Springer Biographies

Louis Harold Gray

A Founding Father of Radiobiology

SINCLAIR WYNCHANK Springer Biographies The books published in the Springer Biographies tell of the life and work of schol- ars, innovators, and pioneers in all fi elds of learning and throughout the ages. Prominent scientists and philosophers will feature, but so too will lesser known personalities whose signifi cant contributions deserve greater recognition and whose remarkable life stories will stir and motivate readers. Authored by historians and other academic writers, the volumes describe and analyse the main achievements of their subjects in manner accessible to nonspecialists, interweaving these with salient aspects of the protagonists’ personal lives. Autobiographies and memoirs also fall into the scope of the series.

More information about this series at http://www.springer.com/series/13617 Sinclair Wynchank

Louis Harold Gray

A Founding Father of Radiobiology Sinclair Wynchank Rondebosch Western Cape South Africa

Springer Biographies ISBN 978-3-319-43396-7 ISBN 978-3-319-43397-4 (eBook) DOI 10.1007/978-3-319-43397-4

Library of Congress Control Number: 2016953482

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This Springer imprint is published by Springer Nature The registered company is Springer International Publishing AG Switzerland To my dear wife, Anny, whose encouragement and help resulted in this book and to whom I owe so very, very much more

Pref ace

Louis Harold Gray (Hal) was a one-in-many-millions sort of man. His personal qualities were remarkable and his scientifi c abilities too. His work has benefi tted innumerable people. (You, dear reader, were safe when your last X-rays were taken, thanks to his work.) Yet Hal is almost unknown outside his specialised fi eld of study. So his story and achievements deserve to be told. Hal’s life was unusual; it could be the subject of a Hollywoodish tale of overcoming life’s hurdles, with participation of a deus ex machina . For those interested, some more details of the relevant science are described in an Appendix. However, the text can be understood without it. Work on this book began in 1982, when many of Hal’s contemporaries were still living. All of those I contacted (except one) were happy to comment on him, and among them there were well over a hundred of his schoolfellows. Family and work col- leagues were equally happy to talk and write about him. Hal’s unusual high school, Christ’s Hospital, had an enormous infl uence on many aspects of his adult life. Distilling all the available information was a long and happy task which caused increasing awe for Hal the man, his scientifi c achievements and his life. His story more than justifi es the telling.

Rondebosch , Western Cape South Africa Sinclair Wynchank

vii

Prol ogue

Just as physics could develop as the younger sister of celestial mechanics, so did biology as the younger sister of physics. (Albert Einstein, 1950)

Louis Harold Gray (Hal) prepared for a showdown interview with his employers. This was to be the most traumatic event of his life. He had immense (and justifi ed) conviction that he was in the right and that his employer, the Medical Research Council (MRC) of Great Britain, must agree with his opinion of the matter being investigated. Hal was the deputy director of a research unit, but he had committed the cardinal sin of writing to the MRC’s chief and stating that ‘he had no confi dence in his director’. So this crucial interview had been totally of his own making. In 1953, such a British quasi-government body (for the MRC was fi nanced by the state but independent regarding all its activities) had a very strict communications hierar- chy. All contacts between the unit’s members and the MRC had to pass through the unit’s director. Therefore this formal comment about Hal’s director was to be taken extremely seriously. A committee had been set up to meet on Friday 15 May 1953 to consider and decide the matter. Hal and his director were summoned to make separate oral presentations to this committee. The meeting took place at the MRC’s headquarters in central London, across the road from the tranquil green spaces of Regent’s Park. Hal (as known by his wife, friends and colleagues, although his parents always called him Harold) was a world-renowned scientist in a highly specialised fi eld. More importantly, he was one of the most modest, honest, considerate and caring of men. His moral standards were very high, yet unusually without any traces of self- righteousness. Virtually all of those with whom he came in contact, especially close colleagues, both senior and the most recently appointed, were devoted to him for personal and professional reasons. He willingly shared his thoughts and ideas for new research, and even more importantly, he always had time to receive the most junior scientifi c colleagues and other co-workers to discuss problems (both personal and work related) and to offer much appreciated advice. If this sounds like the perfect boss, this was true in the eyes of almost all of those who worked closely with him. A new, large project was underway for the unit where he worked. It was the con- struction of a cyclotron, or atom smasher. This device was to produce beams of penetrating particles called neutrons, which would be used to treat cancer. There

ix x Prologue were good reasons at that time to believe that neutrons would fi nally provide many advantages over the other methods then available to treat certain cancers. But, and this is an exceedingly important reservation, very, very much care had to be taken when using neutrons. Some tentative anticancer work with neutrons had been done in California by Drs. Robert Stone and John Lawrence before the Second World War. It provided some successes, but also some horrifying results, with large amounts of damage done to the bodies of some patients. One patient had part of his face fi nally ‘falling off’ as a result of these neutrons. So the Californian neutron therapy programme naturally came to a rapid halt, in spite of any promise it held, because of these totally unacceptable and unexpected side effects. The reason for these bad results was that the size of a safe and effective dose of neutrons was not known. Too many neutrons had been used. But no one knew how many was too many! Also the best ways of applying neutrons to patients were unknown. If it now seems straightforward to solve those problems, that was most certainly not so in the mid-twentieth century, for virtually nothing was then known about treating cancer with neutrons and their effects on humans. As a result, there were no anticancer studies with neutrons till Hal became involved and no neutron treatment for human cancers until a further two decades had passed. The director of Hal’s unit, the Radiotherapeutic Research Unit (RRU) of the MRC, was Dr. Constance Wood. The RRU was located in the prestigious Hammersmith Hospital in West London, thought by many to be the best in the UK for its high-quality medical research and care. Dr. Wood was a clinician, a medical doctor whose speciality was treating patients with cancer, but she had never researched the body’s mechanisms underlying reactions to such treatment. Connie (as she was usually called by colleagues, though never to her face) was a very capa- ble medical doctor. She had made her name by successfully using radium for cancer treatment in the 1930s. Although at that time using radium was considered a great improvement for some cancers, over previously available treatments, radium was fi nally shown to have so many disadvantages that it has not been in general use for well over 50 years. Dr. Wood was not a scientist and not a suitable person to direct a group of research scientists, because she usually did not understand what they were doing, yet she liked to micromanage. But that was not the cause of Hal’s prob- lems. Dr. Wood initially recognised and appreciated Hal’s scientifi c ability and mostly let him and his growing team get on with their work, although not fully understanding what they had achieved or where they were headed. Hal had a very high reputation in his scientifi c fi eld, both in the UK and worldwide. Researchers from many countries wished to work with him, and sometimes they were able to provide funds from non-MRC sources, to support a stay in his group. In that case, if they were capable and space was available, they were very welcome, for Hal’s own research budget from the MRC was meagre. Hal’s research fi eld is called radiobiol- ogy (or radiation biology), a new, and still relatively little known, branch of the biological sciences. Radiations are usually some sort of waves which carry energy and radiate or spread out from their source. They include many forms of energy experienced in daily life such as light, microwaves, radar, radiowaves, ultraviolet rays and X-rays. Prologue xi

But there are also many other less familiar radiations, such as cosmic rays, gamma rays and infrared waves (such as the heat, which can be felt coming from a hot object). Some radiations are not usually thought of as waves, but are rather consid- ered streams of tiny particles, which are typically small parts of an atom. Yet all radiations can behave like and be considered as either waves or particles at any time. So one can choose whichever of these two descriptive labels (particles or waves) is more convenient for a specifi c situation. Radiations most commonly thought of as particles include beams of electrons, protons or neutrons. All radiations are broadly one of two types: ionising or non-ionising. The ionis- ing radiations (which can include all the particle streams just mentioned and some waves too, such as X-rays and gamma rays) carry enough energy to remove elec- trons from some atoms or molecules (that is to ionise them). The non-ionising radia- tions don’t possess enough energy to ionise and in general have no chemical effect on living beings, although they can heat tissues if the radiation is suffi ciently intense. When ionising radiation strikes living tissue, it disrupts the electrons in the tissue’s atoms. The resulting damage can be harmful to the tissue’s cells, molecules and atoms in very many different ways. Also, as a result of these disturbances of elec- trons, the vast number of coordinated biochemical reactions, which run steadily in normal living tissues and are essential for life, can be disrupted. Cancer is an uncontrolled and excessive growth of certain cells which usually will continue to grow forever, if unchecked. (Throughout this book, the word ‘can- cer’ denotes any sort of malignant growth.) These ‘bad’ cancer cells always multiply and may constantly spread to other parts of the body. If left undisturbed, cancers can kill the unfortunate individual in whose body they are growing. But often these malignant cells can be destroyed by ionising radiation. However there are limits on the amounts of such radiation which can be used to kill cancer cells. This radiation can simultaneously kill nearby healthy cells, with which it interacts. Healthy work- ing cells are essential for the normal functioning of the body and are usually inti- mately mixed with the cancer cells. Radiobiology is the study of the interactions of ionising radiation with living material. Apart from possibly killing too many ‘good’, or normal cells, and so endangering the patient, ionising radiation can have another highly undesirable effect. It can itself create new cancers by turning some ‘good’ cells into cancerous cells. So clearly the science of radiobiology deals with a highly complex situation. This science involves understanding aspects of several biological sciences and also some biochemistry, physics (nuclear and non-nuclear), chemistry and more. Radiation treatment of cancer (radiotherapy) uses ionising radiation’s destructive effects to destroy the cancer cells. If all cancer cells in a patient are destroyed or become unable to reproduce themselves, then the patient would be cured. The RRU’s cyclotron was to be built by the unit’s staff, for in the 1950s no cyclo- trons were available commercially. Then the cyclotron was to be used for three dif- ferent purposes. These were (1) radiobiology studies of the effects of neutron beams, (2) neutron beam treatment for appropriate patients with cancer and (3) production of radioactive material (radioisotopes) for medical and research purposes. Hal and Dr. Wood had drawn up these three applications for the cyclotron, when it would be xii Prologue ready for use. As important as the applications themselves was their order of priority which had been agreed. Firstly the cyclotron would be used to determine the safety and correct dosage of neutrons for human patient treatment (i.e. relevant radiobiol- ogy research would be done, using neutron beams to determine the limits of their safe use in patients and optimum ways of applying this radiation). Then , when enough of the safety features were understood, patients would be treated. The third use was quite distinct from the fi rst two applications. It was mainly a manufacturing process and could in principle be done at any time, when the cyclotron was not being used for radiobiology or treatment. However, just before the fateful meeting, Dr. Wood had changed the proposed order of the cyclotron’s priorities, without con- sulting Hal, who was then away from the UK. Patients’ neutron irradiations would now become the fi rst priority, with simultaneous and later radiobiology research. Hal was asked by Dr. Wood to sign and approve the revised priorities. Then it would become the unit’s offi cial workplan once the cyclotron was completed and opera- tional. He refused to sign. This was not mere petulance, although the change had been made in Hal’s absence by Dr. Wood alone, without consulting him. He rightly pointed out that there was a major and most important reason for his refusal. To treat patients before the necessary radiobiology work was completed, which it was thought might take up to 3 years, would be virtually criminal negligence in his opin- ion, after carefully considering the Californian experience and the lack of knowl- edge of neutrons’ effects on humans. He believed that if Dr. Wood’s revisions were accepted, it was highly likely there would be a partial repetition of the catastrophic results obtained from the pre-war neutron irradiations made at the University of California’s cyclotron. So protection of patients’ interests was the reason for Hal’s strong words about lacking confi dence in Dr. Wood’s decisions as director. After lunchtime on the critical Friday, Dr. Wood was invited to present her case to the investigating committee for an hour. Then Hal was to speak to the committee for one hour too. The committee deliberated after the two presentations. Next Hal was recalled to hear the decision and in his own words, ‘In the event I was asked on a Friday to leave the Council’s service, and to vacate the Unit, together with all my books and papers, by the Monday. I was given 6 months leave with pay’. These words accurately confi rm the offi cial confi dential minutes of the committee, which included the words, ‘Dr Gray would have to go’ and ‘be invited to resign, in which case he would be given 6 months’ leave with pay, to take immediate effect’. Another condition for accepting his resignation was that Hal would not enter the unit’s build- ing during that time or the entire Hammersmith Hospital. If Hal declined to resign, he would be dismissed immediately without the 6 months’ leave with pay. But this decision, shattering though it was for Hal and destructive for the RRU, fi nally proved to be the gateway to far better things for Hal, in a remarkable way. Within 6 months, this intensely dark cloud would totally unexpectedly produce a most bright and joyous silver lining for him. Acknowledgements

Firstly and most importantly, I owe this book to my wife Anny, for without her sup- port there would be no book. She suffered from my apparent eccentricity, which distracted me from my family duties (and many other obligations) for many years. But she tolerated and encouraged the work and also read the manuscript twice, mak- ing most valuable comments and corrections. I am most indebted for your gracious support expressed in so many ways. The Gray Cancer Institute, formerly called the Gray Laboratory, and its director, Professor Peter Wardman, allowed me free rein of the institute’s copious records. I was encouraged further by the Gray Laboratory Cancer Research Trust and Mrs. Valerie Moar with funding to study Hal’s archives, housed at the University of Tennessee, in Knoxville, TN, USA. The Rockefeller Archive Center, in Pocantico Hills, New York, USA, provided a grant-in-aid to per- mit a study period in their extensive collections, where any form of assistance I needed was willingly provided. Another fruitful study period in the Library of Trinity College, Cambridge, was facilitated by the college archivist, Mr. J. Smith, who gave me access to the relevant content of the library and aided me in numerous other practical ways. I was welcomed and aided at the Christ’s Hospital Museum and Archives by Mrs. Wendy Killner. For all this I am most grateful. Of over a hun- dred of Hal’s schoolfellows, and too many to list by name, to whom I wrote virtu- ally, all replied using pen and ink, in the days before electronic communications. They gave me information, impossible to obtain otherwise, about their recollections of Hal as a schoolboy, their own school experiences and the school’s ethos in their days. Many persons have allowed me to interview them. Most especially I acknowl- edge Mrs. Freye Gray and Mr. Crispin Gray, Hal’s widow and elder son, who each gave two long interviews on different occasions. Old Blues, who granted me inter- views, were Mr. Victor Harley, Dr. Geoffrey Jennings, Lord Michael Stewart and Mr. S.W. Watson. Other friends of Hal who spoke to me at length were Mr. Paul Beaven, Professor Charles Coulson, Mrs. Eileen Coulson and Mrs. Eileen Lea. Sir Subrahmanyan Chandrasekhar and Dr. John Read are thanked for valuable corre- spondence. Many of Hal’s former work colleagues received me and patiently answered my questions. They were: Drs Tikvah Alper, David K. Bewley, Professor Jack Boag, Mrs Eddie Collins, Drs David Dewey, Shirley Hornsey, Barry Michael, Mr Ronald Post, Sir Oliver Scott, Drs Paul Strickland, R.H. Thomlinson, Norman Veall, Mr Derek Vonberg and Dr Constance Wood. For the illustrations, I wish to thank most warmly Professor Jack Boag, Christ’s Hospital (through the kindness of

xiii xiv Acknowledgements

Mr. Clifford Jones from the collection of the CH Archive), Mrs. W.A. Collins, Dr. Eleanor Deschner, Mr. Crispin Gray, the Gray Laboratory Cancer Research Trust and Mrs. Valerie Moar, the L.H. Gray Memorial Trust and its chair Professor Catherine West, Mr. Victor Harley and Professor P. Wardman of the former Gray Laboratory. Professor Raymond Abratt and Dr. André Hendrikse read, respectively, the sections on radiotherapy and radiobiology, for which I am grateful. However, I remain solely responsible for all errors. Mrs. Elize Mostert spent a long time care- fully transcribing recordings of the interviews and I thank her most warmly. I am most indebted for the time, encouragement, information and support offered by all these persons and institutions, without whom the writing of this book would have been far more diffi cult and its content of much less interest.