Three Parent Embryos Created - Again
Tuesday, 05 February 2008
Three Parent Embryo’s Created.
Wednesday, 15 October 2003
United States and Chinese scientists report the creation in China of a human pregnancy using a DNA-swapping technology resulting in embryos with three genetic parents. The embryo’s genetic material came from their parents and additionally from an egg donor. All of the babies died before birth. The results were reported this week at the annual meeting of the American Society for Reproductive Medicine in San Antonio, Texas.
Beijing earlier this month banned all human nuclear-transfer techniques, when China's Ministry of Health announced broad new restrictions on reproductive medicine. The new rules specifically ban the nuclear-transfer technique in fertility procedures because of its potential use in human cloning or other genetic alterations, and threaten to derail further advances in the field.
A similar technique — cytoplasmic transfer — has earlier been used in the United States. With this method, only a part of the mitochondria-containing cytoplasm, and not the nucleus of a donor egg, is injected into the infertile woman’s egg.
In 2001, Drs. Jacques Cohen and Jason Barritt at the Institute for Reproductive Medicine and Science of Saint Barnabas in New Jersey reported that 12 out of 30 babies born with the help of cytoplasmic transfer carried donor mitochondria. These children thus de facto, have three genetic parents.
However, the Food and Drug Administration (FDA) in the United States, in 2001 put an effective halt to such research with a requirement for regulated scientific studies demonstrating its safety.
This procedure of nuclear transfer is similar in a crucial step to cloning, but it differs in important ways.
To make a clone, like Dolly the sheep, researchers start with a fertilised egg and remove its nucleus. Then they replace the nucleus with a nucleus from an adult animal, electrically stimulate the egg to start its development and implant it in the prospective mother’s womb. Any offspring will be a genetic copy, or clone, of the adult animal from which the cell was taken.
Nuclear transfer and cloning are similar in that both involve taking the nucleus from one cell and slipping it into an egg from a different individual.
They differ in the goals of the procedure and in the kind of nuclei that are switched.
In cloning, the goal is to make a copy of an adult, and the adult nucleus is transferred.
In nuclear transfer for infertility, the nuclei transferred are not from adult cells but from the sperm and egg of the people who are trying to become parents. The offspring will be their child with mixed DNA, not a clone.
Dr. James Grifo of New York University School of Medicine, who developed the technique, and a graduate student, John Zhang, formed a collaboration with Dr. Guan-glun Zhuang of Sun Yat-Sen Medical University in Guangzhou, China. Performing the same experiment in the United States would have required obtaining a time-consuming and expensive Investigational New Drug application from the FDA.
"Cloning is making a copy of a human being who already exists," Dr. James Grifo said in a telephone interview with the N.Y. Times.
"This is nuclear transfer, one element of cloning. It allows a couple to have their genetic baby, not a clone. They shouldn’t even be discussed in the same sentence."
Dr. Guan-glun Zhuang, one of the researchers, also said in an interview from China with the N.Y. Times:
"This isn't cloning. Cloning involves copying whole people."
"It’s a different technique, but the results are the same," said Sean Tipton, a spokesman for the reproductive medicine society to the Reuters news organisation.
The human embryos produced in this way were implanted in China. The 30-year-old Chinese woman involved in the experiment had an unusual fertility problem in which embryos stopped developing when they contained only two cells.
The team first fertilised eggs from the two women in test tubes. Eight patient oocytes and 12 donor oocytes were fertilised by intracytoplasmic sperm injection (ICSI). They then removed the nucleus of one egg at a time and injected it into a donor egg, which they had stripped of its own nucleus. The idea was to surround the transferred DNA with a new cytoplasm, in hopes that such reconstituted eggs would fare better than the woman’s previous attempts at pregnancy.
Grifo’s team implanted five such embryos into the 30-year-old mother who had already undergone two failed attempts at in vitro fertilisation (IVF). Three of the embryos grew large enough for doctors to hear their heartbeats, they report in their abstract.
After a month, doctors ‘reduced’ the pregnancy to two embryos, for the mother’s safety and to limit the risks of a multiple pregnancy. However, one foetus was prematurely delivered at 24 weeks and died by respiratory failure immediately. The other foetus that was left to grow died at 29 weeks of pregnancy also after being prematurely delivered. Whether the process to create the embryos was responsible for their deaths is not known.
"I am troubled that this is being done overseas, avoiding US regulatory oversight," said Mark Frankel, director of the scientific freedom, responsibility and law program at the American Association for the Advancement of Science, according to Reuters.
"It may be a promising technique, but there are risks. We don’t know what the consequences of that will be, both physically and psychologically."
"It’s not cloning in the sense that the intention is not to duplicate a person ... a successful outcome would be a child that reflects the fertilised egg," Frankel said.
"It's extraordinary. You wouldn’t get away with it anywhere else," says IVF doctor Allan Templeton of the University of Aberdeen, UK in a Nature interview.
Templeton argues that there was no compelling reason for using the technique on the woman, because further rounds of IVF might have worked.
"The clinical justification is extremely dubious," he said.
Dr. David Sable, director of the division of reproductive endocrinology at the St. Barnabas Medical Center in Livingston, N.J., stressed that most age-related infertility in women is not due to problems in cytoplasm.
So providing a new cytoplasm could be only "one small tool in the tool kit" for age-related infertility, he said.
Dr. Jeffrey Kahn, director of the center for bioethics at the University of Minnesota in Minneapolis, said he found the experiment in China troubling.
"My concern is that people see this as an end run around oversight and restrictions within the United States," Dr. Kahn said.
He pointed out that stem cell researchers had left California for England and that cloning experts had left Scotland for Singapore to escape rules that they considered demanding.
"What’s next?" he asked. "A ship out in international waters?"
Dr. Kahn also said that even though nuclear transfer was not the same as cloning, it helped demonstrate that cloning might work.
"It is effectively creating the path for other people to do that," Dr. Kahn said.
"You can do a lot of things with that assisted reproductive technology," added Dr. Giuseppe Del Priore, associate clinical professor of gynaecologic oncology at New York University School of Medicine in New York City and part of the university’s cancer fertility group, according to Amanda Gardner, HealthDay News Reporter.
"It may be similar to cloning conceptually, but in every other way it has nothing to do with it. It’s like a nuclear energy plant and a nuclear weapons plant. They’re not the same."
"This is a natural process of all scientific process. People are always going to resist innovative ideas," Del Priore said.
"It’s the usual exciting debate. It makes it fun."
Del Priore visited the hospital in China where the experiment was conducted, but was not a participant.
In a comment to Dr. Grifo’s participation in this research Dr. Keith Krasinksi, chairman of the Institutional Review Board (IRB) at NYU said that Dr. Grifo did not need the board’s approval to do this research because he "didn’t direct or conduct the research."
He further added that the NYU policy does not require a faculty member to seek IRB approval "unless the research is sponsored by NYU or one of its covered facilities or conducted under the direction of a faculty in connection with their institutional responsibility"
"He said he transmitted information to them that enabled them to do it. That doesn’t mean he conducted the research," Krasinksi clarified.
Dr. Guan-glun Zhuang called China’s regulations to ban cloning and nuclear transfer as "nonsense for people who don’t understand these techniques."
"This isn’t cloning. Cloning involves copying whole people. When it’s clear that something like this is to people’s benefit, it should be allowed," he added.
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