 A few of the cloned mice from the experiment announced Wednesday. (Reuters) |
Cloning
Scientists Clone Mice
By Rick Weiss
Washington Post Staff Writer
Thursday, July 23, 1998; Page A01 Using a new and relatively simple cloning technique, scientists in Hawaii have created dozens of cloned mice, marking the first documented cloning of adult mammals since researchers in Scotland announced the birth of Dolly the sheep last year.
Researchers predicted that the newfound ability to study and practice cloning in a laboratory animal as convenient as the mouse would quickly lead to the discovery of even better techniques for cloning various animals -- including, almost certainly, people.
Indeed, one of the key findings of the new work is that a biological roadblock scientists thought might interfere with their ability to clone mice and people is not insurmountable in mice after all, suggesting that human cloning is also achievable with relative ease.
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"I'm absolutely convinced it will happen," said Lee Silver, a professor of genetics at Princeton University, "and I think it will happen sooner than we thought a year ago."
Silver said he would not be surprised if a person were created by a cloning technique within five years.
Separately, two teams of scientists yesterday reported they had used sophisticated DNA fingerprinting techniques to prove beyond doubt that Dolly is a clone -- a perfect genetic copy of the adult sheep from which she was made. Some scientists had disputed her authenticity after several efforts to repeat the experiment in other species had failed. (A report from Japan earlier this month that researchers had cloned an adult cow has yet to be confirmed in a scientific journal.)
The proof that Dolly is a clone, together with the new work in mice, effectively ends a 17-month age of innocence when people could still believe that Dolly's fatherless birth was a fraud or a fluke, or that cloning might be possible only in sheep.
The new reports, which appear in today's issue of the journal Nature, prove there are at least two different ways to clone mammals. And although the method used by the Hawaii researchers can be used only to clone females for now, scientists said they suspected the approach will be improved upon to work in both sexes and in other kinds of animals.
"These are exciting results," said Ian Wilmut, the scientist who told an astonished world last year that he and his colleagues had cloned Dolly. "They suggest it will be possible to produce adult clones from a range of different cell types and species."
While exciting to scientists, that prospect prompted ethicists and others to call for a renewed debate about the morality of human cloning, which would bypass the mixing of genetic material from two people that occurs during normal procreation.
"These experiments ought to restart our public conversation about whether it's wise to clone humans," said Erik Parens, a research associate at the Hastings Center, a bioethics think tank in Garrison, N.Y., who expressed dismay with what he perceives to be a growing public complacency about the notion of human cloning.
"Increasingly, people who think of themselves as sophisticated feel that worrying about these things is just silly or fruitless or both," Parens said. "But I think that if we look into the future and see where we can go with these technologies, we'd be faster to criticize or at least to reflect."
The mouse cloning work was achieved in the laboratory of Ryuzo Yanagimachi, a pioneer in mouse biology at the University of Hawaii who encourages his students to work three days a week on their "official" laboratory work and two days a week pursuing novel interests in the lab.
"I encourage them to ask crazy questions," Yanagimachi said in an interview. "Nine out of 10 of them will be truly crazy questions, but one will lead to something important."
Teruhiko Wakayama, a 31-year-old postdoctoral researcher, took that philosophy to heart. Without telling his mentor, he began to experiment with cloning techniques. One day last August, Yanagimachi said, Wakayama called him over to his lab bench. "He showed me a mouse fetus with the heart beating and said, 'This is a clone.' "
Over the next few months the team improved the method, which differs in a few key ways from that used by Wilmut to make Dolly. Most notably, the Hawaiian technique used cells called cumulus cells, which nourish eggs in the ovaries of both female mice and humans. Wilmut used a cell from a ewe's udder.
The first resulting cloned mouse to survive to adulthood, named Cumulina, was born Oct. 3.
Most of the hundreds of cloned embryos the team produced did not survive, but more than 50 cloned mice have been born so far. Many of those have mated and given birth, indicating they are healthy and reproductively normal.
Moreover, the Hawaii team has taken cells from some cloned mice and made "second generation" clones, and has even cloned mice from the clones of clones. "We think that's the first report in any vertebrate species of a clone being derived from a clone," said Anthony Perry, a member of the Hawaii team.
The Hawaiian researchers tried the same technique with cells taken from the testicles of male mice, but the efforts failed for reasons that remain unclear. They believe, however, that they should be able to eventually overcome that problem and clone males.
The efficiency rate in females is still modest, Yanagimachi said -- one or two clones are born for every 100 efforts. But considering how easy it is to work with mice, he said, that is good enough to allow a wide array of experiments that could shed light on the molecular mechanisms of reproduction, the process of cell aging and the genetics of cancer -- a disease characterized by embryo-like cell division.
Moreover, the low cost of working with mice and their rapid two-and-a-half month generation time will advance research into mammalian cloning far faster than has been possible in sheep and cattle.
The technology has been licensed to ProBio America Inc., a biotechnology company based in Honolulu.
Some scientists had believed that cloning would only work in some farm animals such as sheep, which do not actually use their cellular DNA until relatively late in embryo development -- a delay that might give the newly transferred genes time to get reprogrammed by the egg. By contrast, human embryo development requires properly programmed DNA fairly early on, and mice need it even sooner. Yanagimachi's proof that mice can be cloned indicates that the reprogramming happens quite quickly, said Robert J. Wall, a physiologist with the Department of Agriculture.
While the Hawaii researchers refused to talk about potential human applications, saying they are only interested in mice, others said the implications of that discovery were clear. "If you can clone from adult mouse cells," said Silver of Princeton, "there's basically no reason you can't do this in humans."
Researchers have cited several reasons why they would like to clone human embryos, and perhaps even full-grown human beings. Cloned embryos grown from a person's own cells could potentially grow into virtually any kind of tissue or organ and would not be subject to rejection. Although the technology to grow specific tissues from embryos is still primitive, said John Gearhart, a Johns Hopkins University researcher looking into the problem, it may be just a few years before it becomes practical.
Others, including Silver, advocate cloning as an option for infertile couples, including homosexual couples.
President Clinton has banned the use of federal funds for human cloning experiments, and the National Bioethics Advisory Commission has recommended that Congress pass a law banning human cloning in the private sector as well. At least four such bills are dormant on Capital Hill. Several states have passed anticloning bills however, and a number of others are considering similar bills. In the meantime, the Food and Drug Administration has said it would have to approve any human cloning attempt.
© Copyright 1998 The Washington Post Company
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