Why does programmed cell death, or apoptosis, occur? Does it take place among bacteria and fungi or only in the cells of higher organisms?

H. Robert Horvitz, an expert on apoptosis at the Massachusetts Institute of Technology, gives a brief response:

"In short, the question of why programmed cell death occurs should be subdivided into two related questions: Why are cells that die by programmed cell death generated? and Why do these cells die instead of surviving?

"The answer to the first of these questions depends on the cell being considered. For example, some cells are generated in excess and only those that become properly functional survive (as happens in parts of the nervous system). In some cases, the mechanism that generates cells that are needed also fortuitously generates unneeded ones as well (as happens in the immune system). And some cells that die are needed, but only transiently.

"Cells die either because they are harmful or because it takes less energy to kill them than to maintain them. At present, programmed cell death--as it is described based on the morphology of apoptosis and the biochemistry that involves a specific family of protein-cleaving enzymes--has been demonstrated to occur only in animals, although it remains possible that bacteria, fungi and plants use similar processes to eliminate unwanted cells."

Michael Hengartner, senior staff investigator at Cold Spring Harbor Laboratory, offered a more extensive investigation of the question:

"Let's start with the first part of the question: Why does programmed cell death occur? There are several reasons: it gets rid of cells that are not needed, in the way or potentially dangerous to the rest of the organism.

"Cells that are not needed may never have had a function. In other cases, they may have lost their function, or they may have competed and lost out to other cells. In some organisms, especially lower species, there are cells that die off very soon after they are born. There is no clear reason why they ever existed. These cells are probably evolutionary relics that were useful in the past, but no longer serve any valuable function. For an example of cells that lose their function, consider the cells in the tail of the tadpole, which become superfluous when the animal develops into a frog.

"An instance of cellular competition occurs in the developing human brain. The brain makes many more neurons than we need, probably because the body does not 'know' how many neurons will suffice and because wiring together an intricate structure such as the brain is not easy. For example, many neurons will fail to reach their targets--their axons may take a wrong turn or may terminate prematurely. These strays that fail to establish a proper connection will die. Death here functions as a built-in error-correcting mechanism.

"More generally, building a complex organism like a human being is like creating an intricate sculpture. Cell division forms the clay, whereas cell death sculpts the clay into the desired form. Consider human hands, which start out as paddlelike structures. Fingers develop in the paddles, but then the cells in the tissue between the fingers must die for a proper hand to form.

"One of the most fascinating reasons for cell death is to get rid of dangerous cells, those that could be harmful to the rest of the organism. One might say that the cells kill themselves for the greater good. They could be mutants that would become cancerous--apoptosis is therefore very important in the formation (or nonformation) of cancer. Also, positive and negative selection occur among the cells of the immune system. Cells that recognize 'self' (that is, ones that would attack the organism's own cells) are instructed to die during this process. Finally, cells that are infected by a virus can sometimes recognize the infection and kill themselves before the virus has time to replicate and spread to other cells.

"Programmed cell death, in the sense of suicide deliberately induced by the organism, certainly does occur in multicellular plants and fungi; whether it occurs through the same molecular mechanism as the one found in metazoans (multicellular animals) remains to be determined. Cell death is common among plants, especially among the higher plants. The xylem in trees, through which water rises to the leaves, consists of spaces left by dead cells. Cell death occurs very visibly when deciduous trees drop their leaves in the fall. (Incidentally, this is where the name 'apoptosis' comes from: it is the Greek word for the falling of leaves from trees, as well as the losing of hair from balding men--which incidentally is also thought to involve apoptosis!) Plant cells cannot move, so plants use a slash-and-burn technique to cope with infection: all the cells in an infected area may kill themselves to halt the spread of the disease.

"Is there programmed cell death among single-celled organisms? The answer gets caught up in a question of semantics between a cell choosing to die and being forced to die. But some forms of programmed death are found in unicellular organisms, including bacteria. The death of the mother cell during sporulation, the process in which spores are created, could be considered a kind of programmed cell death. Certain parasites, such as trypanosomes (which cause malaria), change form to elude the immune response from their host; the laggards who o fail to undergo the change will die off in a kind of cellular altruism.

"Another parallel example occurs among slime molds, such as Dictyostelium discoideum, a species at the interface between unicellular and multicellular organisms. These animals spend most of their lives as unicellular amoebae. But, when starved, the cells aggregate and meld into a single 'slug' that migrates and eventually forms a funguslike structure, consisting of a stalk topped by a ball of spores. The spores disperse in search of a more hospitable environment. The stalk cells do not reproduce, so in a sense they sacrifice themselves. In most single-celled organisms (particularly bacteria), it is not clear whether cell death follows the same pattern or biomolecular mechanisms as the apoptosis that occurs in higher organisms.

"One highly unusual form of cell death occurs in cells infected by certain plasmid viruses that instruct the host cell to create two chemicals: a long-lived toxin and an unstable antidote. During replication, about 1 percent of the cells lose the parasitic plasmid in their DNA; the daughter cells still contain the toxin but can no longer manufacture the antidote, so they die. This is a rare instance of cellular murder rather than suicide.

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