DNA and the Cavendish Laboratory - University of Cambridge

DNA and the Cavendish LaboratoryJames Watson and Francis Crick discovered the structure of DNA at the CavendishLaboratory in Cambridge in 1953. Their discovery illustrates the leading role played by theCavendish Laboratory in biological fields such as structural biology and moleculargenetics. It was a major factor in the scientific revolution that focused much of thescientific world on biological issues over the past 50 years. Why was this importantdiscovery made in the Cavendish Laboratory?The Cavendish Laboratory was founded in the late 19 thcentury to encourage the development of experimentalphysics in Cambridge. The Laboratory was designed andbuilt under the direction of James Clark Maxwell, who waswell regarded for his work on thermodynamics andelectromagnetism. Before World War II, the CavendishLaboratory dominated the development of atomic andnuclear physics. Many great discoveries in physics weremade there, increasing its strong reputation in experimentalphysics and attracting many of the best physicists to comeand work in Cambridge. This resulted in a stimulatingintellectual environment, which led to the furtherdevelopment of new ideas and experimental techniques.Figure 1: The old Cavendish Laboratory, Free School Lane, Cambridge.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. Hedescribed 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 separationbetween the planes. This understanding led William Lawrence Bragg and his father,William Henry Bragg, to invent the technique of X-ray structural analysis (X-raycrystallography). For this work they shared the Nobel Prize in Physics in 1915. X-raycrystallography 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 theCavendish Laboratory, decades after the technique was first developed.William Lawrence Bragg became head of the Cavendish Laboratory in 1937, after workingin Manchester for several years. He was intrigued by the beautiful X-ray diffractionpatterns from haemoglobin that Max Perutz, a young scientist, had created at theCavendish Laboratory. Although work at the Cavendish Laboratory was interrupted byWorld War II, Max Perutz continued studying haemoglobin using X-ray crystallography. Hewas joined in this work by John Kendrew in late 1945. The following year the MedicalResearch Council (MRC) Unit for Work on Molecular Structure of Biological Systems wascreated at the Cavendish Laboratory.© University of Cambridge, Cavendish Laboratory, 2003.

DNA and the Cavendish LaboratoryIn 1949 Francis Crick joined the MRC Unit in the Cavendish Laboratory. His job was tocontinue the X-ray analysis of haemoglobin, but he was always eager to absorb andunderstand new areas of science. He liked to discuss ideas, and was not afraid ofspeaking his mind. He had a penetrating voice and laugh that annoyed William LawrenceBragg, and they did not have a good relationship.James Watson came to the Cavendish Laboratory in the early autumn of 1951 to learnmore about X-ray crystallography and its application to biological materials. Francis Crickwelcomed intelligent discussions about structural biology and was soon working withJames Watson to try to discover the structure of DNA.James Watson and Francis Crick worked togethervery well because they were interested in thesame problem, and each of them had a differentbackground experience and area of expertise.Although their early attempts to build models ofthe structure of DNA were not successful, theycontinued to pursue the problem. Making use ofthe X-ray diffraction work of Maurice Wilkins andRosalind Franklin at King’s College in London,James Watson and Francis Crick discovered thestructure of DNA in spring 1953.Figure 2: The DNA Double HelixA second immensely important discovery was made at the Cavendish Laboratory a fewmonths 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 thecrystal, making it possible to completely solve the structure of haemoglobin. He realizedthat this doping technique could be applied to a wide range of complex biologicalmaterials. Experimental techniques had to be developed over several years, organized byMax Perutz and John Kendrew, to put Max Perutz’s idea into practice. In 1960 the correctstructures of both haemoglobin and myoglobin discovered. This work led to a massiveexpansion in the number of people studying the structure of complex biological materials.Although the Cavendish Laboratory provided the simulating environment in which newideas were explored and developed, the successful discovery of the structure of DNA wasalso 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-raycrystallography by William Lawrence Bragg and his father William Henry Bragg. Inparticular, the insight of William Lawrence Bragg that led to the development of Bragg’sLaw for X-ray diffraction was crucial to the continued interest in the use of X-rays to studymaterials.The discoveries of the structure of DNA and the structures of complex biological materialswere recognized in the same year (1962) by the award of a Nobel Prize in Physiology orMedicine to James Watson, Francis Crick and Maurice Wilkins, and a Nobel Prize inChemistry to Max Perutz and John Kendrew. Rosalind Franklin had died of cancer in1958. These discoveries are the basis of many areas of modern biology and medicine andare considered to be amongst the most important discoveries made at the CavendishLaboratory since it opened over 100 years ago.© University of Cambridge, Cavendish Laboratory, 2003.