- Person
- H. Robert Horvitz
- Lived
- b. 1947
- Field
- Genetics, cell death
- From
- American
The story
H. Robert Horvitz, the Chicago-born grandson of Jewish immigrants from the Russian Empire and Galicia, came to biology late: he studied mathematics and economics at MIT and took his first biology course in his final year. After a doctorate at Harvard, he joined Sydney Brenner in Cambridge, England, to study Caenorhabditis elegans, a transparent worm about a millimetre long in which every individual develops in exactly the same way.
Working with John Sulston, Horvitz traced every cell division in the developing worm. The map showed that the worm makes 1,090 cells, and that exactly 131 of them always die, the same cells each time. Cell death was part of a program. At MIT from 1978, Horvitz set out to find the genes that run that program. In 1986, with his student Hilary Ellis, he identified the first two true death genes, ced-3 and ced-4, both needed for a cell to die. His laboratory then found ced-9, which protects cells by holding the death genes in check, and showed that ced-3 resembles a human enzyme and that ced-9 is the worm version of the human gene BCL-2. According to the Nobel committee, most of the genes that control cell death in the worm have counterparts in humans.
The finding mattered because the balance between cell birth and cell death is vital to health. When too few cells die, damaged cells can survive and grow into cancers; when too many die, the result can be neurodegenerative disease or damage after a stroke or heart attack. Many cancer cells survive by over-producing BCL-2, the human counterpart of ced-9. Drug developers designed molecules to block it, and in April 2016 the US Food and Drug Administration approved venetoclax, the first BCL-2 inhibitor, for chronic lymphocytic leukaemia. The drug works by switching the cell’s own death program back on.
Horvitz shared the 2002 Nobel Prize in Physiology or Medicine with Brenner and Sulston. After his father developed ALS, he also joined a collaboration that in 1993 found SOD1, the first gene known to cause inherited ALS.
Why it matters
Horvitz’s cell-death genes revealed a pathway that is now the target of cancer drugs such as venetoclax, which helps patients with leukaemia by restoring cancer cells’ ability to die.
About H. Robert Horvitz
Chicago-born MIT geneticist who found the genes that tell cells when to die, a pathway now targeted by cancer drugs such as venetoclax, and who helped find a gene behind inherited ALS.
Sources
- Press release: The Nobel Prize in Physiology or Medicine 2002 NobelPrize.org
- H. Robert Horvitz, Biographical NobelPrize.org
- FDA approves venetoclax for chronic lymphocytic leukaemia The Pharmaceutical Journal
Another act of tikkun olam. This is part of tikkun olam, the Jewish idea of repairing the world, and every one of us can add to it.