The Organ Factory
Yesterday we learned that human embryonic stem-cell (or hES) research might take too long to produce the transplantable tissue many patients need. To save their lives, we might need to grow embryos beyond the 14-day limit on which governments previously agreed.
Why did we draw this limit in the first place? Is it really worth letting people die?
Legislative references to the 14-day rule cite ethics committee reports. The most influential of these reports were sponsored by 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). If you read these reports, the first thing you'll notice is that they refer to each other. We've agreed to the line because we've agreed to it—and could just as easily move it. The next thing you'll see is that many of them admit that the date is "arbitrary." The British report, from which others copied the rule, concedes that "biologically there is no one single identifiable stage in the development of the embryo beyond which the in vitro embryo should not be kept alive."
So, what's the line based on, besides itself? Officially, a convergence of four principles: individuality, organization, implantation, and neural development. But the principles don't really converge. We stretched them to allow research up to 14 days, based on a fifth principle: utility. We can stretch them beyond 14 days for the same reason.
Start with individuality. About two weeks after conception, the human embryo develops an alignment of cells called the primitive streak. Until this moment, according to the California report, "the pre-embryo is not necessarily one individual—it could lead to identical twins." If it isn't an individual, it can't have a soul or be a person, so it's eligible for research. I've never found this argument reassuring, since it just means we could be aborting two embryos instead of one. But what's interesting is how we came up with the argument.
We didn't pick the 14-day line based on twinning. We drew the line first, then added the twinning rationale. The 1979 U.S. report that first authorized the 14-day line never mentions twinning. Neither does the 1984 Australian report. The British report does, but its lead author, Mary Warnock, explained in a memoir last year that implantation and neural development drove her committee's decision, and individuality was just "another factor." Not until 1994 did government reports make twinning a central theme.
It took plenty of gymnastics to play up the minuscule probability that the embryo would twin while playing down the far greater probability that it would become a baby. The Canadian report suggests that early embryos are no big deal, since "only half of all fertilized eggs survive embryo and fetal development and result in live births." ACT's analysis says the "very high rate of early embryo loss" makes these embryos less valuable. The California report adds, "Only about 40 percent of fertilized eggs ever reach the primitive streak stage." Yet all three reports cite the possibility of twinning as grounds to doubt an embryo's individuality. None of them mentions that the probability of twinning is less than half a percent.
Moreover, twinning doesn't start at 14 days; it ends there. If you wanted to minimize the risk that embryos used in research were individuals—i.e., if you wanted to maximize the chance that they might twin—you'd ban research before the blastocyst stage, when most twinning occurs. That would preclude hES research. The longer you wait, the lower the odds of twinning, and the more certain it is that what you're dissecting is an individual. Fourteen days is when you can no longer tell yourself there's the slightest shred of doubt. The only reason to draw the line that late is to maximize the opportunity for research.
We've stretched the second principle, organization, the same way. The argument for the 14-day rule on this basis is that embryos aren't sacred till they're organized, and they aren't organized till the primitive streak. Early government reports acknowledged that the streak was an "appearance," "mark," or "indicator" of organization. It wasn't necessarily a turning point in reality; it was just the first thing we could see. But as embryos became a more promising medical resource, we reinterpreted the streak as a line in nature. The 1999 U.S. report declared, "At 14 days, the first stages of organized development begin." Two years later, senators embraced the argument, offered by a biotech industry ethicist, that "nature begins by drawing a line on those cells. It's called primitive streak."
Unfortunately, nature doesn't draw lines for our visual benefit. It organizes the embryo well before we see the streak. In 1986 the American Fertility Society explained, "Two divisions after the 8-cell stage, the 32 blastomeres are increasingly adherent, closely packed, and no longer of equal developmental potential. The impression now conveyed is of a multicellular entity, rather than of a loose packet of identical cells." In the blastocyst stage, "The populations of inner and outer cells become increasingly different, not only in position and shape but in synthetic activities." The streak, which appears later, is simply "the visual indication" of an embryonic axis.
The streak, in other words, is a lot like quickening, the point at which a woman can feel a fetus moving inside her. We used to think it was fine to purge the womb before quickening, since we couldn't detect a living fetus. Then we developed ultrasound and saw what was going on. Now we're learning to detect embryonic organization before the streak. Indeed, we're detecting it before the blastocyst. But that gets in the way of hES research, so we've decided that organization before the streak isn't "embryonic" organization.
That brings us to the third principle: implantation. Politicians who favor embryo research up to this point argue that an embryo doesn't acquire the potential for life until it takes root in the womb. Ethics reports don't explain the distinction, but they all invoke it. The 1979 U.S. report approves research if "no embryos will be sustained in vitro beyond the stage normally associated with the completion of implantation." The Australian report bars research "beyond the stage of implantation, which is completed 14 days after fertilization." The Canadian report says the 14th day is "the point at which the zygote has normally completed its implantation." The British report says this marks "the end of the implantation stage."
Notice the pattern? Implantation is "complete" at 14 days. (Some biologists say it's really 12.) When does implantation begin? At seven days, according to the Canadian report. That's too tight for hES research, so we stretched the timeline of implantation, just as we stretched the timelines of twinning and organization. Since then, we've come to equate implantation with 14 days, just as we've come to equate organization with the primitive streak. By 2004, Mary Warnock was erroneously declaring that the 14-day limit chosen by her British committee in 1984 matched "the time when an embryo in the uterus was likely to attach itself to the uterine wall."
These are just a few of the lines we've pushed forward. Government committees originally approved embryo research to help people have babies; now we're doing research to get tissue for transplants. President Bush agreed to fund hES research on cell lines derived before Aug. 9, 2001; now Congress wants to lift the date restriction. Research advocates swore to use only embryos left over from IVF; now they're proposing to clone embryos for research. You can argue the merits of these shifts, but the bottom line is that the only constant in the ethics of embryo research is change.
Are we ready for one more change? Having pushed the line to 14 days, can we push it further? Sure we can. Tomorrow, we'll find out how.
Will Saletan covers science, technology, and politics for Slate and says a lot of things that get him in trouble.