John Kerr holding the Charles IV Prize medallion in Prague in 2002 (courtesy of John Kerr).

John Foxton Ross Kerr, legendary amongst scientists and medical practitioners as “The Father of Apoptosis”, died on 4 June 2024, aged 90.

Born in Sydney on the 24th of January 1934, he was an Australian pathologist. He graduated in medicine (MBBS) from the University of Queensland in 1957 and was awarded a PhD from the University of London in 1964. He trained in pathology at the Royal Brisbane Hospital and at the University College Hospital Medical School in London.

During his PhD studies, supervised by another Australian, Sir Roy Cameron, his project included determining what happened to liver tissue in rats when the portal vein branches to the left and median lobes were ligated. In those affected lobes, foci of confluent hepatocyte necrosis developed around terminal hepatic venules, while cells in periportal areas, supported by hepatic artery supply, remained predominantly viable. Away from the areas of confluent necrosis Kerr observed a different type of cell death. He saw that isolated hepatocytes had shrunk to small, rounded masses, some of which contained small pieces of very condensed nuclear chromatin. He later noticed similar, isolated, individual shrunken cells in the livers of healthy rats.

In 1965, Kerr published a sole author paper in which he described this process [1], that he then termed “shrinkage necrosis”. In the years to follow he published several further papers in which he enunciated the characteristic ultrastructural changes observed in these cells and showed how they differed from the changes typically seen in cells undergoing what had long been known as classical necrosis. However, it was not until 1972, when on sabbatical leave in Sir Alastair Currie’s laboratory in Aberdeen, that the term “apoptosis” was proposed for this process, in the landmark paper “Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics” in The British Journal of Cancer [2].

Together, Kerr, Currie, and Currie’s PhD student, Andrew Wyllie, realized that the appearance of the dying liver cells Kerr had been studying was the same as that in the adrenal cortex which had been observed by Currie and Wyllie. Professor James Cormack, of the Department of Greek at the University of Aberdeen, suggested the term “apoptosis”, which meant “dropping off or falling off” as occurs with leaves from trees in autumn, the nature of the word implying a link with mitosis. Kerr, Wyllie and Currie adopted the term “apoptosis” for the process they had observed:

“We propose our concept of apoptosis as a vital biological phenomenon…. which contributes to the regulation of cell populations in a variety of mammalian tissues under many different conditions”.

They reasoned that for every new cell produced by the process of cell division - “mitosis” - another cell died, maintaining the correct number of cells within a tissue.

It should be observed that the concept of apoptosis was slow to gain favour in the scientific community. The authors had been quite unaware of the work of Carl Vogt in 1842 who saw dead cells in developing tadpoles of the midwife toad, or Walther Flemming, a German cell biologist, who in 1885 described similar light microscopic features occurring during involution of ovarian follicles in adult rats. Also, in 1965, Lockshin used the phrase “programmed cell death”, to describe the death of cells during the development of insects [3]. However, even as late as 1980, the number of papers published that used the terms “shrinkage necrosis”, “programmed cell death”, or “apoptosis” was very small.

In 1980, Wyllie, Kerr and Currie wrote: “The possibility that such ‘normal cell death’ might involve active self-destruction rather than passive degeneration has been virtually ignored: most regard the changes that take place in all dying cells as being akin to the post-mortem autolysis of a corpse, a process hardly likely to stimulate enthusiastic investigation” [4].

However, interest in apoptosis was soon to be embraced by scientists worldwide. A recent search in PubMed for papers using the term “apoptosis” identified more than 567,000 articles, and the total number of citations of Kerr’s 1972 paper is now over 12,500. Increasing recognition of his fundamental insights came with the elucidation of the molecular mechanism of apoptosis. This included, in the late 1980s, demonstration of the suppression of apoptosis by the BCL-2 family of proteins, and in the early 1990s, evidence of its activation by the p53 pathway when a cell’s DNA is damaged. Now, no longer a novel concept, an increasingly comprehensive understanding of the factors which elicit apoptosis and the mechanisms by which it comes about, have enabled the elucidation of many disease processes and the development of appropriate treatments.

Kerr received numerous awards for his work, both within Australia and internationally, including, most notably, the prestigious Paul Ehrlich and Ludwig Darmstaedter Prize in 2000, which he shared with the Boston geneticist H. Robert Horvitz. In 2002, he received the International Charles IV prize from the city of Prague and Charles University. His work was cited by the American Association for Cancer Research as a “Landmark in Cancer Research”. Awards in Australia have included: Fellowship of the Australian Academy of Science, Officer of the Order of Australia (AO), the Royal College of Pathologists Distinguished Fellows’ Award, and the Bancroft Medal, received from both the Queensland Institute for Medical Research and the Australian Medical Association.

In Queensland, Kerr was renowned for his inspirational contribution to education and he amply provided a generation of medical students with a solid understanding of the pathological basis of disease. Even now, decades later, his lectures and tutorials are still remembered by many with both enthusiasm and fondness. Kerr also contributed enormously to the University of Queensland Pathology Museum, helping it to become one of the foremost in the world. He received the University of Queensland Award for Excellence in Teaching in 1988.

In 1995, Kerr retired, after a long career at both the University of Queensland and the Royal Brisbane Hospital.

Kerr was an enthusiastic lepidopterist, and after a lifetime of collecting and studying butterflies and moths, donated his collection, one of the best in the country, to the Australian National Insect Collection, maintained by the CSIRO.

DLV and AS only met Kerr once but knew him to be a thoughtful and gracious man. Having collaborated with Kerr during her PhD studies, RK remembers his excitement as the molecular mechanisms of apoptosis began to be revealed. MC was one of the last of his PhD students and remains very grateful to him for teaching her the importance of meticulous attention to detail, and for his patience and great kindness.

Those of us who stood on his shoulders to make a finding in the field of cell death could count on receiving a highly supportive congratulatory note posted by him from Hipwood Road, Brisbane, Queensland.