Somatic Cell Nuclear Transfer Used to Create Human Embryonic Stem Cells

A international team including scientists from Oregon Health & Science University and the Oregon National Primate Research Center have just announced in Cell that they have successfully used somatic cell nuclear transfer (SCNT) to develop human embryonic stem-cell lines. As I understand the paper, the team removed genetic material from the core of multiple oocytes from two different human donors, and replaced it with nuclear material taken from the skin cells of an embryo. Some portion of the eggs from each donor then proceeded to develop to the blastocyst stage, at which point their cells were plated and tested for pluripotency. Pluripotency was proven when the cells, injected into immuno-deficient mice, formed tumors containing tissue- and cell-types representing all three germ layers.This paper, then, is the most powerful proof of principle to date that we may one day be able to combine SCNT and embryonic stem-cell technologies to generate made-to-order, genetically-compatible replacement tissue for humans with diseases such as diabetes or Parkinson's.

It's important to note that the blastocysts were imperfect in various ways, and could not have successfully been implanted into a woman to make a child. (Members of the same team have not yet been able to create a cloned monkey embryo capable of implantation.) This has created some verbal problems that will no doubt be fodder for the culture wars. Strangely, the mostly-liberal National Public Radio is reporting that the scientists created and destroyed human embryos, while the mostly-conservative Wall Street Journal is saying that the team's achievement "is a long way from creating a human embryo."

Here's how I think of it: while the team used cloning technology to create human embryonic stem cells, they didn't exactly create and destroy a human embryo along the way; they created what they knew to be a faulty approximation of a human embryo, but one close enough to the real thing to generate pluripotent human embryonic stem-cell lines. (Think of the fact that human embryonic stem-cell lines can also be generated from parthenotes which are completely incapable of developing into embryos.)

Nonetheless, I'm pretty sure these scientists would have no problem with creating a perfect, and in principle perfectly implantable, human blastocyst--though they have no intention of implanting one, and no research oversight body anywhere would permit them to, even if they did. They want to generate tissue, and if perfecting human embryo cloning helps them do that, they will. Even if you agree with me that the toughest ethics questions aren't quite yet raised by this work, this work certainly implies that they'll be raised sooner or later.

Romney on Stem Cells

I blogged recently about Newt Gingrich's recent attacks on human embryonic stem cell research, and his intention to investigate and regulate the practices of IVF clinics which create excess human embryos. The news item led me to wonder what Mitt Romney's stem-cell position is. Not surprisingly, it's bounced around a bit.

In his gubernatorial race of 2002, Romney was a supporter of embryonic stem-cell research, and even promised to lobby President Bush for increased research funding in the area. But after a conversation with some Harvard researchers who, Romney often claims, had no moral qualms about destroying two-week-old embryos, he changed his position. Indeed, he credits the stem-cell debate with pushing him toward his current pro-life abortion position. In the run-up to the 2008 presidential election, Romney formulated his current position, namely, that it isn't unethical to use "excess" embryos from IVF clinics for embryonic stem-cell research, but that he opposes government funding for such research, and opposes any laboratory creation of embryos (by cloning or otherwise) for research purposes. This page gathers a number of quotations from Romney on the issue over the years.

He has spoken in favor of shifting research from human embryonic stem cells to induced pluripotent stem cells, since the latter research involves no embryonic destruction. He has also made mention several times of "altered nuclear transfer," the purported "scientific solution" to the ethical problem of embryonic stem-cell research promoted by William Hurlbut, a Stanford professor and member of President Bush's bioethics committee. Altered nuclear transfer essentially produces a severely disabled embryo which cannot develop into a human baby; Hurlbut argued that using ANT embryos thus avoided the problem of killing a viable embryo. Pro-life organizations briefly endorsed, and then pulled away from, the Hurlbut proposal. (There's a website touting ANT here; and brief discussion halfway down this page of the political reception by pro-life groups of Hurlbut's proposal.)

This recent item from Fox News takes Romney to task for continuing to invest in Novo Nordisk, a Danish pharmaceutical firm which uses some stem cells in its research, up until 2010--in spite of having taken a position against embryonic stem-cell research in 2007. But I think that's just a mistake. Romney, as far as I've been able to find, has never taken a comprehensive position opposing all human embryonic stem-cell research. He isn't opposed to privately-funded research on leftover IVF embryos. He opposes laboratory embryo creation, and he opposes the public funding of any embryonic stem-cell research.

Egg Donors and Stem Cell Research

This piece from the Atlantic (summarizing this article from Fertility and Sterility) says that most fertility clinics which accept donor eggs for fertility treatments, and which donate at least some "excess" embryos for research, fail to inform egg donors of the possibility that their eggs might be used in stem-cell research. Most of the surveyed clinics told donors that they would not have control over the future uses of their eggs or the embryos made from them, and 30% mentioned the possibility of research use, but very few mentioned stem-cell research by name. This ought to be remedied. I doubt that most women who are willing to donate eggs for fertility treatment have serious opposition to the use of their eggs in fertility research or in stem-cell research, but a few might. They should be given the information.

The Meaning of Geron's Stem-Cell Decision

Michael Cook at BioEdge says the decision by Geron to end its human embryonic stem cell spinal-therapy research is a huge blow to those who believe in the therapeutic potential of hES cells. I have to disagree. It's true that the tissue-generating potential of hES cells was overblown in the battle to secure funding for hESC research. But I don't think Geron's move stands for anything greater than what it was: the decision of a single firm that its cancer research was more profitable than its stem-cell research. University-based work with hESCs and induced-pluripotent cells have shown real progress toward the tissue-generation goal; and, additionally, researchers are using stem cells as tools for drug-testing and for the analysis of diseased cells--work which is quite apt to have short-term therapeutic payoff.

Note, too, that while Geron had secured funding from the California Institute for Regenerative Medicine for its trial, it has given the money back with full interest, so there's no story here of wasting public funds.

Stem Cell Politics

No real surprises in this piece in NEJM summarizing public-opinion polling results on support for human embryonic stem cell research. 62% of Americans think hESC research is morally acceptable, while only 30% think it's wrong; 55% favor federal funding and 41% oppose it. But only 52% of Republicans favor hESC research, compared to 67% of Democrats; and a 58% majority of Republicans oppose federal funding, which 70% of Democrats favor.

Of 34 European countries, majorities favored prohibition of hESC research only in Luxembourg, Slovenia, Austria and Greece.

Geron Halts Stem-Cell Trial

Here's a report on Geron's decision to halt its human embryonic stem cell spinal-cord therapy trial--the first ever in-human stem-cell trial approved in the US. The decision seems not to have been driven by the trial's progress, but by economics: the trial was costing a lot and not attracting investment, whereas Geron's other work on cancer has drawn the interest of big Pharma investors. Only four people had been enrolled in the trial; all had reportedly tolerated GRNOPC1, a Geron product containing hESC-derived progenitor cells, well and without side effects.

European Court: No Patents on Human Embryonic Stem-Cell Products

The European Court of Justice ("ECJ") has held that scientists cannot patent products developed from any research which involves the destruction of the human embryo. The Court's full opinion is here. Greenpeace (!) began the case in 2004 by suing to block a Bonn researcher's patent on a technique for deriving neural cells from human embryonic stem cells. European law has banned patenting in connection with the "uses of human embryos for industrial or commercial purposes" since 1998, and German law includes similar language. The Greenpeace case turned on whether a blastocyst destroyed in creating a stem-cell line counts as an "embryo;" whether "industrial or commercial purposes" includes university-based research; and whether the European patent-exclusion law applies to research that is conducted significantly downstream from the act of embryonic destruction (for example, on stem cell lines produced many years ago, and purchased by German researchers from researchers in other countries). The German court's 2006 ruling in favor of Greenpeace was appealed to the German supreme court, who referred it to the ECJ for clarity on the meaning and application of the various terms. Earlier this year the ECJ's advocate-general recommended that the court uphold the patent ban, so yesterday's opinion was widely expected. The court held, first, that the term "embryo" includes any fertilized egg, any product of "research cloning" (in which an unfertilized egg has introduced into it a nucleus from a mature cell), and any parthenote (an unfertilized egg whose division and development have been artificially stimulated by researchers). (This last holding is surprising to me, since parthenotes aren't capable of developing into babies.) Next, the court held that scientific research is included within the legal restriction from patentability concerning the use of embryos "for industrial or commercial purposes". Finally, the court found that the patent restriction applies no matter how distant the research or patent is from the original act of embryonic destruction, and even if the patent itself makes no mention of embryos (referring, for example, only to particular cell-lines originally derived from embryos). There's a fine technical overview of the opinion here.