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James Dewey Watson (born April 6, 1928) is an American molecular biologist, best known as one of the co-discoverers of the structure of DNA. Watson, Francis Crick, and Maurice Wilkins were awarded the 1962 Nobel Prize in Physiology or Medicine "for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material". He studied at the University of Chicago and Indiana University and subsequently worked at the University of Cambridge's Cavendish Laboratory in England where he first met Francis Crick.
   In 1956 he became a faculty member of Harvard University's Biological Laboratories until 1976, but in 1968 served as Director of Cold Spring Harbor Laboratory on Long Island, New York and shifted its research emphasis to the study of cancer. In 1994 he became its President for ten years, and then subsequently served as its Chancellor until 2007. Between 1988 and 1992 he was associated with the National Institutes of Health, helping to establish the Human Genome Project. He has written many science books, including the seminal textbook "The Molecular Biology of the Gene" (1965) and his bestselling book "The Double Helix" (1968) about the DNA Structure discovery.

Biography

Watson was born in Chicago, Illinois, on April 6 1928, the son of a businessman, also named James Dewey Watson, and Margaret Jean Mitchell . His father was of midwestern English descent. His mother's father Lauchlin Mitchell, a tailor, was from Glasgow, Scotland, and her mother, Lizzie Gleason, was the child of Irish parents from Tipperary. Watson was fascinated with bird watching, a hobby he shared with his father. Watson appeared on Quiz Kids, a popular radio show that challenged precocious youngsters to answer questions. Thanks to the liberal policy of University president Robert Hutchins, he enrolled at the University of Chicago at the age of 15. After reading Erwin Schrödinger's book What Is Life? in 1946, Watson changed his professional ambitions from the study of ornithology to genetics. He earned his B.S. in Zoology from the University of Chicago in 1947. In his autobiography, Avoid Boring People, Watson describes the University of Chicago as an idyllic academic institution where he was instilled with the capacity for critical thought and an ethical compulsion not to suffer fools who impeded his search for truth, in contrast to his description of his later work at Harvard University. 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 (at age 22).
   Watson then went to Copenhagen in September 1950 for a year of postdoctoral research, first heading to the laboratory of biochemist Herman Kalckar. The experiments, which Watson had learned of during the previous summer's Cold Spring Harbor phage conference, included the use of radioactive phosphate as a tracer to determine which molecular components of phage particles actually infect the target bacteria during viral infection. The intention was to determine whether protein or DNA was the genetic material, but upon consultation with Max Delbrück, 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.
   In 1951 the 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. After obtaining some results from his phage and other experimental research conducted at Indiana University, Statens seruminstitute (Denmark), Cold Spring Harbor Laboratory, and the California Institute of Technology, 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.
   In late 1951 Crick and Watson began a series of informal exchanges with Maurice Wilkins during which some of Rosalind Franklin's findings were given to Watson and Crick by Wilkins without Franklin's permission or knowledge. In November, Watson attended a seminar by Franklin. She spoke about the X-ray diffraction data she'd collected with Raymond Gosling at King's College London. The data indicated that DNA was a helix of some sort. Soon after this seminar, Watson and Crick constructed an incorrect molecular model of DNA in which the phosphate backbones were on the inside of the structure. Franklin asserted that the phosphates almost certainly were on the outside, not the inside. Watson and Crick eventually came to see that she was right and used this information in their final determination of the helical structure. In 1952, the final details of the chemical structure of the DNA backbone were 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. Despite his official assignment, the lure of solving the puzzle of DNA structure continued to tantalize Watson; with his friend Crick, he continued to think about how to determine the structure of DNA.
   In April 1952, Watson's PhD research adviser, Luria, was to speak at a meeting in England. However, Luria wasn't allowed to travel due to cold war fears 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 discussing with others prior discoveries by other researchers such as the calculated width of the B-form DNA 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 benefited from three travel-related strokes of luck in 1952. First, Erwin Chargaff visited England in 1952 and inspired Watson and Crick to learn more about nucleotide biochemistry. There are four nucleobases: guanine (G), cytosine (C), adenine (A) and thymine (T) in DNA. The so-called Chargaff ratios experimental results indicated that the amount of G is equal to C and the amount of A is equal to T. Jerry Donohue explained to Watson and Crick the correct structures of the four bases. The second travel-related event was that Linus Pauling's plans to visit England were disrupted. His planned visit was canceled 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. The third was when Chargaff and Pauling crossed the Atlantic together, they didn't get along and Pauling avoided Chargaff all across the ocean when they could have compared notes on DNA's base pairs!
   In 1953, Crick and Watson were given permission by their lab director and Wilkins to again try to make a structural model of DNA. At this time, Crick and Watson became aware of a research progress report containing some of Franklin's findings. This report contained the data that she'd previously discussed in her research seminar of November 1951. Crick and Watson continued to make use of Franklin's results in their thinking about the structure of DNA.

Breakthrough

Watson's key contribution was in discovering the nucleotide base pairs, the key to the structure and function of DNA. This key discovery was made in the Pauling "tradition", by playing with molecular models. Since he'd have to wait for the Cavendish machine shop to make tin models of the four nucleobases, Watson, on February 28, 1953 made a molecule model of each using a straight edge, an exacto knife, white cardboard and paste. These molecules are all flat in their ring structures, so Watson could slide the cardboard models around on a table and examine how they might interact and fit together. After looking at the possible arrangements of his cardboard molecule models, Watson soon realized that the larger two-ring A and G nucleobases (technically referred to as purines) could be paired with the smaller one-ring T and C nucleobases, known as pyrimidines. Watson examined the possibility of hydrogen bonds between the pairs of purines and pyrimidines. After moving the A and T molecules around on the table he sat at, he brought together the distal (relative to its five-member ring) nitrogen of the A and the correct nitrogen-based hydrogen of T. Fortunately, the A and T were lying on the table both "face up" in that they were in the orientation as they occur in DNA and Watson then noticed the possibility of the second hydrogen bond involving an oxygen atom. He quickly saw that the other pair, C's nitrogen and G's nitrogen-based hydrogen had a similar relationship and that those two molecules formed three such bonds. As the accompanying diagram indicates, all five hydrogens involved have a covalent bond to a nitrogen (which has no "double" bond) and form the weaker hydrogen bond with either a nitrogen or an oxygen that each have one double valence bond to a carbon atom.
   Watson then saw that the two pairs could be superimposed on each other with similar overall structure. In particular, the hexagonal rings were equidistant and the relative orientations of the five-member rings of the "big" molecules, A and G were the same. The nitrogens with the "squiggly" lines are the ones that attach, as "ladder rungs", to the helical backbone and that these nitrogen atoms are equidistant and also superimpose in the two pairs, allowing the helical structure to be smooth. Watson sensed that too many pieces were falling into place for this to be anything but the answer. He was correct. The base pairs discovered by Watson were consistent with the biochemical data Chargaff had already published.

Nobel Prize

Watson and Crick proceeded to deduce the double helix structure of DNA which they submitted to the journal Nature and was subsequently published on April 25 1953. Watson mentions in his autobiography, Avoid Boring People, that he was refused a $1,000 raise in salary after winning the Nobel. It was originally to be published by Harvard University Press, but after objections from both Francis Crick and Maurice Wilkins, among others, Watson's home university where he'd been a member of the biology faculty since 1955, dropped the book and it was instead published by a commercial publisher, an incident which caused some scandal. Watson's original title was to have been "Honest Jim," in part to raise the ethical questions of bypassing Franklin 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. 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 that 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. the textbooks are still in print.

Genome project

In 1989, 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 April 10, 1992. Watson left the Genome Project after conflicts with the new NIH Director, Bernadine Healy. Watson was opposed to Healy's attempts to acquire patents on gene sequences, and any ownership of the "laws of nature." Two years before stepping down from the Genome Project, he'd stated his opinion on this long and ongoing controversy which he saw as an illogical barrier to research; he said, "The nations of the world must see that the human genome belongs to the world's people, as opposed to its nations." He left within weeks of the 1992 announcement that the NIH would be applying for patents on brain-specific cDNAs. In 1994, Watson became President of CSHL. Francis Collins took over the role as Director of the Human Genome Project. He became the second person to publish his fully sequenced genome online, after it was presented to him on May 31, 2007 by 454 Life Sciences Corporation in collaboration with scientists at the Human Genome Sequencing Center, Baylor College of Medicine. "'I am putting my genome sequence on line to encourage the development of an era of personalized medicine, in which information contained in our genomes can be used to identify and prevent disease and to create individualized medical therapies,' said CSHL Chancellor Watson."

Awards

Further Information

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