Perhaps no branch of knowledge has been as exciting over the past 50 years as genetics, the scientific study of heredity.  

The DNA double helix, discovered in 1953, is one of the great icons of science in our society.  Knowledge of DNA and genetics has impacted two important applications of biology in human welfare — agriculture and medicine.  In addition, studies of genes are changing the way we look at ourselves and other organisms with which we share the earth.

One recent example is using gene drives to alter mosquitoes. A gene drive is a self-propagating mechanism by which a desired genetic variant can be spread through a population faster than traditional  inheritance.

This strategy can be so effective that alleles can spread even if they confer a disadvantageous trait, such as sterility, to an organism.  A gene drive can be thought of as a self replicating bit of DNA, and is one of the most anticipated and controversial tools being developed to stop mosquitoes from spreading malaria.

Mosquitoes

Mosquitoes are responsible for a host of other devastating, difficult-to-treat diseases, including  Zika, West Nile Virus, dengue and elephantiasis.  

Together with malaria, these diseases affect more than 10% of the world’s population. Malaria  alone sickened close to 240 million people in 2020 and killed 670,000 worldwide, mostly in Africa. Children 5 years old and younger accounted for 80% of the continent’s malaria deaths according to the World Health Organization.  Mosquitoes are unique in terms of their numbers, varieties, lifecycles, geographic distribution, appetites and habits.

Gene Drive History

Scientists have studied gene drives for more than 50 years, and to most of us this has been a well-kept secret.  The development of a powerful genome editing tool in 2012, CRISPR/Cas9,1 led to recent breakthroughs in gene drive research that built on that half century’s worth of knowledge, and stimulated new discussions of the potential applications and implications of gene drive technologies.

Just prior to the beginning of this study and since the committee was first convened, scientists published four proofs of concept — one in yeast, one in fruit flies, and two in different species of mosquitoes — that demonstrate the successful development of gene drives in the laboratory, at least in these organisms.

Proposed applications for gene-drive modified organisms for basic research, conservation, agriculture, public health and other purposes will likely continue to expand as gene editing tools become more refined. Gene-drive modified organisms are on the horizon. With mosquitoes, the gene drive interferes with the insect’s ability to reproduce.  It wiped out captive populations in eight or 12 generations. The first experimental release could be rolled out in Burkina Faso, Mali, Ghana or Uganda.

Application

Gene drives might be the transformational answer that people are looking for as a adjunct to preventive drugs, insecticide-treated bed nets and even malarial vaccines. The current methods are helping, but mosquitoes are developing resistance to insecticides and some anti-malarial drugs may no longer work well.  

Gene drives could potentially spread to nearly every member of a species quickly, forever altering the species or wiping it out.

The gene drive used currently is used on male mosquitoes and when an engineered male meets with an unaltered female, Cas 9 snips a gene called doublesex inside the fertilized egg.  As the egg tries to repair the cut, the gene drive from the father’s double sex gene is pasted over the copy of the gene inherited from the mother. So the offspring gets two copies of the gene drive instead of one.  The double sex gene is essential for the development of female mosquitoes. When the gene doesn’t work, the mosquito itself fails as well.

Drawbacks

Whether gene drives play a role in combating malaria depend as much on social considerations as on science.  The same was true with genetically modified crops.  Because of the possibility of forever modifying or altering ecosystems, the European Union has rejected using gene drives there. At least 46 theoretical harms could arise from the use of gene drives on mosquitoes.  

These potential downsides include reductions in pollinators and other species directly or indirectly related to the disappearance of the mosquitoes.  It is possible that people could develop allergic reactions to the bite of a mosquito carrying a single copy of the gene drive or to fish that eat the altered mosquito larvae.  

There could be a decline in water quality caused by large numbers of mosquito larvae dying.  There is even a set of scenarios in which malaria cases increase if the mosquito species that are better malaria spreaders take over in areas where the gene drive has thinned out less troublesome mosquitoes. The list of 46 possibilities focused on four areas most important to protect:  biodiversity, human and animal health and water quality.

Final Thoughts

According to a recent article in Science News, gene drives offer a number of potential upsides, not offered by insecticides. Insecticides have proven not to work, and by replacing them, gene drives might help to save bees, butterflies and other pollinators. Gene drives eliminate only the mosquito species that are dangerous.

Max Sherman is a medical writer and pharmacist retired from the medical device industry.  His new book “Science Snippets” is available from Amazon and other book sellers. It contains a number of previously published columns.  He can be reached by email at  maxsherman339@gmail.com.