By Lisa Seachrist

Washington Editor

WASHINGTON - The FDA has stated, in no uncertain terms, that it intends to regulate any attempts to clone a human being.

However, just exactly how the agency will assert its authority over such attempts is still a work in progress. The agency's director for cellular and gene therapies, Philip Noguchi, headed a panel discussing the pitfalls of regulating emerging technology at the Annual Educational Conference of the Food and Drug Law Institute.

"I used to end all of my talks by saying that what can be imagined will be done," Noguchi said. "Now, we are asking, 'Even if you can imagine it, should it be done and when, if at all?'"

Prior to January, the FDA was willing to defer to the National Bioethics Advisory Commission for the ethical issues surrounding cloning. Noguchi noted that, when Richard Seed announced that he intended to clone a human being within two years, that was "the signal in the area of human cloning and how it relates to human reproduction and other areas that no one could remain neutral about the issue."

With wire reports this week that South Korean scientists have used somatic cell nuclear transfer to create a human embryo, the agency's efforts to establish the regulatory framework that will govern the technology seems an even more pressing need.

The Korean scientists reportedly injected a fertility patient's ovarian cell into an egg from which DNA had been removed and let the embryo divide twice, into four cells, before ending the experiment. Researchers elsewhere expressed skepticism about the effort.

Noguchi stated quite plainly that, using its current regulations related to tissue, the agency would block attempts in the U.S. to clone a human being as having unacceptably high risks to human subjects. More complicated now is the regulation of cell therapies derived from pluripotent stem cells, which have the potential to become any cell in the body.

"From an FDA viewpoint, if you are going to use pluripotent stem cells that are going to develop into a therapeutically useful cell line, that potential is the promise and the problem," Noguchi said. "If nothing is fixed, then anything can happen."

Noguchi noted that, when a researcher starts with a single cell that has multiple potentialities, there is no room for error. For example, he told BioWorld Today, it's possible to have two populations of stem cells that are both "normal," but, by virtue of their individual genetic makeup, one cell line may not reliably produce particular types of cells in vitro.

"Quality control is vital at this early stage," Noguchi said. "From what we are learning from developmental biology, even a little bit of a change in a certain pathway can just lead to disaster farther down the road."

As a result, the agency must consider looking at the source material for these cell lines, although Noguchi said he has no interest in making such an invasive foray into the laboratory a routine function of the agency. Nevertheless, he pointed out that it would be quite important to know whether the embryo that served as the source of the stem cells was from an HIV-infected couple.

In addition, he said, in order to grow the stem cells, the researchers are relying on a layer of mouse cells to serve as a feeder layer in culture, which would invoke the agency's oversight on xenotransplantation.

"The complexity of these technologies isn't new - we've seen it with gene therapy and xenotransplantation," Noguchi said. "We still do not have a very satisfactory way to weigh not only the science and the safety concerns, but to balance that against the ethics of a given situation."

Last February, Congress attempted to alleviate that dilemma as it pertains to cloning, with a Senate bill that would have banned somatic cell nuclear transfer to produce a human embryo. Framed as it was in the terms of the abortion debate, the measure met with opposition and failed to pass. Nevertheless, 38 states appear ready to consider anti-cloning measures.

The problem with such legislation, according to Gillian Woollett, associate vice president of biologics and biotechnology for the Pharmaceutical Research and Manufacturers of America, is that it inadvertently bans legitimate uses of technology.

"We have to be very, very precise in wording legislation," Woollett said. "What is it exactly that you are against? If you ban a technology, you risk a new technology coming up that will result in a cloned human being." *