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Cloning by reprogramming?

“Now we have the technology that can make a cloned child” reads the headline of the most-read article in the Independent right now. But the article does not actually break any news, nor does it use the common method of cloning; rather it discusses a well-understood implication of that recent reprogramming breakthroughs might yield yet another weird way of making a baby.

If a technician wanted to do this, here’s how it would work: First, cells would be gathered from an existing human, probably through a skin biopsy. Second, these cells would be reprogrammed to an embryonic like state. (Current techniques to do this require engineered viruses to insert copies of genes into the reprogrammed cells. This makes the cells’ behavior less predictable and more prone to form tumours, but many scientists believe that new reprogramming techniques will soon be available that don’t require genetic modification.) Next, the reprogrammed cells would be merged with an early stage embryo, created by sperm fusing with egg in a laboratory dish. The “chimeric” embryo would be cultured for a few days and then implanted into a woman. If a baby was born, he or she would contain cells from two genetic individuals: the embryo and the human who supplied the cells. The baby would have three parents: two who gave the gametes for the embryo, one who gave the cells from a biopsy. (Such an individual would not be a clone. However, it is feasible that the chimeric embryo could be manipulated such that the original embryo only forms placenta and the reprogrammed cells form the body. This has been accomplished with mixtures mouse embryonic stem cells and mouse embryos, but not with mixtures of reprogrammed mouse cells and mouse embryos. )

The results of some quick internet research suggests that using human iPS cells this way would not be allowed: In the UK, creating or using embryos outside the body requires a special license from the government, so I’d guess that permission would need to happen proactively. The US lacks legislation on reproductive cloning, though some individual states ban it. Australia distinguishes between research embryos (created through technical manipulation or by mixing genes from three or more people) and reproductive embryos (created through fusion of sperm and egg) and allows only reproductive embryos to used to create an embryo. A document dated to 2004 from Japan banned, among other things, the creation of chimeric human-human embryos for research.

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Brits report making hybrid cow-human embryo

Newcastle University says researchers led by Lyle Armstrong have made hybrid embryos containing material from cows and humans. The announcement comes just as the government gears up on whether or not the creation of such embryos should be legal. Newcastle University, which already had approval for the research from UK regulatory authorities, decided to push forward so the research would not risk being stalled by an upcoming vote in the House of Commons, reports the BBC.

The embryos lived for three days, and were not used to make embryonic stem cells, according to that report. They were made by putting human DNA into cow eggs after the cow chromosomes had been removed. Scientists argue that such procedures are valuable both to understand how embryos develop, to develop better techniques for making embryonic stem cell lines, and to develop more useful embryonic stem cells. The hybrid embryos cannot, by law, be allowed to develop for more than two weeks, when some precursors of nerve tissue develops. The first reported human-animal chimeras combined human nuclei with rabbit eggs; other chimeric animals have been made as well. Here’s an old summary. Here’s a newer one.

See Nature Reports Stem Cells commentary on a scientific argument for chimeras by Ian Wilmut , a theological argument for chimeras by Ted Peters, and an argument against creating and destroying embryos for research by Markus Grompe. We also summarized the UK Academy of Medical Sciences’ report on this issue.

The UK press has been roiling with accusations by the Catholic Church that the work is monstrous. Scientists have responded that the Church is misrepresenting the science and have offered to meet with religious officials. For a recent example, see the New Stateman.

Newcastle has a history of dramatically announcing accomplishments before work appears in the peer-reviewed literature. In February, they announced the creation of embryos using material from three people. See Erika Check Hayden’s article in Nature News.

The Science Media Centre has already released statements of scientists’ responding to the news, all saying that they lack data to assess research. Here are those statements:

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Former head of Bush council on bioethics says make embryos for research--in five years

The former head of President Bush’s council on bioethics, now says there shouldn’t be a ban against cloning human embryos for research. Instead, there should be a five-year moratorium against the process. Writing in the Weekly Standard, Leon Kass decries the fact that the US Congress did not pass a law blocking all forms of human cloning, and then says that this stricter form of the law is unnecessary now that researchers can turn to alternate ways of reprogramming.

Instead, he argues for a law that would ban “all attempts to conceive a child save by the union of egg and sperm (both taken from adults).” That’s because the new reprogramming techniques mean that a skin cell could generate egg and sperm cells, whether taken from a man or a woman (or a boy or a girl, for that matter).

Embryos created for the purposes of research would not be outlawed, but instead banned for four or five years as researchers are given more funds to perfect the reprogramming techniques. He does not rebut, because he does not raise, the argument that stopping work the creation of embryos for research through somatic cell nuclear transfer will delay efforts to prefect reprogramming techniques.

Kass writes “Cloning for the purpose of biomedical research has lost its chief scientific raison d'être” (i.e. making a pluripotent cell line genetically matched to a patient.) That’s because it will probably be much easier to reprogram whole cells from adult biopsies than it will be to pull out an adult cell’s nucleus, plop it into a donated egg, grow that “reconstituted embryo” to a blastocyst and make embryonic stem cells.

Kass is probably right, but he fails to mention two caveats.

First, while many scientists are hopeful that so-called induced pluripotent stem cells will really behave like embryonic stem cells, they still aren’t sure. Possibly, a reprogrammed skin cell could be coaxed into a pancreas cell or a heart cell, transplanted, and then “remember” that it started out as a skin cell. Also, no one wants to use the current technique (using viruses to insert genes at random places in the cells’ chromosomes) to make cells that would actually get put into people. Those are serious problems, but most scientists think they can be overcome.

Second, and more important, many scientists think that to understand how reprogramming works with viruses, they have to understand how reprogramming works in an egg. Most people think that requires transferring adult nuclei into eggs or early embryos, and trying to figure out what happens.

Just a little quibble: Kass says that recent success by Stemagen in cloning a human blastocyst depended on the technique that Shoukhrat Mitalipov’s team in Oregon used to clone monkey blastocysts to make embryonic stem cells . Actually, Stemagen did not use this technique but credits its success not with a new technique but with a supply of high quality eggs.

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Blurring embryo-fetus distinctions disingenuous

My post on Inconsistent Christianity prompted this reply from Jessica Kolman, our office manager and art researcher:

In reading your entry about inconsistent Christian views on reprogramming, I can’t help thinking that one reason for the inconsistencies is that so few people actually know what the facts are. Your entry cites the garbling of facts, but it may be that the facts are more garbled in the mind of the average American than this small example indicates. I’m not saying I’m any better—I don’t have a scientific background or claim to understand an iota of technical detail. I only recently learned that an embryo is a bundle of cells that haven’t become tissues of the body yet, and until then, I thought “embryo” was a little dude with a big head and spots where the eyes will go. I’m increasingly convinced that a large segment of the public thinks that, too. Even Richard Dawkins, in his book “The God Delusion,” constantly refers to “embryos” in the context of abortions. I suspect the renowned biologist does know the difference between an embryo and a fetus, but he is pro-choice, so he disingenuously uses “embryo” to make abortion seem less distressing. Similarly, there may be ES cell research opponents who subtly conflate the two, in order to make embryonic research seem more distressing.

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Human-animal hybrids: both sides are half wrong

In the wake of UK’s green light to create human-animal embryos, scientists are protesting a bulletin from a Catholics Bishops Conference. The accusations hurled include “blatant inaccuracy” and “a radical violation of the truth.”

The technique that the Catholic Church highlights in its objections--combining human sperm and animal eggs—has nothing to do with using animal eggs to make human embryonic stem cells. (For that you swap out the nucleus in an animal egg with a human nucleus so that the elixir in the egg can elicit reprogramming.)

What both sides failed to say is that making sperm-egg chimeric embryos has actually been around and legal for decades as a means of assessing sperm’s viability, though it’s not done much now. Any fertilized eggs must be destroyed by the two-cell stage. (Try googling “hamster egg test”) The use of this test has been used to argue that making other sorts of human-animal embryos is ethical.

When the accusations are flying, everyone should still set out the facts.

Kudos to the Anglicans, who seem to me to have done a pretty good job of both explaining the science and their objections to the research. On the Lutheran side, a theological argument for chimeras also does an accurate job with the science.

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Inconsistent Christian views on reprogramming

I’ve been reading the coverage on making embryonic-like stem cells without embryos in the religious press, and two quotes going through my mind, both sarcastic. One is “Shocked! Shocked!” (from Casablanca) and the other is “Oh, Lord! Make me pure, but not just yet.” (from St. Augustine).

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Chimeras are coming: UK allows animal eggs for human cloning

The regulatory body that approves all research on human eggs has just been given the green light for the production of chimeras.
Here is the article from the AP. The idea is that, with human eggs in short supply, researchers should be allowed to practice techniques on more readily available animal eggs. Also, several researchers believe the process can answer questions about how and to what extent an egg resets a nucleus from an adult cell into an embryonic state.

Ian Wilmut (who cloned Dolly the Sheep) put for the scientific rationale for chimeras last year. It’s called Man or beast? Man and beast!


Nature Reports has several related articles.

A summary of the UK Academy of Medical Science’s position paper on human-animal chimeras

In a research highlight, the scientist who cloned frogs has studied how nuclei in cloned embryos remember the differentiated cells they came from.

Following the finding that, at least in mice, fertilized eggs could be used for cloning, we looked at the implications for humans and at the power of the egg to reprogram.

Also, an article on successful monkey cloning showed the necessity of good technique.

And recent news coverage describes advances in cloning human embryos from adult cells.

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My sister, the stem-cell line

A front-page story in the San Francisco Chronicle describes a new service parents can opt for when getting in vitro fertilization services. Instead of storing, donating, or discarding unimplanted embryos, would-be parents can pay to have these embryos used to make stem cell lines.
This would create stem cell lines that would be the genetic siblings to any of a couple’s children.

The company offering this service, StemLifeLine, says over a dozen families have participated as subjects or paying customers.

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Renaming the Embyronic Stem Cell Registry recasts debate

The day that President Bush vetoed legislation to expand federal funding for embryonic stem cell research, he also issued an executive order calling for a plan to promote alternate sources of pluripotent stem cells, the details of which were announced today. Like the original executive order, it calls for the NIH Human Embryonic Stem Cell Registry to be renamed the NIH Pluripotent Stem Cell Registry.

The implication is that existing pluripotent stem cell lines are equivalent to embryonic stem cell lines. That’s not true. Many scientists think it could be true someday if current techniques advance, but many believe advancing pluripotent stem cells cannot be done without continuing to study embryonic stem cells.

The plan released today includes a soon-to-be-formalized program announcement to fund grants for research on alternative sources of human pluripotent stem cells including dead embryos, altered nuclear transfer (putting genetic material into an oocyte that will cause it to divide without forming a viable embryo), single cell embryo biopsy, and reprogramming somatic cells. These areas could all prove extremely valuable in understanding disease and testing therapies. Nonetheless, opponents of embryonic stem cell research must acknowledge that if this work is performed instead of rather than alongside work on embryonic stem cells, science will suffer and its fruits could be delayed.

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Embryonic stem cells made without destroying embryos

Bob Lanza, scientific head of ACT, says he's generated three embryonic stem cell lines without destroying embryos. These would be the first embryonic stem cell lines ever made where an embryo wasn't destroyed. In fact, he's waiting to see if the NIH will fund research on these lines on the grounds that, since no embryo was destroyed, these lines should be eligible for federal grants. Other scientists at the meeting are skeptical. They say they need to see data.

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