17 November 2020

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


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.




16 comments:

Parnassus said...

Hello Hels, I just read the Wikipedia articles on Franklin and Wilkins, and the truth seems to be a complicated affair. From a quick reading, I saw no animosity between Wilkins and Franklin, but there did seem to be a number of people who threw confusion into the laboratory and into Franklin's life. The article stated that Wilkins sent the famous Photo 51 after Franklin had left the lab, and I don't know the legal or ethical standards of the time of who controlled or owned the research, or whether Franklin should have been consulted.

Certainly, Photo 51 was the Rosetta Stone that revealed the structure of DNA, and Franklin should be given her full share of the credit. Perhaps her illness and death in the late 1950's had something to do with it. The odd and questionable "rule of three" I think had a lot to do with pushing her out of the picture. Also, she was a complicated and sometimes disagreeable person, a hero for today, but not necessarily for the 1950's. One admirable trait was that she was openly Jewish, refreshing for a period in which so many hid or (publicly, at least) disavowed their religion.
--Jim
p.s. Wilkins was an interesting and influential scientist. I read that he came from New Zealand, and had five children, so he had some first-had experience with DNA.

Fun60 said...

I think more and more we are realising that great scientific discoveries are often the work of a number of scientists and not just the lead scientist who picks up all the accolades.

Joseph said...

I started Medicine only a couple of years after the 1962 Nobel was given out. So right from those undergraduate years, we understood Franklin's crystallographic evidence of DNA structure. It was impressive to young ambitious students.

Anonymous said...

Clever women and just women being dismissed! And forgotten about or not noted in history. That is what happens. I haven't heard names of those who are behind the two supposed COVID vaccines but I bet some are women and possibly of Asian heritage. Meanwhile I am sure I will hear a pontificating male scientist on the radio tomorrow.

bazza said...

Many years ago I made quite a deep, amateur study of genetics & DNA. Initially through the very accessible books of Richard Dawkins and Steve Jones. I particularly recommend The Blind Watchmaker and, of course, The Selfish Gene. The BBC made an excellent drama about this story with Jeff Goldblum and Tim Piggott-Smith well cast as Crick & Watson.
I wrote about Rosalyn Franklin here:
https://todiscoverice.blogspot.com/2017/08/my-heroes-42-rosalind-franklin.html

Hels said...

Parnassus

admittedly the rule limited any single Nobel Prize to a maximum of three people has always been there and had nothing to do with the candidates' gender. Ditto the rule that a Nobel Prize cannot be awarded posthumously. But those problems could be easily resolved by awarding the prize to the key research institution eg The Berlin University Black Hole Research Team. Individuals within the research team would still be named and honoured.

Hels said...

Fun60

that is very true in publications as well. When a brilliant PhD thesis is broken into journal-size articles and published, the student might find his/her name fifth in the list of writers :(

Hels said...

Joseph

every generation of students believe that all learning came to light in their own era. The scientists who came in earlier generations were either forgotten or too scientifically primitive to be taken seriously. But with the 1953 discovery of the double helix, the twisted struct­ure of DNA, you and your fellow students happened to be quite right. The work in the late 1950s and into the 1960s was brilliant.

Hels said...

Andrew

Since only one Nobel Prize is awarded each year in each science, 99% of scientists will always be disappointed to lose. But some omissions were so egregious, I recommend you read "Which women should have won a Nobel Prize?" In particular examine Lise Meitner, Vera Rubin and Esther Lederberg, as well as Rosalind Franklin:
https://eandt.theiet.org/content/articles/2018/06/nobel-prize-women-the-female-scientists-who-should-have-been-winners/

Hels said...

bazza

I should have remembered your 2017 blog post... thank you for the link.

I read "Rosalind Franklin and DNA" by Anne Sayre 1975 and found it spot on. Now I will read "The Selfish Gene".

mem said...

Bloody Men !!!! I think you and I are on the same page with the ongoing necessity to get men to acknowledge the debt to others including women , when they achieve something fantastic. Mind you I don't find it surprising that is this case it didn't happen . I think James Watson has some pretty dodgy views on the superiority of white males in general. James Watson is an interesting and very flawed person . I just wonder how someone who is so intelligent can hold the views he does.

Hels said...

mem

It is possible that all famous men discounted women's academic achievements or ignored them, throughout the 1950s. But I don't think so. Maurice Wilkins knew perfectly well that he could not steal research work from other academics, and James Watson knew perfectly well that he could not accept stolen research, to absorb it secretly into his own work. That the two men continued with not acknowledging the true owner of the research in the following years just maintained their shifty characters :(

Luiz Gomes said...

Boa noite Hels. Parabéns pela excelente matéria. Bom final de semana.

Hels said...

Luiz

Imagine dying at 37... what a tragedy. And imagine dying without seeing your critical contributions to medicine publicly acknowledged in the academic journals and awards.

Hilary Melton-Butcher said...

Hi Hels - far too many women go unrecognised ... their work/worth not considered enough to be accepted as important enough to be referred to. Our paternalistic society definitely doesn't help ... thankfully in this day and age - women are getting recognised ... mighty slow - but it's been throughout society for much of recorded life. Thanks for reminding us about Franklin - I've always known about her, but realise many haven't. Stay safe - Hilary

Hels said...

Hilary

agreed totally.... it was thus forever. And perhaps we expected sexism in macho organisations eg the police, the armed forces, boxing and rugby, Antarctic explorations.

But I thought that intelligent, educated men changed a long time ago and that women would earn their rightful places in eg science, the law, academe, conducting orchestras. Apparently it is taking longer than we expected.