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Beating the ban

Will embryonic stem cells made without embryos keep politicians happy?

By Sylvia PagÁn Westphal

New Scientist magazine, vol 172 issue 2311, page 14

June 10, 2001

 

COMPANIES in the US and Britain are working on ways to get human embryonic stem cells without destroying viable embryos, New Scientist has learned.

 

Their goal is to create compatible tissue for transplant without falling foul of the legal and ethical objections to getting stem cells from normal or cloned embryos. But will their approach work-and does it really bypass the ethical issues?

 

Stem cells that can grow into all sorts of specialised tissues are thought to have enormous potential in medicine. The most versatile and useful are embryonic stem cells (ESCs), which you get from the ball of cells that forms a few days after fertilisation.

 

The trouble is that to get ESCs you have to destroy an embryo that could become a child. This has led to fierce opposition from some quarters, even though most ESCs come from spare IVF embryos that would otherwise have been discarded.

 

Therapeutic cloning, where you create compatible tissue for transplant by taking ESCs from a cloned embryo, is even more controversial. This will become a crime in the US if the Senate approves an anti-cloning bill later this year.

 

Now, however, at least two groups in the US are working with embryos that never have the potential to become a person. But these clumps of cells sometimes develop far enough for researchers to extract the equivalent of embryonic stem cells.

 

The research carried out at Advanced Cell Technology (ACT) in Massachusetts involves a process known as parthenogenesis. Normally, fertilised egg cells get one set of chromosomes from the mother and one from the father. But in parthenogenesis, the egg cell duplicates one set of maternal chromosomes and develops as if it had been fertilised (see graphic). 

 

Some insects, lizards and even birds can reproduce asexually via parthenogenesis. In mammals, though, having two sets of maternal chromosomes causes such severe problems that parthenogenic embryos never develop into a normal fetus.

 

Despite this, ACT has managed to harvest ESC-like cells from parthenogenic monkey embryos, according to a patent application seen by New Scientist. Like normal ESCs, the cells stayed undifferentiated for four months when kept with mouse cells called feeder cells. When the researchers took away the feeder cells, the parthenogenic cells spontaneously differentiated into what appeared to be more specialised types, such as skin cells and beating heart cells.

 

The patent is the first report of ESC-like cells being derived from primates via parthenogenesis. If it works in humans too, it means ACT may have found a way to get ESCs without destroying a potential person.

 

What's more, ACT thinks that this technique could also make therapeutic cloning unnecessary. For example, when creating transplant tissue for a woman, parthenogenic cells derived from one of her egg cells would have half of her genetic material, so any tissue created from such stem cells would be a close match. In the case of a man, the patent application suggests that one set of his chromosomes could be transferred to an egg that has had its nucleus removed. Then the egg could be induced to undergo parthenogenesis (this could also be done for a woman).

 

ACT wouldn't comment on the research. "The patent speaks for itself," says chief executive Michael West. "We're not going to be releasing any more information until we publish the data in a peer-reviewed journal."

 

But ACT is not alone. In Los Angeles, Jerry Hall of the Institute of Reproductive Medicine and Genetic Testing is also working on parthenogenesis. He wouldn't reveal any details but was confident it would work in humans. "Not only are we optimistic that parthenogenesis in humans would lead us to the same results, I would be surprised if they didn't."

 

However, much remains to be done to show that the technique is feasible. It is unclear how versatile parthenogenic stem cells will be-or how safe. There is much concern that normal ESC implants could become cancerous, and some human ovarian cancers are formed by parthenogenesis.

 

But parthenogenesis isn't the only option. Another method that may yield ESC-like cells without using viable embryos is the transfer of cytoplasm from an egg cell into ordinary adult cells. The egg cytoplasm seems to turn the specialised adult cells back into an undifferentiated state.

 

Several companies are working on this ooplasmic transfer approach, but it is unclear how successful it has been. PPL Therapeutics in Scotland reported this year that cow skin cells injected with cytoplasm from cow eggs dedifferentiated into cells that looked like ESCs, and that the addition of certain growth factors turned them into beating heart cells. The company hopes to try it with human cells, says research director Alan Colman.

 

For companies that can find a way round the proposed ban on therapeutic cloning in the US, the rewards could be great. To satisfy the ethical concerns of critics, however, they will have to prove that none of their techniques could ever create a viable embryo.

 

"It's a positive thing if people are working on technologies that would not damage a human embryo," says Douglas Johnson, legislative director of the National Right to Life Committee. "But we want to see that it's not a word game."

 

© Copyright New Scientist, RBI Limited 2001


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