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Polygenic Selection of Embryos
In vitro fertilization (IVF) is a fertilization procedure in which ova are removed from a woman and combined with sperm in a laboratory culture, with the resulting embryo then implanted in the woman’s or a surrogate mother's uterus. This assistive reproductive technology has been used successfully since 1978, and its use has increased over time, owing in part to women choosing to bear children later in their lives.
Often, combining sperm with extracted ova results in multiple viable embryos. For many years, doctors have been able to perform diagnostic screening tests to check the embryos for chromosomal abnormalities like Down syndrome and gene defects like Tay-Sachs, allowing them to select and implant the healthiest embryo.
However, it is possible to do more than simple single-gene testing. Using our understanding of human genetics, one can sequence an embryo’s genome and perform statistical tests to determine the probabilities of traits controlled by the presence and interactions of multiple genes. (Most traits are of this kind.) It becomes theoretically possible to select with reasonable success for almost any traits whose genes are well-understood. In practice, one could assign different values or weights to the traits, and based on the probabilities, compute a score for the embryo’s genome — a polygenic score (PGS). The embryo with the best PGS can be implanted.
In 2020, the first polygenically screened baby was born. Her name is Aurea, and her parents chose to minimize her chances of major diseases including breast cancer, which she had a higher-than-usual chance of developing and that afflicted other members of her family. Thanks to polygenic testing, Aurea has a lower risk of breast cancer than a hypothetical naturally conceived offspring of the same parents. Diseases are a concrete target for this new technology — minimizing their probabilities is an observable, unambiguous good — and according to this survey, when asked about the ethics of polygenic selection practices 80% of the (American) respondents approved of screening against diseases.
To perform polygenic screening and calculate a PGS, it is necessary to conceive through IVF. Since the costs of IVF are generally significantly higher than the marginal cost of finding the PGSes, the reach of polygenic screening is highly affected by the costs of IVF. And so, for parents who already plan to conceive in vitro, selecting an embryo based on PGSes rather than selecting randomly can often be the superior choice.
What are the advantages of polygenic screening? It can help minimize susceptibility to diseases, but it can do more. Embryos can be selected for any traits whose genetics we somewhat understand such as physical strength, IQ, or facets of physical appearance. This is a commercial reality: the Fertility Institutes is now offering screening for eye color as a part of their PGS services. We can calculate that with a yield of 10 successful embryos from an IVF cycle — an extremely optimistic number — selecting the highest IQ from the set would net a gain of an expected +3 IQ points. (See also: a Metaculus question asking when IVF-based selection for intelligence will start happening). 3 IQ points isn’t a lot, and coupled with the fact that IVF is expensive and might have slightly worse outcomes than natural births, IVF based screening likely isn’t the superior option for most people looking to have children. Even screening for a slight increase in general health outcomes or lower susceptibility to some common diseases might not be worth all the costs. This seems to currently be the case for most qualitative traits that don’t confer an advantage as large as avoiding major genetic disorders.
There are two ways in which this might change in the future, however.
The first is falling medical costs for the relevant procedures in the coming years. Demand for IVF is increasing as women are choosing to bear children later in life. There is clearly space for technological investment, and we might see the cost of the medical procedure drop. Additionally, the cost of the embryo screening also will likely decrease, since human genome sequencing costs have been falling exponentially. This might remove costs enough that some individuals who can have children naturally still choose to use IVF for the slight gains.
The following two questions ask for forecasts on how the usage of the technologies will increase and how the costs of the procedures involved will decrease. If the actual costs fall, conceiving through IVF even for marginal gains may start to become attractive. There is no neat way to operationalize costs, because the prices of medical procedures are illegible and have high variance, so instead we look at an existing question on IVF usage.
The second path to increased IVF-based screening is finding methods that confer a greater advantage than is currently possible. Due to the small number of embryos that can be created per cycle, there is a hard upper limit for gains with the current strategy: Since selection can be done out of only a few embryos, the best out of them isn’t much better than the average. The limiting factor is the number of eggs that can be extracted in a cycle. If this is solved, and if it becomes possible to have many more eggs to fertilize and then select from, gains from polygenic selection would be much more significant. Currently, eggs are extracted by using drugs that cause a woman to produce several eggs in an ovulation cycle, as opposed to the usual one. (There may be ways to stimulate production further, but this is unlikely.) Rather, it may be possible to biopsy a large number of immature eggs from the ovaries and mature them artificially to obtain viable eggs. Alternatively, it might become possible to create or acquire large numbers of stem cells — primordial cells that can transform into any kind of cell — from the woman and induce them all to develop into eggs. Indeed, it might even eventually become possible to induce stem cells from men to develop into eggs (or stem cells from women to develop into sperm), allowing same-sex couples to have fully genetically related children!
The next two questions ask for forecasts of (related) events that are indicative of technological leaps in the field. The first of these asks when it may become possible to perform selection on large numbers of eggs, through any means.
This question asks for a forecast on the timeline of the technology that will most likely be the route to large scale polygenic selection: stem cell regression. It asks when the first baby conceived from stem-cell derived gametes will be born. If it occurs, it will be a landmark event in human history, making it possible for same-sex couples and infertile individuals to have children, which makes it an interesting question to forecast on its own merit.
If any of these happen, it might start to become commonplace for individuals to opt for IVF-based embryo selection. Indeed, it may become the first means of human genetic engineering that sees common use.
(Note that there is one more route to large selection: a process known as iterated embryo selection, wherein after stem cell regression based embryo creation, the embryos instead of being implanted are regressed into stem cells themselves, and the cycle is repeated, conferring an advantage equivalent to selection over many generations. There is a Metaculus question about it here: First human in vitro gametogenesis.)
Other Related questions on Metaculus:
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