Macfarlane Burnet – Selected Diaries and Notebooks

Frank Macfarlane Burnet (1899-1985) was Director of the Walter and Eliza Hall Institute of Medical Research, Melbourne 1944-1966 and in 1960 was awarded the Nobel Prize for Physiology and Medicine with Peter Medawar for discovery of acquired immunological tolerance. Burnet not only played a major role in the development of medical research in Australia but also contributed to public debate of many issues including nuclear energy and weapons, the health effects of smoking and environmental concerns. His was the first extensive set of personal records to be preserved of an Australian Nobel Prize winner in science.

His personal archive is held at the University of Melbourne Archives and is described in an online listing http://www.austehc.unimelb.edu.au/guides/burn/burn.htm

Items in this digital collection are a part of a series titled ‘Diaries and Notebooks’, which contains early diaries, notebooks and diary letters 1880-1928, general and travel diaries, personal diaries and office diaries 1951-1985, notebooks 1932-1985, and Linda Burnet's Travel Diaries 1950-1968.

The formats in the original series include diaries, sketches, notes, catalogue, photographs, photographic negatives, diary letters, notebooks, notes, experimental results, newspaper cuttings, graphs, maps, and photocopied notebooks.

Notes from the front are records of observations of experiments undertaken by Burnet and his research assistants (mainly Dora Lush) on viruses, bacteria and other micro-organisms in animal and human tissue and individuals. It starts in April 1932 when Burnet was a virology research fellow at the National Institute of Medical Research in Hampstead. It documents the later stages of his research on bacteriophages (viruses occurring in bacteria) in which Burnet identified two processes of infection. Lysogeny described the integration and replication of the bacteriophage into the normal reproduction of the bacteria host cell. Another process of lysis described the accumulation of individual phages in a host cell, which caused it to break apart and release thousands of individual phages capable of surviving and infecting other cells. Burnet had acquired his phage collection in around 1930 from excreta samples from pigs, horses, cows, dogs and chicken at his brother’s farm in Gippsland, to see how they would attack the host dysentery bacteria. He brought this collection with him to Hampstead.

Also at the NIMR, Burnet developed his technique for growing viruses on the chorioallantoic membrane of chick embryo, which was to become his standard experimental technique in virus (and immunological) research thereafter. The first notebook (1986.0107.00011) also includes experimental studies of infectious diseases studied at the Walter and Eliza Hall Institute, including influenza, poliomyelitis, myxomatosis, Q fever, herpes and others. In 1933, Burnet returned from NIMR with an old brown suitcase containing a collection of standard strains of viruses from the National Institute’s collection, including vaccinia, neurovaccinia, cowpox, fowl pox and canary pox viruses, and the Rockefeller strain of herpes simplex. These would be used in virus research at the Walter and Eliza Hall Research Institute (WEHI) in Melbourne, where Burnet was to lead the virology department.

Some experiments of note include Burnet’s identification of the agent causing ‘Abattoir Fever’ or Q Fever as a rickettsia (noting in his research summaries 1 December 1939 ‘Rickettsia Burneti christened’). Of interest not least in the choice of experimental subjects is the influenza research in 1935-1936, which involved self-experimentation on the staff and associates of the Institute including Burnet, nurses, family and friends (including children) through the collection of samples and attempts at infection, inoculation, and tests of antibody production. A large range of experimental organisms and biological materials are mentioned in the notebook including parrots and human sputum (Psittacosis), monkeys (polio), chick egg embryos (influenza and other viruses), guinea pigs, ferrets , possums (myxomatosis), sheep (Louping Ill), and human brain tissue.

Notes from the back commencing 4 May 1933 are primarily research summaries that give a monthly account of progress of the research of Burnet and his department at WEHI on his return to Melbourne in 1934, peppered with occasional notes on his career including an invitation to be Vice President of the Virus Section of the Microbiological Congress in May 1938 and the award of the Cilento Medal by the Australian Institute of Anatomy in early 1939. These summaries are reasonably informative about the range of work carried out by Burnet’s team in this period, with the last entry dated 2 June 1939. The summaries are continued in another notebook digitised and described below (1986.0107.00015).

Two other laboratory notebooks (1986.0107.00013, 1986.0107.00014) relate to immunological research using the New Zealand Black strain of mouse as an experimental organism. These are in sequence and date from the period 1960-1965, documenting Burnet’s last experiments. He had been interested in immunological questions dating back to his early bacteriophage research in the 1920s and 1930s and published a monograph on the Production of Antibodies revised with Frank Fenner in 1949, in which Burnet set out his key concept of the immunological self (see Anderson, W., Mackay, I., 2014). In 1957 Burnet developed his clonal selection theory explaining the ‘mechanism for the generation of diversity of antibody specificity’ a fundamental immunological process. He changed the direction of the Walter and Eliza Hall Institute’s research from virology to immunology, as virus research increasingly became in Burnet’s estimation ‘under the biomechanical influence’. (Burnet quoted in Sexton 1999, p. 135) Part of this change of direction, including the orientation of the Institute’s Clinical Research Unit headed by Ian McKay, was studying not just the basis of ‘normal’ immunological function but also immunological dysfunction, where ‘cells or tissues of the body are damaged as a result of an immune response’ otherwise ‘directed against foreign cells entering or arising within the body’ (Sexton, p. 155). The New Zealand Black mouse research relates to autoimmune pathology in this species. Collaborating with Margaret Holmes, she and Burnet demonstrated characteristic thymic lesions indicating an autoimmune response. As well as recording experimental data in the form of numeric results, the notebooks contain Burnet’s pencil sketches of lesions and summaries of observed results. They attributed genetic causes to the inheritance of these lesions and auto-immune disease in the mice. The opening of 1986.0107.00014 also contains some notes on chick egg experiments.

Another notebook (1986.0107.00012) originally dated by an archivist 1951-1952, but probably starting in 1950, is focused on epidemiology. After a few opening notes, Burnet outlines a series of three Herter Lectures delivered at John Hopkins University in Baltimore in 1950 on ‘Some Biological Implications of Studies on Influenza Viruses’. He continues with notes drawn from a wide range of sources on epidemiological studies of the incidence and mortality of various childhood diseases. The notebook includes a large number of Burnet’s own hand-drawn graphs. In the same year Burnet was a visiting professor at Hammersmith in London for 3 months and gave a number of other lectures there. During the visit he spent two weeks with country doctor and amateur epidemiologist Will Pickles at Aysgarth in Wensleydale, joining Pickles on his rounds of Northern villages. In 1947, Burnet and Pickles had co-authored a paper based on Pickles data and observation of the resistance to influenza virus among his patients after an outbreak. On the 1950 visit, Burnet then drove to Newcastle for a visit to eminent pediatrician James Spence, who headed the Department of Childhood Health, where he was conducting a longitudinal study of 1000 families. (Sexton, pp. 125-126) Starting with his third Herter lecture, between 1950 and 1953 Burnet published a number of articles on the ecology of infectious diseases. The second edition of his re-titled Natural History of Infectious Diseases (previously Biological Aspects of Infectious Diseases 1940) was published in 1953. From 1952, Burnet was a member of various advisory panels on influenza, poliomyelitis and immunology of the Advisory Committee of the World Health Organisation, concerned with global public health.

The final notebook (1986.0107.00015) dated 1933-1982 is a rich chronicle. It seems to be a mix of relatively contemporary, more detailed summaries of key research, career, world and life events recorded close to the time that they occurred and later retrospective entries. The first category of entries were mainly written between 1939 and 1949, and may for example have been compiled to aid Burnet to manage activities at the Institute and more broadly, and to keep a note of key developments for future reference. Later sections appear to have been summaries recorded retrospectively for another purpose such as compiling a historical account, possibly his autobiography Changing Patterns (1968) or in preparation for his biography in the mid-1980s.

Burnet started his monthly summaries in 1939 indicating that they continued on from his MRC (Medical Research Council) summaries book (1986.0107.00011) started during his research fellowship at the National Institute for Medical Research (1931-1933). He includes periodic notes on research, experiments, publications, visits, lectures, honours and mentions family holidays and illnesses for example 2 December 1939: ‘Holiday at Wilson’s Promontory quite successful despite L’s german measles: own attack 12 days later.’ The notebook continues along these lines until 1949. As well as accounts of the progress of his own and colleagues’ research at the Institute, are Burnet’s accounts of world events during World War Two as well as what was happening in Melbourne. For example, after entries on poliomyelitis, influenza, V.I.A., mouse pneumonia and a general entry noting ‘antibody production monograph in hands of the printer after much trouble with design of institute crest’ Burnet observes: ‘General sense of uncertainty in the Institute owing to war and feeling that virus research in the lab is nearly exhausted’. He then gives a description of the international situation prefaced by: ‘War with Germany started on my 40th birthday’. There are also notes from the same period starting at the back of the notebook so he seems to have used the notebook from both ends. Some entries in the back pages of the notebook are of a different character from the summaries at the front, containing ideas about research on a particular disease, for example. Annual summaries continue in the 1950s but these appear to be less detailed and immediate records.

Towards the end of the notebook Burnet is clearly in retrospective mode. These pages contain career summaries of milestones by year. There is also a table of names of people probably working in the Institute by year. Another list of people in following pages was possibly compiled to aide Burnet’s autobiography or biography.

The notebooks digitized and published online here are a sample of the variety of documents in this series dating mainly from the period when Burnet was research active. There are related notebooks for example on epidemiology and a diary on the NZB mouse thymus research in the original series that have not yet been digitized. However, there does not appear to be a complete set of laboratory notebooks covering all of Burnet’s experimental research, although his main research in the period 1932-1949 is covered in the two consecutive notebooks containing research summaries (1986.0107.00011, 1986.0107.00015). Scientific notes are spread widely throughout the series, for example in diaries, and the collection as whole, for example in draft manuscripts and working papers. Apart from the NZB, bacteriophage and virus research, which for Burnet raised immunological questions, there is little documentation of experimental immunological research in the collection.

Exceptions are the research summaries contained in the notebook titled by an archivist Laboratory Notebook - Bacteriophage Experiments and Infectious Diseases (1986.0107.00011). An entry on 4 May 1933 notes ‘ideas for work on immunological relations of pox viruses’. Another dated 29 June 1935 on ‘the theory of antigen antibody reactions’ records a ‘hypothesis that double antibody molecules developed by simultaneous immunisation e.g. with bacteria and virus. Tests underway L.I. and Flexner au phage.’ On 31 May 1937 he notes ‘Immunology monograph has been dispatched to Adelaide for publication’ and 2 August that it has been published. On 30 May 1938 an entry on ‘Antibodies’ records ‘Jackson has completed primary and secondary antiphage response showing very good logarithmic rise with same time relations as staph-antitoxin. Attempts to study lymph gland response … being commenced’. Notes under ‘General Immunology’ dated 30 April 1939 record ‘MF expts on local immunity show only accumulation of antibody not production. Experiments in view on destruction of herpetic and antitoxic antibodies in sera. Experiment on 70 Guinea Pigs under way to see whether non-specific experiment of antibody production favours response to other antigens later and also production of histamine.’ And finally on April 30th: ‘Monograph on antibody production 1st draft completed … shorter discussion of theory for University Chemistry Society.’ Questions of immune reactions were clearly on Burnet’s mind throughout the 1930s, while working in the laboratory on bacteriophages and viruses.

His major contributions to immunology – acquired immunological tolerance and clonal selection – were primarily theoretical and drew upon or were confirmed by experiments conducted by others.

Anderson, W., Mackay, I., (2014) Intolerant Bodies: A Short History of Autoimmunity. Baltimore: Johns Hopkins University Press.

Sexton, C. (1999), Burnet: A Life, Oxford: Oxford University Press.

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