Whether or How to Use Artificial Gametes

On April 19–21, the National Academies are hosting an extended Workshop on:

In Vitro Derived Human Gametes as a Reproductive Technology: Scientific, Ethical, Regulatory, Legal and Clinical Implications

Human gametes, of course, are sperm and eggs, which combine to make embryos and eventually, if all goes well, babies. “In vitro derived” means that rather than being generated in the human body, they are created in the lab by manipulating other cells to form artificial gametes. 

In some ways, this concept is not all that new: Induced pluripotent stem (iPS) cells are similar to embryonic stem cells, which are usually found in very early embryo development, but can be derived from ordinary adult cells with techniques that were developed more than 15 years ago. Somewhat similar processes could turn an ordinary adult cell into sperm or eggs – in vitro gametogenesis (IVG for short) is this process of making artificial human gametes in the lab.

Aside from scientific curiosity, why would anyone do this? There are at least three possible reasons: to enable infertile couples to reproduce; to enable gay couples (whether male or female) to have children who are genetically related to both parents; and to make it easier to generate “designer babies” with a specific genetic makeup. (Another possibility might be solo reproduction, with egg and sperm both from the same self-obsessed individual, a concept that even Julian Savulescu rejects.) Experiments with both IVG and synthetic embryos are underway with mice and monkeys (1, 2, 3), the concept of a baby with two dads is being seriously researched, and bioethicists such as Françoise Baylis are starting to consider the various issues these developments raise. If successful, this approach could represent an even more dramatic change in reproduction than the introduction of IVF more than 40 years ago.

Another possibility is to use lab-made gametes for heritable human genome editing, altering them rather than embryos, which thus far have proved difficult to reliably and predictably edit. Some proponents posit that editing just the one cell would be easier than editing an embryo, and would eliminate the risk of mosaicism. Shoukhrat Mitalipov, a pioneering scientist in both embryo editing and IVG, clearly wants to push the envelope but still recognizes that HGE is definitely not ready for clinical use. He notes that: “Human embryos often reject the DNA templates that we use to edit their genome, and we don’t know why.” But IVG raises two possibilities: enormous numbers of sperm or eggs to manipulate, with the idea that only one of each is really required, and a nearly limitless supply of embryos that can be selected or edited and subjected to quality control.

It is important to remember, and to keep stressing, that current gene editing technologies are still a long way from perfect, that artificial gametes have thus far been convincingly created only in animals, and that both technologies raise far-reaching social perils.

So why all the attention to artificial gametes now? Well, people are talking about the possibilities. Science reporters and editors are flocking to the gee-whiz technicalities. And biotech startups, backed by Silicon Valley venture capital, are going all in on commercializing IVG. But should they?

The concluding statement from the March Summit on Human Genome Editing included this clear and notable assertion:

Heritable human genome editing remains unacceptable at this time. Public discussions and policy debates continue and are important for resolving whether this technology should be used. [italics added]

Given the close links between artificial gametes and heritable genome editing, should this statement not apply to IVG as well? In next week's workshop, the  National Academies seem to be reverting to an attempt to define what a 2015 commentary in Science called “a prudent path forward for genomic engineering and germline gene modification.” That is a step backward from last month’s Summit.

The IVG workshop Agenda does include sessions on “Social, Ethical, and Legal Considerations,” “Equity, Access, and Cost Considerations” and “Participatory Public Engagement,” as well as several speakers with deep concerns about the implications of radical human biotechnologies for reproductive and social justice. But the overall sense is one of approval, of “Imagining a Potential Clinical Pathway for Human IVG,” as one session title promises to do. CGS Associate Director Katie Hasson will be attending, and you can expect a detailed report on the proceedings from her in a future post.