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Science Not Silence — A Letter To The 1962 Nobel Prize Committee

Posters Celebrating Women In Science (Source)

My fellow scientists and colleagues at the Nobel Committee,

I must confess I was surprised to receive your request for an expert account on the candidates for the 1962 Nobel Prize in Physiology and Medicine.

Like all biologists, I too closely followed the astounding race for discovering the twisted-ladder structure of deoxyribonucleic acid, DNA, in 1953.

The heated race between research teams at the University of Cambridge Cavendish Laboratory and the Randall Institute at King’s College London — the former led by Jim Watson, Francis Crick, Sir William Bragg, Max Perutz and John Kendrew , and the latter by Sir John Randall, Maurice Wilkins, Raymond Gosling and Rosalind Franklin — has truly revolutionised the modern field of molecular biology and genetics.

However, only three of these scientists can forever rest in the light of Nobel glory.

After some serious of research and much contemplation, the following evidence presented here suggests that one of these victors should be Dr. Rosalind Franklin.

What we knew about DNA in 1951

Granted, Watson and Crick were early to recognise that the key to inheritance was understanding the three-dimensional form of DNA.

In 1951, the pair hoped to solve the DNA structure by building molecular models based on existing experiments:

  1. From the work of Phoebus Levene and Alexander Todd, they knew that DNA mainly consisted of a repeating deoxyribose sugar-phosphate backbone, which was made of individual nucleotide building blocks.
  2. They were also aware that DNA was the fundamental genetic material due to the works of Oswald Avery in 1944.
  3. They knew that DNA could be modelled into single-stranded alpha helices thanks to Linus Pauling in 1948,
  4. And that the four DNA bases — the purines adenine and guanine, and the pyrimidines cytosine and thymine — vary significantly between species, as described by Erwin Chargaff in 1950.

However, no one really knew what DNA looked like or how it sat inside a cell — no comprehensive image of the structure existed, aside from the two dimensional X-ray diffraction images taken by Astbury and Bell in the late 1930’s, which themselves were of relatively crude quality.

Yet instead of investing in new, more accurate pictures, Watson and Crick turned to scientific guesswork.

First (incorrect) models of DNA

By combining Crick’s knowledge of physics and X-ray crystallography with Watson’s background in bacterial genetics, the pair composed a their first physical representations of DNA.

However, their initial models were far from accurate:

  • Some contained triple helices, whereas others showed the four bases protruding outward instead tucked between the backbones.
  • Their models incorrectly displayed guanine and thymine in enol instead of keto forms and did not follow Erwin Chargaff’s rules of base pairing, showing adenines bound to adenines.
  • Their model gave no clear insight into the self replicative nature of DNA, since the nucleotide ladders ran parallel, instead of anti-parallel.

Some of these errors were due to misunderstandings in basic chemistry, such as the configuration of elements in thymine and guanine (specifically, the carbon, nitrogen, hydrogen, and oxygen rings).

The Final DNA model of Watson and Crick (Source)

Regardless, the researchers presented their model to the King’s College team. It’s faults were obvious to Rosalind Franklin, an expert X-ray crystallographer studying DNA with state of the art X-ray cameras.

She pointed the lack of evidence available for the proposed helix configuration, voiced that the model should contain more water molecules, and was sceptical of the electrostatic sodium bridges in Watson’s and Crick’s DNA model. Franklin’s feedback made the Cavendish team to retaliate back to the drawing board.

Franklin’s photograph 51

Franklin’s own work at the time reveals how she better understood the nature of the molecule.

In 1952, 16 months before Watson and Crick published their Nobel winning structure, Franklin took one of the most advanced X-ray images of DNA to date.

I had the privilege to meet Anne Sayre, a personal friend of Franklin, who kindly sent me some of Franklin’s early notes on this photograph 51:

Franklin’s Top Down Photograph of DNA (Source)

According to Franklin, the x-shaped diffraction pattern seen in the image suggests “a helical structure (which must be very closely packed) containing 2, 3 or 4 co-axial nucleic acid chains per helical unit, and having the phosphate groups near the outside.” Franklin had calculated the exact diameter and double helical structure of the right-handed “B-form” DNA molecule.

She went on to present her findings on the B and A-DNA forms at a symposium and correctly stated that the phosphate backbone lay on the outside of the structure:

“Conclusion: Big helix in several chains, phosphates on the outside, phosphate-phosphate inter helical bonds disrupted by waste phosphate links available to proteins.”

It would take several months for Watson and Crick to catch on to any of these observations.

Furthermore, Franklin used her data to solve the A-DNA structure in another organism. Her A-form images had better crystalline dot patterns, compared to the B-DNA, which allowed for unambiguous, albeit tedious, structural analysis using Patterson functions. After Randall had decided to end the DNA research at King’s College, Franklin analysed the tobacco mosaic virus structure at Birkbeck College. Based on her previous knowledge, she demonstrated the helix structure of A-form viral RNA between 1953–58.

It’s likely that Franklin would have solved the B-form DNA helix structure without the help of her colleagues, had she obtained more research time at Cambridge.

Outside help and data theft

Unlike Franklin’s work, Watson and Crick’s model building was influenced by the council of other academics. The American physical chemist Jerry Donohue in particular made a significant correction to the Watson and Crick’s DNA model by pointing out the incorrect carbon, nitrogen, hydrogen and oxygen rings of thymine and guanine. Donohue’s advice caused Watson to rearrange the hydrogen atoms in their base models such that they bonded to nitrogen instead of oxygen.

This form enables the neat A-T and C-G pairing suggested by Chargaff’s rules, and fits the bases inside the sugar-phosphate DNA backbone, forming a twisting double helix ladder. How long until Watson and Crick had figured this out themselves is a topic for endless speculation.

Furthermore, the double helix structure was supported by Franklin’s images, which dubiously fell in the hands of Watson and Crick. In early 1953, Wilkins took some of Franklin’s x‐ray photographs of the B-formed DNA without her knowledge and showed them to Watson. Also unknown to Franklin, the men obtained a write‐up copies of Franklin’s work from her other colleague, Max Perutz. The copies confirmed that the two backbones were held together by complementary base pairing, with the four bases wound around a common axis in a crucially antiparallel configuration. Her findings clearly re-awakened DNA model work at the Cavendish Lab.

By the end of March the same year, Watson and Crick built a new, final version of the B-DNA structure. Before publishing, they even presented the work to Franklin, who was completely unaware that her work had shaped the model. Her credit was diluted in the published DNA paper in Nature Magazine, in which her name appeared as a side mention, bundled together with those of her co-workers at King’s College.

Evidence of personal conflict

Although Watson and Crick published the first DNA structure, I am baffled by the rumour of Maurice Wilkins being the third Nobel Prize candidate.

Despite producing his own X-ray images of B-DNA, Wilkins’ contribution to the DNA structure discovery seems to be merely delivering Franklin’s work to the Cavendish Lab. However, being an old wartime friend of Crick’s, Wilkins may have felt like a more favourable laboratory partner, rather than his less amenable female colleague.

In fact, personal quarrel between Franklin, Watson and Crick likely fuelled the belittlement of her contribution. Franklin’s criticism of Watson and Crick’s first model was a humiliating setback, which drove resentment and the revenge-like justification for using Franklin’s X-ray images without her knowledge.

The purpose of the Nobel Prize

Evidence suggests that the evolution of Watson and Crick’s DNA model depended on the profound work of Rosalind Franklin. Her x-ray images enabled the correct modelling of the antiparallel double DNA helix, and without it Watson and Crick would perhaps still be in the dark. However, teamwork and data sharing enabled Watson and Crick to solve the structure faster than Franklin. Franklin gathered and analysed her data by herself, often competing against colleagues even within her own lab, and chose the long, systematic rout in finding the B-DNA structure.

And so I beg the question, my colleagues — what is the purpose of the Nobel Prize?

Is it a symbol of scientific excellence and advancement, and deep impact left to society as a whole, or a trophy given to those who reached the finish line?

Acknowledging Franklin’s work would be a vocation against data theft, a protest against toxic scientific competition, as well as a victory for the hard labouring female scientists of our time. By contrast, awarding the highest possible honour in research to Watson, Crick and Wilkins encourages a sexist atmosphere among researchers and discourages future female scientists to trust and prosper alongside their male colleagues.

Whatever your conclusion, I hope you will reward diligence rather than dishonesty.

With kind regards,

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Laura Turpeinen

Laura Turpeinen

Synthetic biology| Biotech | Bioeconomy