Two studies published in the past month marked significant advances in the potential for using gene drives to curb the spread of infectious diseases by targeting their insect carriers.
A gene drive is a genetic system that allows a genetic change to spread quickly through a population. In sexually reproducing organisms (including most animals such as humans as well as mosquitoes), an individual generally inherits one copy of its chromosomes from each parent. Typically, a stretch of DNA present on only one of the two chromosomes will only be passed on 50% of the time to the next generation, assuming its mate does not also carry this stretch of DNA. By contrast, in a gene drive, a genetic element on one chromosomal copy will duplicate itself onto the other chromosomal copy. As a result, that sequence will be passed on 100% of the time to the next generation. Such a genetic change may eventually “sweep” the population. While the idea of gene drives has been theorized for many years, the recent development of genome editing tools such as the CRISPR/Cas9 system simplified some of the technical aspects of gene drives, and has led to growing interest in this technology.
A much discussed application of CRISPR gene drives is for the control of disease-carrying insects, such as the mosquitoes that act as vectors for malaria or Dengue fever. Malaria, in particular, is a scourge on public health that infects hundreds of millions of the world’s poorest people every year and kills nearly half a million, most of them children. While the distribution of insecticide-treated bed nets have made a significant contribution to malaria prevention, no malaria vaccine has been approved for widespread deployment, and malaria parasites have developed resistance to varying extents against every available antimalarial drug, including artemisinin, our “last line of defense”. Measures that can hold back, and perhaps eventually eradicate, this disease are much sought after.
In experiments described in a paper published on Nov 23, researchers used gene drives to insert two genes, which are known to confer resistance to carrying the malaria parasite Plasmodium falciparum, into the genome of mosquitoes. When these insects were then mated to unaltered mosquitoes, the inserted genes were passed on to around 99% of the offspring. The inserted resistance genes were shown to be active in the genetically altered mosquitoes, but the researchers did not test to see if these mosquitoes were actually resistant to the malaria parasite.
Then, published on Dec 7, a second study looked at another strategy to control mosquito population using gene drives. These scientists “knocked out” genes that, when disrupted, lead to female infertility. Once again, the gene drives led to efficient inheritance of the genetic change in more than 90% of the offspring. At the same time, the number of offspring from the altered insects dropped to 10% or less compared to unaltered ones. Furthermore, in an experiment where a 50:50 mixed population of altered and unaltered mosquitoes were released into a cage and allowed to mate freely, after four generations the percentage of genetically altered mosquitoes increased to around 75%. Altogether, this study demonstrated the potential of using gene drives to reduce the population size of mosquitoes.
These two studies significantly lowered the technical hurdles to implementing gene drive-based control of disease-carrying mosquitoes. Whether these approaches are effective in wild mosquito populations remains to be seen. But the authors of the studies and many other researchers rightly point out that, before they can be tested in field trials, a lot more discussion must happen in the wider society about whether and how to proceed. While biologists are devising ways to limit or reverse the effects of gene-driven genetic changes as safety precautions for the technology, at the end of the day these are environment-altering interventions for which the ecological consequences are impossible to know with absolute certainty. This is especially true in the case of the infertility-based approach, because reducing or eliminating the population of an important component of the ecosystem can have unpredictable and wide-ranging effect. While gene drive-based approaches to controlling malaria-carrying mosquitoes can have major public health benefits, care must be taken to minimize any unintended ecological and societal consequences.