The Organ Factory
On Monday and Tuesday, we reviewed recent studies and learned that we could hasten life-saving tissue transplants by growing donor embryos for six or seven weeks. Yesterday we looked at the chief obstacle to that idea—the ethical rule against research beyond 14 days—and discovered that we'd already stretched our principles to allow harvesting of cells up to that stage. Can we stretch our principles further? Yes. All of them can be extended a few days. Most can be extended a few weeks or longer.
Let's recap the ethics committee reports that laid down the 14-day rule. They come from the U.S. government (1979, 1994, 1999, 2004), Britain (1984), Australia (1984), Canada (1994), California (2002), the leading U.S. IVF medical association (the American Fertility Society, 1986 and 1990), and a leading U.S. biotech company (Advanced Cell Technology, 2000). They drew the line based on five principles: individuality, organization, implantation, neural development, and utility.
Of these principles, individuality is the strictest: Once the primitive streak (a telltale alignment of cells) appears, we know the embryo is an individual and won't become twins. Fortunately, this principle is also the least important, since it doesn't affect the fact that we're aborting at least one embryo. The second criterion, organization, is easier to adjust, since it's a continuum. That leaves three other principles. Today we'll focus on utility and neural development. Tomorrow we'll talk about implantation.
The ethics reports don't explain utility as a principle, but they all invoke it. In her memoir, Mary Warnock, the lead author of the British report, says her committee's task was "to recommend a policy which might allow the sort of medical and scientific progress which was in the public interest." The 1994 U.S. report notes that under a 14-day rule, "Work on embryonic stem cells, their differentiation and their therapeutic potential, could proceed." The Canadian report argues that the rule "balances the concerns … in favour of beneficial experimentation." Even Leon Kass, the chairman of President Bush's bioethics council, says the council, in deference to "those who care about these things," suggested a 10-day cutoff (and later extended it to 14) so as "not to get in the way of the derivation of stem cells." Sen. Dianne Feinstein, D-Calif., has proposed a legislative line at 14 days because embryos beyond that point are "no longer useful for the purposes of embryonic stem cell research."
The studies we reviewed Monday and Tuesday suggest that these conclusions, while true of stem-cell research, aren't true of "beneficial experimentation" and "medical and scientific progress." Embryos are more useful after 14 days. The utility line has moved.
What about neural development? That's the most commonly cited basis for the 14-day rule. The argument is that it's OK to dissect embryos if they can't think or feel pain. But there's something odd about the way ethics reports apply this principle. They stretch the timelines of twinning and implantation as far as possible to justify research up to 14 days. They do just the opposite with neural development, drawing the line far earlier than they have to. Why? No doubt because 14 days seemed to be enough to get what we needed. Now that we know it isn't, we've got plenty of room to push the neural line forward.
The ethics committees invite us to take this wiggle room if we need it. The 1979 U.S. report draws on contributions from four scholars. One opposes all exploitation of embryos; another says the embryo isn't "truly human" until "two to three weeks after conception"; two others draw the line at primitive sentience and the development of brain tissue. Warnock's memoir says the British committee accepted the 14-day line to "err on the side of extreme caution" and satisfy skeptics that "embryos would not be subjected to suffering." But she argues, "This would still have been true, if we had set a later limit." She says the neural principle could permit research "probably for much longer."
The 1994 U.S. report agrees: "There is no neural tissue whatsoever before the appearance of the primitive streak; hence, there is no possibility of any kind of sentience." The report mentions that some of its authors "wondered whether it might be permissible to extend research briefly beyond the primitive streak stage, since sentience is not possible until considerably later." The California report says, "The development of a nervous system and any possibility of feeling sensations comes much later than the appearance of the primitive streak." The AFS committee notes that "the preembryo does not have the differentiated organs, much less the developed brain, nervous system, and capacity for sentience that legal subjects ordinarily have." The AFS report endorses a 14-day limit only because "it seems prudent at this time."
Well, times have changed. We need more developed tissue. Let's see how far we can get with the principles we've stated. To begin with, the primitive streak isn't really at 14 days. The British report puts it at 15 days. The Canadian report puts it at 15 to 16 days. The British Royal College of Obstetricians and Gynecologists, citing "early neural development," proposes a 17-day limit. The California report, citing variable timing of the streak, offers an outside limit of 18 days. The 1994 U.S. report says research of "outstanding merit" might justifiably be funded until "the beginning of closure of the neural tube … between days 17 and 21." The British report outlines an argument for extending the line to 22 or 23 days, "when the neural tube begins to close."
Now we're through the third week. Let's press on. In its submission to the Warnock committee, Britain's national academy of science, the Royal Society, rejects the 14-day line as "unduly restrictive, especially as it does not take into account the important question of embryonic organization." When does such organization truly begin? "The fourth week," says the society. On the current U.S. bioethics council, panelist Michael Gazzaniga argues that moral concepts make no sense until the embryo has a brain, "so one could say that you at least needed the presence of a nervous system, and a nervous system doesn't start forming for four or five weeks."
We're almost there. In its recommendations to the Warnock committee, Britain's Council for Science and Society says embryo research is unobjectionable when "there is no possibility of any sense of pain." This possibility arises "only after the fetus has developed a nervous system, six weeks after pregnancy being earliest." The council extends this policy to a scenario in which "whole embryos might be grown in vitro for use as replacement tissue." The 1979 U.S. report adds that under proposals to draw the line at "primitive sentience," the "transition from embryonic to fetal status (at the eighth week of gestation) or, at the latest, the tenth gestational week of fetal development would seem to mark the transition from non-protected to protected status."
We made it. At seven weeks, we've reached what the Israeli kidney study called the "window of human … embryogenesis that may be optimal for transplantation." At seven weeks, the Lanza-West research team had extracted transplantable cardiac tissue from calfs (which gestate at roughly the same rate as humans) and were beginning to get transplantable kidney cells. Seven weeks also gets us primordial germ cells, which, according to the Gearhart study (reviewed Monday) and the Czech-Japanese analysis (reviewed Tuesday), might produce safer tissue than we're getting from cloning-derived embryonic stem cells.
Utility, organization, and neural development all justify a new ethical line at eight weeks. This matches the medical definition of an embryo: "the developing human individual from the time of implantation to the end of the eighth week after conception." By drawing a bright line between the embryo and the fetus, we avoid the moral perils of "fetus farming." The only remaining problem is that we promised not to authorize implantation of embryos for research, and without implantation, we can't grow them long enough to get differentiated tissues. Or can we? We'll explore that question tomorrow.
Will Saletan covers science, technology, and politics for Slate and says a lot of things that get him in trouble.