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.

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The Race for DNA: The Ronwin Structure

This post marks the beginning of an extensive series of posts on DNA. The first four posts in the series will cover structures of DNA proposed by various individuals, including one by Linus Pauling, as well as the correct structure discovered by James Watson and Francis Crick. Today, an early structure proposed by Edward Ronwin will be discussed.

Until the 1950s, DNA was not considered to be an important molecule. At that time, it was known that genes were located in chromosomes, structures made up of nucleic acids and proteins that can be found in the nucleus of cells. The nucleic acids, one of which is DNA, were not thought to be the carrier of genetic information, and therefore didn’t garner much interest from scientists. Even Linus Pauling favored the more complicated and abundant proteins as the site of the gene. However, there was still some research being done on DNA.

In November of 1951, the Journal of the American Chemical Society published a paper entitled “A Phospho-tri-anhydride Formula for Nucleic Acids.” This article was written by Edward Ronwin and outlined a possible structure of DNA.

At this time, it was known that DNA was made up of four nucleotides. These nucleotides were understood to each consist of a sugar attached to a phosphate group and to a large flat ring structure called a base. However, it wasn’t known how these nucleotides bonded together to form large molecules. In his structure, Ronwin proposed that the phosphate groups were placed down the middle of the molecule with the large bases sticking out to the sides. According to x-ray data gathered by William Astbury, this was a definite possibility. It also made the molecule much easier to manipulate.

Diagram of the Ronwin structure for the nucleic acids. November 1951.

Diagram of the Ronwin structure for the nucleic acids. November 1951.

Unfortunately, not everything about Ronwin’s structure made sense. Linus Pauling was quick to point out, through a letter to the Journal of the American Chemical Society, that the Ronwin molecule contained a structure for which no theoretical precedent existed. He added that in normal phosphorous compounds, the phosphorous atom is bonded to four oxygen atoms. However, in Ronwin’s molecule, the phosphorous atom is bonded to five oxygen atoms. Therefore, Pauling concluded, there was no significant evidence for such an extraordinary structure and that Ronwin’s idea deserved no serious consideration.

Not long after his letter appeared, Ronwin responded to Pauling and pointed out the existence of four synthesized phosphorous compounds with five oxygen atoms bonded to the phosphorous atom. This information forced Pauling to retract his earlier statement about precedence, but did not otherwise change his opinion of Ronwin’s work. He quickly drew attention to the fact that these compounds decompose rapidly in the presence of water, a prevalent substance in DNA.

All in all, Pauling was rather offended by Ronwin’s proposition. He noted in a May 1952 letter to John F. Tinker the extreme ease with which a scientist in the field of molecular biology could hypothesize structures, and that no reputable worker in the field would do so without significant supporting evidence.

Although Ronwin’s structure had a variety of faults, it appeared to spark some interest in DNA, at least for Pauling. Before long, other structures would begin to appear, and the race for DNA would be well on its way.

Check back on Thursday for the next post in the DNA series. For more information about DNA, please visit the website Linus Pauling and the Race for DNA:  A Documentary History, available at the Linus Pauling Online Portal.