Sunday, December 31, 2000		Article

THE CELLS OF IMMORTALITY

Scientists are tinkering with the natural limits on life span and discovering biological clocks ticking away in each of our cells with the knowledge of how to reset those clocks. Man can now play God, control ageing and lenghten life.

For much of her life, Jeanne Calment's big claim to fame was that she sold pencils to Vincent van Gogh in her youth. But by the time she died in the August of 1997, the charming Frenchwoman had made her way into the Guinness Book of World Records for a grander accomplishment. She had become the longest-lived human on record, dwelling 122 years, 5 months, and 14 days on Earth.

That remarkable record is almost certain not to last long. As medical research teases apart the body's natural aging processes, the promise for extending the average life span beyond Calment's years is growing rapidly. "Over the next 50 years we'll be completely reshaped by biology," says Gregory Stock, director of the programme on Medicine, Technology, and Society at University of California-Los Angeles Medical School. "We'll double human life span, but this will be the small part of all that will happen." A conference at the University of Pennsylvania some time back drew together scientists, theologians, and bioethicists to prepare for the time when people live much longer than is the norm today.

Some see great benefits, others point out ethical quagmires, and all acknowledge that an unprecedented leap in life span will have ramifications as monumental as any event in human history.

Over the past century, vaccines, antibiotics, and good sanitation have upped the average American's life expectancy by decades, to today's 74 years for men and 79 for women. Now, new understandings of the genes and chemicals involved in aging may not only help humans live far past that age but, more important, may also help people retain health and strength in those latter years. The discovery of biological clocks ticking away in each of our cells, and a knowledge of how to reset those clocks, open the possibility that a human would never die–at least not from old age.

Two basic sources of aging affect all of us, and science is finding ways to outwit them both. In the first category are mishaps–assaults from outside the body and mistakes from within–that weaken the system over time until organs simply can't function any longer. Just the act of living contributes to this slow decay: Whenever we take a bite of food, for example, the body makes free radicals, unstable and highly active molecules that tear destructively through cells. "Although the body tries to repair the damage," says Wayne State biologist Robert Arking, "it's never quite as good as new." Using the newest techniques of genetic medicine, scientists are finding ways to prevent this wear and tear. At the University of Colorado-Boulder, for example, geneticist Thomas Johnson has found that by tweaking a certain gene in roundworms to create a "super antioxidant gene," he can double the worms' life span. The altered gene produces an abundance of chemicals that find and destroy free radicals before they ever wreak their havoc.

Research on the second natural aging process points to even more-dramatic possibilities. Genetic codes dictate how long any given organism should keep functioning, and these codes vary from species to species; that's why some insects live only a day, cats live about 20 years, and a type of holly plant in Tasmania lives more than 40,000 years. Evolutionary biologist Michael Rose, at the University of California-Irvine, has created fruit flies with special "longevity genes" simply by breeding flies at older and older ages. "Nature doesn't give a damn about you after you reproduce," he explains. "After 40, you're toast–you don't have to be fit any longer, and you decay." But by finding flies whose genes enabled them to reproduce later and later in life, he created a strain of flies that live twice as long as normal fruit flies. Finding longevity genes in humans could yield similar results. The beauty of longevity genes, says Arking, is that they not only allow creatures to live longer but actually delay the onset of senescence. "It's as if you reach the age of 20 and stay put there for decades," he says. "Then at age 40 or 50 or 60, the clock starts ticking again and you are 21."

But even if everyone were to receive special longevity genes, each cell in the body nonetheless carries the plans for its eventual death right in its DNA. At the end of each chromosome is a long strand of "nonsense" DNA called a telomere. Each time a cell divides, the strand gets a bit shorter, like a burning candlewick. When it runs out, the cell can no longer divide and is left to age and die. But scientists have found that the enzyme telomerase can rebuild the strand over and over again.

No one has yet figured out how to make an immortal human being from a bunch of immortal human cells, but some researchers are coming close to at least creating human parts that might not wear out. At Advanced Cell Technology in Worcester, Mass., scientists have found that by merging a body cell, such as a lung cell, with a cow egg stripped of its cow DNA, they can "reprogram" the cell to rebuild its telomere strand, and also to grow into a whole new organ. Recently, scientists created a new bladder with this method and successfully transplanted it into a dog. The company is now trying to develop heart "patches" that can strengthen ailing hearts in humans. Robert Lanza, director of transplant medicine at ACT, predicts that it will be routine for today's 40-year-olds to trade in old parts for new and improved ones by the time they reach age 70.

That is, if science proceeds unchecked by those with ethical objections. When human DNA is merged with an egg, as it is at Lanza's company, it creates "pre-embryonic" cells that in theory might be able to develop into a human being. And many cells that other researchers use are gathered from embryos discarded by in-vitro fertilisation labs.

Michael Fossel, is a medical professor at Michigan State University who works with children who age prematurely and die by age 12. "I'm not recklessly searching for a fountain of youth," Fossel says. "I'm trying to cure disease and prevent suffering." Aging research can battle almost every known disease, he says, from diabetes to cancer.

Good or evil? Even if scientists could avoid the controversial cells now needed to advance research, they would still hit opposition from those who find the very idea of dramatically extending life to be immoral. "We can make it socially despicable," says bioethicist Daniel Callahan, a senior fellow at Harvard Medical School. "Just like nuclear testing, we can decide that we don't want it." Fellow ethicists use equally strong words about the selfishness of the endeavour. " Others foresee a dangerous future where overpopulation leads to draconian rules about childbearing, and where only a favoured few are allowed to live a second century.

Robert Pollack, director of science and religion studies at Columbia University, offers the reminder that one of Hitler's favourite slogans was: "Politics is applied biology."

Apart from social-justice concerns, many theologians feel that attempts to live indefinitely are a slap in the face to God. God created death for a good reason, they say, and to destroy death would be to destroy our own humanity. But others, scientists and theologians alike, celebrate our coming longevity. Says Rabbi Neil Gillman of the Jewish Theological Seminary: "God is life itself, and we are not only justified, but we are obligated to do everything we can to extend life."

Science is working on several possible weapons to hold off aging and death:

Just a few skin cells could yield the DNA needed to build a new heart, lung, or liver that might never wear out.

The brain is one organ that cannot be replaced, but young neurons could be injected to take over the tasks of ailing cells.

Many animals live up to twice as long when they eat just 60 per cent to 70 percent of the normal number of calories.

Aged immune cells might be removed from the body, altered to a youthful state, and reinserted to invigorate the system.

Certain genes might be coaxed to produce extra defenses against free radicals, dangerous molecules that ravage the body.

When cells have access to a protein called telomerase, they lengthen the telomere tips of their DNA and live indefinitely

Substances abundant during youth, such as growth hormone, estrogen, and testosterone, can stave off aging later.

Glucose binds proteins together into a gunk that ruins organs, nerves, and tissue. New drugs might prevent the blobs.

—Joannie Schrof Fischer