Hypotheses



DEATH WISH
Do our cells want to commit suicide?

IN 1929 JAMES THURBER AND E.B. White asked, "Is sex necessary?" Seven decades later the answer remains shrouded in mystery. We have, however, made some progress on a related question: Is death necessary? The answer appears to be yes–because of sex.

For the first billion years after life appeared on earth, death was a contingent thing. The single-celled organisms that existed back then were essentially immortal. They reproduced over and over again by fission. Given enough food and protection from predators, they never died.

Only when sex entered the picture did death become inescapable. Living things that reproduce sexually have two kinds of cells. Germ cells, which give rise to sperm and ova, pass their DNA on to the next generation. Somatic cells, though required for sexual reproduction to take place, do not. The cells in our muscles and brains and hearts and lungs and just about everywhere else are somatic. The DNA in these somatic cells controls their day-to-day operations. Over time, however, this somatic DNA accumulates errors in the form of mutations–errors that make the genetic material not just irrelevant but harmful. That is why every somatic cell has embedded in it a self-destruct program–a death gene. After a certain predetermined span, the cell stops dividing and commits suicide.

The DNA in germ cells, by contrast, is destined to be implanted in another organism. Not surprisingly, these cells have lots of DNA-repair enzymes that prevent the buildup of dangerous mutations. Furthermore, once enough copies of the germ-cell DNA get out into the world, sexual reproduction is no longer necessary. The somatic cells might add up to the familiar structures and faculties that make sexual congress mechanically (and tactically) possible, but they become just so much excess baggage.

These discoveries are of recent vintage and they remain controversial. Cellular suicide was first described in detail in 1972 by three Scottish scientists at the University of Aberdeen, who gave it the name apoptosis, from the Greek meaning "falling away," as in petals from a flower. Other parts of the picture–like the Hayflick limit, the number of times a somatic cell can divide before its self-destruct program goes into effect–have been supplied since. A complete and superbly written account of it all can be found in Sex and the Origins of Death (Oxford, 1996), by UCLA microbiologist William R. Clark.

The division of labor between somatic and germ cells is eminently reasonable from the DNA’s point of view. From our point of view it is terrible. Gonads aside, we are agglomerations of somatic cells. Our brains–the seat of our consciousness, of our selves–are made up of components intent on commiting suicide as they become genetic garbage. Even if we evade disease and accident, senescence is sure to set in as more and more of our cells undergo programmed self-extinction. When enough of them die, so do we. In Clark’s neat formulation, "Sex can save our germ cells, but it cannot save us."

But what if we could somehow turn off the suicide program in our cells? Mightn’t that be the first step toward bodily immortality? In fact, this seems to be precisely how a rather creepy form of immortality was conferred on one Henrietta Lacks, an African-American resident of Baltimore. In 1951, Lacks, a mother of four then just entering her thirties, was admitted to Johns Hopkins Hospital with cervical cancer. A piece of her tumor was removed and as it happened, passed on by the pathologist to a researcher who was trying to grow human tissue in vitro.

The cells from Lacks–labeled HeLa, from the donor’s first and last names–were astonishing. Unlike other human cell lines, which would grow for a while and then peter out, HeLa cells proliferated nonstop and consumed food voraciously. They seemed to have no senescence clock. Since this made them perfect for studying human cell biology, they were distributed to researchers all over the world. They were even sent into orbit aboard the Discover 17 satellite.

Once introduced into a lab, HeLa cells were so vigorous that they crowded out the other human cell lines. In the mid-1960s it was discovered, to the horror of medical researchers, that hundreds of published scientific papers supposedly describing how certain heart cells or liver cells behaved were actually about HeLa cells. (The fascinating story is recounted in Michael Gold’s A Conspiracy of Cells: One Woman’s Immortal Legacy and the Medical Scandal It Caused, SUNY Press, 1985.)

Since then, the exponential growth of HeLa cells has continued apace. Somehow–scientists are not sure how–their "death genes" have been deactivated. The number of them around the world today (and in space!) defies comprehension. Each contains a genetic blueprint for constructing Henrietta Lacks–who died back in 1951.

This is not the sort of deathlessness anyone desires. We want the immortality of a god, not of a tumor.

Or do we want even that? Most of us harbor a lively fear of death, but that fear is not logically equivalent to a craving for immortality. Though several interesting scientific schemes for immortality are afoot today (I’ll describe them in a subsequent column), there is something very compelling about George Bernard Shaw’s conclusion, at the age of ninety-two, that personal immortality would be an "unimaginable horror."

"What man," Shaw asked, "is capable of the insane self-conceit of believing that an eternity of himself would be tolerable even to himself?"

JIM HOLT


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