Induced Pluripotent Stem Cells and Germline Engineering

Posted by Pete Shanks October 16, 2012
Biopolitical Times
Motherless mice

The Nobel Prize in Physiology or Medicine upstaged an arguably even more significant announcement that built on the same research. Mitinori Saitou and colleagues in Kyoto created mice by using sperm and eggs grown from “induced pluripotent” stem cells (iPSCs).

Think about it: This is extraordinary. They took fully developed adult cells, transmuted them into iPSCs, induced those to develop into gametes — both male and female — which they combined to form embryos that were implanted and brought to term as mouse pups. This is as close as we have come yet to creating life: cloning without a donor egg.

Well, nearly. Most reports slightly exaggerated how far this effort had succeeded. At present, supplied ovaries are needed for the procedure to work, as a sort of scaffold on which the oocytes grew, so they have not yet eliminated the need for eggs, but they expect to in the foreseeable future. According to Science Now:

Saitou says that with a bit more progress in understanding the complex interactions at work, they may be able to coax the cells through the entire oocyte development process in a lab dish. If successful, "we may be able to skip the grafting," he says.

That prospect has already provoked a worldwide round of headlines, many of them jumping immediately to possible human applications. Which is hardly surprising, since the formal academic paper in Science concludes [sub req'd]:

Combined with a previous study, our system serves as a robust foundation to investigate and further reconstitute female germline development in vitro, not only in mice, but also in other mammals, including humans.

It really is not hard to imagine a scenario in which an infertile person becomes artificially (though perhaps unreliably and expensively) fertile. Theoretically, people with no functional gametes, or gay men or women, could have babies genetically related to both members of the couple and to no one else. Indeed, as Ronald Green pointed out, DNA theft becomes a somewhat plausible threat:

When you think about the commercial possibilities of people selling to infertile people babies produced from George Clooney or Jennifer Aniston, or whatever, you have to worry about it.

None of that is going to happen soon, and it might not happen at all — research is never entirely predictable — but these concepts are rapidly moving from speculative fantasy to the point where they deserve serious discussion.

Saitou, like Nobelist Shinya Yamanaka, is well aware of ethical issues: “Right now,” he says, “using oocytes has this moral and legal burden.” On the prospect of “parentless” children, he says that “the biological, ethical, and legal issues they will raise defies the imagination.”

Which is true, but at least as disturbing is the idea of using these technologies not only to create related offspring for the previous infertile but to specify what that child will look like, and maybe more. That’s the prospect that led Hank Greely to respond, on NPR (audio):

Wow. That's my general reaction. Repairing hearts, repairing brains, repairing kidneys, that's all good and important, and we'd all love to be able to do that. But this involves making the next generation. ... It will change the world if it happens, by giving parents — I hope parents, potentially governments or insurers or doctors or somebody else — but in the US, I suspect it will give parents a greater ability to choose the genetic traits of their children.”

That could mean, Rob Stein suggests, "babies with blue eyes or blond hair, or a talent for sports or music." This point was largely lost in coverage that stressed a potential new fertility treatment. The availability of huge numbers of gametes, which could allow the refinement of genetic modification techniques, might wind up bringing germline engineering into the realms of technical possibility.

That is a prospect that goes to the heart of the concerns of the Center for Genetics and Society. As a society, indeed a global civilization, we need a long, deep and well-informed debate. There will be disagreements; we must not flinch from confronting them. It is no exaggeration to say that the future of our species may be at stake.

Previously on Biopolitical Times: