Monday, October 09, 2006

BY THOSE TIMES THINGS GOT SHARPNESS



In 1962 James Watson (1928– ), Francis Crick (1916–2004), and Maurice Wilkins (1916–2004) jointly received the Nobel Prize in medicine or physiology for their determination in 1953 of the structure of deoxyribonucleic acid (DNA). Because the Nobel Prize can be awarded only to the living, Wilkins's colleague Rosalind Franklin (1920–1958), who died of cancer at the age of 37, could not be honored.

The molecule that is the basis for heredity, DNA, contains the patterns for constructing proteins in the body, including the various enzymes. A new understanding of heredity and hereditary disease was possible once it was determined that DNA consists of two chains twisted around each other, or double helixes, of alternating phosphate and sugar groups and that the two chains are held together by hydrogen bonds between pairs of organic bases—adenine (A) with thymine (T) and guanine (G) with cytosine (C). Modern biotechnology also has its basis in the structural knowledge of DNA—in this case the scientist's ability to modify the DNA of host cells that will then produce a desired product, for example, insulin.

The background for the work of the four scientists was formed by several scientific breakthroughs: the progress made by X-ray crystallographers in studying organic macromolecules; the growing evidence supplied by geneticists that it was DNA, not protein, in chromosomes that was responsible for heredity; Erwin Chargaff's experimental finding that there are equal numbers of A and T bases and of G and C bases in DNA; and Linus Pauling's discovery that the molecules of some proteins have helical shapes—arrived at through the use of atomic models and a keen knowledge of the possible disposition of various atoms.

Of the four DNA researchers only Rosalind Franklin had any degrees in chemistry. The daughter of a prominent London banking family, where all children—girls and boys—were encouraged to develop their individual aptitudes, she held her undergraduate and graduate degrees from Cambridge University. During World War II she gave up her research scholarship to contribute to the war effort at the British Coal Utilization Research Association, where she performed fundamental investigations on the properties of coal and graphite. After the war she joined the Laboratoire Centrale des Services Chimiques de l'Etat in Paris, where she was introduced to the technique of X-ray crystallography and rapidly became a respected authority in this field. In 1951 she returned to England to King's College, London, where her charge was to upgrade the X-ray crystallographic laboratory there for work with DNA.

Already at work at King's College was Maurice Wilkins, a New Zealand–born but Cambridge-educated physicist. As a new Ph.D. he worked during World War II on the improvement of cathode-ray tube screens for use in radar and then was shipped out to the United States to work on the Manhattan Project. Like many other nuclear physicists he became disillusioned with his subject when it was applied to the creation of the atomic bomb; he turned instead to biophysics, working with his Cambridge mentor, John T. Randall—who had undergone a similar conversion—first at the University of St. Andrews in Scotland and then at King's College, London. It was Wilkins's idea to study DNA by X-ray crystallographic techniques, which he had already begun to implement when Franklin was appointed by Randall. The relationship between Wilkins and Franklin was unfortunately a poor one and probably slowed their progress.

Meanwhile, in 1951 23-year-old James Watson, a Chicago-born American, arrived at the Cavendish Laboratory in Cambridge. Watson had two degrees in zoology: a bachelor's degree from the University of Chicago and a doctorate from the University of Indiana, where he became interested in genetics. He worked under Salvador E. Luria on bacteriophages, the viruses that invade bacteria in order to reproduce—a topic for which Luria received a Nobel Prize in medicine in 1969. Watson then went to Denmark for postdoctoral work—to continue studying viruses and to remedy his relative ignorance of chemistry. At a conference at the Zoological Station at Naples, Watson heard Wilkins talk on the molecular structure of DNA and saw his recent X-ray crystallographic photographs of DNA—and was hooked.

Watson soon moved to the Cavendish Laboratory. There several important X-ray crystallographic projects were in progress under William Lawrence Bragg's leadership, including Max Perutz's investigation of hemoglobin and John Kendrew's study of myoglobin—a protein in muscle tissue that stores oxygen. (Perutz and Kendrew received Nobel prizes in chemistry for their work in the same year that the prizes were awarded to the DNA researchers—1962.) Working under Perutz was Francis Crick, who had earned a bachelor's degree in physics from University College, London, and had helped develop radar and magnetic mines during World War II. Crick, another physicist in biology, was supposed to be writing a dissertation on the X-ray crystallography of hemoglobin when Watson arrived, eager to recruit a colleague for work on DNA. Inspired by Pauling's success in working with molecular models, Watson and Crick rapidly put together several models of DNA and attempted to incorporate all the evidence they could gather. Franklin's excellent X-ray photographs, to which they had gained access without her permission, were critical to the correct solution. The four scientists announced the structure of DNA in articles that appeared together in the same issue of Nature.

Then they moved off in different directions. Franklin went to Birkbeck College, London, to work in J. D. Bernal's laboratory—a much more congenial setting for her than King's College. Before her death she made important contributions to the X-ray crystallographic analysis of the structure of the tobacco mosaic virus—a landmark in the field. Wilkins applied X-ray techniques to the structural determination of nerve cell membranes and of ribonucleic acid (RNA)—a molecule that is associated with chemical synthesis in the living cell—while rising in rank and responsibility at King's College. Watson's subsequent career eventually took him to Cold Spring Harbor Laboratory of Quantitative Biology on Long Island, where as director from 1968 onward he led it to new heights as a center of research in molecular biology. From 1988 to 1992 he headed the National Center for Human Genome Research at the National Institutes of Health. Crick stayed at Cambridge and made fundamental contributions to unlocking the genetic code. He and Sydney Brenner demonstrated that each group of three adjacent bases on a single DNA strand codes for one specific amino acid. He also correctly hypothesized the existence of "transfer" RNA, which mediates between "messenger" RNA and amino acids. After 20 years at Cambridge, with several visiting professorships in the United States, Crick joined the Salk Institute for Biological Studies in La Jolla, California.

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