Stem-Cell Rift Shows Difficulty Obtaining Eggs
By ANTONIO REGALADO
Staff Reporter of THE WALL STREET JOURNAL
November 14, 2005; Page B1
The breakup of a U.S.-Korean scientific partnership on Friday may derail what supporters had hoped would become a promising source of research into cloning and human embryonic stem cells.
At the heart of the rift is an issue that researchers call a limiting factor in high-tech cloning research: the difficulty of legally and ethically obtaining large numbers of human egg cells.
Human eggs are needed for cloning research, which could lead to customized stem-cell treatments, but they are difficult and costly to obtain. And the procedure poses a small risk to women from the strong hormones used to generate eggs. "It's the pinch-point in the whole technology," says Ronald Green, an ethicist at Dartmouth College in New Hampshire.
Only weeks ago, in Seoul, South Korea, American biologist Gerald Schatten had joined Woo Suk Hwang, director of the cloning laboratory at Seoul National University, to announce an international program to share the fruits of recent Korean stem-cell exploits world-wide.
But on Friday, Dr. Schatten, a professor at the University of Pittsburgh, accused Dr. Hwang of misleading him about the source of human eggs used in a 2004 experiment, and abruptly withdrew from the Korean-U.S. collaboration, which would have established embryo cloning centers in San Francisco and London.
In the U.S., cloning projects have been held back by rules that bar federal funding for any research in which human embryos are harmed. Although cloning of embryos isn't illegal, egg donation is emerging as a tricky hurdle even for projects with private funding. Some critics charge there aren't enough ethical protections in place to allow the research to go forward.
"We feel that women who provide these eggs are going to be the first guinea pigs of stem-cell work," said Marcy Darnovsky, co-director of the Center for Genetics & Society, a public-interest group in Oakland, Calif., that advocates for tighter regulation of human genetics research.
Researchers say they know of no current effort to clone embryos in the U.S., although some could be under way privately. But several efforts are pending approval, including two proposals at Harvard University. The California Institute for Regenerative Medicine, a $3 billion stem-cell program approved by California voters in November 2004, also envisions funding such work.
Egg donors are sometimes paid sums of $10,000 or more when their eggs are used in fertility procedures. But recommendations published this year by the National Academy of Sciences in Washington said stem-cell researchers should avoid any payments.
Some states are now putting such recommendations into law, in order to ensure cloning research doesn't result in a market for human eggs. In Massachusetts, legislators appended a ban on payment of egg donors to a new law that allows for stem-cell and cloning research. Dr. Green, who is also the head of the ethics advisory board for Advanced Cell Technology, a Worcester, Mass., company, says that rule could hurt cloning efforts. "It's highly invasive, very uncomfortable and prolonged. So the question is, why would anybody do this?" he said.
The collaboration between the Korean and American scientists was sparked in late 2003, when Dr. Schatten toured the Korean laboratory, and Dr. Hwang had pulled him aside with an urgent whisper to reveal that his workers had used human eggs to create a cloned human embryo, and the lab workers had extracted its stem cells.
It was a historic first, and after Dr. Schatten helped the Korean team publish their result in Science, the leading American research journal, the breakthrough made headlines around the globe.
The Korean group reported that, using 242 human eggs from 16 donors, they had succeeded in cloning a human embryo. Shortly afterward, the journal Nature printed charges that two female laboratory workers had provided eggs for the project. Obtaining eggs from lab workers is considered unethical because they are in a subordinate position and could be subject to undue pressure to give their eggs to research.
Dr. Hwang has repeatedly denied the charges, and Dr. Schatten says he initially accepted Dr. Hwang's version of events. Last week he said new information came to his attention that changed his mind. "There had been allegations that people in his lab may have donated eggs. I was told those were also false. I now question whether they are indeed false," said Dr. Schatten. He didn't provide details, and Dr. Hwang couldn't be reached to comment.
Over the weekend, ethicists and cloning scientists said they were stunned and confused by the turn of events. The Korean government launched an investigation into the charges, according to a report in the International Herald Tribune.
"The work that has been reported there is extremely important, so we are of course troubled by the allegations that have been made and are hopeful that they are not true," said Kevin Eggan, a cloning researcher at Harvard University.
Harvard researchers have applied to the university for permission to launch their own cloning project, with the aim of making stem cells from people with diabetes. Dr. Eggan said Harvard has an agreement with a local fertility clinic, Boston IVF, to obtain eggs, but is "committed to recruiting compassionate donors" and will reimburse them only for out-of-pocket expenses, such as cab fare to a clinic. That approach would adhere to the standards recently recommended by the National Academy of Sciences.
Ann Kiessling, director of the Bedford Research Foundation in Sommerville, Mass., says her research organization has been paying women about $4,000 each for eggs as part of an ongoing stem-cell research program. She says that sum compensates them for lost time and effort. Only two donors have been recruited this year, she said.
To obtain eggs, doctors give a woman daily hormone shots for about 10 days, then insert a hollow needle through the wall of the vagina to reach her ovaries. The needle is used to puncture cysts that form on the ovary, and contain eggs. Somewhere between 10 and 20 eggs can typically be collected in the procedure.
The process isn't particularly dangerous, but the heavy doses of hormones can cause discomfort and mood swings. "It can be a roller coaster, like extreme PMS," says Dr. Kiessling. "Most handle it OK, but not all." Dr. Kiessling says her group uses very low levels of hormones to reduce risks.
Still, some stem-cell researchers say they aren't working on cloning due to the ethical challenges of collecting eggs. Several research groups are now trying to find other means of making customized stem cells, but these remain at an early stage.
"The goal of all scientists is to learn how to reprogram cells without needing eggs. But until we know how the egg does it, we're stuck with it," said Dr. Kiessling.
In cloning, DNA from an adult is placed inside an egg. Properly coaxed, it can grow to form an embryo. Since 1997, scientists have used the technology to generate cloned animals, including sheep, rabbits and horses.
The Koreans were first to successfully grow a human embryo this way. Stem cells extracted from the embryo were identical to the original DNA donor, opening up the possibility the technology could provide customized stem cells for medical treatment or for research.
Several researchers worried that if the allegations about impropriety in Korea prove true, it could damage cloning research in the U.S. Already, American researchers have had difficulty fending off ethical critics and navigating state and federal laws that make the research difficult to carry out. "Each institution is struggling to put in place appropriate barriers or safeguards to do it," says Dr. Keissling. "If egg donation becomes a problem, it could really be a problem for the whole field."
Several people familiar with the Korean research said they were surprised by the allegations. Insoo Hyun, an assistant professor at Case Western Reserve University in Cleveland, spent the summer in Korea doing a study of Dr. Hwang's egg-donor program. Although he didn't investigate the allegations concerning the original paper, he says the protocols currently in place are rigorous and in line with Western standards.
Mr. Hyun says after the initial paper, the Korean team was inundated with offers from women to donate their eggs, and had to turn away offers. "There is a lot of national pride involved in this," he said.
Dr. Hyun said ethicists involved with the Korean project are now "extremely upset" by Dr. Schatten's charges. "If it is true, it's very damaging. Right now we are of the opinion that Dr. Schatten needs to come forward with the evidence."
On Saturday, a representative of the University of Pittsburgh Medical Center said Dr. Schatten wouldn't provide further information. Dr. Schatten is the recipient of large, multimillion dollar grants awarded by the National Institutes of Health for cloning and stem-cell research in monkeys.
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