James D. Watson

James Dewey Watson was awarded the Nobel in Medicine or Physiology for his work in discovering the double helix structure of DNA along with Francis Crick and Maurice Wilkins in 1962.

Watson has written an autobiography of his journey to uncover the nature of DNA, “The Double Helix” which is a short but engaging insight into the foibles and aspirations of a young man completely lacking in any self-aggrandizement and his humorous and irreverent perspective into one of the major scientific accomplishments in the 20th century.

Watson was born in Chicago, Ill., on April 6th, 1928, where he attended Horace Mann Grammar School and then two years at South Shore High School. He received a scholarship to the University of Chicago, entering their experimental four-year college in the summer of 1943 and receiving his B.Sc. in Zoology in 1947. He then acquired a fellowship for graduate study in Zoology at Indiana University in Bloomington, where he received his Ph.D. degree in 1950.

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DNA

During his time at Indiana, he studied under Italian microbiologist S. E. Luria studying the effect of X-rays on bactriophages. He then spent a desultory post-doctoral year in Copenhagen (Sept. 1950 to Sept. 1951) as a Merck Fellow of the National Research Council studying with the biochemist Herman Kalckar, and then microbiologist Ole Maaløe. However, as he tells it, he was not getting anywhere close to his goal of discovering the nature of DNA and was ready to move on. He was also not impressed with his capacity for learning chemistry.

Linus Pauling

In April 1951, Linus Pauling had announced his version of the structure of proteins, an alpha-helix, at CalTech

Alpha-helix top view.

Alpha-helix, side view.

Pauling had worked through his vision of the alpha-helix by constructing paper and toy-like models to provide himself with a visual model rather than a -x-ray crystallography or mathematical version. Pauling's approach was basically to ask which atoms fit next to what other atoms. This is how he was able to construct a 3-D model that corresponded with the research to date. Watson and Crick were encouraged by this approach and used to extensively - an approach which was not widely accepted at the time and was to create some friction with other researchers.

Watson heard about Pauling's progress while in Geneva at the time of Pauling's announcement. Upon arriving back at Stockholm, Watson acquired the journal with the announcement and the following journal with a number of articles that went into more detail. Fired up by Pauling's progress, Watson began casting about for a means to get involved in this line of research.

Maurice Wilkins

At a Symposium at the Zoological Station at Naples in May 1951, he met Maurice Wilkins who was presenting a paper on the X-ray diffraction pattern of crystalline DNA. This was the first time Watson came into contact with this approach and provided him with a different perspective on uncovering the nature of DNA. It was to prove a critical development in his work. His post-doc supervisor, S. E. Luria was then able to acquire Watson a position working with John Kendrew at the Cavendish Laboratory at Cambridge, James Clerk Maxwell's and Ernest Rutherford’s old stomping grounds.

Francis Crick

Soon after starting work at the Cavendish in August of 1951 he met Francis Crick. Watson and Crick hit it off immediately. Crick had very little intellectual support for his theories about DNA – surprisingly enough, the intense interest we associate nowadays with DNA were not shared by the scientific community at the time. Outside of some researchers at King’s College, London (primarily Maurice Wilkins and Rosalind Franklin) and Linus Pauling in California, research in DNA was not a major emphasis in the 40’s and 50s.

Prior to his work in biology, Crick and Wilkins were both physicists but had switched after WWII. Watson’s reputation as a ‘phage’ man (bacteriophage) was the sort of support they needed to verify their aspirations in biology. This was at a time when research in separate fields was more disconnected than was to later become the norm.

Crick’s intellect was legendary. He was a true inter-disciplinarian and he was knowledgeable about crystallography, to Watson, an intimidatingly complex subject about which he knew little or nothing.

Watson and Crick were soon plotting to beat the science colossus Linus Pauling to the goal line. Watson’s boss at the Cavendish, John Kendrew, quickly saw that Watson was not going to be much help in his research into proteins as he spent his time with Crick in the quest for the secrets of DNA. Watson’s research at the Cavendish was in structural chemistry of nucleic acids and proteins. At that time, given that Linus Pauling was one of the foremost authorities in structural chemistry, and very involved in developing a theory of the structure of DNA, Crick and Watson naturally saw themselves in a race with Pauling to uncover the secrets of DNA.

A different helix

Watson and Crick initially thought of DNA as a large molecule of nucleotides with regular or identical bonds. While this was not definitively supported by the research at the time, they considered the orderly crystalline structure of DNA revealed to date and the necessity of a regular molecule given its hypothesised role in transmitting genetic information - also a novel idea at the time. The alpha-helix proposed by Pauling for the structure of proteins presented a few problems. First the crystallography for the DNA available indicated that the diameter was thicker than would be true of one polynucleotide. They had to accept the possibility that there was more than one chain of nucleotides. Two or three, it was not readily clear how many chains were twisted around each other in a helix. Added to the mystery was the question of how the nucleotides were bonded together, via hydrogen bonds or salt linkages from negatively charged phosphate groups.

At that time, it was also known that there were four nucleotides in DNA, the purines adenine and guanine and the pyrimidines cytosine and thymine. Watson and Crick initially made the assumption that the linkages between the nucleotides only involved the regular and predictable phosphate and sugar groups and not the bases. Such a chemical bond arrangement would give the molecule regular structure whilst the variation in the base sequences would allow for the variety that was essential to distinguish one gene from another.

Thus they set out to solve the riddle, armed with a few facts and a lot of deductive insight into what were only probable options. They thought they had two things to do, establish the best options as attested by the X-ray crystallography evidence and then start building models of the proposed structures.