Lawrence Bragg and Linus Pauling: Comparisons and Rivalries

W. L. Bragg and L. C. Pauling were among the most famous scientists in the world for much of the twentieth century. Each was a Nobel Laureate, and each was admired, not only for their fundamental achievements in X-ray crystallography, but also as exemplary popularizers of science. In the fields of mineralogy (especially the structure of silicates) and protein structures, their interests overlapped. They admired their respective technical virtuosities, but there was deep-seated rivalry between them. It irked Bragg that Pauling had formulated simple stereochemical rules to account for the multiplicity of structures exhibited by vast numbers of silicates, and also that Pauling had proposed the existence of the alpha-helix and pleated sheets as motifs in the structure of proteins like keratin. The details of their rivalry, bordering on envy, is described through specific examples.

A Dispute Between the Cavendish and Caltech: The Emergence and Ubiquity of the α‎-Helix

Bragg, Kendrew, and Perutz at the Cavendish Laboratory, Cambridge, published in 1950 proposals for the nature of the folding of the constituents (the amino acid residues) of proteins such as keratin, the constituent of hair and wool. Almost immediately, Pauling and Corey at the California Institute of Technology published a series of strong critical articles, in which they repudiated the model proposed by the Cambridge trio. Also, they proposed a new motif for the structure of proteins—the so-called alpha-helix. Its nature and importance are described herein, and its subsequent validity (demonstrated by Kendrew at the Cavendish Laboratory and Phillips et al. at the DFRL) was demonstrated by the work done in the United Kingdom on the X-ray studies of the oxygen-storage protein myoglobin and on the enzyme known as lysozyme found in egg white and in human tears.

The Summing Up: The Astonishing Successes of the LMB and the Dawn of a New Structural Biological Era

The contrast between the related pre-World War II attitudes to scientific research and those of the current era are described and how this affects modern research. There follows a summary of the numerous major achievements in advanced research conducted at the Laboratory of Molecular Biology (LMB) from its existence as a biological unit at the Cavendish Laboratory from 1957 onwards. The impressive commercial successes of the LMB, made possible by recent changes in the policy of the Medical Research Council, are also outlined. The second half of the chapter describes the arrival, importance, and immense potential of electron cryo-microscopy (which is described in a non-technical manner) in structural molecular biology, with examples drawn from the study of neurodegenerative diseases and other areas of biology.

Sir Lawrence Bragg at the RI (1953–1966) and the Determination of the First Three-Dimensional Structure of an Enzyme at the DFRL (1965)

The transformation in the affairs of the Royal Institution (RI) and the Davy-Faraday Research Laboratory (DFRL) when W. L. Bragg became the new Director there in 1953 is described. He resuscitated the moribund research efforts and injected fresh impetus into the lecture programmes mounted by the RI. In particular, he recruited a powerful team of protein crystallographers (notably D. C. Phillips, A. C. T. North, R. Poljak, Louise Johnson, and C. C. Blake), as well as strong technical backup from instrumental experts like U. Arndt. In the space of a dozen years, this team of co-workers solved the first ever structure of an enzyme, known as lysozyme, which had been discovered by Alexander Fleming in the 1920s. This was a major breakthrough, and it stimulated similar work elsewhere. The chapter also discusses what has happened to the DFRL subsequently. It is now in abeyance, and the reasons for this situation are outlined.

Max Perutz, John Kendrew, Peterhouse, and the Davy-Faraday Research Laboratory

The accidental way in which Perutz and Kendrew met and the influence of the brilliant, versatile physicist J. D. Bernal upon them and on the third Nobel Laureate chemist Dorothy Hodgkin are described. Perutz and Kendrew, each a member of Peterhouse (a Cambridge College), were also guided by W. L. Bragg of the Cavendish Laboratory in Cambridge, and later at the Davy-Faraday Research Laboratory, London where, in 1953, they became visiting scientists and adept in the popularization of science. The founding of the new subject of molecular biology and the objection to it by some biologists are outlined. The joint efforts of Perutz and Kendrew in establishing two new major research centres—the Laboratory of Molecular Biology in Cambridge and the European Molecular Biology Laboratory in Heidelberg—is outlined. A brief trajectory of their initial work on haemoglobin is also given.

Contributions of Cambridge College Life to Structural Biology: Peterhouse as an Exemplar

How does university life add depth and quality and also opportunity to professional research? This is the key question discussed in this chapter. In answering it, the pre-eminent work of Aaron Klug and his cross-fertilizing interactions with his colleagues in the Cambridge College Peterhouse are analysed. Klug, who won the Chemistry Nobel Prize outright, made many revolutionary discoveries in structural molecular biology, especially the determination of the structure of viruses. He also devised new techniques in electron microscopy that are now of great importance in present-day research in molecular biology. Klug’s indebtedness to colleagues of Peterhouse, including Kendrew and Perutz, and his early mentor at the Cavendish Laboratory Lawrence Bragg, as well as a brief account of the current research pursued by members of Peterhouse and the famous confrontation in 1952 between Erwin Chargaff and Crick and Watson are also described.

Biographical Sketches

The personalities, approaches towards research, and attitudes towards other people of Perutz, Kendrew, and Hodgkin are described, as well as the inspiration they gave to others. Max Perutz’s approach and policy in creating and operating the successful Laboratory of Molecular Biology (LMB) are analysed, and some examples of his personal interest in individuals are outlined. John Kendrew’s role in preventing the privatization of the LMB in 1993 was crucial, and Dorothy Hodgkin’s unique skills as a scientist, leader, and guide to numerous associates, especially her female students at Somerville College, Oxford, are described. Biographical sketches are given of many outstanding scientists who made diverse contributions (direct and indirect) to biology and constitute the second part of this chapter.

Perutz and Kendrew: The Heroic Era of Structural Molecular Biology

When Perutz and Kendrew embarked on their determination of the structures of haemoglobin and myoglobin, most scientists felt that they would never succeed. These molecules contain approximately thousands of non-hydrogen atoms, whereas those molecules that had yielded to X-ray analysis previously contained fewer than a hundred non-hydrogen atoms. For real progress to be made in solving the structures of the giant proteins, a fundamentally new approach had to be evolved, which inter alia required massive computer power to handle the data contained in hundreds of thousands of X-ray diffraction patterns, and new experimental equipment like ultra-stable X-ray sources were required to record the diffraction data. The first successes were registered by Kendrew, who was able to reveal, in unprecedented detail, the atomically resolved structure of myoglobin with its haem group (containing a central iron atom) and all the details of the amino acid residues that constituted the backbone chain of the protein. Likewise, haemoglobin revealed its secrets. This also led to the discovery of sickle-cell anaemia, the first ever recorded molecular disease. It also shed new light on the pathology of anomalous haemoglobins in human populations.

W. H. Bragg and His Creation of a World-Famous Centre for X-ray Crystallography at the Davy-Faraday Research Laboratory

The nature and mode of operation of the Davy-Faraday Research Laboratory (DFRL) and the Royal Institution (RI), within which it is located, are described. Together, they are part laboratory, part library, and part theatre where topics of scientific and cultural interest are presented to the general public, including children. W. H. Bragg, for two decades, from 1923 onwards, made it one of the world’s foremost research centres for the use of X-ray to study molecules of biological and other interest. His associates, especially Astbury, Bernal, and Kathleen Yardley (later Dame Kathleen Lonsdale), and others made major advances in elucidating the nature of a variety of the constituents of living matter, including hair, fingernails, horns, and other examples of proteins. This chapter contains a guide to the nature of proteinaceous and other examples of living matter and serves as an introduction to the total beginner in the study of structural biology and its importance.

The Birth and Initial Exploitation of X-ray Diffraction

A non-mathematical account of the discovery of X-ray diffraction by von Laue and its use as a new kind of high-resolution microscopy by W. L. Bragg is given. There follows a simple explanation of how the electron densities in various regions of any molecule that can be crystallized can be retrieved from its X-ray diffraction pattern. Also, it is explained how the molecular weight of the molecule can be determined from straightforward measurements of the diffraction and the density of the crystal. The identity of the elements in a crystal, as well as the nature of the chemical bonding between them, may also be derived from measurement of the electron density distribution within it. The importance of Bragg’s Law, relating X-ray pattern to interatomic distance, is demonstrated, and initial applications of it by Bragg and Pauling are given.