Finch A Nobel Fellow on Every Floor

A History of the Medical Research Council Laboratory of Molecular Biology
1. Auflage 2013
ISBN: 978-1-84831-670-6
Verlag: Icon Books
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 381 Seiten

In Cambridge in the 1950s, several research groups funded by the Medical Research Council were producing exciting results. In the Biochemistry Department, Sanger determined the amino acid sequence of insulin, and was awarded a Nobel Prize for this in 1958. At the Cavendish Laboratory, in the MRC Unit for the Study of the Molecular Structure of Biological Systems, Watson and Crick solved the structure of DNA, and Perutz and Kendrew produced the first three-dimensional maps of protein structures - haemoglobin and myoglobin - for which all four were later awarded Nobel Prizes. This made it timely to create, in 1962, a new Laboratory of Molecular Biology in Cambridge by amalgamating these groups with other MRC-funded groups from London. The Laboratory has become one of the most successful in its field, and the number of Nobel Prizes awarded over the years to scientists at LMB has risen to thirteen. This book follows the development of LMB, through the people who moved into the new Laboratory and their research. It describes events and personalities that have given the Laboratory a friendly, family atmosphere, while continuing to be scientifically productive.

John Finch joined Rosalind Franklin as a PhD student at Birkbeck College, London in 1955 studying the structure of viruses by X-ray diffraction. He came to the new LMB in 1962 with the Birkbeck group, which was now led by Aaron Klug after Rosalind's death in 1958. In addition to continuing the work on virus structure, as the group's interests diversified, he became involved in other research, studying the structures, for example, of transfer RNA and chromatin. He is at present a 'retired worker' at LMB.

Autoren/Hrsg.

Finch, John

Leseproben

CHAPTER ONE

How molecular biology came to the Cavendish

LAWRENCE BRAGG

W.L. Bragg was born in 1890 and educated in Adelaide, where his father, W.H. Bragg, was the Physics Professor (and his grandmother the Alice of Alice Springs). The family came to England in 1909 when his father was appointed to the Physics chair at Leeds, and Bragg began as an undergraduate at Cambridge.

He had just graduated in 1912 when the first X-ray diffraction photographs from a crystal (of zinc blende, ZnS) were reported from Friedrich and Knipping in Munich. The main aim of the experiment was to demonstrate the wave nature of X-rays, and their paper was accompanied by one from Max von Laue attempting to interpret the results in terms of the crystal structure. However, the structure was more complicated than von Laue assumed and there was also confusion on the mechanism of diffraction, so that even the proponents of wave X-rays did not find the explanation convincing.

Bragg’s father had been interested in X-rays since their discovery in 1895 and because he believed they were particles, Bragg was initially also biased towards this view and suggested that the X-ray patterns were produced by particles being channelled down avenues between atoms. But on thinking of the treatment of light diffraction by a diffraction grating, he realised that the X-ray pattern could be explained by the selective reflection of specific wavelengths from a continuous spectrum of wave X-rays, from planes of atoms in the crystal according to the same equation ?=2sin?. This did not explain the ZnS pattern if a simple cubic lattice were assumed, but did so completely if the cubic lattice were face-centred. Thus Bragg confirmed that the phenomenon was diffraction, that X-rays were of a wave character, and also that they could be used to determine crystal structures. These results were presented at a meeting of the Cambridge Philosophical Society in November 1912, reported in in December, and in more detail in a 1913 paper.

Bragg was keen to pursue the diffraction work and W.J. Pope, the Professor of Chemistry in Cambridge, who was interested in the theories of crystal lattices, suggested he work on NaCl, KCl, KBr and KI and obtained large crystals for him. The X-ray photographs obtained by Bragg were simpler than those from zinc blende and led to a complete solution of their structure. However, the conditions for experimental work at the Cavendish were not very satisfactory as Bragg later described:

When I achieved the first X-ray reflections, I worked the Rumkorff coil too hard in my excitement and burnt out the platinum contact. Lincoln, the mechanic was very annoyed as a contact cost ten shillings (a week’s wages at the time) and refused to provide me with another for a month. I could never have exploited my ideas about X-ray diffraction under such conditions.1

On the detection side too, the X-ray spectrometer at Leeds, built by his father, was far superior to the Laue-film set-up he had used earlier in Cambridge, and so he continued his work immediately in 1912 at Leeds. The crystals were ‘supplied’ by the Mineralogy Department at Cambridge – the Professor of Mineralogy had given strict orders that no minerals should ever leave the collections, but Arthur Hutchinson, who was then a lecturer in the Department, smuggled them out for Bragg. The structures of the selected halides, and of zinc blende (ZnS), fluorspar (CaF), iron pyrites (FeS) and calcite (CaCO3) were published in 1913, but further work was interrupted by the start of the First World War in 1914.

Bragg spent most of the war working on a system of locating enemy guns by recording the arrival of their sounds at different places. Among the problems to solve were the identification of the sound of one particular gun, to distinguish between its report and the associated shock wave, and also to find a way of recording the time intervals precisely. The problems were solved sufficiently well that a fairly reliable system was in use from the beginning of 1917.

It was during this work, in 1915, that Bragg heard that he and his father had been jointly awarded the Nobel Prize for Physics, Bragg for his work on diffraction and crystal structure and his father for his study on the origin and properties of X-rays. Bragg’s ideas on X-ray diffraction and his immediate application in using them to solve structures had made a great impression. It now became possible to establish structure at the atomic level. It was soon applied and resulted in dramatic advances in chemistry, mineralogy and metallurgy, and, more than a decade later, in biology.

After the war, Bragg (the son) succeeded Rutherford in the Physics Chair at Manchester – Rutherford having been appointed the Cavendish Professor at Cambridge. One of the people that Bragg had consulted on which crystals to investigate was the crystal-smuggler Hutchinson, who had remained greatly interested in the X-ray diffraction side of crystallography, and was now the Mineralogy Professor in Cambridge. In 1921, Hutchinson encouraged a graduate, W.A. (Bill) Astbury, to work with Bragg’s father, W.H. Bragg, who was continuing with X-ray studies, now at University College in London, and in 1923 he similarly advised John Desmond Bernal.

J.D. BERNAL

Bernal was born in Ireland in 1901 into an Irish Catholic family and began his secondary education at the Jesuit public school, Stoneyhurst in Lancashire, but left after three months because no science was taught until the sixth form. He transferred to a Protestant English public school, Bedford School, which he also did not enjoy, but which did teach him chemistry and physics and provided him with a library of books to work through and a telescope to watch the stars. In his last year, he was shown Einstein’s early papers on general relativity, and these impressed on him the changing nature of scientific knowledge. He came to Cambridge in 1919 with a mathematical scholarship to Emmanuel College and, because of his wide-ranging interests and knowledge, soon acquired the nickname ‘Sage’ – a name that remained with him for the rest of his life. Another lifetime acquisition was a belief in Marxism inspired by a talk by Henry Dickinson, the son of the curator of the Science Museum. The exuberance and enthusiasm of Bernal was later used by C.P. Snow as the basis of the character of Constantine in his novel , published in 1934 – Constantine is on a committee trying to set up a National Institute of Biophysical Research.2

During his undergraduate studies in Mineralogy and Geology, Bernal had become fascinated with crystallography, and in particular with working out the various possible ways in which atoms or groups of them could be arranged regularly to form crystals – he re-derived algebraically, in his final year, the 230 ways of doing this, the 230 Space Groups. W.H. Bragg had now moved to the Royal Institution in London and Bernal joined his group there in the Davy-Faraday Laboratory in 1923. Bernal would later tell how he had diffidently asked WHB what he thought of his thesis on space groups. WHB replied, ‘Good God man, you don’t think I read it’ – the first page evidently being sufficient to show that he was worth encouraging in research.3

Both Astbury and Bernal were interested in pushing the X-ray technique towards biologically interesting molecules and in particular to proteins. Astbury concentrated on fibrous specimens and obtained X-ray fibre diagrams from wool and silk. Bernal investigated non-fibrous proteins and tried to get X-ray powder photographs from dried specimens of edestin, insulin and haemoglobin, but only obtained obscure bands.

In 1926, Hutchinson succeeded in creating the post of Lecturer in Structural Crystallography in the Mineralogy Department, for which both Astbury and Bernal applied. Bernal was successful and so returned to Cambridge. Thus in addition to supplying crystals for Bragg to develop the early X-ray diffraction work, Hutchinson played quite an important part in propagating the technique in Cambridge. Shortly after this, Astbury went to Leeds and began X-ray studies there.

Both Astbury and Bernal were still keen to try to get better X-ray results from proteins. Astbury was sent some crystals of pepsin from America for X-raying, but obtained very limited diffraction patterns from crystals carefully dried (and as a result, disordered!). On the fibre side he was more successful, and in 1934 published a long paper on the structure of hair, wool and related keratin fibres, demonstrating a contracted (a-) form and an extended (ß-) form. It was suggested that...