O. Harold Warwick: Canada’s first medical oncologist

O. Harold Warwick: Canada’s first medical oncologist


D.H. Cowan, MD*
*Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, and Cancer Care Ontario, Toronto, ON.

O. Harold Warwick graduated in medicine from McGill University as a gold medalist and Rhodes Scholar in 1940. After World War II, he started postgraduate training in Montreal, and in 1946, he began studying the newly described drug treatment of cancer in London, England. There he carried out the first study of nitrogen mustard in a group of adult patients with a non-hematologic solid tumour, lung cancer. After a brief period of practice in Montreal, he moved in 1948 to Toronto, where he became executive director of the Canadian Cancer Society and the National Cancer Institute of Canada. Simultaneously, he joined the staff of Toronto General Hospital and its Radiotherapy Institute, where he became the first physician–oncologist to provide medical care and administer anticancer drugs in a Canadian cancer centre. In 1958, the new Princess Margaret Hospital opened in Toronto; Warwick became its first chief physician, responsible for clinical drug trials. Here he carried out his best known clinical study—the use of vinblastine sulphate in patients with Hodgkin lymphoma. From 1961 to 1971, he served as dean and then vice-president Health Sciences at the University of Western Ontario. He returned to the practice of medical oncology from 1972 to 1980 at the London Cancer Clinic, after which he had a long and productive retirement. He died in October 2009. Although the specialty was not named until the latter years of his career, Harold Warwick satisfied all the criteria for and was undoubtedly Canada’s first medical oncologist.

KEYWORDS: Harold Warwick, history, medical oncology

1. INTRODUCTION

The genesis of modern medical oncology dates to the anticancer chemotherapy era, which in turn began with clinical studies that started in 1942 in the United States and Britain. Those studies demonstrated the usefulness of nitrogen mustard in treating certain malignancies of the blood and lymphatic system. Because the drug was developed as a result of war (mustard) gas research, the results were classified and publication was banned during World War II. The first patient in the United States was treated in December 1942, as discussed in a historical account of nitrogen mustard and the origin of chemotherapy 1. The early American studies were published in 1946 24 after the ban was lifted. The initial British clinical studies of nitrogen mustard also started in 1942, and results were published in 1947 5. In addition, during the 1940s, investigators demonstrated the benefits of hormone manipulation in patients with prostate 6 and breast cancer 7. Those publications stimulated the interest of a young World War II veteran of the Royal Canadian Air Force Medical Corps: Orlando Harold Warwick, known as Harold.

2. WARWICK: A LIFE

2.1 Early Years and Training

Harold Warwick was born in 1915 in Saint John, New Brunswick, Canada a. He had an outstanding academic career. After obtaining a degree at Mount Allison University, he graduated from McGill Medical School in 1940 as a gold medalist. During his years at McGill, he took time out to accept a Rhodes scholarship to study at Oxford University. His youth was enriched by many outdoor and sporting activities. He played for the Maritime championship basketball team and later played ice hockey for Oxford. His passion for golf and fishing—especially salmon fishing in Atlantic Canada—were nurtured during his early days and maintained throughout his life. Upon completion of an internship in Montreal in 1941, he enlisted in the Medical Corps of the Royal Canadian Air Force and became involved in research related to high altitude flying. Later he served overseas as a medical officer at various active aerodromes. In January 1942, Harold and Barbara Gzowski were married; they subsequently had four children.

Warwick returned to civilian life in 1945 and began specialty training in internal medicine at McGill University. The next year, he was awarded a Nuffield Dominion Traveling Fellowship, which took him back to England for further training. It was at this point that he decided to involve himself in the study and care of patients with cancer. He was aware of the nitrogen mustard story and the reported usefulness of hormone manipulation in patients with certain malignancies. His objective was to learn about these hormones and chemicals and to become involved in a newly developing field of medicine, the chemotherapy of cancer, which years later, under the name “systemic therapy,” became an integral part of medical oncology. In his own words, “I was convinced that these methods of treatment, though still in their infancy, would one day take their place alongside surgery and radiation in the treatment of cancer” (autobiography, p. 93).

Warwick had a very productive fellowship at the Royal Cancer Hospital and the Brompton Chest Hospital in London, where he had an opportunity to immerse himself in the activities of a large cancer hospital and also to carry out a clinical trial of nitrogen mustard in a group of patients with cancer of the lung. The project was pursued because of a report of a single patient with lung cancer responding to nitrogen mustard 2. In Warwick’s study, symptomatic relief and objective improvement occurred in approximately one half the patients (19 of 41), although the remissions were disappointingly short. He reported those findings at a meeting of the Royal Society of Medicine in 1947 in London, and the clinical trial was subsequently published in 1948 8. That report was the first of a clinical trial using a chemotherapeutic agent in a large group of adult patients with a single type of solid tumour.

2.2 Dedication to Oncology

Armed with enthusiasm and a unique training, Warwick returned in 1947 to Montreal, where he became a member of the department of medicine at the Royal Victoria Hospital and McGill University. However, events soon dictated a change in professional activities and location for Warwick and his family. On July 1, 1948, he was persuaded to move from Montreal to Toronto where he became the first executive director to simultaneously serve with both the Canadian Cancer Society and the newly formed National Cancer Institute of Canada (ncic) 9. He had a major influence on both organizations, but particularly the ncic, where he played an important role in charting a course for cancer research in Canada.

At the same time, Warwick became a member of the medical staff in the department of medicine at Toronto General Hospital (tgh), which also housed the Ontario Radiotherapy Institute (ori). In his history of tgh, W.G. Cosbie wrote that “there was at this time, a physician on staff ... who had a great deal to do with the development of the medical treatment of cancer. Dr. O.H. Warwick ... brought with him a particular interest in hematology and the chemotherapy of malignant disease and was the first physician appointed to a radiotherapy treatment centre in Canada.... In his 1951 report to the Medical Advisory Board from the special Committee on Chemotherapy for Cancer, Warwick detailed his treatment, [with hormones and chemotherapy], of about two hundred patients” 10. Warwick also taught undergraduate and postgraduate students in the lecture theatre and at the bedsideb. In 1955, he left his administrative responsibilities at the ncic and Canadian Cancer Society and became a full-time physician at the ori11.

In 1958, the new Ontario Cancer Institute, incorporating Princess Margaret Hospital (pmh), opened in Toronto. The ori at tgh closed; its staff and patients moved to the new facility. Harold Warwick became chief physician and was also responsible for developing clinical drug trials of anticancer agents 12.

During his years at tgh, ori, and pmh, Warwick treated and studied hundreds of patients with cancer. He spoke and wrote about treatment with hormones and chemotherapeutic agents and published a number of papers on clinical trials. The best known and most important of those trials involved the use of the vinca alkaloid vinblastine sulphate (vlb), which was provided to Warwick by Canadian scientists Robert Noble and Charles Beer, who had isolated and purified it at the University of Western Ontario (uwo). After a preliminary 1960 publication on vlb13, Warwick, with his colleagues at the pmh, published one of his best known papers (on the value of vlb), particularly in patients with Hodgkin’s disease (now known as Hodgkin lymphoma) 14.

Simultaneously with the work in Canada, vlb was isolated in the United States. The first reports of clinical studies, with small numbers of patients (20 and 8 respectively), were published by U.S. investigators Hodes 15 and Hertz 16 in 1959 and 1960. Warwick’s 1961 paper 14 is the earliest large study (120 patients, 27 with Hodgkin’s disease) to establish the usefulness of the drug. It is still used in combination with other drugs in treating Hodgkin lymphoma.

Warwick’s interests were not restricted to drug studies. He and Dr. Edmund R. Yendt published an important paper on the incidence and manifestations of hypercalcemia in a large group of patients in a cancer hospital 17. Although Warwick did not start a formal medical oncology training program (such a program was led by others about a decade later), he did train and mentor individuals who subsequently practiced the discipline. One person to fall under Warwick’s mentorship was Dr. Ruth Alison, who became Canada’s first female medical oncologist. She was a co-author on the vlb paper and practiced at pmh for her entire career. He also recruited and mentored a young endocrinologist, Dr. William Meakin, to the staff of pmh. Meakin made important contributions to hormone manipulation in patients with breast cancer and subsequently became chief executive officer of the Ontario Cancer Research and Treatment Foundation.

Warwick’s clinical work came to an abrupt halt in 1961, when he was persuaded to become dean of medicine at uwo in London. When the five-year term ended, he became vice-president of health sciences for a further five years. One of his legacies is the leadership role he played in successfully moving the medical school to a new building on the university campus, where it became part of a unified Health Sciences Centre under one roof with the new university hospital and the dental and nursing schools. By that time, he had completed ten years in academic administration, and just as he had in 1955, he returned to full time practice “doing what I liked best, caring for sick people” (autobiography, p. 153).

Before joining the staff of the Ontario Cancer Foundation London Clinic at the Victoria Hospital in 1972 as a medical oncologist (which, by that time, was becoming a recognized subspecialty in the United States), Warwick completed a sabbatical period of study in Toronto, at Wellesley Hospital and pmh, to re-hone his clinical skills and to catch up on recent advances.

Warwick retired from practice in 1980. A fellow medical oncologist, and colleague during those years of practice at the London clinic, recently remarked that Harold was “a compassionate physician and an accomplished scientist. I have the fondest memories of this great colleague” (Lohmann R. Personal communication. November 2010).

2.3 Retirement

With his wife, Warwick had an active and rewarding retirement for almost 30 years in London, Ontario. The couple travelled and spent long periods at their lakeside summer cottage. Until shortly before his death, Warwick kept up his annual fishing trips to his beloved Atlantic salmon rivers. His continued golfing resulted in two holes-in-one at ages 76 and 83. He wrote an autobiography for his family (autobiography, p. 1) and a historical novel 18. He received, with his typical humility and grace, two honorary degrees and membership in the Order of Canada. An ongoing reminder of Harold’s contributions to the cancer field is the ncic’s O. Harold Warwick Prize for excellence in clinical research, which is awarded each year to a prominent Canadian cancer researcher.

3. SUMMARY

Medical oncology developed out of the introduction of anticancer drugs in the 1940s. The discipline has become much more than the study and use of anticancer drugs; it includes study of the malignant process and all the physical and psychological aspects of the patient with cancer, so as to understand the interaction of the disease with the person. The objective of care is, by medical means, to prevent, diagnose, cure when possible, prolong useful survival, control symptoms, and palliate. Research and education are key components of medical oncology, as is the concept of multidisciplinary care. The practitioner must have total dedication to the subspecialty, which in itself constitutes a special body of knowledge. The events leading to the approval of medical oncology as a subspecialty in the United States have been reviewed by Bryl J. Kennedy 19, a pioneer medical oncologist in that country. The American Board of Internal Medicine approved the subspecialty in 1972, and the first certifying examination was offered in 1973. In Canada, the first formal two-year training program in medical oncology was instituted by Dr. Daniel E. Bergsagel at the University of Toronto, with the initial trainees entering the program in 1973 (Evans W. Personal communication. October 2010c). The Royal College of Physicians and Surgeons of Canada ratified a Certificate of Special Competence in the subspecialty in 1982, and the first examination was held in 1985 (Van Oosteroom J. Personal communication. February 2010).

Just as with most subspecialties, physicians practised and developed medical oncology before its recognition by a regulatory body. Harold Warwick followed very closely on the heels of the individuals who first used nitrogen mustard and hormones in the United States and Britain. He was one of the early developers of the discipline that he practised for almost a quarter of a century before it became a named and recognized subspecialty. Except for his ten years of academic administration at uwo as dean and vice-president, he devoted himself entirely to the development of oncology in Canada and to the care and study of people with malignancy. He carried out important clinical drug trials that constituted “firsts” in the field; he taught and mentored young oncologists; and he always worked in concert with radiation oncologists and surgeons in the multidisciplinary environment of a cancer centre. He satisfied all the requirements that now describe a practitioner of the subspecialty. Harold Warwick was Canada’s first medical oncologist.

Warwick died, after a brief illness, on October 21, 2009, in his ninety-fifth year.

4. ACKNOWLEDGMENTS

The author thanks Cancer Care Ontario for support; Dr. John C. Laidlaw for reviewing this article and for valuable advice; and Ms. Luanne MacKenzie for formatting and technical assistance. This paper was presented, in a slightly expanded form, to the Toronto Medical Historical Club on February 28, 2010.

5. CONFLICT OF INTEREST DISCLOSURES

The author declares that no financial conflicts of interest exist.

6. REFERENCES

1. Einhorn J. Nitrogen mustard: the origin of chemotherapy for cancer. Int J Radiat Oncol Biol Phys 1985;11:1375–8.
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2. Rhodes CP. Nitrogen mustards in the treatment of neoplastic disease; official statement. J Am Med Assoc 1946;131:656–8.

3. Goodman LS, Wintrobe MM, Dameshek W, Goodman MJ, Gilman A, McLennan MT. Use of the methyl-bis-(β-chloroethyl) amine hydrochloride and tris-(β-chloroethyl) amine hydrochloride for Hodgkin’s disease, lymphosarcoma, leukemia, and certain allied and miscellaneous disorders. J Am Med Assoc 1946;132:126–32.

4. Jacobson LO, Spurr CL, Barron ESG, Smith T, Lushbaugh C, Dick GF. Studies on the effect of methyl-bis-(β-chloroethyl) amine hydrochloride on neoplastic diseases and allied disorders of the hemopoietic system. J Am Med Assoc 1946;132:263–71.

5. Wilkinson JF, Fletcher F. Effect of beta chlorethylamine hydrochlorides in leukemia, Hodgkin’s disease and polycythemia rubra vera. Report on 18 cases. Lancet 1947;2:540–5.
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6. Huggins C, Hodges CV. Studies on prostatic cancer. I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res 1941;1:293–7.

7. Haddow A, Watkinson JM, Paterson E, Koller PC. Influence of synthetic oestrogens upon advanced malignant disease. Br Med J 1944;2:393–8.
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8. Boyland E, Clegg JW, Koller PC, Rhoden E, Warwick OH. The effects of chloroethylamines on tumours, with special reference to bronchogenic carcinoma. Br J Cancer 1948;2:17–29.
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9. Kelly AD. The cancer movement in Canada 1930–1950. Toronto, ON: National Cancer Institute of Canada; 1950: 16.

10. Cosbie WG. The Toronto General Hospital 1819–1965: A Chronicle. Toronto, ON: MacMillan of Canada; 1975: 292.

11. Ontario Cancer Treatment and Research Foundation. Annual Report. Toronto, ON: The Foundation; 1955: 9.

12. Ontario Cancer Institute/Princess Margaret Hospital. Annual Report. Toronto, ON: The Foundation; 1958: 5.

13. Warwick OH, Darte JMM, Brown TC, Beer CT, Cutts JH, Noble RL. Some biological effects of vincaleukoblastine, an alkaloid in vinca rosea linn in patients with malignant disease. Cancer Res 1960;20:1032–40.

14. Warwick OH, Alison RE, Darte JM. Clinical experience with vinblastine sulfate. Can Med Assoc J 1961;85:579–83.

15. Hodes ME, Rohn RJ, Bond WH. Effects of a plant alkaloid, vincaleukoblastine, in human beings. J Lab Clin Med 1959;54:826–7.

16. Hertz R, Lipsett MB, Moy RH. Effect of vincaleukoblastine on metastatic choriocarcinoma and related trophoblastic tumors in women. Cancer Res 1960;20:1050–3.

17. Warwick OH, Yendt ER, Olin JS. The clinical features of hypercalcemia associated with malignant disease. Can Med Assoc J 1961;85:719–23.

18. Warwick OH. East of the Merrimack: A Novel. London, ON: self-published; 2004. [isbn 0-9735721-9-1]

19. Kennedy BJ. Medical oncology. Its origin, evolution, current status and future. Cancer 1999;85:1–8.
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Correspondence to: Donald H. Cowan, Cancer Care Ontario, 620 University Avenue, 15th Floor, Toronto, Ontario M5L 2L7., E-mail: Don.Cowan@cancercare.on.ca

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aInformation and dates relating to Warwick’s personal life were obtained from his curriculum vitae (family files), interviews with his daughter (Ms. Victoria Warwick), his oral history (Oral History Archives, Hannah Chair for the History of Medicine, McMaster University, Hamilton, Ontario, interview by Charles C. Roland, January 21, 1988), an autobiography (Recollections of a Happy Life. Self published. May 1999), and many interactions and communications between Harold Warwick and the author dating from the mid-1950s to the summer of 2009. ( Return to Text )

bWarwick was both a lecturer (leukemia and lymphoma) and bedside teacher to the author at medical school and during internship at tgh. He not only taught clinical skills, but as a role model, also excellent doctor–patient communication, gentleness, and equanimity. ( Return to Text )

cDr. Evans entered the program with the second cohort of trainees in 1974. ( Return to Text )


Current Oncology, VOLUME 18, NUMBER 3, 2011








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