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Double helix

James Dewey Watson (born April 6, 1928) is one of the discoverers of the structure of the DNA molecule. Watson, Francis Crick and Maurice Wilkins, were awarded the 1962 Nobel Prize for Physiology or Medicine, for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material.

Early life

Born in Chicago, Watson has been fascinated by birds since he was a child due to the influence of his father. At the age of 12, he starred on the Quiz Kids, a popular radio show that challenged precocious youngsters to answer difficult questions. Thanks to the liberal policy of Robert Hutchins, he enrolled at the age of 15 at the University of Chicago. After reading Erwin Schrödinger's book What Is Life? in 1946, he changed his direction from ornithology to genetics. He earned his B.Sc. in Zoology in 1947.

He was attracted to the work of Salvador Luria. Luria eventually shared a Nobel prize for his work on the Luria-Delbruck experiment, which concerned the nature of genetic mutations. Luria was part of a distributed group of researchers who were making use of the viruses that infect bacteria in order to explore genetics. Luria and Max Delbrück were among the leaders of this new "Phage Group", an important movement of geneticists from experimental systems such as Drosophila towards microbial genetics. Early in 1948 Watson began his Ph.D. research in Luria's laboratory and that spring he got to meet Delbrück in Luria's apartment and again that summer during Watson's first trip to the Cold Spring Harbor Laboratory (CSHL). The Phage Group was the intellectual medium within which Watson became a working scientist. Importantly, the members of the Phage Group had a sense that they were on the path to discovering the physical nature of the gene. In 1949 Watson took a course with Felix Haurowitz that included the conventional view of that time: that proteins were genes and able to replicate themselves. The other major molecular component of chromosomes, DNA, was thought by many to be a "stupid tetranucleotide", serving only a structural role to support the proteins. However, even at this early time, Watson, under the influence of the Phage Group, was aware of the work of Oswald Avery which suggested that DNA was the genetic molecule. Watson's research project involved using X-rays to inactivate bacterial viruses ("phage"). He gained his Ph.D. in Zoology at Indiana University in 1950. Watson then went to Europe for postdoctoral research, first heading to the laboratory of biochemist Herman Kalckar in Copenhagen who was interested in nucleic acids and had developed an interest in phage as an experimental system.

Watson's time in Copenhagen had one favorable consequence. He was able to do some experiments with Ole Maaloe (a member of the Phage Group) that were consistent with DNA being the genetic molecule. Watson had learned about these kinds of experiments the previous summer at Cold Spring Harbor. The experiments involved radioactive phosphate as a tracer and attempted to determine what molecular components of phage particles actually infect the target bacteria during viral infection. Watson never developed a constructive interaction with Kalckar, but he did accompany Kalckar to a meeting in Italy where Watson saw Maurice Wilkins talk about his X-ray diffraction data for DNA. Watson was now certain that DNA had a definite molecular structure that could be solved.

In 1951 the highly regarded Nobel Prize winning chemist Linus Pauling published his model of the protein alpha helix, a result that grew out of Pauling's relentless efforts in X-ray crystallography and molecular model building. Watson now had the desire to learn to perform X-ray diffraction experiments so that he could work to determine the structure of DNA. That summer, Luria met John Kendrew and arranged for a new postdoctoral research project for Watson in England.

The Structure of DNA

Template:Single strand DNA discovery2 In October 1951, Watson started at the Cavendish Laboratory, the physics department of the University of Cambridge, where he met Francis Crick. Watson and Crick started an intense intellectual collaboration that in less than a year and a half resulted in their discovery of the structure of DNA. They had unique qualifications to bring to bear on the problem. Crick soon solved the mathematical equations that govern helical diffraction theory; Watson knew all of the key DNA results of the Phage Group.

In April 1952, Watson's PhD research advisor, Luria, was to speak at a meeting in England. However, Luria was not allowed to travel due to cold war hysteria over his Marxist leanings. Watson used Luria's speaking slot to talk about his own work with radioactive DNA and the results of others in the Phage Group that indicated the genetic material of phages was DNA. It has been recorded that during this meeting Watson was passing on to others prior discoveries by local DNA researcher Maurice Wilkins such as the calculated width of the B-form molecule as determined by X-ray diffraction studies. By 1952 estimates from X-ray data and electron microscopy agreed that the diameter of DNA was about 2 nanometers.

Watson and Crick benefitted from two travel-related strokes of luck in 1952. First, Erwin Chargaff visited England in 1952 and rubbed Watson's and Crick's noses in the fact that they knew almost nothing about nucleotide biochemistry: they soon repaired their deficiency. And second, Linus Pauling did NOT visit England. His planned visit was cancelled for political reasons and he never gained access to the King's College X-ray diffraction data for DNA until it was published in 1953, along with the Watson-Crick model. With his extensive expertise, Pauling might very well have deduced the structure of DNA a year before Watson and Crick if only he had had access to this information. It was also in 1952 that the final details of the chemical structure of the DNA backbone was determined by biochemists like Alexander Todd.

During 1952, Crick and Watson had been asked not to work on making molecular models of the structure of DNA. Instead, Watson's official assignment was to perform X-ray diffraction experiments on tobacco mosaic virus. Tobacco mosaic virus was the first virus to be identified (1886) and purified (1935). Since electron microscopy revealed that virus crystals form inside infected plants, it made sense to isolate this virus for study by X-ray crystallography. Early X-ray diffraction images for tobacco mosaic virus had been collected before World War II. By 1954, Watson had deduced from his X-ray diffraction images that the tobacco mosaic virus had a helical structure.

But despite his official assignment, the lure of solving the puzzle of DNA structure continued to tantalize Watson; with his friend Crick, he continued to work on this topic without official sanction. Linus Pauling had made use of molecular models to solve the structure of the protein alpha helix. Pauling had personally attained what was possibly the world's greatest understanding of chemistry. It was to be seen whether Watson and Crick could similarly determine the structure of DNA. Neither Watson nor Crick knew much chemistry. But local X-ray crystallography expert Rosalind Franklin who had already done extensive work on DNA was within easy reach in London for consultations and they had easy access to other key chemical knowledge they needed in 1952. Building upon the unpublished X-ray diffraction research of Franklin and Wilkins, together Watson and Crick deduced the double helix structure of DNA which they published in the journal Nature on April 25, 1953.

Watson's key contribution was in discovering the nucleotide base pairs that are the key to the structure and function of DNA. This key discovery was made in the Pauling "tradition", by playing with molecular models of the four nucleobases. After he realized that adenine:thymine and cytosine:guanine pairs are structurally similar it was immediately clear that such structural pairing accounted for a key biochemical fact of DNA, the so-called Chargaff ratios, experimentally determined ratios of the amounts of the four nucleotide subunits of DNA: the amount of guanine is equal to cytosine and the amount of adenine is equal to thymine. Watson's exercise in molecular modeling was facilitated by Jerry Donohue who explained to Watson and Crick the correct structures of the four bases. This allowed Watson to visually line up the complementary base pairs that could be held together by hydrogen bonds.

Franklin's key contribution was when she told Watson and Crick that the phosphate backbones of DNA should be on the outside of the molecule. When Watson and Crick finally accepted this fact, the bases had to go to the inside of the DNA structure where they would have to interact chemically. Watson discovered the nature of that interaction.

For their efforts, Watson, Crick, and Wilkins were awarded the Nobel Prize in Physiology or Medicine in 1962 for their discovery of DNA structure. Franklin's apparent exclusion from this Nobel Prize was due to her death in 1958 before it was awarded; unfortunately for Franklin, the Nobel Prize is not awarded posthumously. Some in the molecular biology community believe that since Franklin died early, and Wilkins was much less of a publicity-seeker, that Watson and Crick have in the popular mind overshadowed Wilkins and Franklin to an undeserved degree.

In 1968 Watson wrote The Double Helix, one of the Modern Library's 100 best non-fiction books. The account is the sometimes painful story of not only the discovery of the structure of DNA, but the personalities, conflicts and controversy surrounding their work. Watson's original title was to have been "Honest Jim", in part to raise the ethical questions of sneaking around behind Franklin's back to gain access to her X-ray diffraction data before they were published. Watson seems to have never been particularly bothered by the way things turned out. If all that mattered was beating Pauling to the structure of DNA, then Franklin's cautious approach to analysis of the X-ray data was simply an obstacle that Watson needed to run around. Wilkins and others were there at the right time to help Watson and Crick do so. Also in 1968, Watson became the director of the CSHL and made the CSHL his permanent residence in 1974.

The Double Helix changed the way the public viewed scientists and the way they work. In the same way, Watson's first textbook, The Molecular Biology of the Gene set a new standard for textbooks, particularly through the use of concept heads - brief declarative subheadings. Its style has been emulated by almost all succeeding textbooks. His next great success was Molecular Biology of the Cell although here his role was more of coordinator of an outstanding group of scientist-writers. His third textbook was Recombinant DNA which used the ways in which genetic engineering has brought us so much new information about how organisms function. All the textbooks are still in print.

Controversy About Using King's College London's Results

A more enduring controversy has been generated by Watson and Crick's use of Rosalind Franklin's crystallographic evidence of the structure of DNA, which was shown to them, without her knowledge, by her estranged colleague, Maurice Wilkins, and by Max Perutz. Her evidence demonstrated that the two sugar-phosphate backbones lay on the outside of the molecule, confirmed Watson and Crick's conjecture that the backbones formed a double helix, and revealed to Crick that they were antiparallel. Franklin's superb experimental work thus proved crucial in Watson and Crick's discovery. Yet, they gave her scant acknowledgment. Even so, Franklin bore no resentment towards them. She had presented her findings at a public seminar to which she had invited the two. She soon left DNA research to study tobacco mosaic virus. She became friends with both Watson and Crick, and spent her last period of remission from ovarian cancer in Crick's house (Franklin died in 1958). Crick believed that he and Watson used her evidence appropriately, while admitting that their patronizing attitude towards her, so apparent in The Double Helix, reflected contemporary conventions of gender in science.

Genome Project

In 1988, Watson's achievement and success led to his appointment as the Head of the Human Genome Project at the National Institutes of Health, a position he held until 1992. Watson left the Genome Project after conflicts with the new NIH Director, Bernardine Healy. Watson was opposed to Healy's attempts to commercialize genes by granting patents on genes and ownership rights based on the identification of gene sequences. Watson left due to the legal technicality of it not being acceptable for the head of the Genome Project to at the same time have a job like the one Watson still held at Cold Spring Harbor Laboratory.

Watson is an outspoken atheist, known for his frank opinions on politics, religion, and the role of science in society. He has been considered to hold a number of controversial views.

He is for instance a strong proponent of genetically modified food|genetically modified crops, holding that the benefits far outweigh any plausible environmental dangers, and that many of the arguments against GM crops are unscientific or irrational. His views on these matters are covered in some depth in his book DNA: The Secret of Life (2003), particularly in chapter 6.

He has also repeatedly said in public lectures "that if the gene (for homosexuality) were discovered and a woman decided not to give birth to a child that may have a tendency to become homosexual, she should be able to abort the fetus."

In 1994, Watson gave up his position of director and became president of the CSHL for ten years. Currently, Watson gives public speeches and serves as chancellor of the Cold Spring Harbor Laboratory in Cold Spring Harbor, New York.

References

The Nobel Prize in Physiology or Medicine 1962. Nobel Prize citation for Crick, Watson and Wilkins.
"The properties of x-ray inactivated bacteriophage. I. Inactivation by direct effect." by J. D. Watson in Journal of Bacteriology (1950) volume 60 page 697-718. The full text of this article is available for download in PDF format.
See Chapter 2 of The Eighth Day of Creation: Makers of the Revolution in Biology by Horace Freeland Judson published by Cold Spring Harbor Laboratory Press (1996) ISBN 0879694785.
"The structure of tobacco mosaic virus. I. X-ray evidence of a helical arrangement of sub-units around the longitudinal axis" by J. D. Watson in Biochim Biophys Acta. (1954) volume 13 pages 10-19. Template:Entrez Pubmed
Molecular structure of Nucleic Acids by James D. Watson and Francis H. Crick. Nature 171, 737–738 (1953).

External links

Presentation speech at the Nobel Prize ceremony in 1962.

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