The risks of releasing genetically modified animals into the environment

Vir­ginie Courtier-Orgo­gozo. Gene drives make it pos­sible to erad­ic­ate or genet­ic­ally modi­fy an entire spe­cies of wild­life in its nat­ur­al hab­it­at, start­ing with just a few mod­i­fied indi­vidu­als released into the wild. This meth­od involves intro­du­cing a genet­ic modi­fic­a­tion that is passed on almost sys­tem­at­ic­ally to off­spring. A genet­ic muta­tion nor­mally has a one-in-two chance of being passed on. In the con­text of gene drives, trans­mis­sion is altered through the inser­tion of oth­er DNA sequences, which allow the muta­tion to spread to oth­er chro­mo­somes. This ensures that the muta­tion is passed on to off­spring at a rate of 95 to 98 %.

This tech­nique has been developed since 2015, thanks to the CRIS­PR-Cas9 molecu­lar scis­sors. It first emerged with the aim of com­bat­ing mos­quito spe­cies that trans­mit mal­aria. Two meth­ods were pro­posed: either the elim­in­a­tion of mos­quito pop­u­la­tions through the spread of a muta­tion ren­der­ing females sterile, or the devel­op­ment of mos­qui­toes res­ist­ant to the mal­aria para­site. The idea of using gene drives in the field of con­ser­va­tion emerged a few years later. The aim is either to dir­ectly manip­u­late endangered spe­cies to make them res­ist­ant to a threat, or to modi­fy spe­cies that pose a threat to endangered species.

With regard to the genet­ic modi­fic­a­tion of endangered spe­cies, an Amer­ic­an team is attempt­ing to make the leo­pard frog res­ist­ant to a patho­gen­ic fungus that is fatal to it. Sci­ent­ists are also seek­ing to identi­fy muta­tions that enable cor­als to bet­ter with­stand heat. These genet­ic modi­fic­a­tions could be car­ried out without the use of gene drives, fol­low­ing the example of the genet­ic­ally mod­i­fied domest­ic spe­cies we are already famil­i­ar with [Editor’s note: such as cot­ton or soya], since the muta­tion, which is bene­fi­cial to the indi­vidu­als, would spread through nat­ur­al selec­tion. In the case of endangered spe­cies, gene drives would provide an addi­tion­al boost.

Regard­ing the manip­u­la­tion of spe­cies that threaten oth­ers, a flag­ship but highly con­tro­ver­sial pro­ject is under­way in New Zea­l­and to erad­ic­ate rats from the island. These rodents, intro­duced either delib­er­ately or acci­dent­ally by humans, are an invas­ive spe­cies. They are a major source of prob­lems, as they feed on the eggs of vari­ous nat­ive spe­cies of birds. How­ever, all this research is cur­rently only at the exper­i­ment­al stage. To my know­ledge, no genet­ic­ally mod­i­fied indi­vidu­als from a wild spe­cies have been released into the wild as part of a con­ser­va­tion pro­ject. Nev­er­the­less, genet­ic­ally mod­i­fied mos­qui­toes have already been released, in Flor­ida for example, to com­bat the spread of disease.

Gene drives involve risks that are some­times dif­fi­cult to pre­dict. Every liv­ing being is the res­ult of inter­ac­tions between its body, its genet­ic mater­i­al and its envir­on­ment. Even with know­ledge of genes and muta­tions, it is there­fore impossible to pre­dict exactly the impact of inter­ac­tions between the thou­sands of genes in a gen­ome, let alone those with the extern­al envir­on­ment and oth­er liv­ing beings. The first clearly iden­ti­fied risk is the spread of the genet­ic muta­tion to oth­er spe­cies in the event of hybrid­isa­tion or hori­zont­al gene trans­fer. DNA frag­ments can indeed pass from one spe­cies to anoth­er via inter­me­di­ar­ies, such as vir­uses. By manip­u­lat­ing a tar­get spe­cies, we there­fore risk affect­ing others.

Fur­ther­more, it is impossible to pre­dict the impacts at the level of an entire eco­sys­tem. Once the leo­pard frog has become res­ist­ant to the fungus, it could be infec­ted by anoth­er patho­gen that would take over. In New Zea­l­and, the goal of return­ing to a pre-inva­sion state is also not guar­an­teed. Often, an estab­lished invas­ive spe­cies occu­pies its own eco­lo­gic­al niche. Once freed up, this niche could be occu­pied by anoth­er spe­cies, which in turn could be harm­ful. Fur­ther­more, how can we ensure that a genet­ic­ally mod­i­fied rat will not be acci­dent­ally trans­por­ted by boat?

Unlike chem­ic­al meth­ods, the con­sequences of gene drives are dif­fi­cult to con­tain. If a pesti­cide is deemed harm­ful, it is no longer used, and the impact gradu­ally dimin­ishes. When it comes to gene drives, once the mod­i­fied anim­als have been released, the muta­tion con­tin­ues to spread, even when no more are released. In 2016 and 2020, research­ers pro­posed genet­ic brakes designed to neut­ral­ise gene drives. We mod­elled the impact of these brakes and con­cluded that they were too depend­ent on spe­cif­ic cri­ter­ia to be reli­able. How­ever, we only stud­ied cer­tain types of gene drive and brakes. Research­ers are devel­op­ing oth­er drive meth­ods that could be stopped more effect­ively. This field of research is rap­idly expanding.

There are no inter­na­tion­al reg­u­la­tions. The US Nation­al Academy of Sci­ences has con­cluded that labor­at­ory exper­i­ments are accept­able but that the tech­nique is not yet suf­fi­ciently developed to be tested in nat­ur­al envir­on­ments. In 2018, at the Con­ven­tion on Bio­lo­gic­al Diversity, a decision adop­ted and rat­i­fied by 195 coun­tries stip­u­lated that, giv­en the uncer­tain­ties, the release of organ­isms mod­i­fied by gene drive is only pos­sible with the pri­or con­sent of indi­gen­ous and loc­al com­munit­ies. But this remains unclear: how should the loc­al pop­u­la­tions con­cerned be defined? Insects and rats know no borders.

At European level, dis­cus­sions are under­way to adapt the reg­u­la­tions gov­ern­ing GMOs to this spe­cif­ic case of gene drives. Gene drives fall into a par­tic­u­lar cat­egory of GMOs: they are cap­able of spread­ing through­out an entire pop­u­la­tion more rap­idly than con­ven­tion­al GMOs. For the time being, the use of gene drives for con­ser­va­tion is there­fore dis­cour­aged, but not prohibited.

Interview by Pauline Fricot