According to Kevin Eggan, a molecular and cellular biologist at Harvard who is seeking approval from his university to start nuclear-transfer research, “It’s not clear how many eggs we need or how many women will step forward to donate eggs.” Eggan, who also sits on the ethics review board of the California Institute for Regenerative Medicine (and was a member of the 2005 TR35), says he’s spent much of the last year learning about the ethical and medical issues associated with egg donation. Many scientists say access to eggs will determine the success of therapeutic cloning. “We have a therapy that could have revolutionized medicine like antibiotics, but we have a bottleneck that shoots it down,” says Lanza.
The egg donation procedure is uncomfortable and potentially painful and carries some medical risk. 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 failure.
Even ardent supporters disagree over the most ethical ways to handle egg donation. Some scientists don’t want to use human eggs at all. “We feel it’s inappropriate to put women through a risky and potentially dangerous procedure when we don’t know what the efficiency is,” says Stephen Minger, a scientist at King’s College London who is planning to apply for permission from the British government to clone human stem cells using animal eggs. Those who do want to use human eggs disagree about whether women should be paid for their donations. Opponents worry that payment could encourage some women to undergo the procedure without understanding the risks. But others think compensation is the most ethical approach. “When ACT did this, we paid egg donors,” says Green. “I continue to think that’s the best way to do it. It’s fair and open and the least likely to lead to evasion.”
According to Lanza, all the women who recently contacted ACT about donating eggs dropped out of the process when they learned how much time was involved. Lanza says he still plans to proceed, as soon as he can get a new source of eggs. “If I were just starting, I probably wouldn’t do it,” he says. “Sometimes I spend more time on the phone with lawyers than I do on the science….But we’ve invested so much time and energy and so much of ourselves that we want to see this to completion. I still feel there is a very important role for [nuclear transfer] in different diseases.”
Lanza suspects that, because of the shortage of eggs and the unknown efficiency of the cloning process, the therapeutic use of cloned stem cells will end up looking more like a kidney transplant than like the ingestion of a widely prescribed drug. “We do recognize it’s not the broad cure we had hoped, but I’m convinced it will save some individuals,” he says. “Perhaps a mother would donate a round of eggs to create stem cells for her sick child.”
As American scientists gear up for the new race toward nuclear transfer, they face many of the same hurdles that stranded most of them in the starting block two years ago. Hwang had huge sums of money from the Korean government, an adoring public, and an enormous, albeit ethically unsound, supply of human eggs. U.S. scientists face intense public scrutiny, an administration opposed to embryonic-stem-cell research, and a continuous struggle to get funding from private investors.
In 2001, President Bush limited federal funding for embryonic-stem-cell research to work involving a small number of cell lines already in existence. That policy has exerted a disastrously chilling effect on the field. Scientists who wish to do research on newly derived embryonic-stem-cell lines or to derive new lines themselves – as is necessary in nuclear transfer – must find private sources of funding.
Scientists and university administrators also face the arduous task of separating all publicly and privately funded research. “It means everyone is dragging 10-pound weights on their feet,” says Greg Simon, president of FasterCures, a Washington, DC-based advocacy group that aims to speed development of novel therapies. “We’re spending a lot of wasted time separating government money from private money when we should be spending time doing research.”
The federal blockade also means that the National Institutes of Health, the nation’s largest biomedical-research institute, has forsaken its standard regulatory role, leaving many scientists operating in a vacuum. The National Academy of Sciences has tried to pick up some of the slack, publishing a nonbinding set of guidelines for stem cell research in 2005 and creating a stem cell research oversight committee earlier this year.
Many state governments have felt compelled to step in, both regulating and providing funding for stem cell research. So far, California, Connecticut, Massachusetts, and New Jersey have passed laws that permit embryonic-stem-cell research, including work on cloned embryos. Arkansas, Indiana, Iowa, Michigan, North Dakota, and South Dakota prohibit research on cloned embryos.
In addition, California, Connecticut, and New Jersey have all earmarked state funds to support stem cell research not funded by the federal government. The California initiative, by far the biggest at $3 billion, has encountered pitfalls at every turn, demonstrating the difficulties that arise when states get into the research-funding business. The California Institute for Regenerative Medicine, the oversight entity created by the state’s Proposition 71, has grappled with accusations of conflicts of interest among those who determine the distribution of funds and with controversies over how the state will reap the financial benefits of stem cell research – a promise that was part of the proposition.
Almost all embryonic-stem-cell research in the United States faces funding obstacles and ethical objections, but because nuclear transfer is the most contentious topic in the field – it involves not only the destruction but also the creation of embryos specifically for research – scientists and universities planning nuclear-transfer programs are extracautious. “The spotlight is on anyone doing this kind of research,” says Lanza. For example, Massachusetts law mandates criminal penalties for people who violate laws governing egg and embryo procurement. “If we slip up anywhere, we’ll be crucified,” Lanza says.
Other countries have much more supportive environments for embryonic-stem-cell research, which may give them the lead in the new race to perfect nuclear transfer. In the United Kingdom, for example, stem cell research is more intensely regulated but also much more open. Scientists apply to a central government authority for permission to do research involving human embryos. Summaries of research proposals under review – including those involving nuclear transfer – are posted online for public evaluation, along with an explanation of the criteria for approval. “In the U.K., we have enormous government support, from the prime minister on down,” says Minger, an American scientist who migrated to the U.K. “There’s a stigma associated with stem cells in the U.S. that’s not true here.”