Chapter 2
The Double Helix: This is Life
Watson got "hooked on the gene" in his third year at the University of Chicago. His change of heart was inspired by a little book that appeared in 1944, What Is Life:, by the Austrian-born father of wave mechanics, Erwin Shrodinger. The book grew out of several lectures he had given at the Institute for Advanced Study in Dublin, 1943.
DNA located exclusively on chromosomes, but at the time it was too big a molecule for chemists to study. In addition, at the time, most biologists felt that genetic information would be carried by proteins, not by DNA.
DNA had been known for 75 years by then. In 1869, Friedrich Miescher, a Swiss biochemist working in Germany, had isolated DNA, which he called "nuclein."
1930s: DNA shown to be a long molecule containing four different chemical bases: T, A, G, and C. In 1944, it was unknown how these subunits, called deoxynucleotides) of the molecule were chemically linked.
DNA did not move into the genetic limelight until 1944: Oswald Avery's lab, Rockefeller Institute, NYC, reported that the composition of the surface coats of pneumonia bacteria could be changed. For decades, scientists had known there were two strains of Pneumococcus: "smooth" (S) and "rough" (R).
The Pneumococcus coat could transform.
In part because of its bombshell implications, that DNA was the holy grail (genetic material), the resulting February 1944 paper by Avery, MacLeod, and McCarty met with a mixed response.
Avery did not get the Nobel prize. The Nobel committee makes it records public 50 years following each award; it turns out that Swedish physical chemist Einar Hammarsten blocked the nomination of Avery. Hammarsten had produced high quality DNA but still believed that genes to be an undiscovered class of proteins. Even have the double helix was found, Hammersten still said Avery not eligible for the Nobel prize if it couldn't be explained how DNA transmitted information. Avery died in 1955; had he lived a few years long he certainly would have won a Nobel prize for identifying DNA as the genetic material.
When Watson arrived at Indiana University in 1947, Avery's paper came up in discussions all the time.
Cambridge, England: the canny Scottish chemist Alexander Todd identified the chemical bonds that linked together the nucleotides; they were all the same, and thus regular.
At Columbia University, Erwin Chargaff, developed process for measuring relative amounts of A, T, C, and G in each DNA molecule. None were the same.
The Phage Group at Indiana University began after Watson arrived; formed under Watson's Ph.D. supervisor, Salvador Luria (Italian) and Max Delbruck (German) and Alfrey Hershey (American).
Delbruck and Luria (fled Europe; banned from war effort in US) collaborated on phage experiments during successive summers at Cold Spring Harbor. Their theory: phages were "naked genes."
[I had an "aha" moment in medical school when I saw the same thing, that phages/viruses were "naked genes." That was in 1973 - 1974.]
The concept of "naked genes" had been first proposed in 1922 by the imaginative American geneticist Herman J. Muller, who three years later demonstrated that X-rays cause mutations. His belated Nobel Prize came in 1946, just after he joined the faculty at Indiana University. It was his presence, in fact, that led Watson to Indiana.
Watson felt that research on Muller's fruit flies was "the past." The future was Luria's phages, and that's where Watson headed.
Because he was weak in chemistry, Watson would not have survived in a chemistry lab. He therefore took a postdoctoral fellowship in the Copenhagen lab of the biochemist Herman Kalckar in the fall of 1950, studying the small molecules that make up DNA. Watson knew that this would also be a dead end, but his year in Copenhagen turned out to be productive.
To escape the cold Danish spring, Watson went to the Zoological Station at Naples during April and May. During his week there, he attended a small conference on X-ray diffraction methods for determining the 3-D structure of molecules. Initially, he was disillusioned by the conference. And then the last-minute talk on DNA by a 34-year-old Englishman named Maurice Wilkins from the Biophysics Lab of King's College, London.
And then the rest is history as they say.
Wilkins was a physicist; he had worked on the Manhattan Project.
He, too, had read Schrodinger's book and was tackling DNA with X-ray diffraction.
But Wilkins not much interested in talking to Watson at the time.
Watson returns to Copenhagen. Back in America, Caltech's Linus Pauling announced a major triumph: he had found the exact arrangement in which chains of amino acids fold up -- the alpha helix. Short bio of Linus Pauling, p. 43; fascinating.
Then the short history of how Watson ended up at Cavendish, starting at the bottom of page 43.
Chapter Three
Reading The Code: Bringing DNA To Life
The RNA Tie Club -- absolutely fascinating. A small group --
- G. Gamow -- inducted Edward Teller
- A. Rich
- P. Doty
- R. Ledley
- M. Yoas
- R. Williams
- A. Dounce
- R. Feynman
- M Calvin
- N. Simons
- E. Teller
- E. Chargaff
- N. Metropolis
- G. Stent
- J. Watson -- inducted Richard Feynman
- H. Gordon
- L. Orgel
- M. Delbruck
- F. Crick
- S. Breener
DNA: molecule model, 1953. Awarded the Nobel Prize in Physiology or Medicine (Wilkins, Crick, and Watson, in 1962). Had Rosalind Franklin lived, the problem would have arisen whether to bestow the award upon her or Maurice Wilkins. The Swedes might have resolved the dilemma by awarding them both the Nobel Prize in Chemistry that year. Instead, it went to Max Perutz and John Kendrew, who had elucidated the three-dimensional structures of hemoglobin and myoglobin respectively.
Chapter Four
Playing God: Customized DNA Molecules
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