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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 Illinois, Watson has been fascinated by birds since he was a child due to the influence of his father, James D. Watson, a businessman. 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 at Indiana University 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 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. Crick soon solved the mathematical equations that govern helical diffraction theory; Watson knew all of the key DNA results of the Phage Group.

In late 1951 Crick and Watson began a series of informal exchanges with Wilkins. In November, Watson attended a seminar by Rosalind Franklin. She spoke about the X-ray diffraction data she had collected with Raymond Gosling. 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. This assissted them in their pursuit of the correct model. In 1952, the final details of the chemical structure of the DNA backbone was determined by biochemists like Alexander Todd. This knowledge suggested that the nucleobases (see below) were inside of the helical structure and likely interacting with each other.

In December 1951, lab director William Lawrence Bragg asked Crick and Watson to not 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 advisor, Luria, was to speak at a meeting in England. However, Luria was not 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 benefitted from two travel-related strokes of luck in 1952. First, Erwin Chargaff visited England in 1952 and inspired Watson's and Crick to learn more about nucleotide biochemistry. There were four nucleobases: adenine (A) and thymine (T), guanine (G), cytosine (C). The the so-called Chargaff ratios experimental results had already shown that of the the bases were already paired in DNA in that the amount of A is equal to T and the amount of G is equal to C. 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 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.

In January 1953, Bragg, supported by Wilkins, reversed himself and granted Crick and Watson permission by to try to make a structural model of DNA.

The breakthrough

File:AT Watson Crick basepair.png
An AT base pair.
A GC base pair.

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.

Since he would have to wait for the Cadvendish machine shop to make tin models, Watson, on February 21, 1953 made a molecule model of each using a straight edge, an exacto knife, white cardboard and paste. Chargaff had already suggested the pairing, which, in Watson's mind, were the "big" two-ring A and G being paired with the "small" one-ring T and C. After building his cardboard molecule models, Watson was looking for the possiblity of hydrogen bonds. Note also that these molecules are all flat in their ring structures. Afer 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. The reader should note from the diagrams that 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 one each other with similar overall structure. In particular, the hexagnoal rings were equidistant and the relative orientations of the five-member rings of the "big" molecules, A and G were the same. The reader should also note that the nitrogens with the "squiggly" lines are the ones that attach, as "ladder rungs", to the helical backbone and that these nitrogen atoms are equidistanct and also superimpose in the two pairs, allowing the helical structure to be smooth. Watson sensed that too many pieces fell into place for this to be anything but the answer. He was correct.

Nobel Prize

Watson and Crick proceeded to deduce the complete double helix structure of DNA which they published in the journal Nature on April 25, 1953. 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 had died in 1958 and could not be named in the Prize.

The Double Helix

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. 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 dropped the book and it was instead published by a private publisher, and 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. 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.

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. 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.

Controversies

James Watson (February, 2003)
Main article: King's College DNA controversy

Watson was an outspoken man, but the enduring controversy of his life is how attribution was made for Wilkins and Franklin.

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 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 supported genetic screening and genetic engineering in public lectures and interviews, arguing for instance that the "really stupid" bottom 10% of people should be aborted before birth; that all girls should be genetically engineered to be pretty and "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."

According to James Watson at the 2003 conference: DNA: "50 years of the Double Helix" held in Cambridge (England) in 2003 : (quote) "Now perhaps it's a pretty well kept secret that one of the most uninspiring acts of Cambridge University over this past century was to turn down Francis Crick when he applied to be the Professor of Genetics, in 1958. Now there may have been a series of arguments, which lead them to reject Francis. But it really was stupid. It was really saying, don't push us to the frontier. That's what it was saying." (conference transcript)

Watson also had quite a few disagrements with Craig Venter regarding his use of EST fragments while Venter worked at NIH. Venter went on to found Celera genomics and continued his feud with Watson through the privately funded venture. Watson was even quoted as calling Venter Hitler (The Genome War, J. Shreeve)

References

  1. "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.
  2. 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.
  3. Most of the biographical account comes from Watson's 1968 autobiographical account, The Double Helix:A Personal Account of the Discovery of the Structure of DNA. The book was very controversial when it came out, though, as many of the participants still living disputed its account, especially of the role and personality of Franklin. For an edition which contains critical responses, book reviews, and copies of the original scientific papers, see James D. Watson, The Double Helix:A Personal Account of the Discovery of the Structure of DNA, Norton Critical Edition, Gunther Stent, ed. (New York: Norton, 1980).
  4. Bragg's decision near the end of 1951 that Watson and Crick should not work on DNA structure is described on page 128 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. Bragg gave Watson permission to start DNA model work again in January 1953 (see page 162).
  5. "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
  6. Molecular structure of Nucleic Acids by James D. Watson and Francis H. Crick. Nature 171, 737–738 (1953).
  7. The Nobel Prize in Physiology or Medicine 1962. Nobel Prize citation for Crick, Watson and Wilkins.

Further reading

  • Chadarevian, S. (2002) Designs For Life: Molecular Biology After World War II. Cambridge University Press ISBN 0521570786
  • Chargaff, E. (1978) Heraclitean Fire. New York: Rockefeller Press.
  • Chomet, S., ed., (1994) D.N.A.: Genesis of a Discovery London: Newman-Hemisphere Press.
  • Judson, H. F. (1977) The Eighth Day of Creation. Makers of the Revolution in Biology. Jonathan Cape. ISBN 13579108642
  • Hunter, G. (2004) Light Is A Messenger: the life and science of William Lawrence Bragg. Oxford University Press. ISBN 019852921X
  • Olby, R. (1974) The Path to The Double Helix: Discovery of DNA. London: MacMillan. ISBN 046681173; Definitive DNA textbook, with foreword by Francis Crick, revised in 1994 with a 9 page postscript.
  • Olby, R. (2003) "Quiet debut for the double helix" Nature 421 (January 23): 402-405.
  • Ridley, M. (2006) Francis Crick: Discoverer of the Genetic Code (Eminent Lives) New York: Harper Collins. ISBN 006082333X.
  • Watson, J. D. (1968) The Double Helix: A Personal Account of the Discovery of the Structure of DNA. New York: Atheneum.
  • Watson, J. D., T. A. Baker, S. P. Bell, A. Gann, M. Levine, and R. Losick, eds., (2003) Molecular Biology of the Gene. (5th edition) New York: Benjamin Cummings ISBN 080534635X
  • Watson, J. D. (2002) Genes, Girls, and Gamow: After the Double Helix. New York: Random House. ISBN 0375412832
  • Watson, J. D. and A. Berry (2003) DNA: The Secret of Life New York: Random House. ISBN 0375415467
  • Wilkins, M. (2003) The Third Man of the Double Helix: The Autobiography of Maurice Wilkins. Oxford: Oxford University Press. ISBN 0198606656.

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Laureates of the Nobel Prize in Physiology or Medicine
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1926–1950
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