They won the Nobel Prize with one page of thesis only because they saw a classic photo

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blockquote13 There will be one more Nobel Prize announced by the editors of p

p0quote. Winners of various awards this year. As in previous years, the WuXi AppTec content team will also report on the progress of the Nobel Prize for readers and friends as soon as possible. In this September, let us review the important discoveries that have won the Nobel Prize. These scientific breakthroughs have completely changed our understanding of nature.

One late night in February 1953, after biophysicist Francis Crick returned home, he excitedly told his wife, "We seem to have made a major discovery!" But even academically accomplished scientists, it may be Nor will he get much "attention" from his family.

According to Crick, his wife told herself many years later that she didn't believe a word of what she said that day. She felt that Crick “always came home and said similar things, so this time I didn’t care about it at all.” But what she didn’t know was that the major discovery made by Crick this time was not an exaggeration. A few years later, he and his collaborators won the 1962 Nobel Prize in Physiology or Medicine, because he and molecular biologist James Watson and biophysicist Maurice Wilkins found the secret of life-DNA The structure model .

▲Three scientists shared the 1962 Nobel Prize in Physiology or Medicine (Image source: The Nobel Prize in Physiology or Medicine 1962. NobelPrize.org. Nobel Prize Outreach AB 2021. Mon. 30 Aug 2021. )

The secret of the gene

Before the DNA structure has not been revealed yet,Geneticists have discovered that some small genetic units or information can determine the traits of organisms. Before the 1950s, scientists in the field of DNA research used the term "gene" to describe this peculiar molecule. But no one knows the appearance, structure, chemical properties of genes, and how they can be replicated with a very low error rate.

In 1944, through a pneumococcal experiment, Oswald Avery proposed that DNA is a carrier of genetic information, but this conclusion was not accepted by most scientists at the time. The scientific community still generally believes that DNA is too common and simple to be considered complicated. Of living organisms store genetic information. One of the reasons for these endless debates is that no one knows exactly what structure DNA has in , let alone the relationship between it and protein .

Although the research directions of Crick and Watson are X-ray crystallography and virus and bacterial genetics respectively, they unanimously determined that the core problem of molecular biology urgently needs to be solved is the three-dimensional structure of "genes". In the summer of 1951, the two met at Cambridge University , which opened the prelude to revealing the structure of DNA. Since they had not conducted DNA experiments, in the following 18 months, they searched and sorted out a large number of results of other researchers.

▲The classic DNA double helix structure was not known for decades (picture source: 123RF)

At that time, many researchers have independently discovered some basic information about DNA. For example, the chemist Alexander Todd determined that the backbone of DNA is composed of repeated phosphoric acid and deoxyribose; while the biochemist Erwin Chargaff determined the four base types and ratios of DNA, such as bases of different organisms. The ratio is different, but the number of A and T bases, C and G bases is always the same.

Photo "51"

With this scattered information,How to piece them together has become their biggest problem. At the right time, Linus Pauling, who has been studying the structure of protein , made a key discovery. He found a very basic structure in protein-the alpha helix. Pauling's discovery directly inspired the two, they speculated that DNA may also have a spiral structure.

In fact, Pauling not only provided ideas, but he has also been a competitor of the two. The two experimental groups are almost paralleling the analysis of the possible helix structure of DNA. In 1953, that is the year when Crick and Watson proposed the double helix structure model, Pauling also published his own predicted DNA helix structure, but unfortunately, he constructed a triple helix structure, which is different from the actual The structure does not match.

▲Linus Pauling won two Nobel Prizes (photo source: Nobel Foundation, Public domain, via Wikimedia Commons)

Crick and Watson were lucky, they also proposed triple chains before they found the correct answer Spiral structure. But unlike Pauling, they got an extremely precious photo, the photo "51" .

The owner of the photo joined University College London Rosalind Franklin in 1951. She began to study the characteristics of coal as early as the 1940s, and subsequently published a paper in Nature, explaining how carbon electrons are Affect its scattering of X-rays. After Franklin's research interests turned to viruses, and using her good X-ray diffraction imaging technology, she began to explore the RNA structure of tobacco mosaic virus. This method is actually not complicated. Some biological molecules, including DNA, can form crystals under certain conditions.When X-rays are used, the rays will produce special images. By observing the image, the researcher can roughly guess the structure of the crystal.

▲Rosalind Franklin made an indelible contribution to the analysis of DNA structure (Image source: MRC Laboratory of Molecular Biology, CC BY-SA 4.0 , via Wikimedia Commons)

Thanks to her previous experience in the field of X-rays, she quickly found the best way to present DNA when she was exploring the structure of DNA. It took about a year. Franklin improved the conditions in the imaging step, and used more efficient methods to reduce the X-ray scattering rate, and successfully captured the X-ray diffraction pattern of DNA, which is the photo "51" .

▲Photo 51 is the key to the analysis of DNA double helix structure (Image source: MagentaGreen, CC BY-SA 2.0 , via Wikimedia Commons)

Franklin herself has a strong sense of protection of scientific resources. She initially did not agree to Crick and Watson's request to view the photo "51". However, her colleague Wilkins, who also has a lot of research on X-ray crystallography in the direction of DNA, quietly handed Photo 51 and Franklin's data to them.It was this move that allowed Crick and Watson to confirm their speculation. The fuzzy X structure in the photo allowed them to determine that the DNA should be a double helix instead of a triple helix structure.

The birth of a one-page paper

With a spiral skeleton, all that is left is how to put the building blocks one by one. This time, they obtained an important piece of information again. Jerry Donohue, a visiting physical chemist from the United States, shared an office with the two during the study. During the conversation, Donohue told them that the thymine in the spiral building block and the bird The purine information is wrong. The chemical structure of the two molecules given in the chemistry book at that time is wrong, which is why their models always match imperfectly. Then, by adjusting the positions of the atoms of the two bases on the model, the two finally gathered all the correct accessories on the spiral.

▲The DNA structure drawn by Crick and Watson that year (Source: See page for author, CC BY 4.0 , via Wikimedia Commons)

And in the assembly process, Watson had an inspiration. When A and T are connected, G and C are connected, then when paired, they can be connected by hydrogen bond . And this connection method can correspond to Chargaff's law, that is, the number of A and T is equal, and the number of G and C is equal. Through this construction method, the base can be firmly fixed on the double helix and rotate around an axis. This structure is also consistent with the result reflected in the photo "51".

Then, the appearance of the spiral and the molecular composition on it gradually become clear. Finally, on April 25, 1953, a paper describing this double helix structure was published in Nature. Although this paper is only one page, it is enough to change the course of biological development in the following decades . Among them, they pointed out in the paper that the most novel and noteworthy point is the base matching principle of A-T and C-G.

With this principle, biologists only need to know the base sequence of one strand to infer the composition of the other strand, and the process of DNA replication becomes clear. Then at the end of May of that year, they re-posted the idea of ​​ gene duplication to Nature. By the end of the 1950s, DNA structure and replication theory had been linked to protein synthesis, and molecular biology ushered in the golden age of development .

It is precisely because of the subversive nature of this discovery that Crick, Watson and Wilkins won the Nobel Prize in Physiology or Medicine in 1962. Unfortunately, Franklin died of cancer in 1958 and could not wait for the Nobel Prize to be issued.

But in the introduction, the Nobel Prize Committee emphatically mentioned Franklin's contribution. They believe that the classic photo "51" has become the key to Crick and Watson's DNA secret . This is also the recognition and commemoration of the work of this outstanding female scientist by the scientific community.

Reference:

[1] The Discovery of the Double Helix, 1951-1953, Retrieved August 31st, 2021, from https://profiles.nlm.nih.gov/spotlight/sc/feature/doublehelix

[2] The discovery of the molecular structure of DNA-the double helix, Retrieved August 31, 2021, from https://educationalgames.nobelprize.org/educational/medicine/dna_double_helix/readmore.html

[3] The Nobel Prize in Physiology or Medicine 1962, from: The Nobel Prize in Physiology or Medicine 1962. NobelPrize.org. Nobel Prize Outreach AB 2021. Mon. 30 Aug 2021.

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