Human Cloning

Presentation at the Ethical Worlds of Stem Cell Medicine conference, San Francisco and Berkeley, CA

My title was inspired by this advertisement recruiting young women to provide their eggs for stem cell research. It was placed early this year in a free newspaper in Washington DC by Advanced Cell Technology, the company recently in the news for dubious claims about a new method of deriving embryonic stem cells.

It's a small ad, not very flashy, structured around marketing-style clichés: "Which comes first - the egg or the cure?", "It could happen to you or your loved one" and "Let your eggs be part of the cure." These slogans convey a threat of suffering and disease, and a promise of cures; both are in keeping with the hyperbole that characterizes so much of the stem cell debate. They also signal the resumption, after the Hwang debacle of late 2005 and early 2006, of what some U.S. scientists have described as a global "cloning race."

Exaggerated promises like the ones repeated in this ad, competition among researchers for patents and prizes, the increasing influence of the private sector in biomedical research - these are important features of what our conference title terms the "ethical worlds of stem cell medicine." They are part of the social context in which the procurement of eggs for research will take place, in which women will weigh the benefits and risks of providing their eggs for research, and in which policy makers are now deliberating about the sorts of rules, regulations and oversight that are needed.

My remarks today are an invitation to look at what might be called the "conditions of procurement" - that is, at the full social, political, economic and cultural context of egg procurement. This is a different approach than the risk-benefit calculus and individual focus that often characterize bioethical discourse.

Bioethics and biopolitics

Bioethics is good at examining the experience of the individual woman when she walks into a fertility clinic or medical facility to sign a consent document, undergo screening, or get her hormone injections. But I assert that we need to broaden our field of vision, to bring into focus the high-profile and politically polarized environment of stem cell research and stem cell discourse. We need to account for a complex and fraught set of social relationships outside the Petri dish, the laboratory, and the informed consent documents.

We need to think not just about bioethics - understood as a mostly expert endeavor centered in the thickening nexus between the academy and the biotechnology industry - but also about what is increasingly termed, especially outside the US, "biopolitics." This biopolitics is different from the Foucauldian notion of government control of populations through statistics and similar tools; it refers instead to an emerging public, policy, and civil society discourse about the social implications of genetic, reproductive and biomedical technologies.

Before turning to consider these conditions of procurement, I'll first say a few words about my organization, the Center for Genetics and Society, and our experience with the politics of stem cell and cloning research.  Then I'll give a brief account of  how the "missing persons" in the stem cell debate have recently begun to reappear.

CGS and Prop 71

The Center for Genetics and Society is a non-profit organization based in Oakland. We see ourselves as a biopolitical organization. Our mission is to encourage the responsible use and effective societal governance of new human biotechnologies. We work to promote social justice, the common good, and the public interest as guiding values for the use, development, and governance of those technologies; to build the influence of civil society constituencies who share these values; and to bring their voices and perspectives to bear on public understanding of and policy-making about human biotechnologies.

CGS supports embryonic stem cell research, and we want to see it publicly funded and publicly regulated. But we opposed Proposition 71 because of its many serious flaws including conflict of interest, unaccountable power over public funds, inadequate oversight.

Also opposing the initiative were the California Nurses Association, which characterized it as a corporate give-away, an ad hoc group of women's and reproductive health advocates called the Pro-Choice Alliance Against Proposition 71, and a few other progressive and liberal organizations. Most liberals and progressives, of course, understood Prop 71 as an up or down vote on the validity of embryonic stem cell research, and as a way to poke a stick at the Bush administration and its Christian fundamentalist base.

The disappearing woman in the stem cell debate

CGS and the other pro-choice and progressive groups opposed to Prop 71 raised the issue of women's eggs during the campaign. This was an interesting experience. When we first talked about it to reporters, most of them had no idea what we were talking about. It was simply outside of the dominant frame of reference - which of course was the moral status of human embryos - and so it didn't register.

In fact, the first half-decade of the public debate about stem cell research was dominated almost entirely by the politics of abortion and divisions about the moral status of human embryos. Other issues, including the welfare of the women who would provide eggs for cloning research, received little attention.

But the missing persons in the stem cell debate have lately reappeared. By 2004, a number of countries and the European Parliament had adopted rules about egg procurement, including a range of limitations or prohibitions on compensation. In April 2005, a National Academies committee issued guidelines on embryonic stem cell research that recommended reimbursing women who provide eggs for research for their direct expenses only. Though the NAS guidelines have no legal force and no sanctions, the recommendation put researchers on notice about the seriousness of this issue.

In fact, there is now wide agreement among policy makers that exposing women to the risks of egg retrieval for cloning research raises novel ethical concerns. Compensation is one of them, but not the only one. David Magnus and Mildred Cho are among the close observers who have called attention to the novelty of procuring eggs for stem cell research from healthy women. In a 2005 article, they called these women a "new category of research subject" - meaning that none of the available models of tissue donation are a good fit.

The Hwang scandal

The tipping point on media and public recognition of the eggs for research issue was late last year, when the cloning claims and rock-star status of researcher Hwang Woo-suk began to unravel. Hwang's fabricated data, fraudulent claims, and embezzlement of government funds garnered most attention. But accounts of ethical breaches, illegal conduct, and coercion of junior researchers in the procurement of eggs by Hwang and by his associates were also high profile.

When the counting was done, it turned out that Hwang had used over 2200 eggs collected from 119 women, many of whom reported that they had not been properly informed of the risks associated with the procedure. Twenty percent of the donors experienced OHSS and 16 were hospitalized. More than half of the women were paid for their eggs, and several said they agreed to provide their eggs because of dire financial situations.

In the immediate aftermath of the Hwang scandal, a number of US research teams announced that they would resume SCNT work that they had abandoned because Hwang had succeeded in being first. If the "cloning race" ramps up, and especially if SCNT becomes a widely used procedure, researchers will be seeking to procure eggs from many women - perhaps thousands of women.

Some have argued against drawing any general lessons from the Hwang scandal. But I don't think it makes sense just to consider him a single rotten apple in a distant foreign barrel. The atmospheres around stem cell and cloning in South Korea and in the U.S. - and especially here in California - are quite similar, and they comprise the social context, the conditions of procurement, in which women are being recruited to supply their eggs for cloning research.

Conditions of procurement

At this point I want to run quickly through a list of the conditions that I think are most relevant to a full understanding of the context in which women will decide whether or not to provide their eggs for stem cell and cloning research, and the context in which policy makers should be thinking about the appropriate rules and regulations for egg procurement.

The first condition of procurement is one that the bioethics framework should highlight: the inadequacy of existing data about the risks of egg retrieval. The many gaps in our knowledge are widely acknowledged - that's why CIRM asked the IOM to organize the scientific meeting about egg retrieval that's going on today in SF. But for now, the incomplete nature of our understanding of the risks creates a challenge to the possibility of meaningful informed consent.

The second condition of procurement is the speculative nature of the benefits of SCNT. Providing eggs for fertility treatments has a clearly established clinical value, as does providing an organ for transplant. SCNT and stem cell research do not.

It's also important to notice that the young women likely to be recruited to provide eggs for research may be drawn from a different population than those who typically provide eggs for other people's fertility procedures. Everyone knows that in the IVF context, the term "egg donor" is an oxymoron: women are paid from $5000 up to $50,000 or even reportedly $100,000 if they have the sought-after characteristics - usually high SAT scores, white skin, blonde hair and long legs.

When eggs are meant for research, on the other hand, the characteristics of the women who provide them are irrelevant - the DNA will be sucked out; all that matters is healthy eggs. The concern is that rather than going after young women from prestigious universities and competing with the sums that the high SAT scorers command, researchers will be tempted to recruit women for whom the floor-level payment - in the Bay Area, around $5000 - will be an inducement to accept the risks of egg retrieval.

Exaggerated promises, therapeutic misconception, and SCNT hype

The greatest ethical challenge to responsible egg procurement is what one commentator has called the "irrational exuberance" about the prospects of medical treatments based on stem cell and cloning research. Bioethicists speak of therapeutic misconception - that is, the tendency of research subjects to erroneously believe that their participation in early-stage clinical trials will benefit them. This is understood as a serious impediment to meaningful consent, and bioethicists try to design informed consent procedures to address this problem.

But in the case of stem cell and cloning research, there is no informed consent document that can do this trick. Women contemplating providing eggs for research won't be forming their beliefs about the benefits of SCNT on the basis of a legal document or an interview in a clinic. Instead, their understanding will have been previously shaped by:

• The wildly overblown promises and endlessly repeated claims about the imminence of lifesaving cures made by research advocates, politicians, and sometimes researchers themselves;
• the exaggerations about the number and kind of diseases that are likely candidates for stem cell treatments;
• the inflated hopes that all this hype has produced.

This is the context in which women will weigh the benefits and the risks. It is therapeutic misperception on a grand scale, a social scale.

SCNT as a research tool; the "cloning race"

Another important aspect of the social-scale therapeutic misconception is the widespread belief that SCNT will produce cell-based therapies that can be genetically matched to an individual patient. More and more stem cell researchers are acknowledging that this is very unlikely. A still medically important but farm more modest role for SCNT is now foreseen: SCNT as a research tool, a way to produce stem cells against which candidate pharmaceuticals can be efficiently tested.

But researchers and research advocates still repeat the claim about personalized stem cell treatments as part of the stem cell hype engine, and part of the political polarization that makes assessing the potential of stem cell research even more confusing. Many people may remember Ron Reagan, Jr. at the last Democratic Party presidential convention saying that SCNT would produce "your own personal repair kit standing by at the hospital."

There have been hyped treatments before - consider the snake oil. Or more recently, consider gene therapy, also hailed as a medical miracle, also controversial. But there has never before the stem cell debate been a biomedical technology that has generated political wedges, headlines in newspapers across the land, meetings in church basements, presidential vetoes, and state constitutional amendments.

All these aspects of hyperbole around stem cell research foster an over-estimation of the benefits.

There is one final aspect of the overheated stem cell atmosphere that could increase the actual risks to women who undergo egg retrieval. The "cloning race" atmosphere in which SCNT efforts are taking place could encourage the kind of ethical and technical corner-cutting that we saw in Woo Suk's Hwang's work. Without clear standards and effective oversight, it's all too possible that what happened in Hwang's work can happen here.

Unfortunately, existing standards for egg retrieval in the US are for the most part voluntary guidelines, not enforceable in any meaningful way.

SB 1260

An exception to that, and hopefully a harbinger of things to come, is a set of regulations that was signed into law just two days ago by California's governor. The bill was authored by Deborah Ortiz, the Sacramento Democrat who was an early supporter of stem cell research and of Prop 71 but who began working immediately after its passage to fix what she called its "serious flaws." My organization worked closely with Senator Ortiz's office on the bill, along with Planned Parenthood Affiliates of California, and the Pro-Choice Alliance for Responsible Research. It was opposed by the American Society for Reproductive Medicine, the professional organization of the assisted reproduction industry.

SB 1260, which applies to research not funded by CIRM, ensures that any research efforts in California to produce embryonic stem cells using techniques that require women's eggs will meet certain minimum standards to safeguard women's health. Among other things, it mandates that no woman who needs treatment for an adverse reaction will have to pay for it herself, sets some rules to minimize conflicts of interest between the cloning researchers and the medical personnel who conduct the egg retrieval procedures, and in accordance with the NAS guidelines limits compensation to reimbursement for direct expenses.

What is to be done

SB 1260 is a small step toward the kind of comprehensive policies that we need in the US on stem cell and cloning research, assisted reproduction and other human biotechnologies. On egg procurement specifically, there are also other ways to minimize the risks, and to increase women's control over and power in the situation:

1. First: In standards enacted by guidelines, by IRB reviews, by regulations and law, we can ramp up consent procedures, strengthen conflict of interest rules, and limit payments to avoid a market in eggs.
2. Second: We need better data - on best protocols, on outcomes short and long term.
3. Third: We need creative outside-the-box thinking about tissue and gamete donors, and the structures that might be set up to give them more influence and power. David Winickoff, for example, has proposed a public biorepository and trust structure that would establish a "commons" rather than a market approach, and that would include representatives of egg providers on its governing board.
4. Finally, I believe that we need biopolitics. Like other technologies, the human biotechnologies can deeply influence people's lives and life chances, and shape social arrangements and power relations. They are appropriately the subjects of democratic processes.

Many stem cell researchers insist that their job is "just to do the science," and many stem cell advocates decry the intrusion of "values" into the scientific arena. But science and values are never separate. Religious opponents of ESCR have their values (non-destruction of embryos); we have ours (health equity, protecting women, preventing misuse). These values - or the lack of them - are unavoidably being built into stem cell program at many levels of decision making: about particular research projects, about research standards, etc. Without democratic control and public participation, these are values that are all too likely to fall by the wayside.