W

e need powerful tools to take on the deadliest creature in the world: mosquitoes.

Mosquitoes spread malaria, a disease that sickens more than 200 million people each year and kills 430,000. Genetically engineering mosquitoes to stop the spread of malaria offers great promise in saving many of these lives, and could add an estimated $4 trillion to the global economy over the next 14 years.

A new technology known as gene drive can increase the likelihood that desirable engineered traits in a mosquito are passed on to all of its offspring in the next generation, ultimately spreading these traits throughout a target population.

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Since only female mosquitoes feed on blood and transmit malaria parasites from person to person, a gene that boosts the inheritance of the male chromosome would reduce the number of females in the target population and cause it to crash, a strategy known as population suppression. Another type of beneficial gene might kill malaria parasites in mosquitoes before they can be transmitted, a strategy known as population modification.

The result of either scenario — or others in the works — would ultimately stop the spread of malaria.

While the potential to control malaria through genetic manipulation represents an opportunity to make significant advances in eradicating the disease, developing a technology designed to spread new genes through populations must be carefully managed. Any new tools must be as safe as they are effective.

A useful rule of thumb for achieving this appears in an important new paper from the Foundation for the National Institutes of Health. It stipulates that the new technologies “will do no more harm to human health than wild-type mosquitoes of the same genetic background and no more harm to the ecosystem than other conventional vector control interventions.” Showing this to be true requires research as well as patience and dialogue.

Gene drives have the potential to change the genetic makeup of entire populations, like mosquitos that carry malaria. Hyacinth Empinado/STAT

While gene-drive research builds on previous mosquito-control experience and prevailing good practices in biotechnology, this is a new approach with unique aspects. In particular, the genetic modification is designed to spread through wild populations. This poses new questions for how to develop and evaluate gene-drive organisms. The majority of questions fall into two categories: how to limit the spread of genetically engineered mosquitoes to a defined geographical region, and what impact they might have on existing ecosystems.

Population suppression approaches are self-limiting by design — all mosquitoes carrying the genes are sterile or die. Important questions here address the implications of loss of the species from the ecosystem. This is less of a concern in places where the mosquitoes are an invasive species, but some people have expressed opinions that regional success will lead to widespread use and result in global extinction of the target mosquito species.

Population modification strategies are designed to persist. The major questions here focus on what can be done should we, for one reason or another, no longer want these mosquitoes out in the wild.

Fortunately, there are major research efforts to develop chemical and genetic control or “recall” mechanisms for gene drive (Safe Genes). The first open-field trials of these will likely take place only after regulatory agencies are satisfied that appropriate mitigation procedures are available.

All of the scientists I know working on this technology have adopted a phased approach outlined in the new paper (which was adapted from previous publications) to testing safety and effectiveness complete with “go/no go” decision points before any consideration of releasing any insects into the field.

Included in this approach is time to review the implications and the possible risks described above, to engage the public to address concerns they might have, to develop the necessary safety protocols, and to secure regulatory approval.

Inherent in this process is an understanding that each new gene-drive technology is different. While there are some general principles that apply to all, such as containment of the organism during early testing, the risks and challenges of each must be evaluated on a case-by-case basis.

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Much of the research on gene-drive mosquitoes is carried out in countries where the disease is not endemic. Yet control over the use of gene-drive mosquitoes must ultimately rest with scientists, public health authorities, regulators, and the community in affected countries where they will be released. Because insects can cross international borders, such decisions may need to be taken at a multicountry level.

The best way to ensure that gene-drive technology is developed safely is to discuss it openly — in laboratories, within governments, and in public. Engaging nonprofit organizations like the Foundation for the National Institutes of Health contributes to safeguarding public interest in this emerging disease-fighting tool.

With so many people suffering from malaria every year, we cannot afford to leave this potential new tool unexplored. But we must do it the right way.

Anthony A. James, Ph.D., is professor of microbiology and molecular genetics at the University of California, Irvine, School of Medicine and professor of molecular biology and biochemistry at the UCI School of Biological Sciences.

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  • The three species of mosquitoes that carry malaria also carry other devastating diseases such as Zika and West Nile Virus. These species should be treated in the same way as smallpox and polio. We need to weigh the unending desire for matrix level consensus (scientists, governments, environmentalists,etc) expressed in this article against the hundreds of thousands of people that die every year. A consensus of a large enough group is a sentence to kill this technology in the field for decades. None of the three species play a critical biological role in any ecosystem, even their native ones. They should be eliminated as quickly as technology allows.

  • Thank you for this excellent summary of our paper. Africa as a continent will go far and fast if malaria is eliminated.

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