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. Before World War II, the Cavendish Laboratory dominated the development of atomic and nuclear physics. Many great discoveries in physics were made there, 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.

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.

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.

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. Although their early attempts to build models of the structure of DNA were not successful, they continued to pursue the problem. 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 in spring 1953.

Figure 2: 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.

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.