The science of cellular suicide.

The science of cellular suicide

From the earliest days of an organism's development, right up until the bitter end, new cells are born and old ones die. Moreover, cell death can occur in predictable patterns, especially during embryonic development. The fetal hand, for example, looks at first like a paddle. Fingers emerge only after the death of parallel rows of cells.

But what is the actual mechanism of programmed cell death? Do cells simply wither away when their time has come, or do they play an active role in their own demise? Recent research suggests that cells may have suicidal tendencies.

Lawrence M. Schwartz and Brian K. Kay, at the University of North Carolina in Chapel Hill, are exploring mechanisms of cell death in the tobacco hawkmoth. The moth is a popular model of development; it is easily reared in the laboratory, and major anatomical changes can be traced as it undergoes the process of metamorphosis.

The researchers looked at a particular kind of muscle cell that spontaneously degenerates within 36 hours after the emergence of an adult moth from its cocoon. They identified five proteins that are not produced in the cells until just before cell death. To see whether these proteins are crucial to cell death, they treated some moths with a chemical that blocks new protein synthesis. Muscle cells from those moths failed to develop the five proteins, and the cells did not die.

The researchers are currently attempting to inject small quantities of these "cell death' proteins into living, cultured cells, to see if they can stimulate early cell death. They theorize that under certain conditions, hormone levels in the insect (and perhaps in higher animals) "turn on' cell-death genes that code for the production of deadly proteins. They hope that a better understanding of normal cell death may provide insight into diseases in which cells die at inappropriate times, or don't die when they should.

Related research by David Martin and his colleagues at the Washington University School of Medicine in St. Louis suggests that suicide is an inherent tendency in some cells, and that constant intervention is required to prevent it from occurring.

Particularly intriguing are their findings that nerve growth factor (NGF), recognized for years as a critical ingredient for cell growth, may be more properly considered a "death-preventing factor.' Like the North Carolina group, the St. Louis researchers found that cell death didn't occur when protein synthesis was blocked. "This result indicates that the neurons took an active role in killing themselves, rather than wasting away passively,' the researchers report. They say that those findings, in conjunction with earlier evidence that NGF is needed for cell survival, suggest that "NGF normally suppresses the synthesis of killer proteins' that are designed to kill the cell' when triggered by specific chemical cues.