By Lisa Seachrist

Washington Editor

WASHINGTON — Not only wasn't Dolly a fluke, she's got a lot of company now.

Researchers from the University of Hawaii have used a new technique to clone more than 50 mice in an experiment that not only cloned adult mice, but created clones of clones.

The experiments, published in the July 23, 1998, Nature, bring science closer to the day when human clones could be created and likely will heat up the debate over that possibility.

A team of scientists led by Ryuzo Yanagimachi created the mouse clones by microinjecting the DNA from an ovarian cell, called a cumulus cell, of an adult mouse into an enucleated mouse egg. Unlike the Scottish experiment that created the cloned sheep Dolly, the Hawaiian procedure did not rely on electricity to fuse the egg and adult cell. In addition, the Hawaiian team created second and third generations of clones.

As yet, the team hasn't been able to clone males with the analogous testicular tissue. However, Yanagimachi considers that feat only a matter of time.

In the process of creating the mouse clones, the Hawaiian researchers tore down a presumed technical barrier to animal cloning and further toppled dogma surrounding the ability of DNA from differentiated cells to direct the development of a complete organism.

When Dolly was reported last year, many scientists reasoned sheep cloning simply could be a novelty because the DNA in sheep embryos need not be active until relatively late in development. In humans, the embryonic DNA must direct the show much earlier in development, and in mice the time frame is even earlier. With mice now successfully cloned, it has become quite clear the potential for human cloning is real.

"A lot of people were deriving solace from the hope that we wouldn't be able to clone humans," said Erik Parens, a research associate with the Hastings Center in Garrison, N.Y. "Now, it looks likely that it will be technically feasible. Since we already have people who have said they want to clone a human, there is good reason to believe that someone will attempt it."

Newly Cloned Species Raise Specter Of Human Tests

For now, such an attempt would run afoul of the FDA. The agency has stated — in the aftermath of Chicago physicist Richard Seed's disclosure he intended to clone humans — it would assert its regulatory authority over such activities. (See BioWorld Today Jan. 15, 1998, p. 1.)

"The FDA has been quite clear that it has the authority to regulate cloning and that it will not allow attempts to create a human clone because of safety issues," said Carl Feldbaum, president of the Biotechnology Industry Organization. "The safety issue still appears to be a concern. It took 277 attempts to create Dolly; with the mice it was something like two or three out of 100."

While such a low efficiency and questions about longevity and general health make it unlikely the FDA would allow clinical trials of human cloning, as more and more animals are cloned and the technique is refined, the safety argument may become less an issue.

"In the short- to mid-term, we have some time," Feldbaum said. "I think we will find that as one animal species after another is cloned, we will find increasing pressure to dispose of the human cloning issue. All of our surveys, focus groups and everyday experience tells us that there is a strong fundamental feeling that we are not ready in terms of safety, morality and experience to move ahead with any potential for human cloning."

In its June 1997 report to President Clinton, the National Bioethics Advisory Commission (NBAC) suggested Congress legislate a five-year moratorium on attempts to clone humans in order to take a longer, more reasoned look at the issue. (See BioWorld Today, June 9, 1997, p. 1.)

"We haven't taken enough time to really look at the issue; it seems like a five-year moratorium is a good idea," Parens said. "This a large social question which brings up issues of relationships between people and how we view ourselves. To suggest that we understand the implications of human cloning strikes me as just loony."

Feldbaum noted that while BIO was firm in its opposition to human cloning, attempts to legislate human cloning bans in the supercharged atmosphere of an election year would prove difficult and could result in banning necessary and desirable avenues of research.

"We are remaining very watchful as each of these events transpires so there is no misguided effort to ban legitimate research," Feldbaum said.

This year already, Senate Majority Leader Trent Lott (R-Miss.) attempted to bypass the committee process to pass a cloning ban that was framed in the language of the highly contentious abortion debate.

In the House, Rep. Vernon Ehlers has introduced two bills to ban human cloning that he said won't impinge upon legitimate research. However, academic and industry representatives have disagreed.

While NBAC attempted to avoid the human embryo research and abortion debate in completing its report to the president, Parens said people will have to accept that inserting DNA into an enucleated egg creates an embryo.

Nature Report Confirms Dolly's Status

"I am a staunch supporter of some regulated embryo research," Parens said. "But I don't think we can honestly talk about things like the potential to grow tissues using cloning without entering the human embryo research debate."

With a couple of generations of cloned mice, it appears certain Congress will be engaging in that debate in the near future.

As for Dolly, in the July 23 Nature, Ian Wilmut and researchers from the Roslin Institute, in Edinburgh, Scotland, as well as a group from the University of Leicester, confirmed Dolly was an actual clone.

In the aftermath of the report of Dolly's existence, some scientists publicly called into question whether the ewe was a clone of an adult because the sheep that served as Dolly's DNA source was pregnant when the experiment was conducted.

As a result, it was possible the DNA source for Dolly was a fetal or embryo cell, and cloning from these cells already has been accomplished. *

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