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DNA and the Cavendish Laboratory (Page 1)

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 that the diffraction of X-rays by crystals could be understood in a simple way. 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. X-ray crystallography has since been used by several members of the Cavendish Laboratory. The technique was deeply involved in the discovery of the structure of DNA at the Cavendish Laboratory, decades after the technique was first developed.

William Lawrence Bragg became head of the Cavendish Laboratory in 1937, after working in Manchester for several years. He was intrigued by the beautiful X-ray diffraction patterns from haemoglobin that Max Perutz, a young scientist, had created at the Cavendish Laboratory. Although work at the Cavendish Laboratory was interrupted by World War II, Max Perutz continued studying haemoglobin using X-ray crystallography. He was joined in this work by John Kendrew in late 1945. The following year the Medical Research Council (MRC) Unit for Work on Molecular Structure of Biological Systems was created at the Cavendish Laboratory.

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 'B-type' 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.

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