Editing Macfarlane Burnet (section)

==Walter and Eliza Hall Institute==

===Virology and medicine===
When Burnet returned to Australia, he went back to the Walter and Eliza Hall Institute, where he was appointed assistant director by Kellaway.{{sfnp|Sexton|1999|p=66−67}} His first assignment was to investigate the [[Bundaberg tragedy]], in which 12 children had died after receiving a contaminated [[diphtheria]] vaccine.<ref name=b104/> Kellaway was put in charge of a [[royal commission]] to investigate the matter and he put Burnet in charge of the laboratory investigations.{{sfnp|Sexton|1999|p=65}} 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.{{sfnp|Sexton|1999|p=65}} 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.{{sfnp|Sexton|1999|p=66−67}}<ref>''Biographical Memoirs'', pp. 116–117.</ref> 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.<ref name=b109>''Biographical Memoirs'', p. 109.</ref><ref>{{cite journal |doi=10.1038/icb.1929.26 |author1=Burnet, F. M. |author2=McKie, M. |year=1929 |title=Observations on a permanently lysogenic strain of B. enteritidis Gaertner |journal=Australian Journal of Experimental Biology and Medical Science |volume=6 |issue=4 |pages=277–284}}</ref> 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 1969 [[Nobel Prize in Physiology or Medicine]].<ref>{{cite web |url=http://nobelprize.org/medicine/laureates/1960/burnet-bio.html |title=Sir Frank Macfarlane Burnet – biography |year=1960 |access-date=5 October 2010 |publisher=Nobel Foundation |archive-url=https://web.archive.org/web/20080907022726/http://nobelprize.org/medicine/laureates/1960/burnet-bio.html |archive-date=7 September 2008 |url-status=dead  }}</ref>
[[File:Coxiella burnetii 01.JPG|thumb|''[[Coxiella burnetii]]'', the causative agent of [[Q fever]], was named after Burnet.{{sfnp|Sexton|1999|p=95}}]]

Between 1932 and 1933, Burnet took leave of absence to undertake a fellowship at the [[National Institute for Medical Research]] in London.<ref name=b105/> 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 Hallett Dale|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.<ref name=b104/>{{sfnp|Sexton|1999|p=71}}

Significant breakthroughs in virology were made while he was there, including the isolation and first demonstration of the transmission of the [[influenza]] virus. His own research was on the [[canarypox virus]],<ref name=b105>''Biographical Memoirs'', p. 105.</ref> which he used in developing a chick embryo assay for the isolation and quantification of animal viruses. Dale offered Burnet a permanent position but he declined and returned to the Hall Institute. Following his productive work in London, the Rockefeller Institute agreed to fund a new virus research laboratory in Melbourne for Burnet. He brought back a set of viruses from the National Institute to begin the basis of research in Melbourne.{{sfnp|Sexton|1999|pp=77–78}}

When Burnet returned to Australia, he continued his work on virology, including the [[epidemiology]] of [[herpes simplex]]. He was also involved in two projects that were not viral, the characterisation of the causative agents of [[psittacosis]] and [[Q fever]].<ref name=b105/> After finding that parrots and cockatoos were infected with psittacosis and were responsible for transmission, he lobbied the government for a ban in order to prevent human infection, but he was rebuffed and later came to agree with the government position that there was not much danger.{{sfnp|Sexton|1999|pp=79–80}} During the time he worked on Q fever with Australian scientist [[Edward Holbrook Derrick|E.H. Derrick]], the causative organism of which was named ''[[Coxiella burnetii]]'' in Burnet's honour, he became the first person to acquire the disease in the laboratory.{{sfnp|Sexton|1999|p=95}} His epidemiological studies of herpes and Q fever displayed an appreciation of the ecology of infectious disease that became a characteristic of his scientific method.{{sfnp|Sexton|1999|p=96}}

[[File:Burnet in the lab.jpg|left|thumb|Burnet working in the laboratory in 1945]]

During World War II, Burnet's research moved to [[influenza]]<ref name=b105/> and [[scrub typhus]].{{sfnp|Sexton|1999|p=101}} 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.{{sfnp|Sexton|1999|p=97}} 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.{{sfnp|Sexton|1999|p=97}} 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.{{sfnp|Sexton|1999|pp=97–101}} In 1942, the investigations into scrub typhus accelerated after an exodus of researchers in that field from [[British Malaya|Malaya]] after the [[Imperial Japan|Japanese]] conquest of the area.{{sfnp|Sexton|1999|p=101}} However, this ended in tragedy when his collaborator [[Dora Lush]] accidentally injected herself and then died of the infection.{{sfnp|Sexton|1999|p=102}} Nevertheless, his work on immunisation had earned him international recognition by this time.{{sfnp|Sexton|1999|p=102}}

Burnet's first book, ''Biological Aspects of Infectious Disease'', was published in 1940.<ref name=b105/> It had wide influence and was translated into several languages.{{sfnp|Sexton|1999|p=81}} In 1942 he was made a Fellow of the Royal Society,<ref name="frs"/> and in 1944 he travelled to [[Harvard University]] to deliver the Dunham Lectures. There he was offered a chair, but he refused and returned to Australia.<ref name=b106>''Biographical Memoirs'', p. 106.</ref> This was attributed to his nationalistic tendencies, as well as his sense of loyalty to the Hall Institute.{{sfnp|Sexton|1999|p=108}} During his trip he also visited the US military facility at [[Fort Bragg (North Carolina)|Fort Bragg]], where he discussed his work on influenza with the scientists working there.{{sfnp|Sexton|1999|pp=109–110}}

In 1944, he was appointed director of the Institute when Kellaway was appointed director of the [[Wellcome Trust|Wellcome Foundation]].<ref name=b106/> Although Kellaway had groomed Burnet to become a pivotal figure, he was hesitant as to whether Burnet would be at his most effective with a strategic leadership role. Kellaway thought that Burnet might not be suited to the post, and should have continued to focus purely on research for the time being. Burnet had similar doubts, particularly given his taciturn nature, but applied for the position anyway.{{sfnp|Sexton|1999|pp=113–114}} Although he was not known for his social skills, his ability as a scientist and to impart ideas for investigation to his subordinates held his leadership and the Institute in good stead.{{sfnp|Sexton|1999|pp=116–117}} Unlike his predecessor, who valued a broad gamut of research activities, Burnet was of the opinion that the Institute could not make a significant impact at global level in this way, and he pursued a policy of focusing all effort into one area at a time.{{sfnp|Sexton|1999|pp=117–118}} Always a strong-willed and rather isolated man, he became more single-minded and less tolerant of criticism of his work and expected a more hierarchical structure and unquestioning obedience.{{sfnp|Sexton|1999|p=118}} According to biographer Sexton, he "displayed a kind of territorial protectiveness in relation to his own work".{{sfnp|Sexton|1999|p=121}}

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.{{sfnp|Sexton|1999|pp=129–130}} 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.{{sfnp|Sexton|1999|p=131}} 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.{{sfnp|Sexton|1999|p=132}}

In 1946, he initiated the Clinical Research Unit to allow for closer cooperation with the clinical activities of the now named [[Royal Melbourne Hospital#History|Royal Melbourne Hospital]].{{sfnp|Sexton|1999|p=115}} Despite his known derisive views of clinical science as being inferior, he supported the work enthusiastically.{{sfnp|Sexton|1999|p=116}}

[[File:CSIRO ScienceImage 2005 Peter Colman and Frank Macfarlane Burnet.jpg|right|thumb|[[Peter Colman]], Officer of the [[Commonwealth Scientific and Industrial Research Organisation|CSIRO]] at the Division of Protein Chemistry, showing his flu protein (neuraminidase) model to Frank Macfarlane Burnet]]

Under Burnet's direction, scientists at the Institute made significant contributions to infectious disease research during a period that has been called the "golden age of virology".<ref name="Goding">{{cite web |author=Goding, Jim |year=1999 |url=http://www.immunology.org.au/burnet.html |title=Sir Frank Macfarlane Burnet |publisher=Australasian Society for Immunology |access-date=30 September 2010 |url-status=dead |archive-url=https://web.archive.org/web/20110218024516/http://www.immunology.org.au/burnet.html |archive-date=18 February 2011 }}</ref> Virologists including [[Alick Isaacs]], [[Gordon Ada]], [[John Cairns (biochemist)|John Cairns]], [[Stephen Fazekas de St. Groth]], and [[Frank Fenner]] made significant contributions on [[Murray Valley encephalitis]], [[myxomatosis]], [[poliomyelitis]], [[Poxviridae|poxviruses]], herpes and influenza.{{sfnp|Sexton|1999|pp=117–125}}

Burnet made significant contributions to influenza research; he developed techniques to grow and study the virus, including [[hemagglutination]] assays. He worked on a live vaccine against influenza, but the vaccine was unsuccessful when tested during World War II.<ref>''Biographical Memoirs'', pp. 126–130.</ref> His interest in the influenza receptor led him to discover the [[neuraminidase]] that is secreted by ''[[Vibrio cholerae]]'', which later provided the foundation for [[Alfred Gottschalk (biochemist)|Alfred Gottschalk's]] significant work on [[glycoprotein]]s and the neuraminidase substrate, [[sialic acid]].<ref>''Biographical Memoirs'', pp. 106, 129–130.</ref> Between 1951 and 1956, Burnet worked on the genetics of influenza. He examined the genetic control of virulence and demonstrated that the virus recombined at high frequency; this observation was not fully appreciated until several years later,<ref name=b106/> when the segmented genome of influenza was demonstrated.<ref name = "Fenner">{{cite journal | author = Fenner F | year = 1987 | title = Frank Macfarlane Burnet | journal = Historical Records of Australian Science | volume = 7 | issue =1 | pages = 39–77 |doi=10.1071/HR9870710039 | pmid=11619659}}</ref><ref name=b106/><ref>{{cite journal |doi=10.1126/science.123.3208.1101 |author=Burnet, F. M. |year=1956 |title=Structure of the influenza virus |journal=Science |volume=123 |issue=3208 |pages=1101–1104 |pmid=13324158|bibcode = 1956Sci...123.1101M }}</ref>

===Immunology===
[[File:Clonal selection.svg|right|thumb|'''Clonal selection''' (1) A [[Pluripotential hemopoietic stem cell|hematopoietic stem cell]] undergoes differentiation and genetic rearrangement to produce (2) immature lymphocytes with many different antigen receptors. Those that bind to (3) antigens from the body's own tissues are destroyed, while the rest mature into (4) inactive lymphocytes. Most of these will never encounter a matching (5) foreign antigen, but those that do are activated and produce (6) many clones of themselves.]]

In 1957, Burnet decided that research at the Institute should focus on immunology.<ref name=b107>''Biographical Memoirs'', p. 107.</ref> Burnet reached the decision unilaterally, leaving many of the research staff disillusioned and feeling the action was arrogant; for Burnet's part he was comfortable with the decision as he thought it to be effective.{{sfnp|Sexton|1999|p=134}} Many virologists left the Institute and settled the [[Australian National University]]'s [[John Curtin School of Medical Research]].<ref name ="Doherty">{{cite journal |doi=10.1046/j.1440-1711.1999.00812.x |author=Doherty, P. C. |year= 1999 |title= Burnet Oration: Living in the Burnet lineage |journal=Immunology and Cell Biology |volume=77 |issue=2 |pages=167–176 |pmid=10234553|s2cid=24300492 |doi-access=free }}</ref> After 1957 all new staff and students at the Institute worked on immunological problems;<ref name=b107/> Burnet was involved in work relating to [[Autoimmunity|autoimmune diseases]] and the [[Graft-versus-host disease|graft-versus-host]] reaction, and increasingly in theoretical studies of immunology, immunological surveillance and cancer.<ref name = "Fenner"/><ref name=b108>''Biographical Memoirs'', p. 108.</ref>

At the time, immunology was becoming more sophisticated, with the increasing role of [[molecular biology]] and [[biochemistry]]. Burnet was suspicious of the direction in which immunology was headed, and the increasing emphasis on technology and more intricate experiments, and colleagues felt that Burnet's conservative attitude was a factor in his decision to turn the Institute's focus to immunology.{{sfnp|Sexton|1999|p=132}}

Burnet began to switch his focus to immunology in the 1940s.<ref>''Biographical Memoirs'', pp. 105–106.</ref> In 1941 he wrote a [[monograph]] called "The Production of Antibodies",<ref name=b117>''Biographical Memoirs'', p. 117.</ref> which was revised and reissued in 1949 with Frank Fenner as a co-author.<ref name=b155>''Biographical Memoirs'', p. 155.</ref> This book is seen as a key publication in immunology—it marks the move from the study of immunology as a chemical endeavour to a biological one. Importantly in this work, he introduced the concept of "self" and "non-self" to immunology. The distinction between self and non-self was an integral part of Burnet's biological outlook, of his interest in the living organism in its totality, its activities, and interactions.<ref name = "Christ">{{cite journal| doi=10.1023/A:1006657124783|author1=Christ, E. |author2=Tauber, A. I. |year=1999 |title= Selfhood, Immunity, and the Biological Imagination: The Thought of Frank Macfarlane Burnet |journal=Biology and Philosophy |volume=15| issue=4 |pages=509–533|s2cid=170258791 }}</ref> Burnet regarded the "self" of the host body as being actively defined during its embryogenesis through complex interactions between immune cells and all the other cells and molecules within an embryo.<ref>{{cite journal|doi=10.1093/jhmas/jrl002|author=Park, Hyung Wook |title=Germs, hosts, and the origin of Frank Macfarlane Burnet's concept of 'self' and 'tolerance', 1936–1949 |journal=Journal of the History of Medicine and Allied Sciences |volume=61 |issue=4 |year=2006 |pages= 492–534|pmid=16769800|s2cid=30800083 |hdl=10356/96965 |hdl-access=free }}</ref>

Using the concept of self, Burnet introduced a hypothesis about the situation where the body failed to make antibodies to its own components ([[autoimmunity]]) and by extension the idea of [[immune tolerance]]. He proposed that
<blockquote>if in embryonic life expendable cells from a genetically distinct race are implanted and established, no antibody response should develop against the foreign cell antigen when the animal takes on independent existence.<ref>{{Cite book |author1=Burnet, F. M. |author2=Fenner, F. |year=1949 |title=The Production of Antibodies |edition=2nd |publisher=Macmillan}}</ref></blockquote>
Burnet was, however, unable to prove this experimentally.<ref>{{cite journal |doi=10.1038/icb.1950.29 |author1=Burnet, F. M. |author2=Stone, J. D. |author3=Edney, M. |year= 1950 |title=The failure of antibody production in the chick embryo |journal=Australian Journal of Experimental Biology and Medical Science |volume=28 |issue=3 |pages=291–297 |pmid=14772171}}</ref> [[Peter Medawar]], [[Rupert E. Billingham]] and [[Leslie Brent]] did find support for Burnet's hypothesis in 1953 when they showed that [[splenocyte]]s 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.<ref>{{cite journal|doi=10.1038/172603a0|author1=Billingham, R. E. |author2=Brent, L. |author3=Medawar, P. B. |year= 1953 |title='Actively Acquired Tolerance' of Foreign Cells |journal=Nature |volume=172|issue=10 |pages=603–606 |pmid=13099277|bibcode = 1953Natur.172..603B |s2cid=4176204 }}</ref> 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,<ref name=b134>''Biographical Memoirs'', p. 134.</ref> thereby allowing the transplantation of solid organs. Burnet and Medawar were able to coordinate their work effectively despite their rather different personalities and physical separation; Burnet was taciturn whereas Medawar was a young and urbane Englishman, but they greatly respected one another.{{sfnp|Sexton|1999|p=137}}

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,<ref>{{cite journal|author=McCullagh, P. |title=Inability of fetal skin to induce allograft tolerance in fetal lambs |journal=Immunology |volume=67|issue=4 |pages=489–495 |year=1989|pmid=2670751|pmc=1385319}}</ref><ref>{{Cite journal |author1=Le Douarin, N. M. |author2=Corbel, C. |author3=Martin, C. |author4=Coltey, M. |author5=Salaun, J. |title=Induction of tolerance by embryonic thymic epithelial grafts in birds and mammals |journal=Cold Spring Harb Symp Quant Biol |volume=54 |pages=777–787 |year=1989 |pmid=2534843 |doi=10.1101/sqb.1989.054.01.091}}</ref> 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,<ref>{{cite journal |author=Lederberg, J. |title=Genes and antibodies |journal=Science |year=1959 |volume=129 |issue=3364 |pages=1649–1653 |pmid=13668512 | doi=10.1126/science.129.3364.1649 |bibcode = 1959Sci...129.1649L |s2cid=7518224 }}</ref> 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:
<blockquote>My part in the discovery of acquired immunological tolerance was a very minor one—it was the formulation of an hypothesis that called for experiment.<ref>{{cite web |author=Burnet, Frank Macfarlane |date=12 November 1960 |url=http://nobelprize.org/nobel_prizes/medicine/laureates/1960/burnet-lecture.pdf |title=Immunological Recognition of Self: Nobel Lecture |access-date=30 September 2010 |publisher=Nobel Foundation |archive-url=https://web.archive.org/web/20101215042633/http://nobelprize.org/nobel_prizes/medicine/laureates/1960/burnet-lecture.pdf |archive-date=15 December 2010 |url-status=dead |df=dmy-all }}</ref></blockquote>

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.<ref>{{Cite journal |author=Pauling, L. |year=1940 |title=A theory of the structure and process of formation of antibodies |journal=Journal of the American Chemical Society |volume=62 |issue=10 |pages=2643–2657 |doi=10.1021/ja01867a018|bibcode=1940JAChS..62.2643P }}</ref> 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.<ref>{{cite book |author=Silverstein, A. M. |year=1989 |title=A History of Immunology |publisher=Academic Press Inc. |isbn=978-0-12-643770-6}}</ref> In 1956 he became interested in [[Niels Kaj Jerne]]'s natural selection hypothesis,<ref>''Biographical Memoirs'', pp. 134–135.</ref> 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.<ref>{{cite journal |author=Burnet, F. M. |year=1957 |title=A modification of Jerne's theory of antibody production using the concept of clonal selection |journal=Australian Journal Science |volume=20 |issue=2 |pages=67–69 }} Reprinted in {{cite journal|pmid=816431 |doi=10.3322/canjclin.26.2.119 | volume=26 |issue=2 | title=A modification of Jerne's theory of antibody production using the concept of clonal selection |year=1976 |author=Burnet FM |journal=CA Cancer J Clin |pages=119–21|s2cid=40609269 |doi-access=free }}</ref> 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.<ref name = "Nossal Nature">{{cite journal |author=Nossal, G. J. V. |year=1985 |title=Sir Frank Macfarlane Burnet (1899–1985) |journal=Nature |volume=317 |issue=6033 |page=108 |pmid=3897872| doi=10.1038/317108b0 |bibcode = 1985Natur.317..108N |s2cid=4234456 |doi-access=free }}</ref>

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.<ref>{{cite journal |doi=10.1038/1811419a0 |author1=Nossal, G. J. V. |author2=Lederberg, J. |year=1958 |title=Antibody production by single cells |journal=Nature |volume=181 |issue=4620 |pages=1419–1420 |pmid=13552693|pmc=2082245 |bibcode = 1958Natur.181.1419N }}</ref> 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.<ref>{{cite book |author=Nossal, G. J. V. |year=1995 |chapter=One Cell – One Antibody |title=Immunology: The making of a modern science |url=https://archive.org/details/immunologymaking00rbga |url-access=limited |editor1=Gallagher, R. B. |editor2=Gilder, J. |editor3=Nossal, G. J. V. |editor4=Salvatore, G. |publisher=Academic Press |pages=[https://archive.org/details/immunologymaking00rbga/page/n47 39]–47}}</ref> 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,<ref name=b135/> writing that he and Jerne should have received the Nobel for this work.{{sfnp|Sexton|1999|pp=139–140}} 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.

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.<ref name = "Fenner"/><ref>{{cite journal |doi=10.1146/annurev.me.08.020157.001323 |pmid=13425332 |author=Talmage, D. W. |year=1957 |title=Allergy and immunology |journal=Annual Review of Medicine |volume=8 |issue=1 |pages=239–256}}</ref><ref>{{cite journal |author=Forsdyke, D. R. |year=1995 |url=http://post.queensu.ca/~forsdyke/theorimm0.htm#Introduction |title=The Origins of the Clonal Selection Theory of Immunity |journal=FASEB J. |volume=9 |issue=2 |pages=164–166 |pmid=7781918 |access-date=30 September 2010 |doi=10.1096/fasebj.9.2.7781918 |doi-access=free |s2cid=38467403 |archive-date=30 July 2012 |archive-url=https://web.archive.org/web/20120730120916/http://post.queensu.ca/~forsdyke/theorimm0.htm#Introduction |url-status=live |url-access=subscription }}</ref> In his paper Burnet cited Talmage's review,<ref name=b135>''Biographical Memoirs'', p. 135.</ref> and in a later interview, Talmage said he believed that Burnet "truthfully had developed the idea before he received my paper".<ref>{{cite journal |author1=Cruse, J. M. |author2=Lewis, R. E. |year= 1994 |title=David W. Talmage and the advent of the cell selection theory of antibody synthesis |journal=Journal of Immunology |volume=153 |issue=3 |pages=919–924 |doi=10.4049/jimmunol.153.3.919 |pmid=8027564|s2cid=32756505 |doi-access=free }}</ref> The theory is now sometimes known as Burnet's clonal selection theory,{{sfnp|Sexton|1999|pp=137–139}} which overlooks the contributions of Ehrlich, Jerne, Talmage, and the contributions of Lederberg, who conceptualised the genetics of clonal selection.{{sfnp|Sexton|1999|pp=134–141}}

Burnet's work on graft-versus-host was in collaboration with Lone Simonsen between 1960 and 1962. Simonsen had shown in 1957 that when a chick embryo was inoculated intravenously with adult-fowl blood, a graft-versus-host reaction occurred; this was known as the Simonsen phenomenon.<ref name=b136>''Biographical Memoirs'', p. 136.</ref> Their work in this system would later help to explain [[passenger leukocyte]]s in transplantation.<ref name=b136/> The last project he worked on at the Institute was a study with assistant Margaret Holmes of autoimmune disease in the New Zealand black mouse model; this mouse has a high incidence of spontaneous autoimmune [[hemolytic anemia]].<ref name=b137>''Biographical Memoirs'', p. 137.</ref> They looked at the inheritance of autoimmune disease, and their use of immunosuppressive drug [[cyclophosphamide]] to treat the disease influenced the use of immunosuppressive drugs in human autoimmune disease.<ref>{{cite journal |author1=Russell, P. J. |author2=Hicks, J. D. |author3=Burnet, F. M. |year=1966 |title=Cyclophosphamide treatment of kidney disease in (NZB x NZW) F1 mice |journal=Lancet |volume=1 |issue=7450 |pages=1279–1284 |pmid=4160875 |doi=10.1016/s0140-6736(66)91198-6}}</ref>

[[File:Frank Macfarlane Burnet 1960.jpg|thumb|left|upright|Frank Macfarlane Burnet in Stockholm in 1960]]
In 1960, Burnet scaled back his laboratory work, taking one day off per week to concentrate on writing.{{sfnp|Sexton|1999|p=154}} In 1963, ''Autoimmune Diseases: Pathogenesis, Chemistry and Therapy'', which he authored with [[Ian Reay Mackay|Ian Mackay]], was published.{{sfnp|Sexton|1999|p=155}} He also oversaw an expansion of the Hall Institute and secured funding from the [[Nuffield Foundation]] and the state government to build two further floors in the building and take over some of the space taken up by the pathology department at the Royal Melbourne Hospital.{{sfnp|Sexton|1999|p=154}} Despite this, Burnet believed that a world class research body needed to be small enough that one person could effectively run it, and maintained tight control over its activities throughout his leadership. He determined the policies himself, and personally selected all of the research staff and students, relying on a small staff to enforce his plans.<ref>''Biographical Memoirs'', pp. 110–111.</ref>

He continued to be active in the laboratory until his retirement in 1965, although his experimental time began to decrease as the operations became increasingly focused on immunology; Burnet's work in this area had been mostly theoretical.{{sfnp|Sexton|1999|p=155}} Gustav Nossal became the next director of the Walter and Eliza Hall Institute.<ref name=b108/> Under Burnet's leadership the Institute had become "probably the world's best known research centre devoted to the study of immunology."<ref>{{cite journal |doi=10.1086/418433 |author=Marchalonis, J. J. |year=1994 |title=Burnet and Nossal: the impact on immunology of the Walter and Eliza Hall Institute |journal=The Quarterly Review of Biology |volume=69 |issue=1 |pages=53–67 |pmid=8208917|s2cid=20830422 }}</ref> However, with the increasing sophistication in medical science and its reliance on more complicated technology, Burnet's lone-wolf approach became less compatible with the research environment, which required more collaboration. In his final years at the helm, Burnet allowed more technical modernisation during the transition period to Nossal's leadership.{{sfnp|Sexton|1999|pp=132–133}}