The Cell That Removes Itself: Kerr, Wyllie, Currie and Apoptosis, 1972

The Cell That Removes Itself: Kerr, Wyllie, Currie and Apoptosis, 1972

Shrinking cells in the liver

John Foxton Ross Kerr was born in Sydney on 24 January 1934. According to the text that tells his life story, he studied medicine at the University of Queensland and, between 1962 and 1964, did doctoral work in London at University College Hospital Medical School under Sir Roy Cameron. The core of the story is a rat liver: when the portal vein supply of the liver was cut off, Kerr saw that some cells shrank instead of bursting, and that their nuclei looked very dense and dark. Kerr called this "shrinkage necrosis".

There is a conflict about dates. Kerr's biography says he published this finding in 1965; the verified 1965 citation I have is J Pathol Bacteriol 90(2):419-435, October 1965, and its title refers to hypertrophy and ischaemic injury of the liver, especially changes in lysosomes. The paper titled "Shrinkage necrosis: a distinct mode of cellular death", on the other hand, appears in the reference list of the 1972 paper as J Pathol, 1971. I do not know whether the term first appears in the 1965 paper or in the 1971 one; I have marked this row in amber in the diagram.

Precursors of planned cell loss

The idea did not appear from nothing. According to Richard Lockshin's 2023 review and a secondary page that gives the reference citations, Lockshin and Williams used the concept of "programmed cell death" in 1964 while studying the breakdown of the intersegmental muscles of the silkmoth, and in 1966 Saunders wrote in Science that cell loss in embryonic systems is a normal part of development. Lockshin writes that a similar collapse was seen in insect tissue too. Lockshin's introduction cites both 1964 and 1972 as the "emergence" of the term, while the main text credits the name "apoptosis" to 1972; he does not reconcile these two accounts. I tie the idea of "programmed cell loss" to 1964 and the name "apoptosis" to 1972.

A paper in a cancer journal

According to the abstract, apoptosis occurs spontaneously in untreated malignant tumours and takes part, at least in some types, in tumour regression induced by treatment. Kerr's biography says that with Jeffrey Searle he studied cell loss by shrinkage in basal cell carcinomas and proposed that this shapes tumour growth kinetics. My inference: a tumour can grow not only through excess division but also through little cell loss; the sources do not put it in a sentence like this.

The paper's reference list also includes work such as the regression of the prostate after castration and nuclear shrinkage in the thymus under glucocorticoid; I saw the list of references and did not read how the paper discusses them. The line is familiar: when a hormone is withdrawn, tissue regresses; the hormone axis that runs from Beatson on Day 91 to Huggins on Day 112. I mention this as a link, not as a claim of the paper.

Where the genes came in

Linking the morphology to genes took decades. In 2002 the Nobel Committee awarded the prize to Sydney Brenner, H. Robert Horvitz and John E. Sulston "for their discoveries concerning genetic regulation of organ development and programmed cell death". According to the Committee's page, of the 1,090 cells in C. elegans, 131 disappear reproducibly during development; in 1986 Horvitz identified ced-3 and ced-4 and showed that both are required for the cell loss, and later found that ced-9 interacts with them and protects. The page never uses the word "apoptosis". The prize went to the work at the gene level; Kerr shared the Paul Ehrlich and Ludwig Darmstaedter Prize with Horvitz in 2000 (according to the biography), and his name is not among the Nobel laureates. I read this as the scope of the prize, not as a claim of injustice.

The link to cancer reappeared at the gene level. In 1988 Vaux, Cory and Adams reported in Nature, volume 335 (440-442): the t(14;18) translocation, frequent in follicular lymphoma, brings the bcl-2 gene next to the immunoglobulin heavy chain locus; in interleukin-3-dependent cells bcl-2 promoted cell survival, but not division (the cells stayed in G0), and together with c-myc it made pre-B cells permanently able to proliferate. The authors' proposal: by prolonging survival, bcl-2 may allow a clone to live until other oncogenes such as c-myc are activated. So a cancer gene could work not by speeding up division but by preventing cell loss. The tumour-kinetics intuition of 1972 became concrete in a gene.

Venetoclax and chronic lymphocytic leukaemia

I draw no direct Turkish link to Kerr or to Aberdeen. I report a study that shows how the idea of apoptosis reaches a clinical question today: "Real-World Outcomes of Venetoclax in Relapsed/Refractory Chronic Lymphocytic Leukemia" by Odabasi Giden, Özatlı, Erkurt, Karakus and colleagues, published in Hemato in 2026 (volume 7, issue 2, doi:10.3390/hemato7020016). According to the abstract, this multicentre, retrospective study evaluated 147 adults who started venetoclax between April 2019 and August 2025; the drug was given alone or with rituximab, obinutuzumab or ibrutinib, and 78.9 percent of the patients received a combination.

Median age was 64, and the median number of prior treatments was two. The authors write that the drug was generally well tolerated, that the main concern was tumour lysis syndrome during dose escalation, and that survival was worse in bulky disease. The abstract does not give the country or the centres of the study; the first author's address is Ondokuz Mayıs University (Samsun). That it is a Turkish study is my inference from this address. I did not read the full text.

This article is Day 153 of the "365 Days of Cancer History" series and presents the naming of apoptosis as a historical reading. It is historical-popular content; it is not a diagnosis or a treatment recommendation. Consult your physician for treatment decisions. The sources have been verified; details resting on a single secondary source, on an abstract only, or on a text that could not be read are marked in the fact-check notes.