Autobiography : George Herbert Hitchings

Publié le par Nobelprize - George Herbert Hitchings

Nobelprizepublished 01/01/1988 at 16:16 by George Herbert Hitchings

Hitchings GeorgeMy forebears all came from the United Kingdom. On my father's side, they migrated from London and County Derry in Northern Ireland to Londonderry, New Hampshire. When the American Revolution came, they, as loyalists, moved on to Canada. My father, grandfather and great-grandfather were born in St. Andrews, New Brunswick. In 1865, my grandfather, Andrew Hitchings, moved his family to Eureka, California. Andrew was a skilled craftsman in the building of wooden ships, and my father, George Herbert Hitchings, Sr., followed in his footsteps, eventually becoming a marine architect and master builder.

On my mother's side, Scottish and English prevailed. The first American was one Thomas Littlejohn from near Edinburgh, who came to the New World about 1735. His descendants, including Shaws, Eldridges and Thomases, moved about in the Maritime Provinces and New England. My maternal grandfather and great-grandfather were descendants of the Matthews family that emigrated twenty-four strong from near Glasgow to Prince Edward Island about 1800. My grandfather, Peter Matthews, married Sara Elizabeth Eldridge, and my mother, Lillian Matthews, was born in Maine. In 1875, my grandfather moved his family across the United States. He, too, was a shipbuilder and settled in Eureka.

My mother and father met and were married in Eureka, and my two sisters were born there. About 1897, Peter Matthews established a shipyard in Hoquiam, Washington, to build lumber carriers for the E.K. Wood Lumber Company. The company built several schooners a year. When Peter Matthews died, my father succeeded to the management, which then became Hitchings and Joyce. Later, my father was master builder and supervisor in Bellingham, Washington, and Coos Bay, Oregon, and between times he engaged in marine architecture. He worked in the period between sail and steam and was especially noted for the design of the transition vessel, the steam schooner, which had a wooden hull and was steam propelled.

I was born in Hoquiam in 1905. Family wanderings put me in grade school in Berkeley and San Diego, California, as well as in Bellingham and Seattle, Washington. I enjoyed a warm and loving home environment. A high standard of ethics prevailed in our family, together with a thirst for knowledge and an urge to teach. In their schooling, my mother and father were limited to what was available in Eureka, but they were avid readers, especially my father. It is clear to me in retrospect that he would have been a scientist had opportunities been more easily attainable.

My father died after a prolonged illness when I was twelve years old. The deep impression made by this event turned my thoughts toward medicine. This objective shaped my selection of courses in high school and expressed itself when I was salutatorian at my class graduation. I chose the life of Pasteur as the subject for my oration. The blending of Pasteur's basic research and practical results remained a goal throughout my career.

My experiences at Franklin High School in Seattle were notable for another reason. We had a most heterogeneous population, one that blended upper class and minorities including blacks, Filipinos, Japanese, Chinese and first generation Catanians. As a result I lost any self-consciousness I felt in dealing with people from different cultures and backgrounds.

I entered the University of Washington as a premedical student in 1923. The enthusiasm of faculty and students in the Chemistry Department was very infectious, however, and by the end of the first year I had become a chemistry major. I earned top grades, election to Phi Beta Kappa in my junior year, and a degree cum laude in 1927.

I stayed on to earn a master's degree in 1928 with a thesis based on work carried out during the summer of 1927 at the Puget Sound Biological Station at Friday Harbor, Washington. This institution later became a branch of the Oceanographic Laboratories of the University of Washington, largely created and directed by Thomas C. Thompson, who had been my mentor for my master's thesis. Thompson taught analytical chemistry and was notable for the keen wit and humorous twists that made his teaching memorable. Perhaps the most useful lessons I learned from him have to do with the mathematics of the precision of measurement.

For further graduate work I was offered fellowships at the Mayo Foundation and at Harvard. I chose Harvard, and after one year as a Teaching Fellow in the Department of Chemistry at Cambridge, I was accepted as a Teaching Fellow in the Department of Biological Chemistry at Harvard Medical School. I had intended to work with Otto Folin, but it was his habit to assign first-year Fellows to Cyrus Fiske for a year. By the end of the year, I was caught up in the Fiske-Subbarow program, and Folin very generously allowed me to continue there. After the discovery of phosphocreatine, this group had detected and isolated adenosine triphosphate. My assignment was to prepare for physiological studies by developing analytic methods (on a scale then viewed as 'micro' - 1 mg or less) for the purine bases. These methods constituted my dissertation and several early publications.

I earned my Ph.D. in 1933, a year memorable for another great event in my life - my marriage to Beverly Reimer. Her forebears were German, Austrian (Pennsylvania Dutch), Scottish and English. Her father, Azariah Reimer, was a Methodist-Episcopal minister who was pastor of a number of parishes in the Greater Boston area and superintendent of the city missionary society. Beverly had experience with many races and cultures and grew up having friends among all.

Beverly was highly artistic and intelligent. She was very accurate in her intuitive appraisals of people, almost always empathic, almost never disparaging. As she said, "The same quality is often exhibited in a person's most liked and most disliked behavior." Beverly expressed her talents in painting, jewelry making, writing and teaching. As my research career progressed, we traveled together and raised two children - Laramie Ruth and Thomas Eldridge.

Our marriage and my career began in the middle of the Great Depression. I experienced a nine-year period of impermanence, both financial and intellectual. I held temporary appointments at the C.P. Huntington Laboratories of Harvard in cancer research, at The Harvard School of Public Health in nutrition research, and at Western Reserve University, Department of Medicine, in electrolyte research.

My career really began in 1942 when I joined the Wellcome Research Laboratories in Tuckahoe, New York, as head and sole member of the Biochemistry Department. Support was limited, but I was free to develop my own program of research.

Elvira Falco was the first permanent member of my staff; Gertrude Elion joined in 1944, and Peter Russell in 1947. Additional help was added here and there, but our numbers were always small. Russell came from Alex Todd's laboratory at Cambridge University and brought not only competence in organic chemistry but a sense of the workings of medicinal chemistry as well. Elion took part in most of the projects dealing with purines, and Falco participated in everything from bacteriology and animal feeding to organic chemistry. For several years our group was housed in one large laboratory. Under the leadership of Falco, a constant flow of banter developed covering a wide range of subjects and degrees of seriousness. We never had any obstacles to interpersonal communication.

In the mid-1940s we began a project that seemed like a digression at times, but one that had a notable reprise some 40 years later. This was the antiviral work carried out in collaboration with Randall L. Thompson, then at Western Reserve. It focused principally on vaccinia virus, and it produced some active compounds. It also convinced us that effective curative chemotherapy of viral infections would have to be applied early in the multiplication cycle.

In 1947, we began to send compounds to the Sloan Kettering Institute to be screened for activity. Among the first few compounds we submitted was 2,6-diaminopurine, which proved active and later produced several notable remissions in acute leukemia.

The association with Sloan Kettering was a major impetus for our growth. The director, C.P. Rhoads, offered us financial support to enable us to increase our search for antitumor agents. This rather unusual circumstance resulted from Rhoads' realization that our compounds were of special interest, both intrinsically and because they were accompanied by a package of biological information. The external financial help allowed us to expand to about 15 persons. The arrangement continued for a number of years. By that time Burroughs Wellcome Co. was able to furnish our support completely. The arrangement with Sloan Kettering was productive and very satisfying for the contacts it provided, especially with C.P. Rhoads, C.C. Stock, J.H. Burchenal, F. Philips, D. Hutchison and others.

In 1948, we began to divide responsibilities with respect to developing purine and pyrimidine analogs. In 1947, Falco had synthesized p-chlorophenoxy-2,4-diaminopyrimidine, and it was apparent at once that we had a new kind of antifolic acid in hand. This line was pursued vigorously by Falco and Russell, and within a short time yielded a very exciting line of investigation - the end of which is not yet in sight.

The decision to refer the "thiation" of hypoxanthine to Elion was based on her developing expertise in the field of purine metabolism. Elion participated in much of the subsequent work with the compound and the agents that followed, including azathioprine and allopurinol.

It was always stimulating to work with Elion. She is intelligent, hard working and ambitious. She became my first assistant, and as I was promoted she succeeded to the position just left. She became head of the Department of Experimental Therapy, a large segment of the Chemotherapy Division. There she elucidated the mode of action of acyclovir, a study which is described as a major part of her Nobel address.

In 1967, I was offered the position of Vice President in Charge of Research of Burroughs Wellcome Co. It was not a post I had sought, but my experience had suggested that a scientist was much better able to support the interests of working scientists than were administrators who got science second hand. I owe much to D.W. Adamson, Wellcome's Group Research and Development Director, for his support and encouragement.

By 1968, Burroughs Wellcome Co. had outgrown its facilities at Tuckahoe, and we were plunged into a new set of administrative problems by the decision to move the company to a new site. In the end we chose North Carolina and, acceding to my strong representations, selected a site in the new Research Triangle Park. The move provided Lebensraum, a good environment and excellent relationships with the three local universities - Duke, the University of North Carolina at Chapel Hill, and North Carolina State. The move to North Carolina was a monumental undertaking, but the company soon took root and today has grown fourfold.

I left my position as Vice President with its heavy administrative duties to become Scientist Emeritus in 1976. This allowed more time for my own research and for travel. By 1971, Beverly was handicapped by strange afflictions classed as "collagen disease" that required close monitoring and constant medication. She exhibited remarkable courage and continued to be a joy as a companion. During our last 10 years together we traveled nearly 400,000 miles, much of it on lecture tours. Beverly's disease ended in her death in December 1985.

For the past 20 years I have pursued my growing interests in philanthropy. I became Director of The Burroughs Wellcome Fund in 1968 and its President in 1971. The Fund is a nonprofit foundation dedicated to the support of biomedical research. The Fund is supported solely by Burroughs Wellcome Co. and is a relatively small foundation. We have focused The Fund's resources on underfunded areas of medical research with competitive grants in fields including clinical pharmacology and innovative methods in drug design. It has been very rewarding to guide this enterprise and see it grow.

In 1983, I founded what is now the Greater Triangle Community Foundation. It has been remarkably successful in fulfilling needs in the Triangle area. I am designated as Founder and Director for Life.

I have been involved also with a number of volunteer civic activities. These were undertaken partly to provide for activity in the retirement that has not yet come. They include United Way (Director and Vice President), American Red Cross (Director and Committee Chairman), Foundation for Better Health of Durham (Director, President and Chairman), N.C. Board of Science and Technology, Carolina Consulting Scientists and Engineers (Director); Royal Society of Medicine Foundation (Director); The Life Sciences Research Foundation.

Somehow these activities have found a place in my scientific career with no more cliffficulty than my former administrative duties. Today I devote one-third of my time to philanthropy and two-thirds to science.

I am vitally interested in current developments in innovative methods in drug design, and I look back with pride at our contributions to this field. Our research was untargeted, and the line of inquiry we had begun in the 1940s yielded new drug therapies for malaria (pyrimethamine), leukemia (6-mercaptopurine and thioguanine), gout (allopurinol), organ transplantation (azathioprine) and bacterial infections (cotrimoxazole (trimethoprimA). The new knowledge contributed by our studies pointed the way for investigations that led to major antiviral drugs for herpes infections (acyclovir) and AIDS (zidovudine).

My greatest satisfaction has come from knowing that our efforts helped to save lives and relieve suffering. When I was baptised, my father held me up and dedicated my life to the service of mankind. I am very proud that, in some measure, I have been able to fulfill his hopes.

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