Gene Drives and the Hijacking of Origins

Over the last thirty years, genetically modified organisms (GMOs) have struggled to gain the confidence of consumers.  In the European Union, many member states have maintained virtual moratoria on their use in agriculture. Even in the less precautionary U.S., where only the weakest of labeling laws have ever made it through Congress, surveys show that more than 90% of consumers would like to be able to choose if their food is genetically modified. Even though the vast majority of soy, maize, canola, and cotton plants grown in the U.S. are now the products of the technology, large portions of the public are still concerned about their safety, disturbed by what they symbolize, or both.

IMG_1055In the face of these concerns, it is worth noting that all the GMO’s produced to date have been manufactured primarily for agricultural venues.  The organisms are designed for the farm, live their lives on the farm, and are processed for market in industrial facilities in much the same way that other farm products are processed. Setting aside for a moment the contentious issue of GMO’s cross-pollinating plants outside of a farmer’s field, current usage of the technology takes place within the realm of agriculture.  The word ‘agriculture’ indicates an arena that is as much cultural as it is natural. Current GMO’s are designed for, and have mostly remained, within the human orbit.

This limitation of GMO’s to agriculture, however, is rapidly coming to an end.  New genetic tools that can modify genomes and then push these modifications outwards through wild populations are within our reach. For the first time humans are gaining the ability to send traits that they choose into fast-breeding populations of organisms throughout nature. The tool that achieves this is known as a “gene drive,” a technique for genetic tomfoolery that allows humans to bias the normal rules of inheritance to serve their own interests.

For any sexually reproducing organism, one would normally expect a trait to be passed on only 50% of the time. The joining of two chromosomes at fertilization means that any new trait stands only an even chance of appearing in the next generation. And with these unimpressive odds, if the trait does not provide a significant selective advantage, it will rapidly diminish in frequency across each generation.

Genes chosen because they are useful for human purposes are unlikely to be selectively advantageous. Being a product of unnatural selection, the gene is far more likely to be disadvantageous to the organism than it is to be advantageous. Think of how a poodle would fare alongside a timber wolf if both were set free in the mountains. Outside of a highly controlled environment, a modified organism faces slim odds.

A gene drive is a way to bias inheritance in sexually reproducing organisms so that the trait does not quickly fade. It does this by inserting an editing mechanism known as CRISPR into the sex cells of an organism. The CRISPR mechanism works so that, when a sex cell altered to contain a useful trait meets a sex cell that lacks it, the chromosome with the trait can ‘cut and paste’ the useful gene – together with another copy of the ‘cut and paste’ mechanism – into the opposite chromosome. The fertilized ovum now contains the desired trait in both chromosomes, something that remains the case as it starts to divide and grow into an organism. Having the desired trait in both chromosomes helps massively with the chances of it being passed onto the next generation.

Gene drives allow modifications take off across species. Tests on fruit flies have shown a selected gene spreading into 97% of offspring within two generations.

The upshot is that wild populations who never come anywhere near a laboratory can be manipulated by gene drives to contain traits of our choosing. GMO’s, in other words, can leave the farmer’s field and enter wildlife populations.

synbioPeople understandably get nervous at the idea of a technology being released from the lab and running rampant through natural environments, but it turns out that there are plenty of good reasons to be interested in gene drives. It is possible they could be used to engineer sterility into organisms such as mosquitoes that carry zika, dengue fever, or malaria. They could be used to interfere with the lifecycles of the carriers of viruses that are killing off rare bird species. A gene drive might be created to alter the sex ratio of a non-native rodent population that was damaging wildlife, thereby slowing its reproductive rate. Gene drives might also be used to spread resistance to a virulent disease through a vulnerable population threatened with extinction. (For discussions of several case studies, see the US National Academies of Science Report on gene drives).

In many of these cases, the benefit to people and to the environment provides a compelling case to pursue further research. Great harms might be avoided. Significant benefits might be gained.

There are, however, arguments that cut in the other direction. One of these arguments stems from the fact that the genome hosting the gene drive will itself mutate according to Darwinian laws of natural selection. While scientists suspect that these laws are likely to work against the spread of any harmful new trait, they might not, creating a host of unknown consequences.

Another concern is that a gene drive could spread outside of the target population and start impacting populations that are not currently causing a problem. Gene drives, after all, boil down to a mechanism for increasing invasiveness.

A gene drive researcher named Kevin Esvelt, after recently discovering the high likelihood of gene drives affecting non-target populations, bluntly concluded that “conservation and invasiveness don’t mix.” Esvelt went so far as to describe his earlier enthusiastic advocacy of gene drives as “an embarrassing mistake.” Gene drives, he concedes, can look like a perilous game of ecological roulette for species and ecosystems.

Alongside these concerns about ecological impacts, a broader background worry gets into more fundamental matters. This worry involves whether it is humanity’s proper role to deliberately shape the genetics of wild populations of animal species. Prior to the introduction of gene drives, wild populations had almost entirely been the product of evolutionary forces, divine plan, or whatever account of origins you prefer.

Gene drives hijack every origin story. Wild nature increasingly becomes something we design. A report by the British Nuffield Council points out that “… gene drive systems could expedite the expression of human preferences over the composition of the biosphere.” It would signal another aspect of what I call the Synthetic Age.

Certainly, we have been chipping away already at shaping the biosphere so that it better satisfies human preferences. But gene drives more directly insert our designs into the genetic inheritances of wild nature than anything that has come before.

We have a choice about whether to extend our reach this far. If it is true that more than 90% of the public want to know where GMO’s are lurking, perhaps we should be talking more about a technology this powerful before sending our genetic designs into the farthest corners of the natural world.

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