Nature, nurture and my experience with smallpox eradication A career influenced by chance events Frank Fenner
MJA 1999; 171: 638-641 Introduction -
Family and education -
Infectious diseases -
Myxomatosis -
The Intensified Smallpox Eradication Programme -
References -
Career outline -
Why smallpox could be eradicated -
Remaining problems with smallpox -
Subsequent eradication programs -
Authors' details
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| Introduction | I believe that nature (one's genes) and nurture (one's upbringing and education) play equal roles in the life of every person, and that chance plays a critical part in the course of that life. I will try to analyse how these three elements contributed to my role in the global eradication of smallpox. | ||||
Family and education | |||||
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My parents were both talented people, born in Victoria of migrant
(predominantly German) parents, and educated at the Melbourne
Teachers College and the University of Melbourne. I was the second of
five children. When I was two years old my father was appointed
Superintendent of Technical Education in South Australia. He had
been educated in geology and biology and pursued research in
physiography that gained him a DSc from the University of Melbourne.
He continued scientific work in his spare time, producing both
university-level and school books on the geography of South
Australia and scientific papers on physiography and australites,
writing science notes each fortnight for a Melbourne magazine,
The Australasian, and producing three books of essays on
scientific topics.
Influenced by my father, I accumulated a good collection of fossils, and wished to study geology. However, he persuaded me that career prospects for geologists were very poor and that medicine offered a great variety of possible careers, including research, which I even then contemplated. As well as being active in university life and sport (hockey and tennis), I became involved with the University of Adelaide - South Australian Museum anthropological expeditions from my second year in university onwards. My MD degree was based on this work and studies on Aboriginal skulls. After graduating in December 1938, I became a resident medical officer at the Royal Adelaide Hospital, where I heard Prime Minister Robert Menzies announce, on 3 September 1939, that Australia was at war with Germany. Most of my fellow residents enlisted. However, for reasons that I cannot recall, I decided to study for a Diploma of Tropical Medicine at the University of Sydney before I enlisted. If this is viewed as a chance event, it certainly had a major effect on my career. The skills that I acquired led to my appointment, in 1942, as pathologist to the 2/2 Australian General Hospital, a 1200-bed hospital near Hughenden in central north Queensland, and in 1943 as a malariologist in Papua New Guinea. A chance consequence of my transfer to this hospital was meeting my future wife. She was a nursing sister who worked as a transfusion expert and was awarded an Associate Royal Red Cross (a military award given to nurses in the armed forces for outstanding services) for her work. Because at Hughenden there was not a great call for transfusions, she worked part-time in my laboratory, helping with malaria diagnosis. She was subsequently a tower of strength in the social aspects of my role as a departmental head and director of the John Curtin School, as well as raising our family and being involved in community work. | |||||
Infectious diseases | |||||
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My experience with malaria, scrub typhus and dengue in Papua New
Guinea awakened an interest in infectious diseases, and led directly
to my first post-war job, at the Walter and Eliza Hall Institute. Its
Director, Macfarlane Burnet, asked me to work on the experimental
epidemiology of infectious ectromelia of mice, the viral cause of
which he had just shown was related to vaccinia, and thus to smallpox
virus. Scientifically, the most important aspect of this work was the
observation, by chance, that non-fatal cases usually had a rash
(thereafter we called the disease mousepox). This led to experiments
on what happened during the incubation period of this disease, and, by
analogy, during the long incubation periods of human diseases such as
smallpox and chickenpox. Burnet also launched me on my career as a
writer of books on scientific matters, a field exploited by very few
experimental scientists, but in which Burnet was a master. We
coauthored the second edition of The production of
antibodies,2 which was later to
become famous for the prediction of immunological tolerance, cited
as the grounds for the award of the 1960 Nobel Prize to Burnet.
After two and a half years at the Hall Institute, Burnet arranged for me to work with the renowned bacteriologist RenŽ Dubos at the Rockefeller Institute for Medical Research in New York. There, I worked on Mycobacterium tuberculosis. In February 1949, Sir Howard Florey offered me the foundation Chair of Microbiology in the John Curtin School of Medical Research (JCSMR), in the newly established Australian National University. In 1950 Canberra was a very small town and, as there were no suitable laboratories there, the university had arranged with Burnet to allow me to work for a few years in the Hall Institute, where I continued with work on mycobacteria, principally on M. ulcerans, which had been discovered in Melbourne a few years earlier.3 Although I was anxious to work again on viruses, I had decided that I had skimmed the cream off mousepox. | |||||
| Myxomatosis |
Early in 1951, myxomatosis spread throughout south-eastern
Australia. As the CSIRO (the Commonwealth Scientific and Industrial
Research Organisation), which was responsible for introducing the
disease for rabbit control, had no virologists on its staff, I decided
to make myxomatosis the main activity of my embryonic department. The
virus concerned was also a poxvirus. Studies on myxomatosis,
especially on changes in its virulence and the resistance of rabbits
to it, were the focus of my research for the next 14 years, and provided
the best natural experiment on the co-evolution of viral virulence
and host resistance available for a disease of vertebrates.
Initially, myxoma virus was extraordinarily virulent, killing over 99% of naturally infected rabbits. I was anxious to study the genetics of virulence of this poxvirus. However, myxoma virus was difficult to work with in the laboratory, so I screened strains of Orthopoxvirus, the genus to which smallpox virus belongs, and selected a variant of vaccinia virus called rabbitpox virus. Rabbitpox virus yielded many white-pock mutants, which I used to demonstrate molecular recombination. By 1962 sufficient data on myxomatosis had accumulated for me to collaborate with CSIRO zoologist Francis Ratcliffe on the book Myxomatosis.4 Another chance event associated with books occurred about this time, again with Burnet. In 1955 he had written The principles of animal virology,5 a second edition of which was published in 1960. In 1964 the publishers approached him for a third edition; he suggested that they approach me. Looking over The principles of animal virology, I decided that I could not write a third edition of Burnet's book, and offered instead to write another book on much the same topic, entitled The biology of animal viruses.6 Publication of this book (in 1968) influenced my subsequent career. To produce it required giving up full-time laboratory work. The year I finished writing this tome (1967), the then Dean of JCSMR resigned. I was faced with a choice of essentially starting benchwork again, to all intents and purposes as a "PhD student", or seeking the directorship of JCSMR. I chose the latter, and was appointed in September 1967. | ||||
The Intensified Smallpox Eradication Programme | |||||
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The same year was notable for the launch of the Intensified Smallpox
Eradication Programme. In 1968 the Chief of the Smallpox Eradication
Unit of the World Health Organization (WHO), D A Henderson, invited me
to join an international group of virologists with expertise in
poxviruses, to discuss the possibility that monkeys with monkeypox
virus (discovered a few years earlier in a monkey colony in
Copenhagen) might constitute an animal reservoir of smallpox virus.
We met in Moscow in March 1969, commencing an association with the
Intensified Smallpox Eradication Programme that has continued to
this day. I attended meetings of this committee every second year,
initially as rapporteur and then as chairman. My main scientific
contribution was to use my experience with white-pock mutants of
rabbitpox virus to dispose of the hypothesis that smallpox virus was a
white-pock mutant of monkeypox virus.
During this period my term as Director of the JCSMR came to an end and I became Director of the Centre for Resource and Environmental Studies. I resigned from most committees concerned with medicine and took on new responsibilities in the environment field, but maintained contact with the Intensified Smallpox Eradication Programme. Apart from a visionary suggestion by Edward Jenner in 1801, the first proposal to eradicate smallpox had been made in 1953 by the first Director-General of WHO, Dr Brock Chisholm, but the World Health Assembly dismissed his proposal as unrealistic. Smallpox was again considered by the Assembly in 1958, when the Soviet Union put forward a carefully planned proposal for eradication, which was endorsed by the Assembly. The Russian suggestion was that global eradication could be achieved in 4 to 5 years by vaccinating and revaccinating up to 80% of the population of every endemic country, to produce a level of herd immunity sufficient to break the chains of transmission. By 1966 it was clear that progress along these lines, while successful in several small countries, would never achieve global eradication, and the Assembly adopted, by a narrow margin, a resolution which included acceptance of the need for central coordination of national programs and WHO finance from its regular budget. The Intensified Smallpox Eradication Programme was launched in 1967, to be coordinated by a Smallpox Eradication Unit at WHO Headquarters in Geneva and with the goal of global eradication within 10 years. This effort was led by D A Henderson and Isao Arita (Assistant Chief and, from 1976 to 1982, Chief of the Smallpox Eradication Unit). Success was achieved in October 1977, just a few months after the target date. In 1967 smallpox was endemic in 31 countries and imported cases had been reported in another 11 countries; there were probably 15 to 20 million cases of smallpox annually, with some two million deaths. The first problem facing the Smallpox Eradication Unit was to ensure that all vaccine used in the field was of acceptable potency. WHO Reference Centres for Smallpox Vaccine were established in Toronto, Canada, and Bilthoven, The Netherlands, an international meeting of vaccine producers was held, and training courses established. Regular quality control testing by the centres was applied to vaccine donated through WHO, donated under bilateral aid programs, and produced in the endemic countries themselves. By 1970 these measures had ensured that most of the vaccine used in the program reached WHO standards for potency, heat stability and bacterial content. The other major change in strategy was the elevation of surveillance and containment to a pre-eminent place. Discovery of a case was followed by containment by vaccination of all contacts, and then for all persons, in ever-increasing distances from the affected household. Associated with containment, an attempt was made to discover the source of the index case and follow this up with vaccination in that village. By systematically applying these strategies, and by dint of a great deal of hard work and some good luck, smallpox was progressively eliminated from each of the countries in which it had been endemic in 1967. Concurrently with the elimination of smallpox from countries, groups of countries or continents, a system of "certification" of eradication by teams of independent international experts was developed. I served as a member of some of these teams and in 1977 was asked to chair a Global Commission for the Certification of Smallpox Eradication. I became more fully involved with the certification program, and, as well as serving on the International Commissions for India and Malawi, carried out inspections in China, South Africa and Namibia, countries then not members of WHO. On the afternoon of Sunday, 9 December 1979, after four days of intensive discussion and argument, all members of the Global Commission accepted its final report.7 This proclaimed that the world had been freed of smallpox. The report also made 19 recommendations on vaccination, vaccine stocks, stocks of smallpox virus, monkeypox, publications and the like. On 8 May 1980, I presented this report to the World Health Assembly; it was accepted with acclamation. My association with the smallpox eradication program did not end there, for I was appointed chairman of the Committee on Orthopoxvirus Infections, which monitored the implementation of the recommendations and has continued to meet periodically as an ad hoc committee until this year. More demanding was my involvement with fulfilling the recommendation that a book about the program should be produced. Influenced by my father's example and my parents' genes, I had by this time published several scientific books, so I looked forward to this prospect. I had now (1980) formally retired and applied myself full-time to this task, assisted by the three former heads of the Smallpox Eradication Unit. Eight years later, in January 1988, a massive book of almost 1500 pages, Smallpox and its eradication,8 was launched at a meeting of the Executive Board of WHO. Later that year three of the authors, Henderson, Arita and I, shared the Japan Prize, given that year for preventive medicine. | |||||
| References |
Box 1: Career outline -- Frank Fenner | ||||
Authors' details | |||||
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John Curtin School of Medical Research, Australian National
University, Canberra, ACT.
Frank Fenner, MB BS, MD, Visiting Fellow. Reprints will not be available from the author. Correspondence: Professor F Fenner, John Curtin School of Medical Research, GPO Box 334, Canberra, ACT 2601. fennerATjcsmr.anu.edu.au ©MJA 1999
Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company. Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/> © 1999 Medical Journal of Australia. We appreciate your comments. | |||||
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| Jenner vaccinating a child, reprinted with permission from The illustrated history of medicine, by Jean-Charles Sournia. Published by Harold Stark. The observation of Jenner that led to the use of cowpox in vaccination for smallpox has been ranked among medicine's 10 greatest discoveries.1 | |||||
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| Illustration: The smallpox recognition card was widely used from 1971 onwards by field workers looking for cases of smallpox. This card was used in the Indian subcontinent; similar cards using local cases were used in Ethiopia and other African countries. | |||||
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