History and Highlights in Apoptosis Research - 1990s and Later

1990s and Later

In 1991, Ron Ellis, Junying Yuan and Horvitz released a rounded and up-to-date account of research on programmed cell death in their "Mechanisms and Functions of Cell Death". Among other important work at Horvitz's laboratory, graduate students Hilary Ellis and Chand Desai had made the first discovery of genes that encode apoptosis-inducing proteins: ced-3 and ced-4. Michael Hengartner also identified a gene with an opposite effect: ced-9. The product of this gene, which is similar to bcl-2, protects cells from programmed cell death, so its expression conveys a life-or-death decision on individual cells.

In 1992, it was shown by David Vaux and Stuart Kim at Stanford that human bcl-2 gene could inhibit programmed cell death in the worm, thus linking programmed cell death and apoptosis - revealing them to be the same, evolutionarily conserved process.

In 1993, graduate students Shai Shaham and Junying Yuan working in Horvitz's laboratory identified interleukin-1-beta-converting enzyme as the mammalian homolog of the CED-3 enzyme. In 1994, Michael Hengartner published a paper showing that ced-9 had similar sequence to bcl-2.

In 1997, a protein similar to CED-4 was identified and named Apaf-1 (apoptotic protease activating factor). The team published their results in an article entitled "Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3". It identified and reconstituted the mitochondrial pathway to apoptosis and illuminated whole new avenues of research on inflammatory diseases, cancer, and apoptosis in general.

By 1998, research on the topic had already increased, as attested in the editorial "Cell Death in Us and Others", written by an important contributor to apoptosis research, Pierre Golstein, in the 28 August 1998 issue of Science:

Although there have been scattered reports on the topic of cell death for more than a century, the 20,000 publications on this topic within the past 5 years reflect a shift from historically mild interest to contemporary fascination