James D. Watson 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, Watson has been fascinated by birds since he
was a child due to the influence of his father. 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
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 highly regarded Nobel Prize winning 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.
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. They had unique qualifications
to bring to bear on the problem. Crick soon solved the mathematical
equations that govern helical diffraction theory; Watson knew
all of the key DNA results of the Phage Group.
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 hysteria 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 passing on to others prior discoveries
by local DNA researcher Maurice Wilkins such as the calculated
width of the B-form 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 rubbed
Watson's and Crick's noses in the fact that they knew almost nothing
about nucleotide biochemistry: they soon repaired their deficiency.
And second, Linus Pauling did NOT visit England. 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, along with the Watson-Crick model. With
his extensive expertise, Pauling might very well have deduced
the structure of DNA a year before Watson and Crick if only he
had had access to this information. It was also in 1952 that the
final details of the chemical structure of the DNA backbone was
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.
But
despite his official assignment, the lure of solving the puzzle
of DNA structure continued to tantalize Watson; with his friend
Crick, he continued to work on this topic without official sanction.
Linus Pauling had made use of molecular models to solve the structure
of the protein alpha helix. Pauling had personally attained what
was possibly the world's greatest understanding of chemistry.
It was to be seen whether Watson and Crick could similarly determine
the structure of DNA.
Neither
Watson nor Crick knew much chemistry. But local X-ray crystallography
expert Rosalind Franklin who had already done extensive work on
DNA was within easy reach in London for consultations and they
had easy access to other key chemical knowledge they needed in
1952. Building upon the unpublished X-ray diffraction research
of Franklin and Wilkins, together Watson and Crick deduced the
double helix structure of DNA which they published in the journal
Nature on April 25, 1953.
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 of the four nucleobases. After he realized
that adenine:thymine and cytosine:guanine pairs are structurally
similar it was immediately clear that such structural pairing
accounted for a key biochemical fact of DNA, the so-called Chargaff
ratios, experimentally determined ratios of the amounts of the
four nucleotide subunits of DNA: the amount of guanine is equal
to cytosine and the amount of adenine is equal to thymine. Watson's
exercise in molecular modeling was facilitated by Jerry Donohue
who explained to Watson and Crick the correct structures of the
four bases. This allowed Watson to visually line up the complementary
base pairs that could be held together by hydrogen bonds.
Franklin's
key contribution was when she told Watson and Crick that the phosphate
backbones of DNA should be on the outside of the molecule. When
Watson and Crick finally accepted this fact, the bases had to
go to the inside of the DNA structure where they would have to
interact chemically. Watson discovered the nature of that interaction.
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's apparent exclusion from this Nobel Prize
was due to her death in 1958 before it was awarded; unfortunately
for Franklin, the Nobel Prize is not awarded posthumously. Some
in the molecular biology community believe that since Franklin
died early, and Wilkins was much less of a publicity-seeker, that
Watson and Crick have in the popular mind overshadowed Wilkins
and Franklin to an undeserved degree.
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.
Watson's original title was to have been "Honest Jim",
in part to raise the ethical questions of sneaking around behind
Franklin's back 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.
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 food|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 said in public lectures "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."
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. |