PPL Therapeutics

Perhaps the most famous part of the Sistine Chapel ceiling is called “The Creation of Man,” where God and Adam sail through the clouds with arms outstretched, the tips of their index fingers just barely touching. Standing in Rome beneath the ceiling your eye is drawn inexorably to that point of contact, the few square inches of plaster and paint that is Michelangelo’s illustration of humanity’s most enduring mystery: the transmission of the spark of life.

The British scientists who cloned Dolly, the most famous sheep in the history of the world after all the media coverage last week, also used a spark to jump-start their creation. But lacking the hand of God, they employed an altogether more prosaic jolt of electricity to coax a sheep ovum — the DNA-containing nucleus of which they had replaced with a mammary gland cell taken from a six-year-old ewe — to life.

In so doing those scientists set off another spark as well, one that has traveled around the globe setting off fierce debates about the possibilities and pitfalls inherent in this brave new world, a world where it is now suddenly and surprisingly possible for scientists to create exact genetic copies of large mammals — perhaps including, someday, humans.

As a center for both biotechnology and intellectual theorizing, Princeton offers no shortage of opinions on the new horizons opened by cloning and its implications. Unlike many of the alarmist scenarios painted by commentators in the national media, however, the view of most Princeton experts is more sanguine. With few exceptions, the Princeton point of view can be characterized as “wait and see.”

“It is a startling development to be able to have cloned a sheep in this manner,” said Harold Shapiro, president of Princeton University. In part as testimony to the university’s importance in the biotechnology field, President Clinton named Shapiro, an economist, to head a bioethics think tank created in 1995. The National Bioethics Advisory Commission is a 15-member advisory panel of legal and medical academics established to counsel the President on biogenetic research, animal husbandry, and biotechnology in general.

Following the announcement about the cloning of Dolly the Sheep, the President directed the panel to review the implications of cloning for humans and report to him within 90 days. Shapiro released a written statement to the press after White House spokesman Michael McCurry announced the directive: “It is very important for us to think extremely carefully about what ethical considerations arise when we even consider the idea of cloning human beings,”

Shapiro need look no further than his own faculty for help. Lee Silver, professor of molecular biology, and Norm Fost, professor of bioethics, have been quoted extensively in the media for their views on the subject (http://www.princeton.edu/~bioethic). We talked to a number of other experts, whose opinions appear below. But first, some background for those who managed to miss the hullabaloo last week regarding the story of Dolly the Sheep.

PPL Therapeutics

On Saturday, February 22, Ian Wilmut, a scientist at a tiny biotechnology company in Edinburgh, Scotland called PPL Therapeutics, announced that after years of work during which only four people knew the full details of what he was doing he had cloned — that is, made an identical genetic copy — of a sheep. Born in July, 1996, the sheep was named Dolly after Dolly Parton, a reference to the mammary cell that was the source of Dolly’s DNA, according to published reports.

Unknown outside the small world of embryology until last week, Wilmut is regarded as a major force in the field, having developed the technology for preserving frozen embryos, which is now widely used in animal breeding and in-vitro fertilization. His company, an offshoot of a government-funded research laboratory, was interested in cloning to further its work in transgenic animals, which are animals genetically engineered for medical purposes, such as producing medically useful proteins in their milk or even growing organs that may be able to be used as transplants in humans.

To clone Dolly, Wilmut and his colleagues took a mammary gland cell from a six-year-old sheep, and by depriving the cell of nutrients in the laboratory put the cell’s DNA into a semi-dormant state. Wilmut then removed the nucleus of a sheep egg cell taken from a different ewe, and inserted the mammary cell into the now nucleus-free egg cell.

Wilmut then zapped the two combined cells with a jolt of electricity, and to general amazement the combined cells acted like a fertilized egg cell and began to divide, using the DNA from the mammary cell as its genetic blueprint. He then implanted the now developing embryo into yet another ewe, and in a few months Dolly was born, an exact genetic copy of the ewe from which the mammary cell had been taken.

This technique, published in the current issue of the British scientific journal Nature, surprised the scientific world because it throws into question previously accepted theories about the nature of DNA.

Scientists had believed that once DNA was in a specialized cell — such as a mammary gland cell, a nerve cell, or a muscle cell — it had lost its ability to issue the generalized commands for all kinds of cells required to create an embryo, and from that a whole animal. Although scientists had already cloned embryos, and although Wilmut himself previously took the nucleus from the cell of a developing embryo and successfully implanted it in an unfertilized egg cell, few believed cloning using DNA from a specialized cell, as was achieved by Wilmut with Dolly, was possible.

Although it was successful, the technique still has a few glitches. Of the 29 eggs implanted into 13 ewes in Wilmut’s experiment, only one, Dolly, actually became a living, breathing sheep. But Dolly alone was enough to raise all kinds of sci-fi horrors in the minds of many: http://www.nsplus.com/nsplus/insight/clone/clone.html and http://www.economist.com. Genetic engineering and cloning has long been a staple of science fiction, from the humans eugenically bred to perform certain tasks in society in Aldous Huxley’s 1932 novel “Brave New World,” to Woody Allen and Diane Keaton’s bumbling efforts to clone a dead dictator in 1973’s “Sleeper,” to Gregory Peck’s creation of 94 little Hitlers in the 1978 film “The Boys from Brazil.”

With the birth of Dolly, many now wonder if those kinds of scenarios might become reality. Will someone clone an entire basketball team of Michael Jordans? Will the fabulously rich and famous, like Bill Gates III, decide that a half-strength Bill Gates IV is just not Bill Gates-like enough and decide to have an exact duplicate made from scratch?

Kelly Smith at CNJ

Not likely, say our Princeton area experts. “What people don’t understand is that with cloning you’re creating twins, and like identical twins that occur naturally, they are not necessarily identical in the sense of personality,” says Kelly Smith, professor of philosophy at the College of New Jersey. “If you cloned yourself, there’s no guarantee that your clone would be just like you. In fact, there are a lot of reasons why your clone would probably be very different in some important ways.”

Your clone would be raised under significantly different environmental conditions than you were, notes Smith, who has master’s degrees in biology and zoology in addition to a PhD in philosophy. He specializes in the philosophy of biology, focusing on the roles of genetics and environment in development and evolution. “The bottom line is, we don’t know much about the relative contributions of the cytoplasmic egg and the nuclear genome,” Smith says, theorizing that the egg cell itself, separate from its DNA-containing nucleus, may play more than just a mechanical role in the development of an embryo. “Add to that the environment in the womb, and then the different life experiences, and I think you’d have to conclude that a lot of the public hype over this thing is overblown.”

Smith notes that your clone would have a different mother than you did. Indeed, your clone could have three different mothers — the egg donor, the mother that carries the fetus, and the mother that raises the child. In addition, your clone would grow up in a world that was different than the world you grew up in. “I’d say the similarities would be even less powerful than with traditional twins,” Smith says of hypothetical human clones. “Even if the clone would look like you, at most you’d get a younger twin, and probably not even that. It would be something between a twin and regular sibling.”

Or in other words, a cloned Hitler might turn out to be a very nice guy. As Smith sees it, genes are not destiny. But that won’t stop people from thinking that human cloning needs to be stopped before it starts, he says. Laws will soon be passed to ban human cloning, and other laws may be considered to put limits on animal cloning, Smith believes. Now that the cat is out of the bag, however, Smith thinks that bans on cloning won’t stop it from happening.

“It’s like nuclear technology,” he says. “Once it’s discovered, it’s difficult to constrain. And unlike nuclear research, cloning is not high-tech in the sense that one needs sensitive equipment or training. Most fertility labs already have a lot of the equipment you need to do this, and there are a lot of people with expertise in molecular biology. If there is a demand, there will be some lab in the world where rich people can get themselves cloned.”

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