator, please visit the website “Linus Pauling and the Nature of the Chemical Bond: A Documentary History.”