Magazine article Science News

A Time to Live, a Time to Die: Biologists Probe the Genetics of Programmed Cell Death

Magazine article Science News

A Time to Live, a Time to Die: Biologists Probe the Genetics of Programmed Cell Death

Article excerpt

"First, you murder," Michael O. Hengartner forthrightly told a horde of expectant faces. "Next, you get rid of the body. Then you hide the evidence," he explained, pacing back and forth in the dimly lit room.

Hengartner wasn't instructing a group of apprentice hit men. Instead, the Massachusetts Institute of Technology (MIT) biologist was addressing a gathering of cancer researchers, detailing the functions of a recently identified set of genes that controls life's only inevitable process: death.

Together, Hengartner and his MIT colleagues constitute one of scores of research teams around the world who are reviving scientific interest in the molecular mechanisms of a phenomenon called apoptosis, or programmed cell death. Among other things, this phenomenon (pronounced apa-tosis, with the second "p" silent) prevents humans from having webbed fingers and eliminates cells of the immune system that can't tell "self" from "nonself." It also underlies metamorphosis -- the magic wand that turns caterpillars into butterflies and tadpoles into frogs. In adults, it phases out old body cells so they can be replaced by new ones.

Over the past year, biologists from a range of disciplines have uncovered evidence that this seemingly salutary process has a dark side. Several new studies suggest that apoptosis can play roles in AIDS and autoimmune diseases; others indicate that disruptions in the usual orderly progression of apoptosis lead to the uncontrolled cell growth of cancer.

Apoptosis -- which means "dropping off" in Greek--was first described in 1951 as a step in animal development. The process takes its name from its appearance as it unfolds under the microscope: Within minutes, cells undergoing apoptosis shrink and shed tiny, membranous blebs that neighboring cells quickly gobble up, mirroring Hengartner's colorful description. In contrast, during necrosis -- cell death arising from injury -- cells swell for hours and then burst, spraying their contents about as a chemical signal that attracts immune-system cells to fight the injurious microbe or substance.

In the late 1960s and early 1970s, researchers began gathering evidence that apoptosis occurs as part of the normal turnover and replacement of worn-out tissues in adult organisms. They discovered that apoptosis resembles suicide in some ways: Old cells actively participate in their own demise by turning on genes and making new proteins that will shortly cause their death.

Since the mid-1980s, cell biologists and geneticists have started sorting out the causes and implications of apoptosis in a wide range of animals, including humans. Last spring, they began reporting evidence of the role played in apoptosis by the cancer-causing c-myc gene -- named for its initial discovery in myelocytomas, tumors consisting of tightly packed bone marrow cells.

The c-myc oncogene becomes overactive in a wide range of mammalian tumors, including human cancers of the breast, bladder, colon, lung, and cervix (SN:6/1/91, p.347). In many cases, c-myc's hyperactivity begins when a cell inexplicably creates extra copies of the gene, reproducing it over and over within the cell nucleus.

Because cells with such c-myc amplifications grow and divide nonstop -- and further, because the c-myc gene encodes protein-containing regions that can bind to DNA -- scientists hypothesize that c-myc regulates other genes involved in cell division. Ironically, Gerard I. Evan of the Imperial Cancer Research Fund Laboratories in London and his colleagues reported in the April 3 CELL that c-myc can also cause apoptosis under certain conditions.

Evan's group found that while laboratory-cultured cells with hyperactive c-myc genes can grow faster than cells with less active c-myc genes, they also die faster than those cells when deprived of growth medium. Moreover, the researchers noted, the cells with overactive c-myc genes died with all the visible hallmarks of apoptosis. …

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