Daisy restoration drives

Given our growing ability to engineer organisms and even wild populations, it seems prudent to invent safeguards.

In an ideal world, we would be able to restore any given population to its original genetic state.

There's just one problem: how can we eliminate the CRISPR editing machinery needed to spread changes through populations?

Our solution (described in a preprint on bioRxiv) is based on democracy: we link all the edits into a genetic coalition using a daisy drive, and have them 'vote' against the wild alleles. Whichever version loses the local 'quorum' vote replicates increasingly poorly until it's gone.

How does it work? A 'daisy quorum drive' swaps two genes that are absolutely required for life and places a CRISPR gene next to each of them. Organisms that have both swapped and wild genes replicate poorly because half of their offspring don't inherit exactly one copy of each gene.

To eliminate a specific engineered gene, we could use a daisy quorum drive to replace every copy of the target gene with a daisy element linked to the swapped genes via CRISPR. This would transform the local population into an engineered genetic coalition while immediately removing the targeted change. Thanks to the quorum effect, there would be little genetic mixing with the surrounding wild populations.

To restore the original genetics, we could then impair the reproduction of organisms encoding CRISPR by introducing a linked suppression element that disrupts recessive fertility genes: the offspring of two carriers are sterile. As infertility spreads through the engineered population, its numbers would decrease. Ever-steeper losses in the once-per-generation quorum vote would further impair replication of the engineered genes, returning the population to its original genetic state.

Importantly, daisy restoration drives could even counter and remove an active global gene drive system:

So why does this matter? It's conceivable that some forms of gene drive might have unexpected side-effects and will need to be reversed. This is a safe way to reverse effects, but we already had immunizing reversal drives that could restore traits, if not genetics.

Daisy restoration matters because many people do care about genetics. Without it, any accidental or deliberate release of a global gene drive system could unilaterally engineer entire populations, severely and deservedly damaging trust in science and governments. Such an event would be particularly distressing to people who revere the perceived wilderness and do not wish it sullied by any form of human intervention.

By ensuring that genes can call quorum votes, we can tightly control the spread of engineered genes, restore populations to their original genetics, and reassert our shared control over the ecological commons.