Frank Macfarlane Burnet

Burnet was born in Traralgon, Victoria; his father, Frank Burnet, a Scottish emigrant to Australia, was the manager of the Traralgon branch of the Colonial Bank. His mother Hadassah Burnet (née Mackay) was the daughter of a middle-class Scottish immigrant, and met his father when Frank was working in the town of Koroit. Frank was 36, and 14 years older than Hadassah when they married in 1893. The family was socially conservative Anglo-Saxon Protestant. Frank Macfarlane Burnet was the second of seven children and from childhood was known as "Mac". He had an older sister, two younger sisters and three younger brothers. The eldest daughter Doris had a mental disability that consumed most of Hadassah's time and the family saw Doris's condition as an unspoken stigma, discouraging the other children from inviting friends home, lest they come across the eldest daughter. From his early years in Traralgon, Mac enjoyed exploring the environment around him, particularly Traralgon Creek. He first attended a private school run by a single Teacher before starting at the government primary school at the age of 7. Mac was distant from his father—who liked to spend his free time fishing and playing golf—from a young age. He preferred bookish pursuits from a young age and was not enamoured of sport, and by the age of eight was old enough to analyse his father's character; Mac disapproved of Frank and saw him as a hypocrite who espoused moral principles and put on a facade of uprightedness, while associating with businessmen of dubious ethics. Hadassah was preoccupied with Doris, so Mac developed a rather solitary personality.

The Burnets moved to Terang in 1909, when Frank was posted to be the bank manager there, having declined a post in London. Burnet was interested in the wildlife around the nearby lake; he joined the Scouts in 1910 and enjoyed all outdoor activities. While living in Terang, he began to collect beetles and study biology. He read biology articles in the Chambers's Encyclopaedia, which introduced him to the work of Charles Darwin. During his early teens, the family took annual holidays to Port Fairy, where Burnet spent his time observing and recording the behaviour of the wildlife. He was educated at Terang State School and attended Sunday school at the local church, where the priest encouraged him to pursue scholastic studies and awarded him a book on ants as a reward for his academic performance. He advised Frank to invest in Mac's education and he won a full scholarship to board and study at Geelong College, one of Victoria's most exclusive private schools. Starting there in 1913, Burnet was the only boarder with a full scholarship. He did not enjoy his time there among the scions of the ruling upper class; while most of his peers were brash and sports-oriented, Burnet was bookish and not athletically inclined, and found his fellow students to be arrogant and boorish. During this period he kept his beetle-collecting and disapproval of his peers a secret and mixed with his schoolmates out of necessity. Nevertheless, his academic prowess gained him privileges, and he graduated in 1916, placing first in his school overall, and in history, English, chemistry and physics. The typical university path for a person of his social background was to pursue studies in theology, law or Medicine. By this time, he was becoming disillusioned with religion and chose Medicine. Due to World War I, military Service was a possibility and he felt that a medical background would increase his chances of being given a non-combat post.

From 1918, Burnet attended the University of Melbourne, where he lived in Ormond College on a residential scholarship. There, he read more of Darwin's work and was influenced by the ideas of science and society in the writings of H. G. Wells. He enjoyed his time at university and spent much of his free time reading biology books in the library to feed his passion for scientific knowledge. He also had fleeting sporting success, holding down a position in Ormond's First VIII rowing squad for a brief period. He continued to pursue his study of beetles in private, although his classmates found out and there was no loss in this as they viewed his hobby positively. Despite an ongoing shyness, Burnet got on well with staff and students at university. Burnet was self-motivated and often skipped lectures to study at his own faster pace and pursue further knowledge in the library, and he came equal first in physics and chemistry in first year. The following year, 1918, he became increasingly immersed in laboratory work, but he was also dogged by peer pressure to enlist in the military, which he saw as a distasteful prospect. However, this was averted by the end of the war. In 1919, he was one of 12 high-performing students selected for extra tuition, and he came equal first in third year physiology. He began clinical work in the same year, but found it somewhat unpleasant as he was interested in diagnosing the patient and had little interest in showing empathy towards them.

While at university, he became an agnostic and later an aggressive atheist; he was sceptical of religious faith, which he regarded as "an effort to believe what Common sense tells you isn't true." He was also disgusted by what he regarded as hypocritical conduct by religious adherents. Towards the later years of his undergraduate years, his unhappiness with religion began to dog him to a greater extent. He tried to become involved with communism for brief period but then resolved to devote himself to scientific research. The length of time required to study Medicine had been reduced to five years to train doctors faster following the outbreak of World War I, and Burnet graduated with a Bachelor of Medicine and a Bachelor of Surgery in 1922, ranking second in the final exams despite the death of his father a few weeks earlier. His fellow graduates included Ian Wark, Kate Campbell, Jean Macnamara, Rupert Willis and Roy Cameron, who became distinguished Scientists in their own right.

While in London, Burnet became engaged to fellow Australian Edith Linda Marston Druce. She was a secondary school Teacher and daughter of a barrister's clerk and the pair had met in 1923 and had a few dates but did not keep in touch. Druce sought out Burnet while on a holiday in London and they quickly agreed to marriage although she had to return to Australia. They married in 1928 after he had completed his Ph.D. and returned to Australia, and had a son and two daughters. At the time, there was a vacancy for the Chair of Bacteriology at the University of London, and Ledingham was lobbying his colleagues to offer Burnet the post, but Burnet returned to Australia, partly because of Druce.

When Burnet returned to Australia, he went back to the Walter and Eliza Hall Institute, where he was appointed assistant Director by Kellaway. His first assignment was to investigate the "Bundaberg disaster", in which 12 children had died after receiving a contaminated diphtheria vaccine. Kellaway was put in charge of a royal commission to investigate the matter and he put Burnet in charge of the laboratory investigations. He identified Staphylococcus aureus in the toxin-antitoxin mixture that had been administered to the children; it had been picked up from the skin of one of the children and then transmitted to the others in the injections. However, it turned out to be another toxin that had caused the children's deaths; this work on staphylococcal toxin piqued his interest in immunology. During this time, he continued to study bacteriophages, writing 32 papers on phages between 1924 and 1937. In 1929, Burnet and his graduate assistant Margot McKie wrote a paper suggesting that bacteriophages could exist as a stable non-infectious form that multiplies with the bacterial host. Their pioneering description of lysogeny was not accepted until much later, and was crucial to the work of Max Delbrück, Alfred Hershey and Salvador Luria on the replication mechanism and genetics of viruses, for which they were awarded the 1960 Nobel Prize in Physiology or Medicine.

At the time, the Hall Institute was in the early stages of rapid expansion. The new Director of the Institute, Charles Kellaway, wanted to increase the activities of the organisation to not only support hospital operations but have separate research groups in physiology, microbiology and biochemistry that would also do independent studies. He also hoped to raise the standards to make the Institute comparable to the world-class operations in Europe and America. Kellaway took a liking to Burnet and saw him as the best young talent in the Institute with the ability to help raise it to world leading standards. However, he thought that Burnet would need experience working in a laboratory in England before he could lead his own research group on bacteriology in Australia. Burnet left Australia for England in 1925 and served as ship's surgeon during his journey in exchange for a free fare. On arrival, he took a paid position assisting the curator of the National Collection of Type Cultures at the Lister Institute in London. Burnet prepared or maintained bacteria cultures for other researchers in the morning and was free to do his own experiments in the afternoon. During the latter half of 1926, he experimented to see if Salmonella typhimurium was affected by bacteriophage.

He was awarded the Beit Memorial Fellowship by the Lister Institute in 1926; this gave him enough money for him to resign his curator position and he began full-time research on bacteriophages. He injected mice with bacteriophage and observed their immunological reactions and believed bacteriophages to be viruses. For this work he received a Ph.D. from the University of London in 1928 under the direction of Professor J. D. Ledingham and was invited to write a chapter on bacteriophages for the Medical Research Council's System of Bacteriology. He was also given an invitation to deliver a paper at the Royal Society of Medicine in 1927 on the link between O-agglutinins and bacteriophage. Burnet began attending the Fabian Society functions and befriended some communists, although he refrained from joining them in overt left-wing activism. He also spent his free time enjoying theatre, engaging in amateur archaeology and cycling through continental Europe.

Between 1932 and 1933, Burnet took leave of absence to undertake a fellowship at the National Institute for Medical Research in London. The Great Depression had resulted in Burnet's salary being cut from 1000 to 750 pounds, and the National Institute had been given a large grant from the Rockefeller Foundation that allowed them to hire Burnet at 1000 pounds per annum. The National Institute's Director Sir Henry Dale gained permission from Kellaway for the two-year move; Kellaway promised to hold Burnet's job for him when he returned and felt that the experience would make Burnet—whom he saw as the Hall Institute's brightest young scientist—better equipped to expand operations when he returned to Melbourne. Dale also paid for Burnet's sister to travel to England to help look after her brother's young children.

From 1937 Burnet was involved in a variety of scientific and public policy bodies, starting with a position on a government advisory council on polio. After he became the Director of the Walter and Eliza Hall Institute in 1944, he was considered a public figure and overcame shyness to become a good public speaker. He recognised the importance of co-operation with the media if the general public was to understand science and Scientists, and his writings and lectures played an important part in the formulation of public attitudes and policy in Australia on a variety of biological topics. However, despite making many appearances on radio and television, he never became at ease with interviews and had to be selective with outreach engagements due to the many invitations he received, and tended to accept those that had the potential to promote the Institute. Over time, he began to increase his activism, as he felt more confident that he would be able to make an impact as his reputation grew, especially after winning the Nobel Prize, and even more so after his retirement from the directorship of the Institute. Although Burnet was not naturally outgoing, he saw it as the social responsibility of a scientific leader and scholar to publicly speak out and impart wisdom and foresight to the wider community.

During World War II, Burnet's research moved to influenza and scrub typhus. With the outbreak of war, Burnet was handed more responsibility and made acting Director and had to oversee the move into a new building as Kellaway was seconded to the military in 1939. Due to Kellaway, many of the infectious disease problems afflicting the military were referred to the institute. Fearing a repeat of the massive global influenza outbreak that occurred after World War I, Burnet focused the institute in the search for a vaccine. He first tested the vaccine on a group of medical students, and after a promising test on 107 army volunteers in February 1942 following a rise in infections, a large-scale program was introduced two months later to inoculate all new recruits after an influenza A outbreak. In this trial, 20,000 personnel were vaccinated, without success, and the scheme was abandoned. In 1942, the investigations into scrub typhus accelerated after an exodus of researchers in that field from Malaya after the Japanese conquest of the area. However, this ended in tragedy when his collaborator Dora Lush accidentally injected herself and then died of the infection. Nevertheless, his work on immunisation had earned him international recognition by this time.

Burnet was interested in how the body produces antibodies in response to antigens. The dominant idea in the literature through the 1940s was that the antigen acted as a template for antibody production, which was known as the "instructive" hypothesis. Burnet was not satisfied with this explanation, and in the second edition of "The Production of Antibodies", he and Fenner advanced an indirect template theory which proposed that each antigen could influence the genome, thus effecting the production of antibodies. In 1956 he became interested in Niels Kaj Jerne's natural selection hypothesis, which described a mechanism for immune response based on an earlier theory of Nobel-winning immunologist Paul Ehrlich. Jerne proposed that the antigen bound to an antibody by chance and, that upon binding, more antibodies to that antigen would be produced. Burnet developed a model which he named clonal selection that expanded on and improved Jerne's hypothesis. Burnet proposed that each lymphocyte bears on its surface specific immunoglobulins reflecting the specificity of the antibody that will later be synthesised once the cell is activated by an antigen. The antigen serves as a selective stimulus, causing preferential proliferation and differentiation of the clones that have receptors for that antigen.

In 1944, it was decided by the University of Melbourne that Burnet would be appointed a professor as part of a cooperative program so that university students could be experimentally trained at the institute, while the researchers engaged in some teaching. This was not a success, and there was much tension, as Burnet repeatedly expressed his opinion in public that university teaching and research should be kept separate, at one point leading to a series of open letters from university professors decrying his attitude. Burnet was also not interested in the politics of university funding, and his disengagement from administrative matters engendered resentment. On the other hand, Burnet was vigorous in obtaining funding for the Hall Institute from government bodies, resorting to the bluff of feigning interest in moving overseas to secure continued strong backing. However, he was criticised for being thrifty and refusing to invest in cutting edge equipment, despite the Hall Institute's high standing in research circles. Colleagues believed that he was sceptical of modern Technology and thought his outlook to be limiting.

In 1946, he initiated the Clinical Research Unit to allow for closer cooperation with the clinical activities of the Royal Melbourne Hospital. Despite his known derisive views of clinical science as being inferior, he supported the work enthusiastically.

Burnet served as a member or chairman of scientific committees, both in Australia and overseas. Between 1947 and 1953, he was a member of the National Health and Medical Research Council's Medical Research Advisory Committee. The committee advised on funding for medical research in Australia. During this same period (1947–52), he was also a member of the Commonwealth government's Defence Research and Development Policy Committee. Declassified files from this committee show that Burnet made the recommendation that Australia pursue development of chemical and biological weapons to target neighbouring countries' food stocks and spread infectious diseases. His report was titled War from a Biological Angle. Between 1955 and 1959, he was chairman of the Australian Radiation Advisory Committee; he was concerned that Australians were being exposed to unnecessary medical and industrial radiation.

Burnet received extensive honours for his contributions to science and public life during his lifetime. He was knighted in the 1951 New Year Honours, received the Elizabeth II Coronation Medal in 1953, and was appointed to the Order of Merit (OM) in the 1958 Queen's Birthday Honours. In 1960 he was the first recipient of the honorary Australian of the Year award. He received a Gold and Silver Star from the Japanese Order of the Rising Sun in 1961. He was appointed Knight Commander of the Order of the British Empire (KBE) in the 1969 New Year Honours, and received the Elizabeth II Jubilee Medal in 1977. In 1978 he was made a Knight of the Order of Australia (AK). He was only the fourth person to receive this honour.

Burnet was, however, unable to prove this experimentally. Peter Medawar, Rupert E. Billingham and Leslie Brent did find support for Burnet's hypothesis in 1953 when they showed that splenocytes could be engrafted by intravenous infusion into mice in utero or just after birth and that when these mice matured, they could accept skin and other tissues from the donor but not from any other mouse strain. Burnet and Medawar were co-recipients of the 1960 Nobel Prize in Physiology or Medicine for this work, as it provided the experimental basis for inducing immune tolerance, thereby allowing the transplantation of solid organs. Burnet and Medawar were able to coordinate their work effectively despite the rather different personalities and physical separation; Burnet was taciturn whereas Medawar was a young and urbane Englishman, but they greatly respected one another.

There is some contention over Burnet's publication of his version of the theory in the Australian Journal of Science in 1957. Some commentators argue he published in an Australian journal to fast-track his hypothesis and obtain priority for his theory over ideas that were published later that year in a paper written by David Talmage, which Burnet had read prior to its publication. In his paper Burnet cited Talmage's review, and in a later interview, Talmage said he believed that Burnet "truthfully had developed the idea before he received my paper". The theory is now sometimes known as Burnet's clonal selection theory, which overlooks the contributions of Ehrlich, Jerne, Talmage, and the contributions of Lederberg, who conceptualised the genetics of clonal selection.

In 1958 Gustav Nossal and Lederberg showed that one B cell always produces only one antibody, which was the first evidence for clonal selection theory. Burnet wrote further about the theory in his 1959 book The Clonal Selection Theory of Acquired Immunity. His theory predicted almost all of the key features of the immune system as we understand it today, including autoimmune disease, immune tolerance and somatic hypermutation as a mechanism in antibody production. The clonal selection theory became one of the central concepts of immunology, and Burnet regarded his contributions to the theoretical understanding of the immune system as his greatest contribution to science, writing that he and Jerne should have received the Nobel for this work. Jerne was recognised for his contributions to the conceptualisation of the immune system when he was a co-recipient of the Nobel Prize in 1984.

However, later studies showed that cells or tissues transplanted before the immune system development of the recipient, such as in embryonic recipients, could be treated as foreign and trigger rejection, countering Burnet's explanation for self tolerance. In contrast to the Burnet hypothesis of a special tolerance-inducing period defined by the age of the animal, Joshua Lederberg proposed in 1959, that it is the age of the lymphocyte that defines whether an antigen that is encountered will induce tolerance, with immature lymphocytes being tolerance-sensitive. Lederberg's concept is now known as central tolerance, and is widely accepted. It may also explain the success of some transplants given early in life and the failure to induce tolerance in other studies. Burnet noted that his contributions to immune tolerance were strictly theoretical:

Burnet was opposed to the use of nuclear power in Australia owing to the issues of nuclear proliferation. He later retracted his objections to uranium mining in Australia, feeling that nuclear power was necessary while other renewable Energy sources were being developed. In the late 1960s and 1970s, he was also vocal in the anti-smoking movement; he was one of the first high-profile figures in Australia to educate the public on the dangers of tobacco, and he appeared in a television advertisement criticising the ethics of tobacco advertising, and broadcasters for displaying such material. He and fellow Activists were surprised that the commercial was allowed to run briefly, before being taken off air by the station, which only further generated attention for the anti-smoking campaign. A former smoker, he had rejected the habit in the 1950s after several friends died. Burnet was also a critic of the Vietnam War and called for the creation of an international police force.

Internationally, Burnet was a chairman of the Papua New Guinea Medical Research Advisory Committee between 1962 and 1969. At the time, Papua New Guinea was an Australian territory, and Burnet had first travelled there as his son was posted there. His role on the committee allowed him to explore his interest in human biology. He was particularly interested in kuru (laughing sickness), and lobbied the Australian government to establish the Papua New Guinea Institute of Human Biology. Burnet later helped oversee the institute's contribution to the Anglo-Australian participation in the International Biological Programme in the Field of Human Adaptability.

In 1964, he was appointed to sit on the University Council of Victoria's third university La Trobe on an interim basis until the institution was formed in 1966. He served until 1970. He advocated a less hierarchical relationship between a professor and student, something seen as a move away from the English tradition prevalent in Australia towards and American model. He also called for the downgrading of the importance placed on the liberal arts. His ideas were too radical for his peers and he stepped down from the role in 1970 after none of his suggestions had made an impact.

He became President of the Australian Academy of Science in 1965, having been a foundational fellow when the Academy was formed in 1954. He had been offered the presidency in 1958 to replace the inaugural head Sir Mark Oliphant, but declined, although he served on the council and as vice President in 1961–63. As President he was recognised by both government and the public as the leading scientist in Australia. His stature as a scientist gave him the gravitas to end policy disputes, and gave the Academy and its advocacy more credibility in the eyes of government and industry. As such his term was considered to be highly successful. Oliphant said that Burnet's personal prestige was very important in the increased respect the AAS won and that he "made the biological sciences far more acceptable in Australia".

Burnet spoke and wrote widely on the topic of human biology after his retirement, aiming to reach all strata of society. He courted the media as well as the scientific community, often leading to sensationalist or scientifically unrigorous report of his outspoken views. This often angered colleagues, who viewed him as abusing his stature to deliberately cause a stir. In 1966 Burnet presented the Boyer Lectures, focusing on human biology. He provided a conceptual framework for sustainable development; 21 years later the definition provided by the Brundtland Commission was almost identical. In 1970 he revised an earlier book which was published as Dominant Mammal: the Biology of Human Destiny; it was followed by Endurance of Life, which was published in 1978. The books discuss aspects of human biology, a topic which Burnet wrote on extensively in his later years. In Dominant Mammal he argued that the roots of all human behaviour can be found in the behaviour of animals; in Endurance he addressed issues of ageing, life, death and the Future of mankind. The books strongly polarised the scientific community, and one reviewer described his ideas of sociobiology as "extreme" and giving "a dismal, unappealing view of humanity". In Endurance of Life, he also called for society to accept euthanasia of ill older people, repeat violent Criminals, and most controversially, abortion of pregnancies likely to result in disabled children, and infanticide of handicapped newborns. Knowing that there would be a strong backlash for such policies, he departed overseas for a two-month lecture series at the time of the book launch. In his absence, he was strongly assailed in newspaper letters and some correspondents compared his stance on infanticide to that of Adolf Hitler. At the same time, he also changed his stance on nuclear power and advocated its use, and the reinvestment of revenue for research into solar power. This about face angered the environmental movement.

Following his resignation from the Walter and Eliza Hall Institute, Burnet was offered an office at the University of Melbourne in the School of Microbiology. While at the university, he wrote 13 books on a variety of topics including immunology, ageing and cancer, and human biology. He also wrote an autobiography entitled Changing Patterns: An Atypical Autobiography, which was released in 1968. In all, he wrote a further 16 books after his retirement from the Hall Institute. He was known for his ability to write quickly, often without a final draft, and his ability to convey a message to readers from a wide spectrum of backgrounds, but he was himself sceptical that his opinions had much influence. In 1969 he published Cellular Immunology, considered his magnum opus on immunity, attempted to show how various phenomena could be predicted by the clonal selection theory. The following year, he wrote Immunological Surveillance, which expounded his established opinion that mammals could immunise themselves through their ability to detect foreign patterns in the body. He continued to maintain an intense and focused work schedule, often shunning others to keep up a heavy writing load.

He helped establish the Academy's Science and Industry Forum, which was formed in the second year of his leadership in order to improve dialogue between researchers and industrialists. It investigated whether a national science policy should be formulated and led to the eventual creation of the Australian Science and Technology Council. He also laid the foundations of the Australian Biological Resources Study. When his presidency ended in 1969, the Academy founded the Burnet Lecture and Medal, which is the Academy's highest award for biological sciences.

In 1971–72, he wrote four books, most notably, Genes, Dreams and Realities, which caused great controversy due to its strident attacks on molecular biology, cellular biology, and claims that cancer and various other diseases were incurable and that it was pointless to try to do so. He also predicted that scientific progress would end soon.

His first wife, Edith Linda Druce, died from lymphoid leukaemia in 1973, after a four-year struggle. During her final years, Burnet refused all offers of lectures overseas to spend more time nursing his ailing wife. For a period after this he became very lethargic and reclusive, numbed by his wife's death. He then moved into Ormond College for company, and resumed beetle collecting, but for a year after her death, Burnet tried to alleviate his grief by writing mock letters to her once a week. Gradually he regained his enthusiasm and began writing again. In 1975, he travelled to California to deliver a series of lectures. In 1976 he married Hazel G. Jenkins, a widowed former singer from a Business family in her 70s who was working in the microbiology department as a librarian, and moved out of Ormond College.

In 1978 Burnet decided to officially retire; in retirement he wrote two books. During this time, he missed his laboratory work, and he was constrained to social events and theorising. In 1982, Burnet was one of three contributors to Challenge to Australia, writing about genetic issues and their impact on the nation's impact. As a result of the success of the book, in early 1983, Burnet was appointed to the 70-person Australian Advisory Council of Elders to offer counsel to policymakers, but the group folded after several members became too frail or died.

Burnet continued to travel and speak, but in the early 1980s, he and his wife became increasingly hampered by illness. Having surmised his illness two years earlier, in November 1984 he underwent surgery for colorectal cancer. He made plans to resume scientific meetings, but was then taken ill again, with significant pain in his thorax and legs. Secondary lesions were found in June 1985 and declared to be inoperable and terminal. A supporter of euthanasia, Burnet was unfazed by his imminent death, and he died on 31 August at his son's home at Port Fairy after two months of illness. He was given a state funeral by the government of Australia; many of his distinguished colleagues from the Hall Institute such as Nossal and Fenner were pall-bearers, and he was buried near his paternal grandparents after a private family Service at Tower Hill cemetery, near Port Fairy. Following his death he was honoured by the House of Representatives; Prime Minister Bob Hawke took the highly unusual step of moving a condolence motion, an honour typically reserved for parliamentarians.

After his death, Australia's largest communicable diseases research institute—the Macfarlane Burnet Centre for Medical Research was renamed in his honour. The Burnet Clinical Research Unit of the Walter and Eliza Hall Institute was also named in his honour in 1986. In 1975 his work on immunology was recognised by a 33-cent stamp released by Australia Post. Seven Australian medical Scientists were commemorated in the issue of a set of four Australian stamps released in 1995; he appears on the 45-cent stamp with fellow University of Melbourne graduate Jean Macnamara. He also appears on a Dominican stamp that was issued in 1997. The centenary of his birth was celebrated in Australia in 1999; a statue of him was erected in Franklin Street, Traralgon; and several events were held in his honour including the release of a new edition of his biography by Oxford University Press.