Baby, You Can’t Drive Those Genes

One risky aspect of the practice of gene editing—exploding because of the powerful CRISPR/Cas9 technique—is the prospect for widespread and permanent genetic alteration of whole species from a process called “gene drive.”

In classical genetics, initially defined by the 19th-century Moravian cleric Gregor Mendel, frequency of the inheritance of genes is controlled by more or less simple arithmetic.  Higher organisms (animals and man) have two copies of each gene, and sexually reproducing organisms pass on one copy from each parent to the offspring.  If the copies are all the same (homozygosity), all progeny get all the same gene.  If the copies are different (heterozygosity), half of Mom’s progeny get one of her copies, half get the other, and so on.

As a recent cautionary policy article in the journal Science points out (subscription or purchase required),  “Gene drive systems promote the spread of genetic elements through populations by assuring they are inherited more often than Mendelian [genetics] would predict.”  That is, they tilt the balance in favor of a particular genetic trait.  In one form of these, where the CRISPR system is used in close combination with a particular gene edit of interest, heterozygotes are converted to homozygotes and the changed gene can propagate unchecked through an entire population of an organism, like wildfire, eventually making all members of the population alike with respect to that gene.  The environmental costs may be unpredictable, and they quite probably irreversible.  For this reason, the scientists who signed on to the Science article are urging caution over DNA editing in the wild.  A CRISPR gene drive experiment in fruit flies was reported earlier this year, and there is enthusiastic speculation about applying the technique to certain species in the wild, such as mosquitoes, to try to make them incapable of spreading diseases, notably malaria.

There are less incendiary ways to practice gene drive in the laboratory.   Using one of those other methods is one recommendation made by the Science article writers for stringent precautions that should be taken—effective immediately—to protect against widespread effects of gene-driven organisms on entire populations.  Other recommendations:  do experiments in a place inhospitable to the organism, so it can’t survive if it gets out of the lab; do experiments in areas without potential wild mates; use a laboratory strain that cannot reproduce with counterparts in the wild; build and maintain, with scrupulous vigil, barriers between the lab organisms being tested and the surrounding world.

All of these sound pretty reasonable.  But the technology is threatening to run ahead of the controls.  Last Thursday (July 30, 2015), the National Academy of Sciences held a workshop on the subject.  (There are no archives of the meeting or its result available online, yet—just a description of the project and last week’s agenda.)  The concern is that they are playing catch-up.  As is usually the case when “what we can do” gets out of front of “what we should do.”

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