I wrote this article as an assignment for a course "Culture of Scientific Research" where we discussed the events leading to the discovery of the structure of DNA and debated on the ethics behind Watson and Crick's actions. The assignment was to assume the role of one of the people involved in DNA research during the 1950's and write what they might have written. I decided to be Linus Pauling!
A double helix structure for the nucleic acid is now the accepted DNA structure. The nucleic acid is christened D.N.A. I appreciate how James Watson and Francis Crick used ball and stick models to figure out the elusive structure. It is much similar to my methods and Crick most graciously declared the structure as a tribute to me. They were of course aided by the excellent photographs taken by Rosalind Franklin. I would have been much more pleased by these gentlemen if they had had the scientific courtesy of accrediting peers for their contribution.
I myself was keenly interested in studying the structure of nucleic acid. My first interest in large molecules arose in 1930s while I was studying haemoglobin. Even since 1929, I wanted to learn how life works. Genes being a part of chromosomes was a new discovery then. Between the two components of chromosomes (nucleic acid and proteins), I felt proteins, having more complexity must be the unit of inheritance overseeing the growth of organisms. Robert Corey and I had studied the molecular structure of amino acids and protein subunits for almost two decades. In the spring of 1951, we published papers detailing protein structures at the molecular level most importantly that of alpha helix. X-ray diffraction was a newly discovered technique and was used widely to study many large molecules.
Astbury and Bernal had published X-Ray data for numerous biomolecules including nucleic acid present in the chromosomes and certain glandular tissues, then called thymonucleic acid. Its sodium salt forms viscous solutions from which oriented preparations could be made that gave excellent x-ray fibre photographs. Though I had referred Astbury’s X-ray data for proteins and tried to fit it to a model (which I had failed to do), I had not put much effort into understanding the nucleic acid structure. It was not until the summer of 1951 that my interest shifted to nucleic acids. I heard about the work done on sodium thymonucleate by Dr. Maurice Wilkin’s laboratory at King’s College, London. But Wilkins, quite understandably was not willing to share the experimental data and wished to publish independently. Astbury published one more photograph of thymonucleic acid in 1947. The strongest period along the fibre axis was at 3.34 Angstrom. The molecule had high density and the solid state was fibrous. Astbury proposed a structure where a column of nucleotides were piled up on each other. He also believed that each nucleotide in a nucleic acid is linked to its neighbours through phosphoric acid.
In 1951, Edward Ronwin outlined a possible structure of DNA based on Astbury’s data. Ronwin proposed that the phosphate groups were present in the middle of the molecule and the large bases stick out to the sides. This structure again sparked my interest. There were many inconsistencies in Rowin’s structure. His proposed structure would decompose rather rapidly in presence of water which seems to be abundant in DNA. I myself was contemplating a helical structure for nucleic acid which seemed logical for any molecule with repeating units. A helix with the nitrogen bases at the centre would be constrained sterically and hence phosphates in the centre and bases towards the outer side made more sense. Yet, I continued to work on protein structure which was in a very exciting stage then.
In the summer of 1952 at a meeting in France, I realized from the Hershey-Chase experiments that DNA, indeed contained the gene and I shifted my attention to it. I expected the structure of DNA to be much easier to eludicate as it was made of just four nucleotides as opposed to proteins made of 20 amino acids. Subsequent papers from different research groups described different aspects of the bonding between the numerous groups in DNA. Linkages between atoms of nucleotides and nitrogen bases as well as sugar and phosphates were known. Electron micrographs by R.C.Williams seemed to support the helical model. The meridional reflection in the X-Ray with spacing of 3.40 Angstrom indicated a unit consisting of three nucleotide residues. This could not be found in a single helix structure. Hence, we proposed a three stranded helix where each the three strands coiled around each other. The biggest mistake I made was in putting phosphate groups having no net charge at the centre of the helix. I ignored the crucial fact that at physiological pH, the phosphate groups would not possess hydrogen atoms and hence there would be no hydrogen bonds to hold the structure together. Also so many negative charges could not be accommodated in the core of the molecule as they would all repel each other. The model also did not account for the formation of sodium salts of DNA as sodium ions could not be accommodated within the core. This model failed to obtain acceptance. I had sensed this and started to correct some of the mistakes. I still thought our proposed structure needed more empirical evidence to be proved right which would require a couple of years.
Meanwhile Peter sent me an advanced manuscript by his collegues at the Cavendish which described a double helix D.N.A structure with phosphates towards the outer side and bases towards the inner side, paired according to Chargaff’s rules and held together by hydrogen bonds. I still hadn’t seen the photograph taken by Rosalind Franklin which aided Watson and Crick’s discovery and hence considered it prudent to withhold my judgement. In April 1953, I was at last able to have a look at the model of the double helix as well as the now famous photograph 51. Then, I realized, I was wrong and James and Watson, indeed had the right model. They are jubilant on winning their “race”!
In retrospect, I rushed towards finding the structure. Some more research on chemistry of purine and pyrimidines would have helped a lot in the same way that Chargaff’s rules helped Watson and Crick. As a parting note, I stress on the importance of this discovery. It will contribute immensely to the field of molecular genetics.
Linus Pauling
References:
1. Horace Freeland Judson(1979) The Eight Day of Creation.
2. Francis Crick(1988). What Mad Pursuit.
3. Watson, J. D. (1968). The Double Helix: A Personal Account of the Discovery of the Structure of DNA.
4. W. T. Astbury. (1939) X-ray studies of the structure of compounds of biological interest. Annu. Rev. Biochem. University of Leeds 113-133
5. Linus Pauling and Robert B. Corey. (1952) A Proposed Structure for the Nucleic Acids. Proc. N. A. S. (39)
6. J. D. Watson and F. H. C. Crick. (1953) Molecular Structure of Nucleic Acids. Nature. Vol. 171
7. https://paulingblog.wordpress.com/2009/04/28/the-pauling-corey-structure-of-dna/
Acknowledgements:
The course instructors and teaching assistants for the idea and help in execution.
