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Nobel Prizes and Laureates

The Nobel Prize in Physiology or Medicine 2015
William C. Campbell, Satoshi Ōmura, Youyou Tu

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William C. Campbell - Biographical

William C. CampbellBefore any of the present fuss I was, of course, born; and that turned out to be slightly complicated - not in an obstetrical sense, but in a political one.

Several years before the event, an international border was created between my parents' rural town and the nearby city where maternity facilities were available at a price. Thus it came about that I was born in Northern Ireland, U.K. (in Londonderry city) but was raised in Eire, the Irish Republic (in Ramelton town, County Donegal). The year was 1930, and that was a long time ago (the Great Depression was in full swing, but I did not learn about that until much later).

My parents were strong believers in the value of education. My father, having had little formal education himself, went so far as to employ a professional teacher, Miss Elisabeth Letitia Martin, as a live-in tutor for me, my two brothers and my sister. (There were cultural factors at play as well as educational values.) For a considerable period I was the only pupil in school (my sister being too young for school and my brothers having departed for boarding school). Miss Martin instilled in me a desire to learn, and to remember the things that were considered good. Science was not mentioned. In those years before and during World War II, it did not, I think, occur to either of us that a multicultural, multidisciplinary transformation was taking place in the tumultuous world outside our attic classroom. I do not think that anyone now cares that I still remember a few lines of Wordsworth and Tennyson; but learning to love learning, through Miss Martin's influence, was a gift for which I shall be forever grateful.

Having been taught by Miss Martin from the age of 6, I moved at the age of 13 to a boarding school: Campbell College, Belfast, Northern Ireland. The school had a reputation for excellence; it was said to be "the Eton of Ulster" and indeed it was run on the lines of a classic British boarding school. It had been evacuated from Belfast to the seaside resort of Portrush because of the war, and for the same reason the teaching faculty was composed largely of teachers brought out of retirement. On arrival, I did not even know the difference between physics and chemistry (today I begin to suspect that there might not be one). I was thrown into those subjects very much as I was thrown into rugby football - without even a rudimentary instruction as to which way to run. Physics was hard; chemistry seemed like magic. Biology, however, I found fascinating. I was not robust enough or pugnacious enough to be good at contact sports, and playing tennis was not an option until the final years. Perhaps it was that factor, combined with the rather solitary prior period under Miss Martin's tutelage, that I became more interested in learning than in sports. In those school-days, and especially in the college years that were to follow, there was a great deal of peer pressure to be knowledgeable and "cultured." Certainly, my scholarly interests did not arise from any effusion of intellectual brilliance.

Life at Campbell College was an awesome adventure for a country boy who had led a rather sheltered life. It was not always fun (nor should it have been) but it was never boring. It meant making new friends in a regimented and hierarchical system. Traveling to school at the beginning of each term meant traveling to a country at war. It meant carrying a gas-mask in a little box slung around my shoulder. As a member of the Air Training Corps, I trained in the methods of, and at camps of, the Royal Air Force. I used to see fighter planes rising from RAF airfields, and I longed to be old enough to fly them. I pictured myself an ace fighter pilot, strolling nonchalantly in my beribboned uniform and impressing the girls. In reality I was sequestered in an all-boys school and didn't know what I would say to a girl if I met one. The war ended while I was still a school-boy, and with it ended my dream of soaring into the sky in my trusty Spitfire. Campbell College moved back to Belfast.

Holding an infected sheep.

It was at Campbell College that I first learned of the existence of a parasitic worm. It was Fasciola hepatica, the common liver-fluke of sheep and cattle. In the course of a school outing to an agricultural show, I was fascinated to learn that a drug could be used to treat liver-fluke disease. When it was time to move on to university, my biology teacher, Mr. Wells, advised me to go into biology while the head master advised me to go into medicine. I took Mr. Well's advice, but devoted my subsequent career to biology in the context of human and veterinary medicine.

Upon entering Trinity College, Dublin University in the autumn of 1948, I was again confronted with sciences that were not much to my liking. Swedish chemist Tomas Lindahl recalls that when he was a child a teacher gave him a failing grade in chemistry, but he went on to get a Nobel Prize in Chemistry (as recorded in Nobel speeches). When I was a university freshman, the standard grade for passing was 40% - and my final mark in chemistry was 39.7%. Fortunately the mark was rounded up to the nearest whole number. But for me chemistry remained mysterious. Physics, too, was a challenge. Perhaps my physics professor (Ernest Walton) was distracted by the news that he had just won the Nobel Prize in Physics; but I cannot blame my teachers for the fact that I found the "hard sciences" hard. Biology was about to become vastly more chemical and physical: across the Irish Sea, Watson and Crick were building models with a novel twist. Luckily for me, my strong interest in zoology carried me through to graduate from Trinity with first-class honors.

Children.

Even in the earlier Trinity years, the pleasures of botany and zoology more than made up for the struggles in other sciences. Soon I came under the influence of Dr. J. D. Smyth, about whom I have written elsewhere [1]. Desmond Smyth was making a name for himself in the field of invertebrate physiology and especially in the area of experimental parasitology. He became (informally, of course) my mentor; and he changed my life. Among the things that Professor Smith did for me as I approached graduation was to respond positively to inquiries from Professor Arlie Todd of the University of Wisconsin, USA. The result of that communication was my application for graduate school at the University of Wisconsin along with two other Trinity students. Both of the others dropped out, and before I set out on that journey alone, one of them sent me a note saying, "For God's sake, don't panic when you get off the boat." I thought that was a very easy thing for him to say.

As it turned out, getting on and off the boat (which turned out to be the liner Britannic) was made easier by two wonderful organizations. Prof. Smyth encouraged me to apply for a Fulbright Travel Grant, which led to various complications relating to the foundation of the Fulbright grants and my rather confusing British and Irish citizenship. All was settled favorably and I set off on my big adventure to the New World and graduate school, with all my travel expenses covered by the Fulbright grant. I was therefore one of the innumerable beneficiaries of the generous impulse and astute insight of United States Senator William Fulbright and his conjuring of international good will from the horrors and economics of war. Getting off the boat in the dockyards of New York City (in January 1953) would indeed have been a fearsome affair had it not been for the other organization, the Committee on Friendly Relations Among Foreign Students (founded in 1915, with funds given by Andrew Carnegie and Cleveland Dodge). Its angelic Mrs. Minucci met me on the dock and soon had me installed in a nearby hostel where I was assigned to one of the many beds in a large dormitory room, and was advised to keep my belongings close about me. I am still haunted by the realization that I always intended to write that kind woman a thank-you note, but never did.

Family in Australia.

I was dismayed to find that the U.S. system required graduate students to take many academic courses, but the requirement proved advantageous. My doctoral program was a "joint major" program in Veterinary Sciences (supervised by Arlie Todd) and Zoology (supervised by Chester Herrick). Professor Todd's laboratory in the Department of Veterinary Sciences was my campus ‘home'. Since I knew something about the trematode Fasciola hepatica, I was delighted to learn that my research project would be on a giant relative, Fascioloides magna.

Todd's method (unspoken by him, unsuspected by me) was to set a new student to some routine task such as tending the snail tanks where the vector snails were raised, and waiting for the student's curiosity to take its course. Gradually and unwittingly I discovered the joy of being able to do something in the lab to test some item of casual curiosity - the fun of actually doing an experiment that no one had done, to answer a question no one had asked. Those graduate school explorations led to half a dozen scientific papers.

Climbing Mt. Errigal.

For most of my years in Madison, Wisconsin, I lived rent-free in the old Governors' Mansion on the edge of Lake Mendota! This extraordinary bit of  good fortune resulted from being awarded a Kemper K. Knapp Fellowship - a grant that enables a group of graduate students from various disciplines to live together in a an environment conducive to intellectual ‘cross-fertilization.' The "Knapp House" experience was a major highlight of my University of Wisconsin years.

In 1957, as the graduate school experience came to an end, Professor Todd responded positively (echo of the end of my Trinity days) to an enquiry from Dr. Ashton C. Cuckler, Director of Parasitology at the Merck Institute for Therapeutic Research. Todd encouraged me to at least go for an interview at the Merck organization in Rahway, New Jersey. With considerable misgiving I decided to give the pharmaceutical industry a try - and stayed for 33 years. It was a marvelous experience - challenging, exciting and (at least in the early years!) remarkably free of workplace politics. I am deeply indebted to Cuckler for his leadership in those early years [2]. Sharply focused research was exactly what I needed to keep me from wandering indefinitely into tangents and sub-tangents of a project; yet at the same time I was always free to make refreshing forays into the most enticing tangential byways.

With brothers.

Given my struggles with chemistry as a student, it is ironic that I went on to have a career in experimental chemotherapy. That happened quite naturally because at the Merck Institute I was surrounded by brilliant chemists and close interdisciplinary collaboration was a way of life. During my years at Merck, collaboration between Parasitology and many other scientific disciplines enabled the company to introduce several anthelmintic (anti-worm) drugs: thiabendazole (ThibenzoleR, TBZR); cambendazole (CamvetR); rafoxanide (RanideR); clorsulon (CuratremR); ivermectin (MectizanR, IvomecR); eprinomectin (EprinexR). For several years I had administrative responsibility for the Merck poultry coccidiosis program, and the amebiasis and trypanosomiasis programs, but my contribution to protist biology was essentially nil.

It was a chemist who imbued me with confidence in the empirical approach to drug discovery. The parasitologists and chemists at Merck had weekly lunch meetings, co-chaired by Cuckler and Dr. Lewis H. Sarett. Sarett was one of the great medicinal chemists of that era (he was renowned especially for his partial synthesis of cortisol). He quickly deflated my naïve assumption that the best way to find a new antiparasitic drug was to devise a rational therapy based on the latest discoveries in the field of parasite biochemistry. Sarett convinced me that, at least in the near term, the probability of finding a drug by empirical screening (for which there was much historical precedent) was higher than the probability of finding one through research on the biochemical processes of parasites (for which there was no precedent). That assessment has, of course, no bearing on the importance of research on parasite biochemistry. Cuckler placed great faith in the use of animal (in vivo) models, and dietary medication, for the routine screening of test substances. In the era of biochemical biology there was a high price to pay for adherence to such traditional assay methodology; but I do not regret my espousal of it.

Family in the US.

Chemotherapy has by no means been my only parasitological interest, and I will mention just a few of the others. I devoted a lot of time to the study of Trichinella and trichinellosis, including much "burning of midnight oil" to produce a book on that subject. I was privileged to become deeply involved in the activities of the International Commission on Trichinellosis. My passion to be the first person to deep-freeze worms without killing them led to the discovery of a laboratory manipulation that allowed the cryopreservation of strongyle nematodes for at least 10 years [3, 4]. It turned out to be useful because it made possible the maintenance of species and strains of nematodes without the enormous cost of serial passage in sheep, cattle or other large animals. My close association with chemotherapy prompted me to use drugs as tools for the study of stage-specific immunity to helminth parasites. The first of these was a demonstration of the protection conferred by pre-pulmonary migration of Ascaris suum in rats [5].

Skiing in Colorado.

My decades of work at the Merck labs in Rahway NJ were punctuated by two leaves of absence and one temporary re-assignment. I requested, and was granted, leave to travel to the University of Cambridge to become a visiting researcher in the laboratory of Lawson Soulsby (now Lord Soulsby, Baron of Swaffham Prior), who is recognized as an outstanding pioneer in the field of immunity to helminth parasites. My wife and I sailed on the Queen Elizabeth in 1963, and our life in England was marked by immunological studies on trichinellosis, many new friendships, and the birth of our daughter Jenifer. Our son Peter was born in the US at the beginning of 1966; and later that year I was granted a brief second leave - this time to accept an Inter-American Fellowship in Tropical  Medicine under the auspices of the Louisiana State University. Previously this fellowship had not been open to scientists employed in industry. Professor Harold Brown, a legendary parasitologist at Columbia University, appealed for a lifting of that restriction and I had the great benefit of visiting laboratories and hospitals in Central and South America. A third departure from the United States (1972–73) was not a leave of absence, but rather a temporary transfer from Company headquarters in New Jersey, USA to Australia to assume directorship of the Merck, Sharp and Dohme Veterinary Research and Development Laboratory in Campbelltown, N.S.W. That, too, was a memorable and instructive period, with novel administrative responsibilities, research on the use of cambendazole for the control of tapeworm in sheep (with colleague Richard Butler); further research on the cryopreservation of strongyle nematodes [6, 7], lasting new friendships - and the birth of our daughter Betsy.

On a motorbike.

Beginning in 1975, and continuing for a period of 15 years, I was mostly preoccupied with matters relating to ivermectin [8]. Advancing years and perturbations in career pathway brought thoughts of retirement. There was no doubt about what to do. I knew that Drew University in Madison, NJ had an unusual program that enables retired industrial scientists to turn their years of experience to the benefit of undergraduate students, while at the same time enabling the scientists to continue to be active in their fields of interest. In doing this, the scientists give up much in absent salary, and they gain much in an incomparable "job satisfaction." The Charles A. Dana Research Institute for Scientists Emeriti had been founded at Drew University to provide this sort of opportunity. In 1990, Merck and Company announced an offer of increased retirement benefits to employee scientists who opted to take early retirement in order to teach mathematics or science. I therefore moved quickly, at the age of 59, to Drew University. Few experiences are as gratifying as that of mentoring undergraduate students as they discover the joy of doing an experiment that is not a classroom exercise but an experiment that constitutes real research. Several of my undergraduate students have published their research findings in reputable peer-reviewed journals by the time they graduated. I had always enjoyed teaching and had held adjunct professorships at University of Pennsylvania, New York Medical College and Drew University for many years. I was delighted to find new opportunities to teach at Drew University: teaching a course on Parasitology (in the Biology Department) and a course on the History of Biomedical Science (in the graduate school). I cannot imagine a more rewarding professional finale than retiring a bit early to profess one's calling in such an environment.

On stage.

Leaving the land of my birth (Northern Ireland) and of my upbringing (Ėire) had never been my intent; but circumstances changed and the New World got hold of me. The people of the United States welcomed me, and in 1964 I became a citizen.

Three mentors.

In accord with instructions, I have devoted these pages to education and career. Recreational, avocational and social activities have been left out. But that sort of limitation is not the hardest part of writing such a biographical sketch. The hardest part of all is coping with the realization that one is evading the most important part. Without family (at least in the ancestral sense), there would be no biography to write. With family, there is no way a really true biography can be written. I have no words to say how much I love my wife and children; and how much, magically, I feel loved by them. My wife Mary, and my children Jenifer, Peter and Betsy must be counted in whatever honors come my way. And then there is the love that emanated (unspoken, in the manner of the time and place) from my parents Robert and Sarah Campbell, and was shared by my sister Marion and my brothers Bert and Lexie. Without my being aware of it, my younger self must have been molded by the nurturing care of my parents, their commitment to honest and industrious living, their stalwart religious faith and their admiration of learning. Beyond the family circle and our extended families, many other people have granted me the blessing of friendship. I may not be able to express my gratitude here, but of this I am certain: I have a great deal to be thankful for.

Literature

  1. Campbell, W.C. 1999. In Memoriam: James Desmond Smyth, Honorary Member ASP. J. Parasitol. 85:992–993.
  2. Campbell, W.C. 2001. In Memoriam: Ashton C. Cuckler. J. Parasitol. 87:466–467.
  3. Campbell, W.C., Blair, L.S. and Egerton, J.R. 1973. Unimpaired infectivity of the nematode Haemonchus contortus after freezing for 44 weeks in the presence of liquid nitrogen. J. Parasitol. 59: 425–427.
  4. Rew, R.S. and Campbell, W.C. 1983. Infectivity of Haemonchus contortus in sheep after freezing for ten years over liquid nitrogen. J. Parasitol. 69:251–252.
  5. Campbell, W.C. and Timinski, S.F. 1965. Immunization of rats against Ascaris suum by means of non-pulmonary larval infections. J. Parasitol. 51:712–716.
  6. Campbell, W.C. and Thomson, B.M. 1973. Survival of nematode larvae after freezing over liquid nitrogen. Australian Vet. J. 49:110–111.
  7. Kelly, J.D. and Campbell, W.C. 1974. Survival of Nippostrongylus brasiliensis larvae after freezing over liquid nitrogen. Internat. J. Parasitol. 4:173–176.
  8. Campbell, W.C., Fisher, M.H., Stapley, E.O., Albers-Schonberg, G. and Jacob, T.A. 1983. Ivermectin: A potent new antiparasitic agent. Science 221:823–828.

 

From The Nobel Prizes 2015. Published on behalf of The Nobel Foundation by Science History Publications/USA, division Watson Publishing International LLC, Sagamore Beach, 2016

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.

Copyright © The Nobel Foundation 2015

 

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