DNA and the Cavendish Laboratory
James Watson and Francis Crick discovered the structure of DNA at the Cavendish
Laboratory in Cambridge in 1953. Their discovery illustrates the leading role played by the
Cavendish Laboratory in biological fields such as structural biology and molecular
genetics. It was a major factor in the scientific revolution that focused much of the
scientific world on biological issues over the past 50 years. Why was this important
discovery made in the Cavendish Laboratory?
Figure 1: The old Cavendish Laboratory,
Free School Lane, Cambridge.
The Cavendish Laboratory was
founded in the late 19th century to
encourage
the
development
of
experimental physics in Cambridge.
The Laboratory was designed and built
under the direction of James Clark
Maxwell, who was well regarded for his
work
on
thermodynamics
and
electromagnetism. He was succeeded
as head of the Cavendish Laboratory
by Lord Rayleigh, who was then
succeeded by J. J. Thomson. Before
World War II, under the leadership of
J. J. Thomson, and then Ernest
Rutherford, the Cavendish Laboratory
dominated the development of atomic
and nuclear physics. Many great
discoveries in physics were made at
the Cavendish Laboratory, increasing
its strong reputation in experimental
physics and attracting many of the best
physicists to come and work in
Cambridge. This resulted in a
stimulating intellectual environment
which led to the further development of
new
ideas
and
experimental
techniques.
For example, in 1912 a young research student at the Cavendish Laboratory, William
Lawrence Bragg, realized the simple way in which the diffraction of X-rays by crystals
could be understood. He described this as reflection by sheets of atoms within the crystal,
known as ‘Bragg planes’. Bragg planes can diffract strongly at specific angles that are
dependent on the separation between the planes. This understanding led William
Lawrence Bragg and his father, William Henry Bragg, to invent the technique of X-ray
structural analysis (X-ray crystallography). For this work they shared the Nobel Prize in
Physics in 1915.
© University of Cambridge, Cavendish Laboratory, 2003.
X-ray crystallography has since been used
by several members of the Cavendish
Laboratory. In the early 1930s John
Desmond Bernal and Dorothy Crowfoot
(later Hodgkin) used the technique to study
crystals of the protein pepsin. They got
excellent results by studying the crystals
while they were still in the liquid from which
the crystals had formed. This was the first
use of the X-ray technique to study
biological molecules at the Cavendish
Laboratory. In the late 1930s Max Perutz
used the technique to study haemoglobin
and the enzyme chymotrypsin. The
technique was deeply involved in the
discovery of the structure of DNA at the
Cavendish Laboratory, decades after the
technique was first developed.
Figure 2: X-ray diffraction image of ‘Btype’ DNA taken by Rosalind Franklin.
William Lawrence Bragg became the head of the Cavendish Laboratory in 1937, following
the unexpected death of Ernest Rutherford after a fall from a ladder in his garden. Before
he returned to the Cavendish Laboratory, William Lawrence Bragg was professor of
physics in Manchester. While in Manchester he had continued to develop and use X-ray
analysis, applying the technique to complex problems. He spent a lot of time working on
silicates, but his ideas for these compounds were overshadowed by the work of Linus
Pauling in the United States. The rivalry that was thus established between William
Lawrence Bragg and Linus Pauling continued throughout their careers.
When William Lawrence Bragg returned to the Cavendish Laboratory he was intrigued by
the beautiful X-ray diffraction patterns from haemoglobin that Max Perutz showed him. He
recognized that the importance of interpreting the patterns correctly, and obtained enough
money to pay for Max Perutz to stay in Cambridge and his family to join him from Austria.
This work was interrupted by World War II, during which Max Perutz was interned and
then deported to Canada for a time because he was an Austrian national.
Although work at the Cavendish Laboratory was interrupted by World War II, the people
who had worked there continued to think about the problems they were working on. John
Desmond Bernal had left the Cavendish Laboratory and taken a job at Birkbeck College in
London before the start of the war, but he was still using the X-ray technique to study
proteins. During the war John Desmond Bernal met John Kendrew when they were both
working in the jungles of Ceylon (now Sri Lanka). They talked about X-ray diffraction by
proteins, and John Kendrew decided that he would like to work at the Cavendish
Laboratory when the war was over.
© University of Cambridge, Cavendish Laboratory, 2003.
Towards the end of the war, Max Perutz returned to the Cavendish Laboratory and
resumed his studies of haemoglobin. John Kendrew came to the Cavendish Laboratory in
late 1945 and joined Max Perutz in studying haemoglobin. The following year William
Lawrence Bragg convinced the Medical Research Council (MRC), that their work should
be supported, and The MRC Unit for Work on Molecular Structure of Biological Systems
was created at the Cavendish Laboratory. At first only the crystalline proteins haemoglobin
and myoglobin were studied, but it was planned that the X-ray technique would later be
used to study other interesting and suitable biological materials.
In 1949 Francis Crick joined the MRC Unit in the Cavendish Laboratory. His job was to
continue the X-ray analysis of haemoglobin, but he was always eager to absorb and
understand new areas of science. He liked to discuss ideas, and was not afraid of
speaking his mind. He had a penetrating voice and laugh that annoyed William Lawrence
Bragg, and they did not have a good relationship. William Lawrence Bragg was
particularly annoyed by his impression that Francis Crick thought that he knew more about
X-ray crystallography (the technique that William Lawrence Bragg had invented) than
William Lawrence Bragg himself did.
James Watson came to the Cavendish Laboratory in the early autumn of 1951 to learn
more about X-ray crystallography and its application to biological materials. Francis Crick
welcomed intelligent discussions about structural biology and was soon working with
James Watson to try to discover the structure of DNA. James Watson and Francis Crick
worked together very well because they were interested in the same problem, and each of
them had a different background experience and area of expertise.
Figure 3: A model of the alpha helix.
Francis Crick explained to James
Watson how Linus Pauling had found
the structure of the alpha helix by
applying the laws of structural
© University of Cambridge, Cavendish Laboratory, 2003.
chemistry and building models of
possible structures based on a small
amount of X-ray diffraction results.
They agreed to use a similar approach
to try and discover the structure of
DNA. Their early attempts to build
models of the structure of DNA were
not successful. As the head of the
Cavendish
Laboratory,
William
Lawrence Bragg was humiliated when
James Watson and Francis Crick
showed one of their incorrect models of
DNA to Maurice Wilkins and Rosalind
Franklin, who were using X-ray
crystallography to study DNA at King’s
College in London. Following this
embarrassment
William
Lawrence
Bragg banned James Watson and
Francis Crick from continuing to work
on DNA. Even though they could not
continue to work on DNA Francis Crick
and James Watson continued to think
about and discuss the problem of how
to find the correct structure.
After many months, James Watson and
Francis Crick found out that Linus Pauling
had also created an incorrect model of the
structure of DNA. They realized that Linus
Pauling would soon recognize the mistakes
that he had made, and would then be
inspired to discover the correct structure of
DNA. They told William Lawrence Bragg of
his rival Linus Pauling’s work on DNA, and in
February 1953 they were allowed to resume
their own work on DNA. Making use of the
X-ray diffraction work of Maurice Wilkins and
Rosalind Franklin at King’s College in
London, James Watson and Francis Crick
discovered the structure of DNA just a few
weeks later in spring 1953.
Figure 4: The DNA Double Helix
A second immensely important discovery was made at the Cavendish Laboratory a few
months later in 1953. Max Perutz realized that attaching a single large atom (e.g. Mercury)
to a haemoglobin molecule would change the X-ray diffraction pattern obtained from the
crystal, making it possible to completely solve the structure of haemoglobin. He realized
that this doping technique could be applied to a wide range of complex biological
materials. Experimental techniques had to be developed over several years, organized by
Max Perutz and John Kendrew, to put Max Perutz’s idea into practice. Eventually the
correct structures of both haemoglobin and myoglobin were discovered. Their work was
dependent upon tens of thousands of highly accurate measurements and interpretations
of X-ray diffraction images. It was greatly assisted by the building models of possible
structures and the use of early model computers housed nearby. The importance of this
work was quickly recognized, and led to a massive expansion in the number of people
studying the structure of complex biological materials.
Although the Cavendish Laboratory provided the simulating environment in which new
ideas were explored and developed, the successful discovery of the structure of DNA was
also dependent on fortuitous circumstances and the personalities of the people involved.
The entire field of structural biology can be traced back to the development of X-ray
crystallography by William Lawrence Bragg and his father William Henry Bragg. In
particular, the insight of William Lawrence Bragg that led to the development of Bragg’s
Law for X-ray diffraction was crucial to the continued interest in the use of X-rays to study
materials. The discoveries of the structure of DNA and the structures of complex biological
materials were recognized in the same year (1962) by the award of a Nobel Prize in
Physiology or Medicine to James Watson, Francis Crick and Maurice Wilkins, and a Nobel
Prize in Chemistry to Max Perutz and John Kendrew. Rosalind Franklin had died of cancer
in 1958. These discoveries are the basis of many areas of modern biology and medicine
and are considered to be amongst the most important discoveries made at the Cavendish
Laboratory since it opened over 100 years ago.
© University of Cambridge, Cavendish Laboratory, 2003.