How did the work of other scientists help Crick and Watson to develop their theory for the structure of DNA?

and rungs. Soon after Wilkins shared ‘Exposure 51’, Franklin’s image, with Watson and Crick, they published a paper[3] on Nature explaining the DNA’s structure, DNA replication during cell division and the idea of mutations. This demonstrates that both Franklin and Wilkins’ work in the research of DNA was key and greatly aided Watson and Crick develop their theory of the structure of DNA. Maurice Wilkins was not only involved in the initial development of X-ray diffraction images of DNA, but he also played a very important role in checking the validity of Watson and Crick’s proposed theories and models. Erwin Chargaff was an American biochemist who discovered the ratios between the nitrogenous bases in DNA. Through investigating and comparing quantities of different bases in DNA, he concluded that the proportion of Adenine to Thymine and Guanine to Cytosine are equal, 1:1. These equalities between the proportions of Adenine and Thymine and Guanine and Cytosine gave clues and helped to propose theories on the chemical pairings of the double helix. This 1:1 ratio allowed Watson and Crick to see how the bases fit together and had to bond in a certain way within the double helix structure, introducing the idea of base pairs and complementary base pairs. This accurate measure of the amounts of each nucleotide in the DNA obtained by Chargaff was necessary to understand how the DNA could all fit together as well as aiding the discovery that one strand of the DNA acts as a template for replication. Erwin Chargaff investigated the quantities of bases in the DNA not only in humans, but also in other species. During his experiments he found that the proportion of bases in the DNA is different for each species, arousing theories that the DNA is the genetic material for life and codes for genetic instructions. Chargaff described in his book, ‘Heraclitean Fire’, that he ‘ran out of atoms and even more of patience’[4] when trying to build molecular models of the nucleotides which meant he did not manage to develop a model for the whole structure of the DNA however his discovery of the pairing of bases, their ratios and their unique proportions within each species was key information to allow Watson and Crick to make this discovery. Despite his important and inspirational help towards the development of a theory for the structure of DNA, Chargaff’s contributions were ignored by the Nobel Prize Committee like Rosalind Franklin; however, he was recognised by the National Academy of Sciences in 1965 by being elected and has received many awards[5] .

Crick and Watson’s discovery of the DNA structure was also aided by the discoveries of Friedrich Miescher and Phoebus Levene. Miescher was the first scientist to isolate nucleic acid. During his research he separated the nucleic acid into its protein and acid components, leading him to name it deoxyribonucleic acid, more commonly known as DNA. He determined that nuclein was made up of hydrogen, oxygen, nitrogen and phosphorus, with a unique ratio of phosphorus to nitrogen, which helped Watson and Crick have a deeper and more detailed understanding of all the different components within DNA. The more information they had about the structure and

layout of all the individual components of the DNA, the easier and clearer it became to discover the structure of DNA. Phoebus Levene also played an important role in contributing to the discovery of the structure of DNA. Levene discovered ribose sugar and deoxyribose sugar and the difference between them. This distinction between these two sugars demonstrated that there is DNA and RNA separately within the nucleus. This discovery made by Levene helped and allowed Watson and Crick to determine how DNA is transcribed during protein synthesis within the nucleus by suggesting that there had to be a way for the two types (DNA and RNA) to exist. In addition to this, Phoebus Levene also discovered that within each individual building block of the DNA there is a phosphate group, a sugar and a base and called this phosphate-sugar-base unit a nucleotide. By isolating the nucleotides and the sugars within the nucleotides, the structure of the DNA became clearer, and Watson and Crick had more information in order to determine the structure of DNA. Overall, the discovery of the structure of DNA was not solely due to Watson and Crick’s discoveries; the work, time and effort of many scientists allowed the development of the theory of the structure of DNA. All the

discoveries that each scientist made by specialising their work were pieced together by Watson and Crick who developed the final theory of the structure of DNA. However, without these other scientists and their incredible work, this would not have been possible.

‘Exposure 51’: ‘The most important photo ever taken?’, BBC News, 16 May 2012

Sources

● NobelPrize.org, ‘The Nobel Prize Award

Ceremony 1962’, Sat. 9 Oct 2021 (nobelprize.org/prizes/medicine/1962/awardvideo/) ● James Watson and Francis Crick, ‘Molecular

Structure of Nucleic Acids: A Structure for

Deoxyribose Nucleic Acid’, Nature , 25th April 1953 ● ‘The Discovery of DNA Structure’ (pbs.org/wgbh/evolution/library/06/3/l_063_01. html) ● Fergus Walsh, ‘The most important photo ever taken?’, BBC News, 16 May 2012 (bbc.co.uk/news/health-18041884)

● Maurice Wilkins biography (whatisbiotechnology.org/index.php/people/su mmary/Wilkins) ● Erwin Chargaff, Discovering the rules of complementary base pairing (dnalc.cshl.edu/view/15251-Discovering-therules-of-complementary-base-pairing-Erwin-

Chargaff.html) ● National Medal of Science, Erwin Chargaff (nationalmedals.org/laureate/erwin-chargaff/) ● Doug Stewart, "Erwin Chargaff", Famous

Scientists 9 August 2016 (famousscientists.org/erwin-chargaff/) ● Kara Rogers, ‘Friedrich Miescher, The

Encyclopaedia Britannica, 22 August 2021 (britannica.com/biography/Friedrich-Miescher) ● ‘Friedrich Miescher’, DNA From the Beginning (dnaftb.org/15/bio.html) ● Erik Gregersen, ‘Phoebus Levene’, The

Encyclopaedia Britannica, 2 September 2021 (britannica.com/biography/Phoebus-Levene) ● ‘Phoebus Levene’. DNA From the Beginning (dnaftb.org/15/bio-2.html)

Footnotes

[1] ‘The Discovery of DNA’s Structure’ (pbs.org/wgbh/evolution/library/06/3/l_063_01.html) [2] See the end of the paper for picture of ‘Exposure 51’ [3] James Watson and Francis Crick, ‘Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid’, Nature, 25 April 1953 [4] Erwin Chargaff, ‘Heraclitean Fire’, 1 June 1978 [5] Awards Erwin Chargaff received included: Pasteur Medal in 1949, Carl Neuberg Medal in 1958, Charles Leopold Mayer Prize in 1963, Heineken Prize in 1964, Gregor Mendel Medal in 1974, and the National Medal of Science in 1975

Take 2. How did the work of other scientists help Crick and Watson to develop their theory for the structure of DNA?

By Sia Patel Year 12 James Watson and Francis Crick reached a groundbreaking conclusion in 1953[1], when they discovered that the DNA (deoxyribonucleic acid) molecule, which contains the hereditary information of cells, is in the shape of a three-dimensional double helix. However, they were not the only people who had been working on this theory at the time, and were heavily influenced by other scientists of their era. Without these other scientists’ research, it is highly unlikely that Crick and Watson would have developed their pioneering hypothesis. One of the most influential scientists on Crick and Watson’s theory was English chemist Rosalind Franklin. After completing extensive research on the chemistry of carbon and coal, which allowed great strides to be made in the war effort, Franklin joined the Biophysical Laboratory of King's College, London as a research fellow in 1951. Whilst at the College, she completed extensive Xray diffraction work on DNA. This led to her discovering first the density of DNA as well as the fact that it could exist in 2 forms. Franklin and PhD student Raymond Gosling (1953)[2] subsequently captured one of the most significant photographs of all time: an image of one of the forms of DNA that revealed its double helical structure, known as Photo 51 (left). Franklin (1953)[2] states that, according to her research, it is highly probable that the structure of DNA is helical. Franklin’s image helped to confirm Crick and

Watson’s hypothesis that DNA exists in a double helical structure, allowing them to continue their work and eventually build their model and making Franklin one of the most influential scientists on the double helical theory. Another scientist who greatly aided Crick and Watson in their work was New Zealandborn British biophysicist Maurice Wilkins. Following World War II, Wilkins joined King’s College London as Assistant Director of a new biophysics unit. It was then that he and Ray Gosling began to use X-ray diffraction to obtain images of different forms of DNA, a technique that Rosalind Franklin later built upon to take Photo 51. Wilkins and his team (1953)[3] spent years confirming the accuracy of the Watson-Crick (1953)[1] proposal, and in 1962 he received the Nobel Prize in Physiology or Medicine alongside Watson and Crick. Franklin, who had passed away due to ovarian cancer four years earlier, was not included in this. Another way in which Wilkins contributed greatly to Crick and Watson’s research was by showing the pair Franklin’s (1953)[2] Photo 51. This was integral to the development of their theory, although Franklin was not informed of this and did not gain credit when their findings were published. Overall, Wilkins had a profound impact on Crick and Watson’s theory by both confirming its accuracy and by revealing the significant Photo 51 to them, clarifying their theory further. Although Crick and Watson worked directly with Franklin and Wilkins to advance their theory, they may not have reached this conclusion to begin with without the momentous discoveries of past scientists. One notable example is Russian-born American biochemist Phoebus Levene. After emigrating to the US at the age of 22, Levene was appointed to the Rockefeller Institute for Medical Research, where he remained for the duration of his career. Although it was known that nucleic acids existed in two forms, and that they contained the bases Adenine, Guanine, Cytosine and Thymine/Uracil, virtually nothing was known about the structure or function of nucleic acids. It was also found that one of the two types of nucleic acid was found in the thymus of animals and that the other was found in yeast. Levene (1908)[4] made the discovery that the pentose sugar ribose is found in yeast nucleic acid, and subsequently established the tetranucleotide hypothesis. This hypothesis suggested that the four bases were present in approximately equal ratios in nucleic acids. Levene, along with L.A Mikeska and T. Mori (1929)[5], states that deoxyribose is the carbohydrate found in animal thymus nucleic acids. Levene continued to work on his model for the structure of nucleic acids until 1935[6], when he published a paper stating his improved model, in which the links of the phosphates between the deoxyriboses are correct. Although Levene’s model of RNA contained some errors, his groundbreaking work allowed scientists of Crick and Watson’s time to further their conclusions as they knew the basic structure of nucleic acids and could focus on developing the existing models. Another scientist who laid the foundation for Crick and Watson’s discoveries was AustroHungarian-born biochemist Erwin Chargaff. At the time of Chargaff’s research, it was widely accepted that the carriers of genetic information were the amino acids, which could combine in numerous ways to form a

complex basis for genes. However, Chargaff’s research suggested that it was instead the DNA that carried genetic material, due to the fact that differences between the DNA of different species were discovered. Chargaff then performed experiments on DNA involving the separation of the purines and pyrimidines using paper chromatography. By doing this, he discovered that adenine and thymine exist in roughly equal proportions in the DNA of all species, as do guanine and cytosine. However, he also discovered that the amount of the purines and pyrimidines varied across different species, giving the reason for genetic variation within species. Chargaff’s work directly led Crick and Watson to determine their theory, as the two scientists reached the conclusion that, because adenine and thymine are always present in equal proportions, they must always bond together, and the same for guanine and cytosine. This further allowed Crick and Watson to develop their model with the pyrimidine and purine bases bonding the two strands of DNA together. In conclusion, the cumulation of decades of research done by other scientists allowed James Watson and Francis Crick to develop their theory that the DNA molecule has a double helical structure. Rosalind Franklin and Maurice Wilkins confirmed the accuracy of the theory, whilst Phoebus Levene and Erwin Chargaff laid the foundation for the theory with their extensive research on components of the structure of DNA.

References

[1] Watson, J.D and Crick, F.H.C (1953) Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid. Nature. 171, 737-738 [2] Franklin, R.E and Gosling, R.E (1953) Molecular Configuration in Sodium Thymonucleate. Nature. 171, 740-741 [3] Wilkins, M.H.F, Stokes, A.R and Wilson, H.R (1953) Molecular Structure of Deoxypentose Nucleic Acids. Nature. 171, 738-740 [4] Mandel, J.A, Jacobs, W.A and Levene, P.A (1908) On Nucleic Acids. Journal of Biological Chemistry. 4, 92-94 [5] Levene, P.A, Mikeska, L.A and Mori, T (1929) On the Carbohydrate of Thymonucleic Acid. Journal of Biological Chemistry. 785-787 [6] Levene, P.A and Tipson, R.S (1935) The Ring Structure of Thymidine. Journal of Biological Chemistry. 110, 623-630 All of these are scientific papers written in collaboration with other scientists. Scientific papers are also peer reviewed and so have a high reliability. They are also primary sources, written by the scientists themselves, and so are very reliable sources to use in my research.

Sources

● Nature Education (2008) Discovery of DNA

Structure and Function: Watson and Crick.

Available from:nature.com/scitable/topicpage/discoveryof-dna-structure-and-function-watson-397/ [Accessed 09/10/21]