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: and .
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."
Which would not necessarily be bad, Smith says.
"I'm fairly ambivalent. I'm not sure it's going to be a horrible situation," Smith says of the possibility of human cloning. "For one thing, I can't imagine it will be that popular. I doubt it's a thing most people are going to demand. So say that one percent of the population decides to clone itself. I don't know that that would do anything horrible to population diversity. And I think it's possible that useful possibilities may be developed for human cloning.
One example Smith offers is the possibility of using fetal cells to treat conditions such as Parkinson's disease.
"If I have Parkinson's, and I can get someone to donate an egg so I can clone myself and then grow that fetus to, say, 16 cells and then use those cells to treat my condition, it could be argued that it would be less ethically problematic to kill a 16-cell organism than a two-month-old fetus," Smith surmises. "A 16-cell fetus has no nervous system, no heart. I'm not endorsing this, but there's the potential for arguing that those two fetuses are very different."
And in animals, Smith believes that cloning will prove to be a very useful tool for research.
"First of all, you're not creating something new," he says. "You're making more copies of a sheep that's already available. Genetically uniform strains of animals and insects are already important in research in the cases of mice and drosophila, and having a way to make lots of genetically uniform animals for research would save a lot of effort."
For now, Smith believes that the issue of cloning requires more thought and less doomsaying. In his opinion, research should continue.
"My reaction is that people are getting upset for emotional reasons," Smith says. "Right now, it's not clear that cloning will be all that problematic. It's not clear that there won't be something useful to come from it. And ultimately, once it's been discovered, we're probably not going to be able to stop it even if we want to.
Jennifer Lobo at Peregrine
That may be because the idea of taking a newly discovered idea and putting it back into its box for moral or ethical reasons is not the kind of thing that occurs to most scientists, says Jennifer Lobo, a Palmer Square-based biotechnology venture capitalist and CEO of Peregrine Pharmaceuticals, a developer of cancer treatments (U.S. 1, February 19, 1997).
"I don't think most scientists are thinking about ethical issues when exploring new technology," Lobo says. "They're more concerned with solving a part of the puzzle. It occurs to them, sure, but solving the puzzle is the focus."
Lobo compares the ethical questions raised by cloning to other questions raised by identifying new genes, which unlike cloning is a major area of current biotechnology research.
"Think about identifying new genes that cause certain kinds of diseases," she says. "There are many ethical issues. Do you tell a patient that they may develop a terminal form of a disease because of something in their genetic makeup? Do you tell a child that because of a genetic disorder, he may have only 20 years to live?"
Those kinds of questions are important ones, Lobo says, but they don't constitute reasons not to identify genes that may play a role in disease development. Likewise, the fact that there are ethical questions raised by cloning does not mean that research on the subject should stop.
"Cloning is already common in all kinds of research," Lobo notes. "People clone genes every day of the week to produce new drug products. Cloning a whole animal is a considerably greater task, certainly, but the only thing that makes it different is that it's pretty dramatic."
And as Lobo notes, cloning technology may lead to many useful new advances in treating disease. She points to the example of Chrysalis, a contract research organization involved in the development of transgenic animals in Raritan that was formerly known as DNX and based in Princeton (US 1, February 26, 1992).
Paul Schmitt at DNX/Chrysalis
"This will shorten the time frame it takes to breed transgenic animals by at least two to three years," Paul Schmitt, CEO of Chrysalis, told the Wall Street Journal. Schmitt notes that once scientists have inserted human genes into the embryo of an animal that will give it useful characteristics for human healthcare and have thus created a transgenic animal, they must wait through years of breeding programs to develop a herd of animals that share the useful trait. With cloning, transgenic researchers may eventually be able to bypass the time consuming and not always successful breeding route by creating exact copies of animals with the trait.
But not everyone in biotechnology believes that the potential represented by cloning automatically outweighs the risk of unseen consequences.
Don Drakeman, CEO of Medarex, an Annandale-based company that researches monoclonal antibody therapeutic agents for cancer, auto-immune, and infectious diseases, supports a temporary moratorium on cloning research until people have had an adequate opportunity to think things through.
"You'll be hard-pressed to find anybody who has been able to give it a lot of mature thought at this early date," says Drakeman, a lawyer who also has a Princeton University Ph.D in religion. He set up Medarex in 1990 in Princeton but moved the corporate headquarters to Annandale (U.S. 1, July 17, 1991). "Most people either thought it was impossible or expected it would happen well into the future. So I think the extent to which science should use these possible tools in human healthcare or in human use at all needs to be studied real hard. It's a prospect that until now nobody had really thought about."
Because cloning entire animals is so surprising, so unexpected, and so distant from anything technology has previously been able to accomplish, Drakeman believes that the biotech industry needs to exercise extreme caution.
"Declaring a moratorium before banning it may be a good approach," he says. "We have to get our theology and philosophy and legislation all sort of thought through in light of this extraordinary new set of circumstances."
Others, however, are less circumspect, among them the Green Party of New Jersey. Cloning "not only makes my blood crawl, it makes it boil," wrote the party's Greg Merritt in an E-mail widely distributed February 26. "I don't think we should be cloning any animals, let alone humans!"
Merritt believes that the risk of high disease rates among cloned animals and a possible reduction in biodiversity make necessary a total ban on cloning, including plant cloning, widely used in agricultural research. "The genetic manipulation of life on this planet in the hopes of eventual profit is insane," Merritt writes. "The moral, spiritual, ethical issues alone convince me."
Max Stackhouse, UCC
Well, it does raise interesting questions," says Max Stackhouse, an ordained United Church of Christ minister who teaches Christian ethics at Princeton Theological Seminary. "The larger issue is, should humans have control over the totality of their own destiny, and whether for religious, theological, or moral reasons there should be limits."
In terms of animal research, Stackhouse does not believe that cloning is particularly problematic. He notes that through breeding humans have long controlled the characteristics of generations of farm animals. But human cloning is another matter.
"When you begin thinking about what it means for humans, it seems a little like atomic research," Stackhouse says. "We cracked the atom, and now we've cracked the genetic code in a certain way. And just as with the atom, this can create great energy and promise, but also damage. It think that with the idea of human cloning we do have the spiritual danger of people playing God."
That danger is not necessarily imminent, Stackhouse notes. No one knows yet if humans can be cloned. And there remain important questions about Dolly the Sheep as well. Because her DNA came from an adult sheep, it may be older than she is -- that is, the naturally occurring age-related degradation of certain chromosomes may mean that Dolly's genetic age is six years, even though her chronological age is just seven months. Dolly's health will be watched very closely.
"On the other hand, there is a need for humans to be responsible stewards of the minds and hearts that we've been given," Stackhouse says. "And it's conceivable that this kind of research could lead to better control of some genetic illnesses, and so it should be explored. But there are perils hovering in the corners of even that suggestion. If we can manipulate something for good, chances are we can also manipulate it for evil."
