New in vitro fertilization technology is making it possible for someone to have two moms–one that provides the genome in the nucleus of the cell, and one that provides the rest of the egg cell, including the mitochondria. Since all mitochondria are passed down from the mother in the egg (sperm are just too small to provide anything but the father’s genetic material to the fertilized embryo), transplanting the nucleus from a fertilized embryo to an egg from a different woman can bypass the transmission of any mitochondrial diseases that the mother carries. Because mitochondria have their own small genomes (mitochondria are the descendants of bacteria that lived inside larger cells through endosymbiosis and therefore maintain a small percent of their original genomes), a handful of the embryo’s genes will now come from the mitochondrial mother, while the bulk of the genome will still come from the nuclear mother/father combo. The procedure isn’t approved for making real babies right now, but I think it highlights some of the complications of what it means to be a parent using new reproductive technologies, as well as some issues for the design artificial bacterial life.
The nuclear transplantation process that allows doctors to trade out broken mitochondria is actually remarkably similar to how Dolly the sheep was cloned back in 1996. The nucleus of an egg from an anonymous sheep was removed and replaced with the nucleus of a regular old cell from Dolly’s clone-mom. The new pseudo-egg was reprogrammed to think it was a real fertilized egg, implanted into a third surrogate sheep, and after a few months Dolly was born. Dolly therefore has three moms and no dads: one mom that provided the egg (and the mitochondria), one that provided the entire nuclear genetic material, and one that gave birth to her. I don’t know how parenting works in sheep, but if she was a human and was raised by a fourth person, he or she would count as a parent too! Of course, this doesn’t happen in humans due to the tricky legal and ethical boundaries (and rightly so!) of doing research on human babies. In animal cloning, only a very small percentage of cloned embryos survives to birth, and of those, few survive infancy, and of those, there are still many uncharacterized differences in animal behavior and health. There are of course so many other ethical issues involved in new and potential future reproductive technologies and I have to admit that in most cases I take the bio-conservative stance. However, while I do want to bring it up (and maybe save for another time) that’s not what I want to focus on right now.
This kind of technology is also being used in bacteria, as a way to make “synthetic life.” The J. Craig Venter Institute is developing methods to synthesize whole genomes from scratch, using machines that can string together the chemical bases that make up the genetic code: A,T,C, and G. But genomes don’t do anything without a cell, and cells aren’t anything without a genetic code, leaving us with the original chicken/egg problem. Once a genome is synthesized, it needs to be transplanted into a living bacterial cell whose genome has been removed. The ability to transplant the natural genome from one species of bacteria into the cell body of another was demonstrated in 2007, with the host cell literally turning into the donor cell as it replicated the donor genome and divided.
I’m fascinated by the chicken/egg-ness of this genome/life problem. Life isn’t just in the genome, it’s in the chemicals that make the cell, the proteins that can read, regulate, and replicate the genome that are in the host cell to begin with, the thermodynamics of the cell boundary–life inside, non-life outside. Chemically synthesized bacterial genomes exist, and soon they’ll be transplanted into living cells, but what emerges won’t be entirely synthetic life. For that we’ll have to understand a lot more about the origin of life and that tricky boundary that separates a living cell from a slippery bag of DNA and proteins.