Human eggs can turn back time. And that miraculous property captivates stem cell researchers, who need human eggs to make cloned stem cells. But as scientists gear up to do cloning experiments, they are worried that the ethical and medical considerations surrounding egg donation will create a formidable obstacle to their work.

“Without eggs, there’s no research,” says Robert Lanza, vice president of medical and scientific development at Advanced Cell Technologies (ACT), a biotechnology company in Worcester, MA, that plans to clone stem cells. “It’s been a bottleneck for this research from the get-go.”

Scientists want to create cloned stem cells because these cells can be turned into different cell types, such as brain cells or insulin-producing cells, to treat patients with diseases such as Parkinson’s or diabetes. Because the cloned stem cells are genetically matched to the patient, they are not subject to immune rejection. Stem cells created with DNA from a patient could also be used to generate cell lines that exhibit the genetic abnormalities of these diseases, giving scientists new models to study disease (see The Real Stem Cell Hope).

To make cloned embryonic stem cells, scientists insert the DNA of an adult cell into an egg stripped of its own genetic material. The egg, by an unknown mechanism, reverts the adult DNA back to its embryonic state and develops into an early-stage embryo, much like a normally fertilized egg, eventually generating stem cells whose DNA is identical to that of the adult.

This process, known as either therapeutic cloning or somatic cell nuclear transfer (SCNT), has been the source of major ethical debates. Critics, including President Bush, oppose the creation and destruction of human embryos for research purposes, while supporters say the technology will ultimately save human lives.

But even among proponents of stem cell research, a major ethical question remains: How can scientists get enough eggs without putting women at risk?

In 2005, discredited Korean researcher Hwang Woo Suk claimed to have efficiently generated 11 lines of cloned stem cells. His research was lauded in large part because he claimed to have used very few eggs, which meant the technology might be practical for clinical use. But investigations this year revealed that Hwang’s human cloning research was a massive fraud, rife with both scientific fabrication and ethical violations.

For one thing, a report released this month by Korea’s National Bioethics Committee concluded that Hwang’s team did not adequately inform women of the risks associated with egg donation. The report also found that he used more than 2,000 eggs in his experiments, five times as many as originally reported.

That revelation alarms stem cell researchers in the United States because it adds to the uncertainty over how many eggs are required to clone a human cell. The human embryonic stem cell lines used in current research are generated using naturally fertilized embryos discarded from in vitro fertilization clinics. But SCNT will likely require fresh unfertilized eggs, which are not available from fertility clinics and therefore must be donated specifically for research.

“It’s not clear how many women will step forward to donate eggs,” says Kevin Eggan, a biologist at Harvard who has sought permission from his university to start SCNT experiments. Eggan says he’s spent much of the last year learning about the ethical and medical issues associated with egg donation. Women must undergo hormone treatments to stimulate ovulation, counseling sessions to understand the risks involved, and a medical procedure in which a needle is inserted into the vagina to remove eggs from the ovary. A small percentage of donors develop ovarian hyperstimulation syndrome, which in rare cases can cause kidney damage or death.

Several states have recently enacted regulations governing stem cell research, hoping to avert the kind of questionable egg donation practices that occurred in South Korea. One of the most heated debates concerns payment for eggs. Opponents of the practice say paying women could lead them to undergo the procedure without fully considering the risks. But others are concerned that laws restricting payment will drastically reduce the number of donors.

The American Society for Reproductive Medicine estimates that egg donation requires an average of 56 hours for all counseling and medical procedures. ACT used to pay donors $4,000 for the procedure. However, a new Massachusetts law, designed to encourage stem cell research in the state, limits reimbursement to expenses directly related to the donation process. It’s unclear if that law prohibits compensation for lost pay; if so, though, it could actually hinder the research, says Lanza.

Lanza says that all the women who recently contacted ACT about donating eggs dropped out of the process when they learned how much time was involved. “I think it’s abuse to subject women to this and not at minimum compensate women for lost wages,” he says.

The California Institute for Regenerative Medicine, the agency that oversees state money designated for stem cell research from Proposition 71, has just adopted a set of ethical guidelines limiting payment to reimbursement for expenses such as lost wages and child care. “It’s nothing in the way of an incentive, it’s simply to remove a disincentive,” says David Magnus, an ethicist at Stanford University in Palo Alto, CA. Magnus says other states should enact similar regulations, so that stem cell lines generated from future SCNT experiments can be shared between states without ethical concerns.

Many scientists, including Lanza and Eggan, are so concerned about the egg-donation issue that they’re developing alternative technologies to create cloned stem cells – alternatives that eliminate the need for human eggs. Those just-emerging technologies, however, won’t be developed anytime soon. “Some tantalizing data suggest that once we understand the magic of eggs, we can replicate it,” says Lanza. “But for now, it’s still a big mystery.”