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Macfarlane Burnet
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===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>
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