Macfarlane Burnet

Macfarlane Burnet’s best known contributions to science are:

• the theory of acquired immunological tolerance, for which he received the Nobel Prize for Medicine or Physiology in 1960;
• the theory of clonal selection, which he regarded as his most important work and is the basis of the science of molecular immunology.
  

A remarkably prolific researcher, he published over 400 original research papers and authored 10 books on virology, 11 on immunology, an autobiography, and several books about subjects such as ageing and genetics.

Beginnings

Frank Macfarlane Burnet was born on September 3, 1899 in the small city of Traralgon, Victoria, Australia, which lies about 100 miles (160 km) south east of Melbourne.

His father, Frank Burnet, was a bank manager who had moved to Australia from Scotland as a young man. His mother, Hadassah Pollock Mackay, was the daughter of a Scottish school teacher. Frank Jr., the second of their seven children, was known to his family and forever more as Mac.

Mac’s elder sister Doris was mentally handicapped and took up most of her mother’s time. Mac’s father was a man of business, who enjoyed golf and fishing. Mac, however, disliked sport, preferring to read. He grew to disapprove of religion because his father would faithfully attend the Presbyterian church, but would also deal with businessmen whose practices did not seem especially Christian to Mac.

Mac grew up to be shy and solitary.

Schooling & Development

In 1909, Mac’s father was transferred over 200 miles west by his bank to the country town of Terang. Now age 10, Mac was schooled at Terang’s primary school. He joined the Boy Scouts, loving the outdoor life, and he continued to enjoy reading, becoming a fan of H. G. Wells and George Bernard Shaw.

He also began a hobby that became a lifelong passion – beetle collecting. Initially he was hampered in his new hobby, because the only information about biology he could find was in a 50 year-old edition of the Chambers Encyclopedia. From this he learned about the theory of natural selection, still decidedly new when the encyclopedia was published.

As his interest in biology grew, his parents subscribed to the fortnightly magazineHarmsworth’s Natural History, and then, casting his net wider, Mac purchased books about beetles and insects by mail order from Melbourne.

In his final year at primary school, he obtained a full residential scholarship for Geelong College, a prestigious private school.

In 1913, age 13, Mac traveled 100 miles east to begin boarding at Geelong College. He had grown to love the outdoor life in Terang, and he found he did not enjoy high school much. He was an academically inclined, bookish scholarship boy, not entirely comfortable with the other students, who were excessively wealthy, assertive, and whose lives seemed to revolve around sport.

Fearful of derision from his fellow students, he kept his devotion to the study of beetles secret.

He graduated from Geelong College in 1916 as its top student, winning a full residential scholarship to the University of Melbourne’s Ormond College.

Influenced by his high regard for Charles Darwin and H. G. Wells, and the need to make a career for himself, he decided to study medicine.

Melbourne and London

Burnet matriculated at the University of Melbourne in 1917, the penultimate year of World War I.

He joined the university’s army corp, not because he approved of war, but because he felt that after the war anyone who had shown unwillingness to take part would find life difficult.

He graduated with a Bachelor of Medicine and a Bachelor of Surgery in 1922, age 22. He hoped to become a hospital doctor, enjoying the job satisfaction he felt while training in the operating theater and emergency department, but his hospital supervisor judged his personality to be more suited to research work.

In 1923, he became senior resident pathologist at the Walter and Eliza Hall Institute at the Melbourne Hospital.

He left Australia in 1925 to work as an assistant curator at the Lister Institute in London, England. He was free to carry out his own research most of the time and he decided to study micro-organisms. The Institute was impressed by his ability, and awarded him a fellowship, allowing him to pursue his interests further.

In 1928, the University of London awarded him a Ph.D. for his research into bacteriophages – viruses that infect bacteria.

He returned to Melbourne in 1928 as Assistant Director of the Walter and Eliza Hall Institute and, apart from returning to London for a year in 1932-1933 he remained in Australia for the rest of his career. He was appointed Director of the Walter and Eliza Hall Institute in 1944, and also appointed Professor of Experimental Medicine at the University of Melbourne.

Macfarlane Burnet’s Contributions to Science

Burnet’s scientific discoveries and achievements were legion; he published over 400 papers documenting his own research work, mainly in the field of virology. It is, however, his work in immunology, only a minor part of his work, that he is best remembered. Here we shall concentrate on just two contributions: the theory of acquired immunological tolerance, for which he received a Nobel Prize; and the theory of clonal selection, which he believed was his most important work.

The Theory of Acquired Immunological Tolerance

How does your body know what is self and what is non-self? This is a question that fascinated Burnet. How can our body’s immune response tell the difference between our own cells and invading cells?

Burnet noted that our bodies do not make antibodies against their own cells. In 1949 he proposed, in a paper with Professor Frank Fenner, that if foreign cells are introduced into an embryo, then when the embryo develops into an independent individual, it will have no immune response to foreign cells of the type it encountered as an embryo: the embryo would have been made tolerant of the foreign cells. In other words, the immune system of an individual could be made to tolerate cells it would normally reject and attack.

In 1956, a team led by Peter Medawar at University College, London, confirmed Burnet’s theory with experiments on mice.

Normally, skin grafts from one mouse to another would fail, because the immune system of the mouse the skin was grafted to rejected the new skin. However, if a mouse at its embryo stage was exposed to cells from another mouse, then as an adult, it would accept a skin graft from that mouse. In other words, it was possible for foreign cells to be treated as ‘self.’

The fact that tolerance of foreign cells could be acquired by a body led to advances in reducing the human immune response to transplants, allowing organ transplants to be carried out without rejection of the transplanted organ.

Burnet and Medawar shared the 1960 Nobel Prize in Physiology or Medicine for their discoveries.

The Theory of Clonal Selection

Lymphocytes are a type of white blood cell that responds to invading cells, which are called antigens. They do this using antigen receptors – the surface of each lymphocyte cell has about 100,000 receptors on its surface.

Burnet proposed, correctly, that the antigen receptors on lymphocytes are specific to the lymphocyte. If a lymphocyte meets the antigen its receptors are programmed to fight, then this lymphocyte is triggered to make clones of itself, producing a large-scale immune Burnet explained that after we have been exposed to a disease, there is an immunological memory of the disease because there are two types of lymphocyte:

• one type fights the infection immediately
• the other persists for a long time, resulting in immunity

Burnet proposed that some receptors are a very precise match to antigens, while others are less precise to try to ensure some sort of immune response to virtually any invading pathogen.

Burnet’s clonal selection theory is the basis of the science of molecular immunology.

His theory led to the development of some of the most important drug treatments available today based on monoclonal antibodies – these are made by immune cells, all identical, that are all clones of a single parent cell. Today monoclonal antibodies can be made that can bind specifically to almost any substance.

Other Discoveries

In addition to his two biggest discoveries, Burnet also:

• discovered the causes of Q-fever and psittacosis
• described the recombination of influenza strains
• described the epidemiology of herpes simplex
• demonstrated (in part by injecting himself with the virus) that the myxomatosis virus does not attack humans
• improved the methods for cultivating viruses in hens’ eggs: his methods are the basis of today’s methods

Prizes

Burnet was awarded the 1960 Nobel Prize in Physiology or Medicine for his discoveries. He had previously, in 1951, been knighted, becoming Sir Frank Macfarlane Burnet.

During his career, Burnet received many prestigious awards, including:

• 1935: Stewart Prize of the British Medical Association
• 1942: Fellow of the Royal Society of London
• 1946: Honorary Doctor of Science, University of Cambridge
• 1947: Royal Medal, Royal Society of London
• 1950: Honorary Member, New York Academy of Sciences
• 1951: Knight Bachelor
• 1952: Lasker Award, American Public Health Association
• 1952: Von Behring Prize, University of Marburg
• 1953: Fellow of Royal College of Physicians, Edinburgh
• 1954: Foreign Associate, US National Academy of Sciences
• 1957: President of Australian and New Zealand Association for the Advancement of Science
• 1958: Order of Merit
• 1959: Copley Medal, Royal Society of London
• 1960: Nobel Prize in Physiology or Medicine
• 1960: Australian of the Year
• 1962: Mueller Medal, Australian and New Zealand Association for the Advancement of Science
• 1962: New York University Medal
• 1969: Knight Commander of the Order of the British Empire
• 1975: The Hebrew University of Jerusalem Jubilee Medal
• 1977: Elizabeth II Jubilee Medal
• 1978: Knight of the Order of Australia

Some Personal Details and the End

Burnet married Edith Linda Marston Druce in 1928. They had known each other in Australia, met again in London, and agreed to marry when they both got back to Australia. The couple had one son and two daughters: Ian, Elizabeth, and Deborah.

Although he officially retired in 1966, age 66, he remained at the University of Melbourne as Professor Emeritus and continued to have a secretary to help with his work. He wrote 13 books in the 1966-77 period.

His wife Linda died of lymphoid leukemia in 1973. In 1976, Burnet married Hazel Jenkin.

Burnet was:

• a fast writer – often his first draft was identical to the final copy
• an atheist who supported euthanasia
• strongly anti-smoking – he quit in the 1950s
• so moved by the death of his first wife that he could barely do any work for a year
• highly skeptical about the benefits of molecular biology

Macfarlane Burnet died, age 85, of cancer of the rectum, on August 31, 1985 at his son’s home in Port Fairy. The Australian Government organized a state funeral in his honor at the Toorak Uniting Church, Melbourne. He was buried at Tower Hill Cemetery, Victoria, close to a wildlife reserve.