Dec 03 2021

Using CRISPR For Sex Selection

Each year 6-7 billion male chicks are culled, because only females are needed for egg laying. Many other animals are also culled because one sex is desired either for food production or research. There are many research questions that are sex specific, and therefore large numbers of a single sex of a specific strain of mice may be required. Culling is a crude way to achieve these ends, and raises concerns about humanely treating animals.

For these reasons researchers have been looking for ways to achieve high degrees of sex selection in animals more efficiently and humanely. A new study published in Nature Communications seems to have made a significant advance in this direction, using CRISPR-Cas9 (a gene-editing system) to create a sex-selection system for either male or female mice that operates with 100% efficiency. The idea is clever – insert one half of a CRISPR-Cas9 kill switch into the X-chromosome of a female mouse, then insert the other half into either the X or Y chromosome of a male mouse. Only those embryos that get both halves of the CRISPR-Cas9 system (either XX or XY) will be killed at the early embryo stage.

This approach has been used before, in insects and zebrafish, but never in mammals. There are also other methods for sex selection that don’t rely on culling, such as sperm sorting, but this approach is not very efficient, and doesn’t work in birds where the females gametes determine sex. This new system has proven 100% effective in mice, and should easily port to other mammals such as pigs and cattle. The researches targeted a gene, the Top 1 gene, that codes for an enzyme critical for early DNA replication in a developing embryo. Inactivating this gene is a “suicide switch” for the embryo. This gene is also highly conserved, and the reason why it should work in all mammals, not just mice.

The researchers discovered that the early activity of this suicide switch has a specific advantage in sex-selection systems – it actually increases the yield (not just the ratio) of the desired sex compared to unselected litters. This happens because is many mammals with litters of multiple offspring, the females overproduce eggs, and not all eggs implant in the uterus. Therefore, if the eggs of the undesired sex are killed very early on more eggs from the desired sex can implant in the uterus and develop.

Finally the research found that this system is safe, without any unwanted effects on the offspring of the desired sex. The researchers also point out that the suicide effect occurs too early in the development of the embryo to be used as part of a gene-drive effect that can alter future generations.

Obviously more research needs to be done to confirm these results, further demonstrate safety, and demonstrate effectiveness in other mammalian species. A version will also have to be developed in order to apply to the poultry industry, since birds have a different chromosomal sex system (ZW) than mammals (XY). But the potential here is very promising. The researchers state that the express purpose of this research was to eliminate the need for culling in animal research and food systems.

I can’t think of any legitimate ethical concerns here either (other than those who object to all animal research or food use). If you accept the premise that animals can be used ethically and humanely in research and food production, then this technology should not introduce any new ethical concerns. In fact, it potentially eliminates the ethical concerns around culling for sex selection, and results in more humane treatment of animals. Killing early embryos should also not introduce any ethical concerns, in my opinion, especially when you consider that in the target species the normal process of pregnancy results in multiple excess fertilized embryos being lost. This system is mostly a way of determining which embryos are lost, not whether embryos are lost.

If this process proves to be as safe as it looks from the current research, and it gains regulatory approval, then the final determining factor for whether or not it is widely adopted will be economics. Because CRISPR is so fast and efficient, it is likely that it will be more economical than massive culling in many contexts. It’s even possible that in some countries the CRISPR system of sex selection may become required by regulation, as a more humane alternative, essentially making it practical to ban the culling of animals for sex selection.

I predict there will still be opposition, however, from those with a knee-jerk reaction against any gene-editing. They will argue that it’s not natural, or that there are potential unknown risks (abusing the precautionary principle). When it is pointed out that this is actually more humane than the alternative, they will argue that all use of animals in research and food should be banned, which is a non-sequitur, and an example of making the (allegedly) perfect the enemy of the good. The question is – while use of animals is legal and widespread, which system of sex selection is better, culling or gene-editing?

This is a frequent and sometimes interesting dilemma – when you oppose a system fundamentally, how do you react to methods of making the system less bad? Purists tend to oppose such methods out of fear of inadvertently supporting the underlying system they oppose. Should we regulate, for example, the sex industry in order to protect workers and minimize the risks and abuses inherent in the industry, or will that make a fundamentally flawed industry more palatable?

In this case, however, I think those who appose genetic engineering are wrong on all levels. They therefore work to prevent improvements and benefits resulting from a technology which itself is perfectly fine, and which they oppose for illegitimate reasons. We’ll see what the reaction to this new technology is –  technology which has the potential to prevent the culling of billions of animals a year.

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