I was born in Halifax, Yorkshire on January 7th, 1941 to Thomas Ernest Walker and Elsie Walker (née Lawton). My father was a stone mason, and a talented amateur pianist and vocalist. I was brought up with my two younger sisters, Judith and Jennifer, in a rural environment overlooking the Calder valley near Elland, and then in Rastrick. I received an academic education at Rastrick Grammar School, specializing in Physical Sciences and Mathematics in the last three years. I was a keen sportsman, and became school captain in soccer and cricket. In 1960, I went to St. Catherine’s College, Oxford, and received the B.A. degree in Chemistry in 1964.
In 1965, I began research on peptide antibiotics with E. P. Abraham in the Sir Willian Dunn School of Pathology, Oxford, and was awarded the D. Phil. degree in 1969. During this period, I became aware of the spectacular developments made in Cambridge in the 1950s and early 1960s in Molecular Biology through a series of programmes on BBC television given by John Kendrew, and published in 1966 under the title “The Thread of Life”. These programmes made a lasting impression on me, and made me want to know more about the subject. Two books, “Molecular Biology of the Gene” by J. D. Watson, first published in 1965, and William Hayes’ “Bacterial Genetics” helped to assuage my appetite for more information. My knowledge of this new field was extended by a series of exciting lectures for graduate students on protein structure given in 1966 by David Phillips, the new Professor of Molecular Biophysics at Oxford. Another series of lectures given by Henry Harris, the Professor of Pathology and published in book form under the title “Nucleus and Cytoplasm”, provided more food for thought.
Then followed a period of five years working abroad, from 1969-1971, first at The School of Pharmacy at the University of Wisconsin, and then from 1971-1974 in France, supported by Fellowships from NATO and EMBO, first at the CNRS at Gif-sur-Yvette and then at the Institut Pasteur.
Just before Easter in 1974, I attended a research workshop in Cambridge entitled “Sequence Analysis of Proteins”. It was sponsored by EMBO (The European Molecular Biology Organization), and organised by Ieuan Harris from the Medical Research Council’s Laboratory of Molecular Biology (LMB) and by Richard Perham from the Cambridge University Department of Biochemistry. At the associated banquet, I found myself sitting next to someone that I had not met previously, who turned out to be Fred Sanger. In the course of our conversation, he asked if I had thought about coming back to work in England. I jumped at the suggestion, and with some trepidation, approached Ieuan Harris about the possibility of my joining his group. After discussions with Fred Sanger, it was agreed that I could come to the Protein and Nucleic Acid Chemistry (PNAC) Division at the LMB for three months from June 1974. More than 23 years later, I am still there.
It goes without saying that this encounter with Fred Sanger and Ieuan Harris transformed my scientific career. In 1974, the LMB was infused throughout its three Divisions with a spirit of enthusiasm and excitement for research in molecular biology led by Max Perutz (the Chairman of the Laboratory), Fred Sanger, Aaron Klug, Francis Crick, Sidney Brenner, Hugh Huxley, John Smith and César Milstein, which was coupled with extraordinary success. For example, along the corridor from my laboratory Fred was inventing his methods for sequencing DNA, immediately across the corridor César Milstein and Georges Köhler were inventing monoclonal antibodies, and elsewhere in the building, Francis Crick and Aaron Klug and their colleagues were revealing the structures of chromatin and transfer RNA. Fred’s new DNA sequencing methods were applied first to the related bacteriophages fX174 and G4, and then to DNA from human and bovine mitochondria. I analyzed the sequences of the proteins from G4 and from mitochondria using direct methods. These efforts led to the discovery of triple overlapping genes in G4 where all three DNA phases encode proteins, and to the discovery that subunits I and II of cytochrome c oxidase were encoded in the DNA in mitochondria. Later on, I helped to uncover details of the modified genetic code in mitochondria.
In 1978, I decided to apply protein chemical methods to membrane proteins, since this seemed to be both a challenging and important area. Therefore, in search of a suitable topic, I read the literature extensively. The enzymes of oxidative phosphorylation from the inner membranes of mitochondria were known to be large membrane bound multi-subunit complexes, but despite their importance, they had been studied hardly at all from a structural point of view. Therefore, the same year, I began a structural study of the ATP synthase from bovine heart mitochondria and from eubacteria. These studies resulted eventually in a complete sequence analysis of the complex from several species, and in the atomic resolution structure of the F catalytic domain of the enzyme from bovine mitochondria, giving new insights into how ATP is made in the biological world. Michael Runswick has worked closely with me throughout this period, and has made contributions to all aspects of our studies.
In 1959, I received the A. T. Clay Gold Medal. I was awarded the Johnson Foundation Prize by the University of Pennsylvania in 1994, in 1996, the CIBA Medal and Prize of the Biochemical Society, and The Peter Mitchell Medal of the European Bioenergetics Congress, and in 1997 The Gaetano Quagliariello Prize for Research in Mitochondria by the University of Bari, Italy. In 1995, I was elected a Fellow of the Royal Society. In 1997, I was made a Fellow of Sidney Sussex College, Cambridge and became an Honorary Fellow of St. Catherine’s College, Oxford.
I married Christina Westcott in 1963. We have two daughters, Esther, aged 21 and Miriam, aged 19. At present, both of them are university students, studying Geography and English, respectively, at Nottingham-Trent and Leeds Universities.
This autobiography/biography was written at the time of the award and later published in the book series Les Prix Nobel/ Nobel Lectures/The Nobel Prizes. The information is sometimes updated with an addendum submitted by the Laureate.
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