George Bellamy Mackaness (20 August 1922 – 4 March 2007) was an Australian professor of microbiology, immunologist, writer and administrator, who researched and described the life history of the macrophage. He showed that by infecting mice with intracellular bacteria, macrophages could be activated to attack other bacteria, triggering further research on "macrophage activation", a term he has come to be associated with.
George Bellamy Mackaness was born on 20 August 1922 in Sydney, Australia, the third child of James Vincent Mackaness, a Sussex Street grocer, and his wife Eleanor Frances Bellamy Mackaness.[1] He used his name in full to distinguish himself from his uncle, George Mackaness, an author and historian.[1] He attended Fort Street High School, before gaining admission to study medicine at the University of Sydney, from where he graduated with a Bachelor of Medicine, Bachelor of Surgery.[1]
Early career
Mackaness completed a one year residency in medicine at Sydney Hospital followed by a year in pathology at the hospital's Kanematsu Institute, before becoming a demonstrator in pathology.[1] After WWII he moved to London and completed a Diploma in Clinical Pathology (DCP) at the University of London.[1] In 1948 he matriculated from Lincoln College, Oxford.[1]
Howard Florey offered Mackaness a job in his laboratory at the Sir William Dunn School of Pathology in Oxford. There, Mackeness worked for his DPhil alongside James Learmonth Gowans and later Henry Harris.[1] Mackaness's main study for his thesis was on the role of monocytes and macrophages in killing Mycobacterium tuberculosis.[1] He showed that by infecting mice with intracellular bacteria, macrophages could be activated to attack other bacteria.[2] It resulted in an increase in research on "macrophage activation", a term he has become associated with.[2][3] Discovering antibiotics was his side interest and his work in this field later earned him a fellowship to the Royal Society.[4] At Florey's suggestion, Mackaness simultaneously took to studying anti-tuberculous medicines, including streptomycin and isoniazid.[1]
His investigations into how isoniazid acted in tuberculosis, published in 1952, were some of the first on this topic.[1] He used the techniques he had developed during his study of the life history of monocytes and macrophages to show that for a drug to be effective against tuberculosis, it had to be effective inside the macrophage, and showed that isoniazid entered the macrophage to be active against M. tuberculosis.[1][5] He delayed completing his thesis while working on isoniazid and received his DPhil in 1953.[1] A year later, he moved back to Australia.[1]
John Curtin School of Medical Research
JCSMR Canberra Australia
On returning to Australia, Mackeness moved to Canberra having been appointed to at first staff and then acting head of the Department of Experimental Pathology at the John Curtin School of Medical Research (JCSMR), an institution he saw being planned by Florey while in Oxford.[1]
In 1959 he took a sabbatical to the Rockefeller Institute, by which time he was professorial fellow, having written extensively on renin and hypertension.[1] There he worked with René Dubos, who had worked with Selman Waksman and had a quest to find cures for tuberculosis.[1] Mackeness was set to buddy up with Jim Hirsch and focus on anti-infection immunity.[1] In 1960 they published a paper on the phagocytosis of staphylococci.[1]
While at the JCSMR, he found that mice were good at producing an antibody-independent immune response to the bacteria Listeria monocytogenes.[2] Once infected with L. monocytogenes, the mice developed temporary protection to L. monocytogenes, but also to other bacteria, an observation he termed "acquired cellular resistance", and he attributed this to macrophages. Compared to macrophages from uninfected mice, these macrophages could then be removed and were found to kill several other bacteria.[2] The protection faded with time, but regained when the mice were re-challenged with the original bacteria.[2] The macrophages were activated immediately. When challenged with other un-related bacteria, the macrophages did not respond.[2] He concluded that the macrophage response was dependent on the particular original infection and the findings were published in The Journal of Experimental Medicine in 1962 and 1964.[2] His experiments have since been described as "classic".[6] With his colleagues, he confirmed that specifically committed T-lymphocytes reacting with antigen, activated the macrophages.[6]
In 1965, he became director of the Trudeau Institute, where over the subsequent ten years he appointed and led staff on work relating to cell-mediated immunity to infection and, later, cancer.[7]
He became president of the Squibb Institute for Medical Research in New Jersey in 1976.[4] While at Squibb, the FDA had denied a license to the first ACE inhibitor, captopril, due the side effects being too unacceptable, particularly the risk of producing a severe low blood count.[1] Mackaness persuaded the company to reduce the dose by half, resulting in FDA approval and significant profits for the Squibb. His last publication before retirement was a review article on ACE inhibitors.[1]
In 1945, after graduating, Mackaness married Gwynneth Patterson, an army nurse, who he met during the early years of the Second World War, whilst a medical student.[1] They had one son, Miles.[1]
His death on 4 March 2007 in Charleston, South Carolina, at age 84, was followed a few days later by his wife's. Both had spent a year together at the same extended care facility.[1]
