Structural Biochemistry/Nucleic Acid/DNA/Watson and Crick's Article

Inspirations to the Discovery of DNA Structure
James Watson began his research on DNA structure when he was in college. In 1945, during his third year of college, he reads Erwin Schrödinger's What Is Life? and takes away the message: Genes are the key components of living cells, so "we must know how genes act". In 1950 at an international conference in Naples, Maurice Wilkins of King's College, London, shows his clear X-ray pictures of DNA to Watson. Determined to work on DNA structure, Watson moves to Sir Lawrence Bragg's biophysics unit of the Cavendish Laboratory at Cambridge, England, where he meets biophysicist Francis Crick. Many scientists, including Rosalind Franklin, began her research on DNA structure with the help of X-ray diffraction. During the same year, she held a seminar at King's College in London, where Watson was invited. Her X-ray photo revealed the physical structure of DNA as a helix. During the seminar, Watson learned that Franklin's research confirmed that DNA had a helical structure, which consisted of two to four interlaced helical chains. Each helix had a phosphate-sugar backbone, with attached bases (adenine, guanine, thymine, and cytosine). The bases were proved to attached to the inside of the helix, possibly forming links between the helical chains. After Franklin's seminar, Watson decided to build DNA models.

Continuation on the Discovery
Nevertheless, the diffraction pictures of these models did not fit that of real DNA. The models that Watson built turned out to be wrong—the bases are on the outside of the helix and the helix is dehydrated—because he misinterpreted Franklin's findings. Watson's and Crick's research on DNA structures was terminated by King's College, and they must continue with their previous researches, which are tobacco mosaic virus (TMV) for Watson and proteins for Crick.

Although banned from researching on the structure of DNA, Watson was able to continue because one of the main components of TMV was nucleic acid and Francis Crick continued with it outside of his research. In 1952, Watson described Alfred Hershey's discovery that the genetic material of viruses is DNA, comparing the DNA in virus heads to "a hat in a hatbox". Watson and Crick had a disastrous meeting with Erwin Chargaff of Columbia University, who had discovered the ratios of the amount of the DNA bases. From John Griffiths, the nephew of Fred Griffiths who contributed to the fact that DNA is a genetic carrier, Crick learned that guanine (G) is attracted to cytosine (C), and adenine (A) to thymine (T), and Crick deduced that the bases must fit together like two interleaved decks of cards—they were stacked on top of one another inside the entwined backbones.

Watson was convinced that DNA must be helical due to Crick's proposed DNA structure and the X-ray diffraction plates. When Franklin showed Crick and Watson the X-ray pictures of DNA, even though the pictures did not show the radial symmetry necessary for helices, they show that the crystals were overlapping.

In autumn of 1952, Watson became friends with Linus Pauling's son, Peter. At that time, Linus Pauling was one of the few men in the scientific community who pondered the importance of DNA structure. From Peter, Watson learned that Linus Pauling published a paper on DNA structure—there are three helically entwined chains with sugar phosphate backbone outside of the coil, and the outdated X-ray pictures "proved" the structure to be true. Such structure is known as alpha helix. Watson immediately knew that Pauling's structure was incorrect because of the previous models that Watson had built. In fact, Pauling's structure left out important details: he had omitted to assign ionization charges on the phosphate groups. When there is no electric charge holding the long thin chains together, the chains would unravel and fall apart; without the charges, the nucleic acid structure was not even an acid.

Watson and Crick knew that Linus Pauling was their main competitor in determining the structure of DNA. Knowing that one of the greatest scientists made several mistakes in deducing DNA structures, Watson and Crick resolved to tackle the DNA structure at Cavendish laboratory. They worked on the DNA model using metal plates and Franklin's pictures of DNA by X-ray crystallography, provided by Maurice Wilkins and Max Perutz. Besides matching the bases, they also determined that the width between the two DNA strands must be less than two nanometers. In order to fit the bases inside the strands, Watson believed that the base pairs that are alike should be put together. However, they were unable to fit the similar bases within a small width. Watson then discovered that the keto-form base pairs joined A-T and C-G, and now the base pairs are able to fit inside the double strands. In five weeks of time, Watson and Crick built a DNA model that is indeed the correct structure of DNA.

In April 25, 1953, Watson and Crick published their article "Molecular structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid" in Nature, becoming the first to publish the structure of DNA as a double helix.

Importance of Discovery
This discovery shed light on how genetic material could be passed on from generation to generation, and proves the simplicity of the transfer of genetic material. In fact, our present understanding of the storage and utilization of a cell’s genetic information is based on work made possible by this discovery.

DNA Structure – Leading to Function
After looking at the X-ray crystallography made by Rosalind Franklin, Watson and Crick were able to deduce that the shape of DNA was a double helix, and by Chargaff’s experiment, were able to deduce that the G pairs with C and A pairs with T. The pairs’ base lengths are equal, and fit exactly between the two chains of phosphates. The bonds between the two phosphate groups are hypothesized by Watson and Crick to be hydrogen bonds, which are easily broken. The discovery of DNA structure thus gave them a very good idea on how DNA might replicate itself, and thus the passing of genetic material.

Within Watson and Crick's article they claim that DNA is a double helical structure and that Pauling's previous attempt to define the structure noting that it did not have the much needed hydrogen bond stabilization and underestimated the van der Waals interactions of base stacking. The helix would of right handed as the two chains run in opposite directions. Bases were linked towards the inside of the helix and the sugar phosphate linkage created the outer backbone. The helix would repeat every 10 residues or 3.4 Angstroms, as they saw in the crystallographic data from Rosalind Franklin. The diameter of the helix was found to be 20 Angstroms and there was a rotation of 36 degrees per base, thus having 10 bases every 360 degrees. The most innovative ideas of Watson and Crick's model was that the two chains were held together by bases of purines and pyrimidines. By hydrogen bonding, a purine must be bonded to a pyrimidine creating a complementary pair. Using experimental data that showed the ratios of adenine and thymine were very close as were guanine and cytosine they stated that adenine bonds to thymine and guanine binds to cytosine. They discovered this based on comparing the ratios of A-T, C-G and A-G, and they found that the first two ratios were the closest to 1 where as the second was varied. This helped them make the conclusion that A bonds with T and C bonds with G only. The pairs’ base lengths are equal, and fit exactly between the two chains of phosphates. The bonds between the two phosphate groups are hypothesized by Watson and Crick to be hydrogen bonds, which are easily broken. The DNA nucleotide must also contain deoxyribose and not ribose because the extra oxygen on ribose would interfere with the structure due to van der waals interactions. The discovery of DNA structure thus gave them a very good idea on how DNA might replicate itself, and thus the passing of genetic material. Also, they found that each of the bases was capable of tautomerizing between the enol and keto forms. Experimentally, it was determined that the keto form predominates at a physiological pH. Thus, they also came up with a method for demonstrating how DNA may denature as pH changes due to conversion from the keto to the enol form.

Later Discoveries
Watson and Crick’s discovery led to many new investigations, such as the structure of RNA, how DNA contains all the information for protein production, and the Human Genome Project, whereby all the 100,000 human genes are attempted to be mapped.