For 100 million years, all our ancestors reproduced basically the same way. A male reproductive organ deposited sperm into a female reproduction organ, where it could fertilize eggs–leading to baby ancestral tetrapods, mammals, primates, and eventually humans. The past 60 years have seen this begin to change, first with clinically available artificial insemination and then with in vitro fertilization (IVF).
In the United States today, these two techniques lead to about 100,000 births each year, roughly 2.5 percent of the 4 million children born annually. Within the next few decades, that percentage will skyrocket. Developments in bioscience, galloping forward in most cases for reasons having nothing to with reproduction, will combine to make IVF cheaper and much easier.
These new techniques will allow safe and easy embryo selection–but they will also open doors to genetically edited babies, “their own” genetic babies for same-sex couples, babies with a single genetic parent, and maybe babies from artificial wombs.
Starting in the next few decades, these new methods of reproduction will give people new choices. They will also raise a host of vexing legal and ethical questions, questions we need to start discussing.
Closest at hand is greatly increased genetic selection of embryos. For more than 25 years, clinicians have been able to take cells from embryos growing in vitro in petri dishes, do genetic tests on those cells, and use the test results to decide which embryos to transfer to a womb for possible pregnancy. This process, known as preimplantation genetic diagnosis, or PGD, led to about 2,500 births last year in the US.
If PGD has been clinically available since 1990, why does it remain relatively uncommon? Two reasons.
First, PGD has only been able to look at one or two of a limited set of characteristics: a genetic disease known to run in the prospective parents’ families, syndromes caused by the wrong number of chromosomes, and sex. Looking at more costs too much and takes too long.
Second, the in vitro part has been essential. The reason is simple: otherwise the embryos are somewhere in one of the woman’s two fallopian tubes. Good luck finding them. With IVF, the embryos are in the dish you put them in.
And IVF is neither cheap nor fun. In California, it costs about $15,000–typically not covered by insurance–for the most basic version. IVF is always uncomfortable and sometimes risky. Most of the cost, and all of the discomfort and risks, lies in harvesting eggs. Egg harvest requires weeks of injections with powerful hormones, the side effects of which lead to several hundred hospitalizations a year in the US. Until IVF becomes less burdensome, PGD will not be easy.
Today, we can sequence an entire human genome–think of it as 6.4 billion letters, or a thousand copies of The Lord of the Rings–in a day or two for about $1,500, a price that continues to plummet. It’s harder and more expensive using a few cells from an embryo, but that will change, too. Cheap sequencing will allow parents to learn all the things about their prospective children that genetics can reveal.
So the genetic testing is improving, and its price is coming down. Meanwhile, stem cell research holds the promise of eliminating egg harvest. In 2007, Shinya Yamanaka, a professor at Kyoto University (and now a Nobelist), discovered how to make skin cells become like embryonic stem cells. These “induced pluripotent stem cells,” or iPSCs, are among today’s hottest areas of biomedical research. Scientists hope to turn them into brain, heart, pancreas, and other cells that a patient’s immune system will recognize as his own.
Such a development would open up a world of therapeutic possibilities, but it also will transform reproduction. Eggs and sperm (collectively, “gametes”) are also human cell types. Scientists should be able to turn iPSCs into gametes that carry a prospective parent’s own genetic variations. Gametes derived from iPSCs have already been used for successful births in mice; research is now beginning in humans.
When you add cheap whole-genome sequencing to stem cell–derived gametes, you get what I call “Easy PGD.” In, let’s say, 30 years (following extensive safety testing and FDA approval), a couple who want to have a baby will go to a clinic. She will provide a small skin sample; he will provide sperm. The clinic will turn her skin cells into mature eggs and then fertilize them with his sperm to make embryos.
PGD today is constrained by the number of ripe eggs harvested–usually around a dozen. Easy PGD has no such limit, because the eggs are being created from tissue samples. Assume the clinic makes 100 embryos. Each embryo will then have its whole genome sequenced, and the parents will be asked what they want to know from what those genomes can tell them.
Parents will be able to learn lot from these whole genomes. First, genetic variations can confidently predict thousands of nasty early childhood diseases, each individually rare but collectively accounting for 1 or 2 percent of all births. Second, genomic sequencing can predict the risk of developing many later-life diseases, such as certain cancers and Alzheimer’s disease. Third, parents will be able to learn something about how their future child would look: hair color, eye color, skin color, height, and more.
Fourth, genetic variations provide hints about behavioral traits, like personality type or intellectual ability. Since genetic associations with non-disease behaviors are both complex and weak, this could probably only tell prospective parents whether, for example, an embryo has a 60 percent chance of being in the top half for some trait; still, that’s something. Finally, the tests can easily tell parents “boy or girl.”