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John Kerr and apoptosis

Med J Aust 2000; 173 (11): 616-617.
Published online: 4 December 2000

The Research Enterprise

John Kerr and apoptosis

Michael G E O'Rourke and Kay A O Ellem

MJA 2000; 173: 616-617

On 14 March 2000, John Foxton Ross Kerr, Emeritus Professor of Pathology at the University of Queensland, received the Paul Ehrlich and Ludwig Darmstaedter Prize for his description of apoptosis, a form of cell death. The prize, which he shared with Boston biologist Robert Horvitz, is considered to be one of the most prestigious European awards in science, second only to the Nobel Prize.

  John Kerr's discovery, initially called "shrinkage necrosis" but which he later renamed "apoptosis", came about in the late 1960s, when his attention was caught by a curious form of liver cell death during his studies of acute liver injury in rats. The findings of this seminal study were first published in 1965.1 Subsequently, Kerr and his co-authors (including Jeffrey Searle) described the unique morphological changes of this type of cell death, compared with those of necrosis, in a series of articles published during the 1970s and 1980s.2-4 These studies extended the range of pathological and physiological states in which apoptosis is known to occur. Further studies with other collaborators (who later included Alastair Currie and Andrew Wyllie)5 led to an increase in the understanding of the role of apoptosis in embryogenesis, spermatogenesis, cancer growth, and tissue remodelling during healing or functional regression. At first thought to be somewhat arcane as a topic, the literature on apoptosis initially grew slowly. However, recognition of the significance of this "protected" form of cell death on immune function and regulation was followed by an explosion of related publications in immunology. Biochemists now recite a mantra of enzymes involved in apoptosis, and chant a list of factors capable of modulating or regulating its expression. It has become de rigueur to adorn seminars and lectures with charts of the increasingly complex interactions which occur between signalling pathways as they are traversed by the informing reactions (which either trigger or defuse the suicidal steps leading to apoptotic cell death).

The astonishing total number of publications on apoptosis is now over 35 539, including some of the world's leading scientific journals, such as Nature6-8 and Science.9-11 Apoptosis is now a growth industry, the clinical implications of which can be applied to chemotherapy, the endocrine treatment of cancer, autoimmune disease and neurodegenerative disease. This body of evidence is a tribute to the catalytic influence that John Kerr's insights have had in so many disparate disciplines and areas of biological study. These insights revealed the importance of this process as a universal microphenomenon in the macroevents of tissue and organismal function, and in disease.


References

  1. Kerr JF. A histochemical study of hypertrophy and ischaemic injury of rat liver with special reference to changes in lysosomes. J Path Bact 1965; 90: 419-435.
  2. Kerr JF, Cooksley WG, Searle J, et al. The nature of piecemeal necrosis in chronic active hepatitis. Lancet 1979; 20: 827-828.
  3. Searle J, Lawson TA, Abbott PJ, et al. An electron-microscope study of the mode of cell death induced by cancer-chemotherapeutic agents in populations of proliferating normal and neoplastic cells. J Pathol 1975; 116: 129-138.
  4. Weedon D, Searle J, Kerr JF. Apoptosis. Its nature and implications for dermatopathology. Am J Dermatopathol 1979; 2: 133-144.
  5. Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 1972; 26: 239-257.
  6. Wallach D. Apoptosis: Placing death under control. Nature 1977; 388: 123-126.
  7. Hengartner MO. Apoptosis: death cycle and Swiss army knives. Nature 1998; 391: 441-442.
  8. Martinou JC. Apoptosis: key to the mitochondrial gate. Nature 1999: 399; 411-412.
  9. Barinaga M. Apoptosis: forging a path to cell death. Science 1996; 273: 735-737.
  10. Barinaga M. Apoptosis: death by dozens of cuts. Science 1998; 280: 32-34.
  11. Brenner C, Kroener G. Apoptosis: Mitochondria -- the death cell integrators. Science 2000; 289: 1150-1151.
  12. Cotran R, Kumar V, Collins T, editors. Pathological basis of disease. 6th ed. Philadelphia: W. B Saunders, 1997: 18-24.
  13. Kerr JF, Winterford CM, Harmon BV. Apoptosis. Its significance in cancer and cancer therapy. Cancer 1994; 73: 2013-2026.
  14. Walker NI, Harmon BV, Gobe GC, et al. Patterns of cell death. Methods Achiev Exp Pathol 1988; 13: 18-32.
  15. Sandford N, Searle JW, Kerr JF. Sucessive waves of apoptosis in the rat prostate after repeated withdrawal of testosterone stimulation. Pathology 1984; 16: 406-410.
  16. Soubrane C, Mouawad R, Antoine EC, et al. A comparative study of Fas and Fas-ligand expression during melanoma progression. Br J Dermatol 2000; 143: 307-312.
  17. Andrane F, Casciola-Rosen L, Rosen A. Apoptosis in systemic lupus erthymatosus. Clinical implications. Rheum Dis Clin North Am 2000; 26: 215-227.


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Photo of John Kerr
John Kerr (right) with Roland Koch, Prime Minister of Hesse, Germany, and Honorary Chairman of the Board of Trustees of the Paul Ehrlich Foundation, at a dinner for award recipients.
 
1: Other awards and lectures recognising John Kerr's achievements
  • Keynote opening addresses at the Cold Spring Harbor, New York, Symposia, 1990.
  • Opening lecture, The cell and molecular biology of apoptosis, at the Queensland Institute of Medical Research Cell and Molecular Biology Symposium, 1992.
  • Opening lecture at the conference Apoptosis in AIDS, Paris, 1993.
  • 12th Mildford D. Schultz Lecture, Harvard Medical School, Boston, 1993.
  • Bancroft Medal (Queensland AMA), 1993.
  • John Earnshaw Memorial Lecture, International Melanoma Conference, Brisbane, 1994.
  • Fred W Stewart Award, Memorial Sloane-Kettering Cancer Center, New York, for contribution to cancer research, 1995.
  • Doctor of Science honoris causa, University of Queensland, 1998.
  • Fellowship of the Australian Academy of Science, 1998.
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2: Apoptosis: programmed cell death
  • The term "apoptosis" is derived from the Greek for "falling off" and describes a distinct form of cell death whereby cells die in a tightly regulated and morphologically uniform fashion.12

  • Morphologically, there is condensation of the nucleus and cytoplasm, membrane blebbing, and the formation of discrete, packaged apoptotic bodies which are phagocytosed by nearby cells, without provoking an
    inflammatory reaction.13
Photo image of emcells
  • In contrast to necrosis, a degenerative process in which cells swell and lyse after irreversible tissue injury, apoptosis appears to be an active process14 which is subject to genetic regulation.

  • Apoptosis can be triggered either from within the cell, or from outside the cell (mediated by binding of surface membrane receptors to "death activators" such as Fas-ligand and tumour necrosis factor).
Electron micrograph showing apoptosis occurring spontaneously in cell culture. Note the discrete, membrane-enclosed nuclear fragments, with characteristic segregation of uniformly compacted chromatin, the crowding of well preserved cytoplasmic organelles and the marked convolution of the cellular surface, which is a prelude to conversion of the cell into a number of membrane-bound fragments or apoptotic bodies. N = nucleus, O = organelles.
  • Apoptosis may occur in several different physiological, adaptive and pathological settings. For example, apoptosis acts as a homoeostatic mechanism for controlling cell populations, and in hormone-dependent tissue involution such as endometrial breakdown during menstruation, prostatic atrophy after castration,15 and cessation of lactation after weaning.12 Localised apoptosis plays a role in embryonic development, such as formation of interdigital clefts and involution of phylogenetic vestiges.5 In malignant tumours, apoptosis may occur spontaneously, or may increase in response to cytotoxic chemotherapy or irradiation.13 Impaired regulation of apoptosis is known to be associated with the development of various types of cancer,16 and with the pathogenesis of some autoimmune diseases such as systemic lupus erythematosus.17
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Received 29 March 2024, accepted 29 March 2024




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