Solving old embryo debates—and starting new ones.

Science, technology, and life.
Oct. 20 2005 2:59 AM

Stem-Cell Shakeup

Solving old embryo debates—and starting new ones.

This week, Nature published two papers suggesting, based on mouse experiments, that we could get human embryonic stem (ES) cells without killing embryos. The reports threaten to radically realign the stem-cell war, abolishing old problems and raising new ones. Here's a look at their implications.

1. They divide opponents of embryo killing from opponents of in vitro fertilization. Regular ES research involves removal of cells from a human embryo at the blastocyst stage, which kills the embryo. One of the new methods, biopsy, removes the cells earlier, at the eight-cell stage, which doesn't kill the embryo. The authors of the biopsy paper, led by Robert Lanza of Advanced Cell Technology, present data showing that in mice, the remaining seven cells develop, implant, and produce live births with roughly the same rate of success as non-biopsied IVF embryos. Since biopsy has already been done to every human child who was genetically tested as an early embryo (through pre-implantation genetic diagnosis, or PGD), we know it isn't lethal. The population of kids born after PGD is still relatively small—reportedly 1,000 to 2,000—but we've yet to see evidence of significant differences between these kids and kids who weren't biopsied.

William Saletan William Saletan

Will Saletan writes about politics, science, technology, and other stuff for Slate. He’s the author of Bearing Right.

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If you've opposed federal funding of ES research on the grounds that embryos shouldn't be killed, biopsy solves your problem. The only people bound to oppose biopsy are those who oppose IVF because it's artificial or who object to exposing embryos to the same risks involved in PGD. Richard Doerflinger, the point man on stem cells for the U.S. Conference of Catholic Bishops, is in the anti-IVF/PGD camp. He says biopsy "poses unknown risks of future harm even to the child allowed to be born." Rep. Roscoe Bartlett, R-Md., an ally of the bishops against funding regular ES research, is in the anti-killing camp. Biopsy "gets around all of the ethical arguments, except for that small minority of the pro-life community that doesn't even support [IVF]," Bartlett tells the New York Times. The billion-dollar question is which way President Bush will go. His past statements indicate that his concern is embryo killing and that he's looking for a way forward. Both factors suggest that he'd allow funding of research on ES lines derived from biopsy.

2. They divide the stem-cell lobby's fighters from its compromisers. Facing a split between opponents of embryo killing and opponents of IVF, supporters of ES research have to decide whether to 1) cut a deal with opponents of killing to support the new methods or 2) dismiss the new methods and attack IVF opponents as an obstacle to regular ES research. Lanza is encouraging compromise. His paper says biopsy "could circumvent the ethical concerns voiced by many." But the chief ES research lobby, the Coalition for the Advancement of Medical Research, is trying to keep the press focused on intransigent enemies and intractable issues. The new methods "will not sit well with many who oppose embryonic stem cell research," warns CAMR.

3. They erase the line between donor and beneficiary. Bush has said the government shouldn't fund ES research because no human life should be taken for another's benefit. Even if biopsy removes the certainty that an embryo's life will be taken, Bush's bioethics council worries that lesser damage from the biopsy might show up later in the embryo-turned-child. This risk might be unacceptable, according to the council, because the biopsy "is not being performed for the good of the embryo."

Lanza and his colleagues hit this objection head-on. Biopsy could "allow the banking of autologous ES cell lines for children born from transferred embryos," they write. Ron Green, an ethics adviser to Lanza's company, envisions a day "when every fertility clinic embryo has a cell removed and banked for future tissue use or organ replacement." In short, the embryo not only survives the biopsy but becomes its chief beneficiary. In the creepy old scenario, we would clone an embryo from one of your adult cells and kill the embryo to get customized ES cells to grow tissues for you. In the new scenario, we would get the customized ES cells and tissues directly from you when you were an embryo. No victim necessary. This appeases people like me who fear the reduction of human embryos to a medical resource.

4. They blur the line between embryos and non-embryos. The second method outlined in Nature, altered nuclear transfer (ANT), tweaks a gene prior to the cloning process so that the resulting entity produces embryonic cells but not a whole embryo. ANT's original proponent, Bill Hurlbut of the Bush council, insists that the product of ANT must grow chaotically, not in the self-organizing way characteristic of an embryo. For him and other pro-lifers, this principle is as crucial as the project's feasibility: If the thing that ends up being dissected to get stem cells is an embryo, the project is ruined. But the authors of the paper on ANT's feasibility, Rudolf Jaenisch and Alexander Meissner, don't share Hurlbut's concern. They support regular ES research and cloning. In the paper, they have no problem calling ANT-produced entities "embryos" and writing that ANT "cripples an already compromised blastocyst." This has led to a lethal cascade of press reports calling the ANT products "gene-altered embryos," "crippled mouse embryos," and "unimplantable embryos." If pro-lifers buy this description, they'll bail out of the ANT project, making it pointless.

Not all pro-lifers are bailing out. Some, uneasy that Meissner and Jaenisch allowed their ANT products to develop like embryos too long, are looking for alternative genetic tweaks that would thwart embryo-like development earlier in the process. What used to be a clear distinction—embryo or not embryo—is becoming a question of degree: How much and how long can something look like a developing embryo before we call it an embryo? If it's OK to get stem cells by dissecting something that stops developing like an embryo at the first cell division, what about something that stops developing like an embryo at the third? And why draw the line there? Jaenisch and Meissner say regular clones, the kind we already know how to make, "lack the potential to develop into normal human beings with any acceptable or practical efficiency." If it's just a difference of degree, why not skip years of ANT refinement and fund cloning instead?

5. They blur the line between human beings and human parts. Biopsy works—it gets stem cells without killing the embryo—because the embryo's seven remaining cells are still flexible enough to take on the tasks and powers that were assigned to the extracted cell. But what if they're so flexible that each could become a whole human being? In that case, the extracted cell must have the same power, known as totipotency. To some pro-lifers, a totipotent cell is an embryo, and biopsy, by using lab cultures to turn that embryo into ES cells instead of a baby, kills it.

If you think this complaint is nutty, you're not getting the magnitude of the problem. In the current stem-cell scenario, the killing is straightforward: you puncture the embryo; you take cells from its inner mass; the embryo dies. In the new scenario, there's no killing. You just put one of those eight early embryonic cells in this or that culture, and it becomes, accordingly, a human being or a clump of stem cells. Lanza says there's no evidence that such early human cells have never produced a viable embryo. But according to the Bush council, "In mice, apparently normal and fertile animals have been produced from single blastomeres [early cells] isolated from a 4-cell embryo (and from two blastomeres isolated from an 8-cell embryo)." Furthermore, "In experiments with non-human primates (rhesus monkeys), Chan, et al. … have reported that two blastomeres isolated from an 8-cell embryo gave rise to a live-born monkey."

If you can make the seventh and eighth cells become one thing or the other—a baby if placed in Petri Dish A, a bunch of stem cells if placed in Petri Dish B—why can't you do the same to the first cell? Some pro-lifers see this as the next breakthrough. They report that "scientists are already discussing a modified version [of ANT] in which adding the nucleus to the egg would result in a single stem cell, not an embryo." Meanwhile, researchers are studying how to reprogram an adult cell backward—making it capable, like an ES cell, of producing many kinds of tissues instead of just one. Take this technology back far enough, and you'll reprogram the cell all the way to totipotency. Take it forward, and you'll turn a would-be embryo into a skin cell. The stem-cell war will be dead. So will the biological sanctity of human life.

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