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Biomedicine

William Hurlbut

Embryonic stem cells without embryos.

William Hurlbut, a physician and ethicist, is best known as a member of the President’s Council on Bioethics. Though he has spoken out against the destruction of embryos for research purposes, he is nonetheless a supporter of ­embryonic-stem-cell research. He avoids what would otherwise be a terminal para­dox through a proposal that he calls “altered nuclear transfer,” or ANT. His goal: to create embryonic stem cells without destroying human embryos.

One of the most promising methods for creating embryonic stem cells is cloning: the nucleus of an egg cell is replaced by the nucleus of an adult cell, a process called somatic-cell nuclear transfer. The egg is then induced to divide, and the stem cells harvested from the resulting embryo are pluripotent, meaning they can form any sort of tissue in the body. But harvesting the stem cells destroys the embryo. By contrast, ANT (which has been shown to work in mice, if not humans) switches off vital genes–through alteration of the somatic-cell nucleus, the cytoplasm of the egg, or both–before the transfer takes place. Hurlbut says the resulting cell mass could not become an embryo but could produce pluripotent stem cells.

Hurlbut recently spoke with Michael Fitzgerald about ANT.

TR: What compelled you to come up with altered nuclear transfer?

William Hurlbut: When the President’s Council met [to debate the ethics of stem-cell research, in 2002], it was clear that both sides of this debate are promoting important positive goods: that on the one hand you have people trying to defend human dignity from its earliest stages, and on the other hand you have people trying to promote advances in science and medicine. And as I sat there and listened to this debate, I thought, “Isn’t there an answer to this? Isn’t there some third option, some way that both of these goals can be achieved?”

I thought of dermoid cysts, benign ovarian tumors that produce all the cell types, tissues, and partial organs of the human body. Clearly something like embryonic stem cells is being produced in those tumors. And I thought to myself, “If nature can do this, we can do it. There must be simple technological alterations we could use in concert with nuclear transfer such that we produced embryonic­-type, pluripotent stem cells, but without producing the unitary organism that is a human embryo.”

TR: Does ANT produce truly pluri­potent stem cells?

WH: [MIT’s] Rudy Jaenisch got pluri­potent cells. He injected some of the cells into living mice, and they formed tumors with all the tissue types in them. So yes, it works. The next step with altered nuclear transfer is to study it in primates. If it works in primates, specifically in rhesus macaques, then we can proceed with pretty good confidence, but also caution, in working with human cells.

TR: How does mutating an embryo so it is no longer a viable embryo really solve the problem?

WH: That is exactly the wrong way to frame the description of what’s being done. The idea that we’re mutating an embryo is an inaccurate and misleading representation of what we’re doing. The key to the project is that no embryo is ever created. It’s not a deficiency in an embryo but an insufficiency in the starting component, such that it cannot rise to the level of a living being.

TR: Shinya Yamanaka and others are having success reprogramming adult skin cells into embryonic stem cells. Why should we continue with ANT?

WH: Yamanaka’s cells are very, very interesting and may solve the issue of how to procure embryonic-type stem cells. But altered nuclear transfer takes things back to the very beginning, to the single-cell stage. So ANT would give us the ethical framework and technological tools for probing early development, without the creation and destruction of human embryos.

TR: Are there circumstances that you could imagine under which you might condone embryonic­-stem-cell research?

WH: I’m in no sense an opponent of research with embryonic stem cells as such. I have moral concerns about how the stem cells are obtained, not about the use of the cells themselves. I’m not in favor of the destruction of human embryos for research purposes.

TR: What are the ethical and moral issues we face in neuroscience?

WH: One of the most fundamental questions is how you correlate the neurological development during embryogenesis with moral standing. Some people argue that until you have a conscious being, or maybe a self-conscious being, you don’t have moral value. We don’t know exactly what consciousness is, but most neuro­physiologists don’t think there’s consciousness present before 18 or 20 weeks at the earliest. If that’s your criterion, you could probably justify the instrumental use of human embryos up to maybe 20 weeks. So without a strong moral prin­ciple, you may very well see the argument over stem-cell research move from 14 days to later stages. So at least at the federal-funding level, we should preserve the principle of the defense of human life from its earliest origins in the one-cell stage.

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