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Nobel prizes for Watson, Crick, Wilkins and who? Oh.. Rosalind Franklin.

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I do not understand DNA at all, so I have totally depended on Profiles in Science. But I do understand the sexist treatment of clever female intellectuals. British Rosalind Franklin (1920-58) was not the first woman to have endured indig­nit­ies in the male-dominated world of science, but Franklin's case was the most unfair.

James Watson, Francis Crick, Maurice Wilkins, Rosalind Franklin. 
Credit: Understanding Science (top images)

In 1944 Canadian-American Oswald Avery had shown that DNA was the transforming principle, the carrier of hereditary information, in pneumococcal bacteria. Nevertheless many scientists continued to misunderstand the gene. Researchers working on DNA in the early days used the term "gene" to mean the smallest unit of genetic information, however a gene actually functioned.

The 1953 discovery of the double helix, the twisted struct­ure of deoxy-ribonucleic acid/DNA, was made by two molecular biologists: British Francis Crick (1916-2004) and American James Watson (1928- ). The two men recog­nised early in their careers that gaining a detailed knowledge of the three-dimensional configuration of the gene was the central problem in molecular biology. Without it, heredity and reproduction could not be understood.

They seized on this problem in 1951, and focused on it. This meant taking on the monumental task of immersing themselves in genetics, biochemistry, chemistry and X-ray crystallography (X-ray diffract­ions used to deter­mine the atomic and molecular structure of a crystal). They took advantage of their great backgrounds in physics and X-ray crystal­l­ography (Crick) and viral and bacterial gen­etics (Watson). The two showed that DNA had a structure sufficient­ly complex to be the master molec­ule of life.
 
Watson's book: The Double Helix,1968

Other researchers made vital findings about the composition of DNA. Organic chemist Alexander Todd determined that the backbone of the DNA molecule contained repeating phosphate and deoxyribose sugar groups. Biochem­ist Erwin Chargaff found that while the amount of DNA, and its four types of bases, varied widely between species, A and T always appeared in ratios of one-to-one, as did G and C. New Zealand-British Maurice Wilkins (1916-2004) and British Ros­a­lind Franklin obtained high-resolution X-ray images of DNA fibres that suggested a helical, corkscrew-like shape. Am­erican chemist Linus Pauling discovered the single-stranded alpha helix, the struc­t­ure found in many proteins. Plus he pioneered the method of model building in chemistry by which Watson and Crick were to uncover the struct­ure of DNA. They had to unify these disparate find­ings into a coherent theory of genetic transfer. 

American Jerry Donohue, a visiting physical chemist, pointed out that the configuration for the rings of carbon, nitrogen, hyd­rogen and oxygen, the elements of all four bases, was incorrect in most chemistry textbooks. Acting on Donohue's advice in Feb 1953, Watson put the two bases into their correct form in cardboard models; he moved a hydrogen atom from a position where it bonded with oxygen to a neighbouring position where it bonded with nitrogen. While shifting around the cardboard cut-outs of the accurate molecules on his office table, Watson had a flash! He realised that A, when joined with T, very nearly resembled a combination of C and G, and that each pair could hold together by forming hydrogen bonds.

Watson and Crick published their findings in the British scientific weekly Nature, April 1953. They notably described the pair­ing of the bases on the inside of the two DNA backbones: A=T and C=G. The pairing rule immediately suggested a copying mech­anism for DNA, an idea which was developed in a second article in Nature, May 1953. The seq­u­ence of the bases in DNA formed a code by which genetic inform­ation could be stored and transmitted.
  
Watson and Crick's original article in Nature was rarely cited. Its true sig­nificance became apparent only later in the 1950s, when the their DNA structure was shown to provide a mechanism for control­l­ing protein synthesis. Watson wrote of their collaboration in The Double Helix (1968).

But note Watson and Crick's use of Ros­a­lind Franklin's crystallo-graphic evidence of DNA structure. It had been leaked to them by Franklin’s angry colleag­ue, Maurice Wilkins, WITHOUT Franklin’s knowledge or permission. Wilkins took Franklin’s Photo 51, an image of DNA and the result of over 100 hours on an X-ray crystallography machine she had perfected, and showed it to Watson and Crick.

Her evidence demonstrated that the two sugar-phosphate backbones lay outside the molec­ule, confirming Watson and Crick's guess that the back­bones formed a double helix. Franklin's superb work proved crucial in Watson and Crick's thesis; it was Photo 51 that enabled their breakthrough! While acknowledging their patronis­ing attitude towards this very clever female scientist, Crick stated they used Frank­lin’s findings appropriately. But the men gave Franklin no form­al acknowledgment, even after she died in 1958.

Franklin, X-ray diffract­ion and double helix model. 
Credit: Pinterest 

Although they conducted no DNA experiments of their own, Crick and Watson’s work became a landmark in science and gave rise to modern molec­ul­ar biol­ogy, answering how genes con­trol the chemical proc­esses in cells. The Nobel Prize in Physiology or Medicine 1962 was awarded jointly to Crick, Watson and Wilkins for their discov­eries. Franklin would not have been a Nobel recipient, even had she had been alive for the presentation in 1962 - 3 members in the team were the maximum accepted. 

But her role was investigated in Anne Sayre’s book Rosalind Franklin and DNA (1975). Chil­l­ing reports concluded that science was a breeding ground for this kind of inappropriate behaviour, due to a strict, male-dominated hierarchy. So writing Franklin’s role back into this critical scient­ific breakthrough was doubly important.





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