Microbiology and Immunology

(Axel Boer) #1
Crick, Francis WORLD OF MICROBIOLOGY AND IMMUNOLOGY

140


biologists and who began their careers around the end of
World War II, Crick read and was impressed by Erwin
Schrödinger’s book What Is Life?,but later recognized its lim-
itations in its neglect of chemistry.
Following his undergraduate studies, Crick conducted
research on the viscosity of water under pressure at high tem-
peratures, under the direction of Edward Neville da Costa
Andrade, at University College. It was during this period that
he was helped financially by his uncle, Arthur Crick. In 1940,
Crick was given a civilian job at the Admiralty, eventually
working on the design of mines used to destroy shipping.
Early in the year, Crick married Ruth Doreen Dodd. Their son
Michael was born during an air raid on London on November
25, 1940. By the end of the war, Crick was assigned to scien-
tific intelligence at the British Admiralty Headquarters in
Whitehall to design weapons.
Realizing that he would need additional education to
satisfy his desire to do fundamental research, Crick decided to
work toward an advanced degree. Crick became fascinated
with two areas of biology, particularly, as he describes it in his
autobiography, “the borderline between the living and the non-
living, and the workings of the brain.” He chose the former
area as his field of study, despite the fact that he knew little
about either subject. After preliminary inquiries at University
College, Crick settled on a program at the Strangeways
Laboratory in Cambridge under the direction of Arthur
Hughes in 1947, to work on the physical properties of cyto-
plasmin cultured chick fibroblast cells. Two years later, he
joined the Medical Research Council Unit at the Cavendish
Laboratory, ostensibly to work on protein structure with
British chemists Max Perutz and John Kendrew (both future
Nobel Prize laureates), but eventually to work on the structure
of DNA with Watson.
In 1947, Crick was divorced, and in 1949, married
Odile Speed, an art student whom he had met during the war.
Their marriage coincided with the start of Crick’s Ph.D. thesis
work on the x-ray diffraction of proteins. X-ray diffraction is
a technique for studying the crystalline structure of molecules,
permitting investigators to determine elements of three-
dimensional structure. In this technique, x rays are directed at
a compound, and the subsequent scattering of the x-ray beam
reflects the molecule’s configuration on a photographic plate.
In 1941 the Cavendish Laboratory where Crick worked
was under the direction of physicist Sir William Lawrence
Bragg, who had originated the x-ray diffraction technique
forty years before. Perutz had come to the Cavendish to apply
Bragg’s methods to large molecules, particularly proteins. In
1951, Crick was joined at the Cavendish by James Watson, a
visiting American who had been trained by Italian physician
Salvador Edward Luria and was a member of the Phage
Group, a group of physicists who studied bacterial viruses
(known as bacteriophages, or simply phages). Like his phage
colleagues, Watson was interested in discovering the funda-
mental substance of genes and thought that unraveling the
structure of DNA was the most promising solution. The infor-
mal partnership between Crick and Watson developed, accord-
ing to Crick, because of their similar “youthful arrogance” and
similar thought processes. It was also clear that their experi-

ences complemented one another. By the time of their first
meeting, Crick had taught himself a great deal about x-ray dif-
fraction and protein structure, while Watson had become well
informed about phage and bacterial genetics.
Both Crick and Watson were aware of the work of bio-
chemists Maurice Wilkins and Rosalind Franklin at King’s
College, London, who were using x-ray diffraction to study
the structure of DNA. Crick, in particular, urged the London
group to build models, much as American chemist Linus
Pauling had done to solve the problem of the alpha helix of
proteins. Pauling, the father of the concept of the chemical
bond, had demonstrated that proteins had a three-dimensional
structure and were not simply linear strings of amino acids.
Wilkins and Franklin, working independently, preferred a
more deliberate experimental approach over the theoretical,
model-building scheme used by Pauling and advocated by
Crick. Thus, finding the King’s College group unresponsive to
their suggestions, Crick and Watson devoted portions of a two-
year period discussing and arguing about the problem. In early
1953, they began to build models of DNA.
Using Franklin’s x-ray diffraction data and a great deal
of trial and error, they produced a model of the DNA molecule
that conformed both to the London group’s findings and to the
data of Austrian-born American biochemist Erwin Chargaff.
In 1950, Chargaff had demonstrated that the relative amounts
of the four nucleotides, or bases, that make up DNA con-
formed to certain rules, one of which was that the amount of
adenine (A) was always equal to the amount of thymine (T),
and the amount of guanine (G) was always equal to the
amount of cytosine (C). Such a relationship suggests pairings
of A and T, and G and C, and refutes the idea that DNA is noth-
ing more than a tetranucleotide, that is, a simple molecule con-
sisting of all four bases.
During the spring and summer of 1953, Crick and
Watson wrote four papers about the structure and the supposed
function of DNA, the first of which appeared in the journal
Natureon April 25. This paper was accompanied by papers by
Wilkins, Franklin, and their colleagues, presenting experimen-
tal evidence that supported the Watson-Crick model. Watson
won the coin toss that placed his name first in the authorship,
thus forever institutionalizing this fundamental scientific
accomplishment as “Watson-Crick.”
The first paper contains one of the most remarkable
sentences in scientific writing: “It has not escaped our notice
that the specific pairing we have postulated immediately sug-
gests a possible copying mechanism for the genetic material.”
This conservative statement (it has been described as “coy”
by some observers) was followed by a more speculative paper
in Natureabout a month later that more clearly argued for the
fundamental biological importance of DNA. Both papers
were discussed at the 1953 Cold Spring Harbor Symposium,
and the reaction of the developing community of molecular
biologists was enthusiastic. Within a year, the Watson-Crick
model began to generate a broad spectrum of important
research in genetics.
Over the next several years, Crick began to examine
the relationship between DNA and the genetic code. One of
his first efforts was a collaboration with Vernon Ingram,

womi_C 5/6/03 2:05 PM Page 140

Free download pdf