25th April 2023
Jen Willows, Editor at PET (the Progress Educational Trust)
2023 marks the 70th anniversary of the discovery of the structure of DNA. In February 1953 James Watson and Frances Crick made the breakthrough that would eventually make them household names, and the Nature article in which the discovery was made public was published on 25 April.
Crick and Watson along with Maurice Wilkins, were later awarded the 1662 Nobel Prize for Medicine in recognition of their discovery.
Who gets credit?
There has been a great deal of debate in recent years about which other researchers' contributions to the discovery were overlooked. Notably Rosalind Franklin, whose X-ray crystallography 'photograph 51' was one of the most crucial pieces of evidence leading to the discovery.
This conversation will likely re-ignite around this 70th anniversary, and it's a great opportunity to engage with wider questions around who receives credit for research, in historical contexts but also today.
One of the points that was made in several sessions at the Third International Summit on Human Genome Editing which took place in London on March 2023 was about re-evaluating how credit is given to non-scientists who participate in genomic research.
To facilitate genomic research there is a demand for people to share their genomic data, and that is especially true for rare disease patients, but also for people from ancestral groups that are currently underrepresented in genomic datasets.
Representatives of these communities explained that they want to be able to be part of increasing data diversity and equity of outcomes, but they also want to engage with research throughout the decision-making processes. As Māori researcher Maui Hudson from the University of Waikato, New Zealand, put it, that means "acknowledgment, attribution, authorship, access and authority".
What was known before?
DNA was first isolated in 1869 by Swiss physiological chemist Friedrich Miescher – a contemporary of both Darwin and Mendel. He realised that the substance he had isolated from human white blood cells was quite different from the proteins he intended to study, and named it 'nuclein' as a reference to its location in the cell nucleus. The structure of individual DNA and RNA nucleotides was discovered by Russian scientist Phoebus Levene in the early 20th century.
It was known that across all the known types of life on Earth, proteins are key components in cell structure and function. It was also understood that proteins are composed of polypeptides – but how the information to create these specific amino acids sequences was stored was a mystery.
Before Oswald Avery's 1944 publication Studies on the chemical nature of the substance inducing transformation of pneumococcal types…, the prevailing hypothesis was that hereditary information was encoded in proteins. However, Avery demonstrated that what we would now call genetic information was stored in DNA and not in proteins.
Erwin Chargaff realised the implications of Avery's finding beyond bacteria, and his research led to the discovery that the numbers of adenine and thymine bases were always the same, as were the numbers of cytosines and guanines, although he stopped short of proposing that they formed pairs. He also noted different rations of A/Ts to C/Gs in the genomes of different species, supporting a molecular basis for observable hereditary difference.
Chromosomes had been viewed under microscopes in the 19th century and had been observed dividing. By around 1902, Walter Sutton and Theodor Boveri had both come to the same conclusion that chromosomes were the vectors of inheritance, in keeping with Mendel's laws.
So scientists knew the chromosomes were the key to inheritance, and that they were made of DNA bases, but not how the bases were arranges or how they encoded information.
The Nature paper
Watson and Crick's Nature article, Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid was published on 25 April 1953.
The paper is very concise –just over a page – and well worth a read if you haven't done so.
"We wish to put forward a radically different structure for the salt of deoxyribose nucleic acid. This structure has two helical chains each coiled round the same axis," they wrote.
The double helix, with its simple but striking shape, has become an icon in its own right; instantly recognisable even to those with the least interest or education in science. However, in terms of providing insight into biological processes its spiral grace is perhaps a distraction from the fact that it is, essentially, a ladder-shape.
The paper describes what we now know so well: two chains with sugar-phosphate backbones are linked by paired nitrogen-containing bases.
For many biological molecules, the visible structure can be very little help in discerning their function, but for DNA the structure immediately indicates the key to the two biggest discoveries: how information can be encoded in DNA, and how it can be replicated.
The DNA sequence and the route to replication.
Knowing that proteins are composed of strings of amino acids arranged in a specific sequence, by showing that the DNA is composed of chains of base-pairs, the idea that one sequence can encode another is a small step.
Watson and Crick did not propose a mechanism for this in their paper, but this is the beginning of starting to see DNA as a sequence, rather than simply a chemical.
Knowing that the bonds between the sugars and phosphates in the backbones are strong, and that the base-pairs are held together by weak hydrogen bonds, it was quickly obvious that the structure would be able to 'unzip,'. Add the fact that the bases always pair A to T and C to G, it was apparent that each of the separate chains can act as a template to rebuild its partner strand.
Watson and Crick allude to this in their Nature paper: "It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material."
Other researchers would take these findings, and use them as the foundation towards accumulating the genomic knowledge we have today.