New Stem Cell Ethics Issue Emerges
UC San Francisco researcher Renee Reijo Pera has a well-equipped laboratory, generous funding and an ample staff of scientists working to create new lines of embryonic stem cells.
She has everything she needs to do cutting-edge work except one thing: fresh human eggs.
While the world debates the morality of stem cell research, scientists are grappling with a more basic issue -- a shortage of eggs that they say is crippling their work.
“Without eggs, there’s no research,” said Dr. Robert Lanza, medical director of the biotechnology company Advanced Cell Technology Inc.
Women routinely provide their eggs to fertility clinic patients, who pay $5,000 to $50,000.
But stem cell researchers are forbidden to pay for eggs by ethical guidelines from some of the most influential scientific organizations in the world, including the National Academies, which advises the U.S. government on scientific issues. California, Massachusetts, Canada, South Korea and the European Union all have passed laws barring payments.
Laurie Zoloth, a bioethicist at Northwestern University’s Feinberg School of Medicine, said payments to donors would create an exploitative trade, taking advantage of women who might be so desperate for money that it clouded their judgment about the medical risks of the harvesting procedure. Bone marrow and kidney donors are unpaid for that reason, she said.
But stem cell researchers argue that it is only fair to pay donors because of the time, discomfort and risks involved. They note that research subjects are compensated for their time.
Researchers have so far complied with the payment restrictions, but the shortage has become so acute that some scientists are beginning to contest the ethical underpinnings of the status quo.
“We need to make a decision: Do you want the research to proceed or not?” Lanza said.
Though much stem cell research can be conducted without human eggs, they are key to one of the most important areas: the creation of stem cells that are genetically matched to patients.
These cells could generate replacement tissues for damaged hearts, spinal cords and other organs without requiring patients to take anti-rejection drugs. Researchers also say they would be able to create cells with the genes for specific disorders to study without risking a patient’s safety.
Traditional embryonic stem cells are derived from fertility clinic leftovers. Their genetic makeup is left to chance. Customized stem cells are given a specific genetic identity from a particular patient. They are clones of a patient’s cells.
Creating them requires a bit of biochemical magic. Scientists remove the DNA from an egg and replace it with DNA from the patient. Then the egg must be tricked into dividing as if it had been fertilized.
The technique, called somatic cell nuclear transfer, produced Dolly the cloned sheep in 1996. It has since been used to clone horses, cats, one dog and other animals.
Stem cell researchers aren’t interested in cloning babies. They only want the cloned cells to divide for a few days until they form a cluster of about 150 cells, known as a blastocyst. Then they can harvest the stem cells.
The problem is that getting cells to reach that point is difficult. Disgraced South Korean scientist Hwang Woo-suk went through 2,236 eggs, and as government investigators later discovered, he did not produce a single embryo.
British researcher Alison P. Murdoch at Newcastle University created three human embryo clones, but none lasted long enough to produce stem cells.
Acquiring thousands of eggs will take more than an appeal to the altruism of volunteers, scientists fear.
Extracting eggs involves weeks of psychological and medical testing, followed by more than a week of hormone injections. When the time is right, the donor is sedated as a doctor uses a long needle to extract eggs in their follicles. One cycle typically produces seven or eight usable eggs.
The procedure, though routine, includes such possible risks as bloating, headaches and ovarian hyperstimulation, which can be fatal.
Despite opposition from some social conservatives, paying women to donate eggs for in vitro fertilization has become a largely accepted practice, partly because the goal is to help a someone have a baby.
Stem cell research, on the other hand, is steeped in controversy, and the idea of donors profiting from a process that ultimately destroys embryos is viewed by many as unseemly.
The first explicit prohibition on paying egg donors appeared in Proposition 71, the 2004 California initiative that authorized $3 billion in state spending on stem cell research. In an effort to prevent the exploitation of women and to make the measure more appealing to voters, it specifically ruled out compensation to publicly funded researchers, though it does permit reimbursement for some expenses.
That policy influenced the National Academies, which warned in a 2005 report that payments to egg donors “might undermine public confidence” in stem cell research.
Although the organization can’t enforce its guidelines, they became the ethical blueprint for most American universities and private labs.
The controversy has delayed UCSF’s plans to accept donor eggs for research. The result is that Reijo Pera’s lab must rely on leftover eggs that didn’t merge with sperm in the university’s in vitro fertilization clinic.
Such “failed-to-fertilize” eggs have become the workhorse of nuclear transfer experiments, even though researchers suspect the eggs are too flawed to produce cloned embryos.
Scientists have been speaking out, testifying before legislators in Massachusetts, where compensation was outlawed last year, and California, where a bill banning all compensation was sent to Gov. Arnold Schwarzenegger on Aug. 31.
The controversy prompted the American Society for Reproductive Medicine’s ethics committee to revisit the issue. The panel concluded that if it was permissible for fertility patients to pay women for their eggs, stem cell researchers should be able to do so too.
“Regardless of the application of the eggs, the process was still the same,” said the committee’s chairman, Dr. Robert G. Brzyski, a reproductive endocrinologist at University of Texas Health Science Center at San Antonio.
So far, the lobbying efforts haven’t made much difference. The payment restrictions in California’s Proposition 71 have become the de facto standard throughout the world, in large part because researchers elsewhere have to play by those rules if they want to collaborate with state-funded scientists.
Proposition 71’s rules cannot be changed until three years after its passage.
That has forced researchers to get creative. Murdoch, of Newcastle University, is offering to fund fertility treatment for women who are willing to give half their eggs to scientists.
Though critics see the bargain as tantamount to paying women for their eggs, Murdoch notes a key difference: The women are already seeking in vitro fertilization, so they aren’t taking on medical risk for money.
Researchers also are pursuing scientific solutions, such as trying to artificially ripen immature eggs that are discarded by fertility clinics. Scientists also have considered salvaging eggs from ovaries that are removed during routine surgeries and growing them from scratch using human embryonic stem cells.
“The egg bottleneck will be overcome,” said Dr. Irving L. Weissman, director of Stanford University’s Institute for Stem Cell Biology and Regenerative Medicine. But “it will take time.”
In the meantime, Advanced Cell Technology is relying on newspaper ads to recruit egg donors. Several women responded to the ads, which began running in December, but backed out when they learned they could not be compensated, Lanza said.
After 10 months, one woman has passed the physical and mental health exams. She was scheduled to begin the egg retrieval regimen last week and could have eight eggs ready to harvest in early October.
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