Human-Animal Cybrids
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TR: Scientists here in the United States have tried cloning using rabbit eggs, with no success. Does that suggest that the method won’t work?
IW: Those results are disappointing, but they aren’t surprising. Very small changes in these procedures can be critical. For example, many labs that successfully cloned farm animals could not get the technique to work in mice.
We’ve already learned certain lessons about how to go about it. One group in Japan has used rabbit eggs to generate stem cells from macaque monkeys. They discovered that cells should first be grown in the medium used for rabbit cells, then later in the medium used for macaque cells. Simple changes like that can dramatically change success.
TR: In the past year, scientists made a breakthrough in “reprogramming”–turning back the clock on an adult cell to produce stem cells without using eggs. Simply triggering expression of four genes seemed to create stem-cell-like cells, which could obviate the need for human eggs. Are you also pursuing this type of research?
IW: I first suggested something like that back in 1997: I said it would be the offspring of Dolly. I’m sure a lot of other people were thinking that way as well, but it’s been a very difficult experiment to do.
The efficiency for that method [the reprogramming method described earlier this year] was very low, so there should be lots of room for improvement. We just developed an assay in which we add an extract from mouse embryonic stem cells onto human cells, which triggers expression of those four genes. We plan to use that system to figure out which factors in the extract are crucial for turning on gene expression.
TR: The U.S. administration, which has hindered embryonic stem-cell research with drastic funding restrictions, has suggested that advancements in reprogramming technologies are a reason to move away from traditional embryonic stem-cell research. What do you think?
IW: In the short term, we don’t know which approach will work best, so I think we should pursue both. But in the end, I think reprogramming will be preferable.

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