The Race to Conquer the Secret of Life

Arguably, the greatest discovery of the 1900s came with the elucidation of the structure of deoxyribose nucleic acid, otherwise known as DNA, our genetic blueprint. DNA can be thought of as letters of the alphabet that come together to form words of functional significance. And though there are 26 letters in the English language, in the language of DNA, there are only four letters. These are known as Adenine (A), Cytosine (C), Guanine (G) and Thymine (T). Similar to the rules of English grammar, DNA has a base-pairing rule—that is, the base (or letter) A can only pair with T, and C can only pair with G to form hydrogen bonds between A-T and C-G, respectively. This base pairing allows the compact organisation of DNA with sections of these paired letters creating genes that code for particular amino acids that go on to form protein structures, which are involved in complex functions.

How was this grand discovery made? To find this answer, we will have to travel on the tantalising wings of history to appreciate the underlying science. We are in 1952, where the main cast of this particular story includes scientists James Watson, Francis Crick, Maurice Wilkins and Rosalind Franklin. Others, such as Linus Pauling, Erwin Chargaff and Raymond Gosling also play a role. The story really begins on May 1^st, 1952, in the famous King’s College London laboratory, where an X-ray camera is clicking on a 100-hour exposure of a hereditary molecule called DNA in a process known as X-ray crystallography. The work is being carried out by a talented 32-year-old molecular biologist by the name of Rosalind Franklin. Once developed, this photograph will be instrumental in revealing the structure of DNA and hold the key to understanding how the blueprint for every cell of the body is passed down through generations. Close by, at Cambridge University, are two scientists targeting the same prize: Watson, a 23-year-old American viral geneticist, and Crick, a 35-year-old British physicist. They have been offered the chance to work at the famous Cavendish laboratory at the University of Cambridge, in order to unravel the elusive structure of DNA.^[1]

They were not successful in the beginning: Watson and Crick presented their first model at a seminar hosted at the Cavendish Laboratory. Prominent personalities such as Rosalind Franklin, Maurice Wilkins and Professor Lawrence Bragg were in the audience, but the meeting went poorly since Watson and Crick represented DNA as a triple-stranded helix (as opposed to a double helix) and placed the bases on the outside of the structure, with the phosphate molecules placed on the inside.

For the benefit of readers not familiar with DNA structure, DNA is composed of two components: the basic building blocks known as bases (A, C, G, T) and a deoxyribose sugar-phosphate backbone. Rosalind Franklin fervently objected to this duo’s premature model, correctly pointing out that since DNA could readily take up water, the phosphate molecules (which are a water-loving chemical group) should be on the outside whilst the bases should be on the inside. Professor Bragg, who supervised Watson and Crick, reprimanded the duo and suggested they cease working on the DNA structure. Despite these setbacks, both continued to work secretly on this project. Watson and Crick quickly realised that there was just enough evidence out there to build the structure of DNA using their models and it was just a matter of putting the clues together for a complete and coherent model. In addition, they knew that quite a few zealous scientists were working on the problem; hence it became a race against colleagues to beat them to the finish line. Recognition and glory was up for grabs.^[2,3]

And so in January of 1953, attempting to put the pieces of the DNA puzzle together, Watson procured a draft copy of a scientific manuscript written by chemist Linus Pauling through his son, Peter, who was working in Cambridge as a Ph.D student. Interestingly, Pauling had made exactly the same mistake Watson and Crick had made a year earlier, by suggesting that DNA possessed a triple helix structure. Conscious of the fact that Pauling might be able to resolve the issue, Watson made haste to King’s College London with Pauling’s manuscript in hand. Rosalind Franklin was a renowned expert and this was the very place where Watson could see the best X-ray images of the DNA structure. During Franklin’s short time at King’s University London, she had discovered the existence of DNA in two states referred to as the A-form (dry form) and B-form (wet form, found in living cells). In an attempt to possibly work with Franklin on this problem, Watson tried to convince her that DNA was a helix but she remained defiant. According to Watson, she became angry and confronted him upon which Watson had to make a retreat fearing she would strike him.^[4,5]

But before Watson left that day, he popped in to see Maurice Wilkins and insisted on being shown the famous X-ray photograph 51 that Rosalind Franklin had acquired through such painstaking work. When he saw it, Watson was astonished and was convinced with this conclusive evidence that DNA was actually a double helix, and not a triple helix. On the train ride home, Watson sketched the image he had seen on a newspaper, which he showed to an elated Crick. Both agreed that DNA was a double helix, but they still needed to figure out how the chemical constituents of DNA fit into this amazing structure.^[6]

Recollection of clues from the past reminded Watson and Crick about the dinner they had with a great chemist, Erwin Chargaff. The unlikely heroes asked such very basic questions of Chargaff that he was surprised at their lack of basic chemistry knowledge, especially regarding the key differences between the bases of DNA. Chargaff taught the two curious investigators that the amount of Guanine equalled the amount of Cytosine (G = C) while the amount of Adenine equalled the amount of Thymine (A = T).^[7,8] Thus, through assimilation of different pieces of information, they deduced that the bases would form hydrogen bonds internally whilst the phosphates would hang on the outside—just as had been originally proposed by Franklin. Moreover, Crick concluded that DNA must form an anti-parallel double helix, where the two complementary strands of DNA run in opposite directions. And all of this progress was only possible because of the final piece in the puzzle, the famous image from Rosalind Franklin’s painstaking work.^[9]

The new model put together by Watson fitted the experimental data exceptionally well and Crick later observed that they had found the gold before anyone else in this treasure hunt. Crick began telling everyone at the Eagle pub, just around the corner from the Cavendish lab, that he and his colleague had found the secret of life.^[10,11] On April 25^th,1953, a modest 900-word article appeared in the journal Nature, titled ‘Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid’ by Watson and Crick.^[12] It was an article that would revolutionise the world of science forever!

But the crux of this enigmatic story lies in this question: why did Maurice Wilkins disclose Franklin’s data to a competing scientist without her permission? Perhaps it was a case of a clash of personalities. It is known that Franklin was an articulate, passionate, strong and fierce individual, always up for debate. She stood in complete contrast to the soft-spoken, deliberate and shy Maurice Wilkins. Unsurprisingly, this created a harsh environment of intense conflict, an environment quite typical of research laboratories. Perhaps this was the reason that led Maurice Wilkins to surreptitiously share Franklin’s precious data. It is likely that we shall never know.^[13]

The journal Nature published a set of three papers, the first being Watson and Crick’s, followed by Maurice Wilkins’ and last but certainly not least, Franklin’s ^[14,15,16]
“Thus our general ideas are consistent with models proposed by Watson and Crick (1953)”, Franklin stated in her paper, oblivious to the fact that their model was indeed based on her data.^[17] Sadly, Franklin passed away in 1958 from ovarian cancer, possibly due to frequent X-ray exposure. In 1962, Watson, Crick and Wilkins were awarded the Nobel Prize but none of them made any particular mention of Franklin.^[18]

In 1968, James Watson wrote a controversial book, The Double Helix: A Personal Account of the Discovery of the Structure of DNA.^[19] In this, he defamed the memory of Franklin by tagging her as “terrible, bad tempered Rosy” who never shared her data with anyone, despite the fact that she had died ten years previously. She was cast as a villain in his narrative at a time when she was not present to defend herself. Crick and Wilkins both objected to this portrayal because in Crick’s words, “The book was misleading and in bad taste. It doesn’t illuminate the process of science, rather distorts it.”^[20] One cannot take away the passion and zeal with which Watson and Crick worked away to solve the mystery surrounding the secret of life; however, it is worth stating that without the access to Franklin’s X-ray images and data, it would have certainly taken longer for the duo to solve the riddle.

Franklin had moved to Birkbeck College on April 25^th, 1953, to work on viruses. Here, she famously discovered the complex structure of viruses and the location of their infectious elements. Sir Aaron Klug, who was her last collaborator, studied her notebooks and letters after her demise. He won a Nobel Prize in 1982 on his impressive work in the field of electron microscopy and the structure of viruses, most of which was based upon and a continuation of the work Franklin started. Klug, unlike Watson, Crick and Wilkins, acknowledged Franklin’s contribution to his work in his prestigious speech at the auspicious occasion of the Nobel Prize ceremony.^[21]

This is a melancholic story indeed. Franklin’s crucial contribution to Watson and Crick’s work became a footnote in scientific history with the price of Franklin’s hard work being the offering of her life, at the tender age of thirty-seven. Franklin was a great scientist who could have possibly secured two Nobel Prizes for her work both on the elucidation of the structure of DNA and viruses; sadly though, Nobel Prizes are not offered posthumously.

Endnotes

1. Brenda Maddox, Rosalind Franklin: The Dark Lady of DNA (HarperCollins Publications, 2002).

2. Brenda Maddox, Rosalind Franklin: The Dark Lady of DNA (HarperCollins Publications, 2002).

3. James D. Watson, The Double Helix: A Personal Account of the Discovery of the Structure of DNA (W&N Publications, 1968).

4. Brenda Maddox, Rosalind Franklin: The Dark Lady of DNA (HarperCollins Publications, 2002).

5. James D. Watson, The Double Helix: A Personal Account of the Discovery of the Structure of DNA (W&N Publications, 1968).

6. James D. Watson, The Double Helix: A Personal Account of the Discovery of the Structure of DNA (W&N Publications, 1968).

7. Erwin Chargaff, “Chemical Specificity of Nucleic Acids and Mechanism of Their Enzymatic Degradation”, Experimentia 6, (1950): 201.

8. Erwin Chargaff, “Preface to a Grammar of Biology: A Hundred Years of Nucleic Acid Research”, Science, 172 (1971): 637-642.

9. James D. Watson, The Double Helix: A Personal Account of the Discovery of the Structure of DNA (W&N Publications, 1968).

10. Brenda Maddox, Rosalind Franklin: The Dark Lady of DNA (HarperCollins Publications, 2002).

11. James D. Watson, The Double Helix: A Personal Account of the Discovery of the Structure of DNA (W&N Publications, 1968).

12. James D. Watson, Francis H. Crick, “Molecular Structure of Nucleic Acids; A Structure for Deoxyribose Nucleic Acid”, Nature 171(4356), (1953): 737-738.

13. James D. Watson, The Double Helix: A Personal Account of the Discovery of the Structure of DNA (W&N Publications, 1968).

14. James D. Watson, Francis H. Crick, “Molecular Structure of Nucleic Acids; A Structure for Deoxyribose Nucleic Acid”, Nature 171(4356), (1953): 737-738.

15. Maurice H.F. Wilkins, Alex R. Stokes, Herbert R. Wilson, “Molecular Structure of Deoxypentose Nucleic Acids”, Nature 171 (1953): 739.

16. Rosalind E. Franklin, Raymond G. Gosling, “R. G. Molecular Configuration in Sodium Thymonucleate”, Nature 171 (1953): 742.

17. Rosalind E. Franklin, Raymond G. Gosling, “R. G. Molecular Configuration in Sodium Thymonucleate”, Nature 171 (1953): 742.

18. Brenda Maddox, Rosalind Franklin: The Dark Lady of DNA (HarperCollins Publications, 2002).

19. James D. Watson, The Double Helix: A Personal Account of the Discovery of the Structure of DNA (W&N Publications, 1968).

20. Brenda Maddox, Rosalind Franklin: The Dark Lady of DNA (HarperCollins Publications, 2002).

21. Brenda Maddox, Rosalind Franklin: The Dark Lady of DNA (HarperCollins Publications, 2002).

22. Rosalind E. Franklin, Raymond G. Gosling, “R. G. Molecular Configuration in Sodium Thymonucleate”, Nature 171 (1953): 742.

23. Aaron Klug, “Historical perspective; The Discovery of the DNA Double Helix”, J Mol Biol 335 (2004): 3–26.