WHO issues new guidelines for GM mosquito R&D

By Joan Conrow

May 21, 2021

The World Health Organization has issued a new set of guidelines to shepherd the research and development of genetically modified (GM) mosquitoes.

Research and field trials are currently under way to determine the efficacy of using GM mosquitoes to control diseases like malaria, Zika, dengue and yellow fever, which sicken and kill millions around the globe annually, with young children particularly vulnerable. GM mosquitoes, which suppress populations without the use of insecticides, could be a innovative tool in reducing the human and economic toll of these diseases.

Disease experts agree that new strategies are needed to limit the transmission of mosquito-borne illnesses, especially due to the increasing threat of insecticide resistance.  Interventions that can effectively control outdoor biting are also sought, with research suggesting GM mosquitoes could be a powerful and cost-effective tool to supplement existing interventions.

“We urgently need innovative approaches to help control mosquito-borne diseases, which have a devastating impact around the world,” said Dr. John Reeder, director of the Special Program for Research and Training in Tropical Diseases (TDR). “Genetically modified mosquitoes is one such approach, but we want to be sure it’s fully and responsibly evaluated, as outlined in a recent WHO position statement.”

Added Dr. Pedro Alonso, director of the WHO Global Malaria Program: “Over the last two decades, we have achieved remarkable results with existing malaria control tools, averting more than 7 million deaths and 1.5 billion cases of the disease. However, progress towards key targets of our global malaria strategy remains off course. Genetically modified mosquitoes are one of a number of promising new tools that could help speed the pace of progress against malaria and other vector-borne diseases.”

The guidance framework for testing GM mosquitoes was developed under a partnership between WHO, TDR and the GeneConvene Global Collaborative, an initiative of the Foundation for the National Institutes of Health. It lays out best practices to ensure a safe, ethical and rigorous process guides the study and evaluation of GM mosquitoes as public health tools. It updates the first guidance framework to address the substantial technical advances that have occurred in the past seven years, as well as more sophisticated thinking about the role of ethics, stakeholder engagement, risk assessment and regulation.

“Like any new public health intervention, genetically modified mosquitoes raise new questions for researchers, affected communities and other stakeholders,” said Dr. Michael Santos, director of the GeneConvene Global Collaborative. “The updated guidance framework aims to answer these questions and help ensure that testing of genetically modified mosquitoes is as rigorous as it is for other public health products — and that it generates quality results to guide decisions about if and how these technologies are used.”

The guidance establishes a common set of expectations unique to GM mosquitoes and addresses specific issues, including standards for making decisions about how and when testing should proceed. The goal is to guide researchers, developers, policy makers and citizens through an informed and rigorous evaluation process. Special emphasis has been placed on ethics, safety, affordability and effectiveness.

The guidance also outlines methods for evaluating the implications of GM mosquitoes on human health, animal health and the environment; processes to increase understanding of the most effective strategies for risk assessment and stakeholder engagement; clearer criteria for projects to proceed from one testing phase to the next, incorporating descriptions of the steps needed to safely and responsibly take GM mosquito technologies — including those incorporating gene drive — into the field; and a concrete set of safety and efficacy considerations that should be evaluated at each phase of testing, to inform decisions about further testing and implementation.

Some technologies have already been tested in the wild. Oxitec Ltd., a leader in the field, has moved to a second generation of its technology in which fertile males are released, which is intended to make the suppression effect last slightly longer in the local mosquito population but eventually disappear — an approach being trialed in Brazil and the United States. Target Malaria, a vector control research alliance, conducted a very small single field release of a male sterile version of its technology in Burkina Faso as part of its local capacity strengthening activities in preparation for future trials.

Though mosquitoes modified with gene drives have not yet been tested in the wild, the guidance discusses new factors that should be considered in risk assessment and reviews relevant precedents for regulatory oversight of gene drive mosquitoes. The updated guidance describes best practices for safety and efficacy testing, ethical and engagement obligations and regulatory oversight for different types of GM mosquitoes, including various types of gene drive-modified mosquitoes, at each phase of the testing pathway.

“We welcome this new guidance from WHO, which will help countries suffering from mosquito-borne diseases to evaluate a promising new intervention,” said Prof. Aggrey Ambali, senior advisor at the African Union Development Agency-New Partnership for Africa’s Development (AUDA-NEPAD), the development agency of the African Union.

GeneConvene was established last year to advance the safe, ethical and rigorous exploration of gene drive approaches in preventing malaria. One way it operates is through collaboration. For example, it is working with the Genetic Biocontrol of Invasive Rodents (GBIRd) program to organize a series of panel discussions on stakeholder engagement around the technology. The final session on “investigating the independence of stakeholder engagement activities” will be held June 8 and is open to the public.  GeneConvene and the McMaster University Institute on Ethics and Policy for Innovation are organizing another series of panel discussions on ethical questions, starting in July.

GeneConvene also maintains a virtual institute that aggregates the latest research, media coverage and events related to gene drives and other genetic biocontrol technologies, as well as links to all of its recorded webinars.

Image: Shutterstock/Yusuf Kamal