By Tali Woodward

IT'S CLOSE TO impossible these days to avoid the debate over the ethics of stem cell research. George W. Bush raised the curtain on his presidency in 2001 by barring federal funding for research on new stem cell lines. Last month, South Korean cloning pioneer Hwang Woo-suk announced a global initiative designed, in part, to circumvent some nations' squeamishness about this promising research.

But for all the discussion, the origins of those controversial embryonic stem cells are rarely acknowledged.

"It's as if these embryos just came from nowhere," Susan Berke Fogel, head of the nascent California activist group the Pro-Choice Alliance for Responsible Research (PCARR), told the Bay Guardian.

Actually, they come from the eggs of women – living, breathing women who will have to undergo risky procedures to have their eggs removed in the name of science.

That's because scientists have placed much of their hope in customized embryonic cells they grow themselves, using a technique called nuclear transfer. The process involves extracting genetic material from an easy-to-obtain skin cell, placing it inside an oocyte that has had its genetic material removed, and then prompting the cell to develop into a clonal embryo, from which stem cells can be extracted.

What's not evident from that description – and is so often left out of such explanations – is that an oocyte is a human egg.

That may not seem like a big deal: Women have been offering their eggs for use in fertility treatments for a quarter century. But experts say the prospect of hundreds of women undergoing egg extraction in order to supply researchers with custom-made stem cells raises novel ethical and medical questions.

Many women's health advocates believe egg extraction causes medical problems that the largely unregulated fertility industry has never been forced to address – and they worry that if this research is not handled carefully, there could be significant health risks to donors.

Bioethicists also warn that great care must be taken to ensure that donors don't have an unrealistic idea of the impact their donated ova could have on ailing friends or family.

Some even fear that without careful regulation, market forces could someday drive this whole process – and that low-income women would bear the brunt of this commercialized market in human eggs.

Until now, experts concerned about egg donation have been focused on the California Institute for Regenerative Medicine, which was set up by last year's Proposition 71 and is poised to distribute $3 billion in grants for stem cell research. Assuming the CIRM would effectively be in charge of how egg donation happens here in California, these activists have lobbied the institute to establish strict donor guidelines. Although many of the stickiest issues have yet to be worked out, both the advocates and the institute's officials have been feeling pretty good about their progress.

But nearly all were taken by surprise last month when Hwang's team announced its plan for an international network of labs that will supply new stem cell lines to researchers around the world. Dubbed the World Stem Cell Hub, the consortium will include a lab right here in the Bay Area, which could begin collecting ova from local women as early as January. And it would not automatically be subject to CIRM rules.

What will keep lab operators from offering high prices for eggs? And how can we be sure local women will get an accurate sense of the risks?

The egg harvest

In the 25 years since the first "test-tube baby" was born, the fertility industry has grown into a sprawling multimillion-dollar business. Most of the women who go through in vitro fertilization have their own eggs extracted and used in the procedure. But one in ten IVF pregnancies depends on eggs offered up by another woman, the so-called "egg donor."

It's illegal to sell body parts in the United States, but fertility centers almost always pay the women who give up their eggs – they say the money is compensation for time and discomfort and not really a payment for eggs. The going rate in California is about $5,500 per surgery, but some women get far more. At elite universities, student papers are stuffed with ads seeking eggs from accomplished, attractive women presumed to have superior DNA. In a 1999 article in the New Yorker, Rebecca Mead described an ad that appeared throughout the Ivy League offering $50,000 for eggs from a tall and athletic donor who had scored at least 1,400 on the SAT.

Getting a single egg out of an ovary would require a fairly simple surgery under sedation. But women naturally produce only one or two mature eggs a month, and fertility doctors try to get at least 10 ova from each surgery. So the doctors prescribe a battery of hormones that prompt that many eggs to ripen all at once.

These drugs are what concern some health experts.

The hormonal cocktails commonly cause what could be seen as a bad case of PMS, complete with moodiness and nausea. But once in a while, the drugs kick the ovaries into overdrive, causing a buildup of fluid that, in turn, can lead to kidney failure, stroke, or even death. Repeated egg extractions can also scar the ovaries, which can cause donors themselves to become infertile. (Some have claimed that the drugs increase women's chances of specific kinds of cancer, but the research is inconclusive.)

"A significant portion of women who undergo egg extraction have side effects," Fogel told us. But the biggest problem, these critics say, is that there isn't good data on how common the effects are – fertility therapies are largely unstudied.

"Women can make good decisions, but only if they have good information," Fogel said. "We need to find a way to do good medical research without putting women at risk."

Fogel's group formed last year to publicize concerns about the state proposition that created the CIRM. Group members predicted that, despite the measure's ban on payment for eggs, a large influx of funding could stir up such a demand for eggs that women would be pressured to undergo what could be risky medical procedures.

They warned that poor women would be vulnerable to offers of cash reimbursements and pointed out that since each egg used in nuclear transfer has its genetic material sucked out and discarded, the bias toward more educated, privileged women that currently exists among egg banks would evaporate.

"Frankly, I'd be happy for women to have this as a way to make money – if I knew it was safe. But I suspect it's not," Francine Coeytaux, founder of the Pacific Institute for Women's Health and another member of PCARR, told us recently.

Several prominent bioethicists have argued that this kind of egg donation also poses complex ethical problems. There is, they say, a key difference between donating eggs for reproduction and handing them over for research: While the goal of making a baby is clear-cut, the benefits of contributing ova to a field of research still in its infancy are impossible to predict. And that makes it much trickier for a potential donor to weigh the benefits against the risks.

In a May 2005 article in Science, Stanford bioethicists David Magnus and Mildred Cho argued that the hype about stem cell research could be particularly misleading. "Researchers must make every effort to communicate to these volunteers that it is extremely unlikely that their contributions will directly benefit themselves or their loved ones," they wrote.

Fogel says that in its first year, the CIRM has approached these complex issues in a rushed manner, but advocates acknowledge that the institute has taken some promising steps.

"The folks at the CIRM have started to take the issue of egg donation very seriously," said Jesse Reynolds of the Center for Genetics and Society, an Oakland-based watchdog group that has been closely monitoring the institute.

The CIRM has adopted guidelines for egg donation drawn up by the National Academy of Sciences as interim rules and has held several meetings to formulate complete scientific regulations of its own. The institute plans to release its draft regulations to the public sometime early next year and is aiming to have them in place by July 2006. CIRM president Zach Hall recently proposed holding a one-day workshop on the health effects of egg donation sometime in the spring.

Geoffrey Lomax, the CIRM staffer who is coordinating the development of these regulations, told us that there has been detailed discussion about "what critical pieces of knowledge need to be communicated to potential donors" regarding both risks and benefits.

"We are taking every step to develop the most effective guidelines for what we fund," he added.

To market, to market

Francine Coeytaux wasn't prepared for the Oct. 19 announcement that the South Korean cloning team led by Hwang was launching an international network of labs. When she heard about their plan for a California office, she told us, "My first reaction was 'Oh, here it is – exactly what we've been trying to prevent with the [CIRM].' "

Hwang is a bit of a rock star in his country, where he's known as the "Korean Elvis," and he has a well-deserved reputation for making brash advances in cloning and stem cell technology. He was the first scientist to clone a cow and the first to clone a dog. He was the first to extract stem cells from an embryo, and just last May, the first to successfully grow cloned embryo cells using nuclear transfer.

Hwang's World Stem Cell Hub, which will be based at Seoul National University and have satellite labs here and in London, is designed to provide scientists all over the world with a ready supply of embryonic stem cells, though exactly how the consortium will function remains something of a mystery.

The hub has yet to establish a direct relationship with the CIRM or any research institution in the state, and officials from several of them have said they want to wait and see what ethical rules are established. But the lack of stem cell customers won't necessarily keep the local lab from getting started – and the hub won't be required to have the public discussions about process and standards that the CIRM has been slogging through.

The World Stem Cell Hub has already set up some kind of partnership with the Pacific Fertility Center, a large IVF center based in downtown San Francisco. PFC doctor Philip Chenette told us that most of the details – such as how egg donors will be found and what they will be paid – have yet to be worked out.

"I hope the World Stem Cell Hub will be able to produce their own donors," he said. "We're consultants on how you get the eggs [out of the donors]."

When asked about the concerns about research donation voiced by bioethicists, Chenette said, "I think they want the donors to be informed. We have to make our best effort to let the donors know what the plusses and minuses are."

But he also mentioned something that underscores how much public hope has already been placed in stem cell research: "The feedback I've gotten has been 100 percent supportive," he said, adding that, already, "people are calling me asking when can they donate their eggs."

Although it may be hard to imagine a full-fledged commercial trade developing in women's eggs, if stem cell research really gets going, it will require a unprecedented number of women to offer up their ova. Hwang's team used 242 human eggs to create the first clonal embryo. They were able to derive 11 separate stem cell lines earlier this year using far fewer eggs, but the holy grail of stem cell research is to develop personalized therapies. That would mean developing a new genetically matched stem cell line for each patient. And unless there's some unforeseen technological advance, each line would require at least one ovum.

The current level of demand has apparently led South Korea to develop something of a black market. In early November, police there arrested four men they said were operating an illegal Internet egg ring in which they recruited donors, paid them for their eggs, and then sold them at higher prices to infertile women. Soon after the arrests, a member of Hwang's research team named Roh Sung-il acknowledged, on TV, having used illegally traded ova in fertility treatments.

"Even though Roh said all stem cell research has been conducted with voluntarily contributed eggs, suspicions still run deep that the cloning research also might use purchased eggs," the Korea Times reported.

Just days later, University of Pittsburgh researcher Gerald P. Schatten, who is a collaborator with Hwang and has been the point person for the US plans for the World Stem Cell Hub, abruptly severed his ties to Hwang. Schatten didn't return our calls, but he told the Washington Post that he thought eggs used by Hwang's team may have been gathered unethically.

"My trust has been shaken," he said. "I am sick at heart. I am not going to be able to collaborate with Woo-suk."

The San Francisco Chronicle reported Nov. 15 that PFC was also withdrawing from the hub and that the whole plan for a Bay Area lab might therefore be abandoned. But there was no word from South Korea, and Hwang could very well find new collaborators.

Observers also warned that the larger concerns about egg donation are very much alive.

Jesse Reynolds told us that the controversy over how Hwang's team obtained eggs underscores that "where the eggs are going to come from is a serious matter – and something of an ethical minefield." E-mail Tali Woodward at tali@sfbg.com.