standard WHO’s Guidance on Testing Genetically Modified Mosquitoes

The World Health Organization (WHO)  has published a guidance document that provides a framework by which genetically modified mosquitoes might be developed and tested as tools for controlling mosquito populations and/or pathogen transmission. This guidance comes at a time when mosquito control operations using genetically modified mosquitoes are beginning to be tested with field trials.

Mosquito-borne diseases impose an enormous burden on the world’s population. While malaria and Dengue fever create the largest burden, other diseases such as those caused by the West Nile  and  Chikungunya viruses have demonstrated how mosquito-borne diseases can move into regions and quickly spread. Mosquito-borne diseases are very challenging to control. In the cases of malaria and dengue, there are no vaccines and mosquito control is the primary means by which transmission is reduced or eliminated.

This is an example of a GMM used for laboratory studies in which cells associated with all sensilla are expressing a red fluorescent protein.

This is an example of a GMM used for laboratory studies in which cells associated with all sensilla are expressing a red fluorescent protein. From the author’s laboratory

Advanced insect genetic technologies now enable the creation of genetically modified mosquitoes (GMM) with very specific genotypes. There are efforts to use insect genetic technologies to create genotypes that will allow mosquitoes to be controlled using ‘classical’ genetic control strategies such as the Sterile Insect Technique. Other efforts are focused on creating mosquitoes that upon release into wild populations will skew the sex ratio in favor of males and eventually reduce the number of females to the point where the population ‘crashes’ and becomes locally extinct. Finally, some are using insect genetic technologies to create mosquitoes that can no longer serve as hosts for either Dengue virus or malaria parasites. Spreading these ‘resistance’ genotypes through natural populations would leave the mosquitoes in the environment but would remove the threat they pose as transmitters of deadly pathogens.

Some of these technologies have matured to the point where they are beginning to move from the laboratory to the field.

Most of the needs for mosquito control for the purposes of reducing disease transmission are located in countries and regions that are not well prepared to evaluate and regulate activities associated with the release of transgenics into the environment. This is new territory for insect biologists as well and how best to proceed has been a looming question.

The WHO has brought together a diverse group of stakeholders to formulate a guidance document that should be helpful to scientists and government officials.

The document addresses a number of questions but these two are of particular interest:

Why genetically modified mosquitoes?

“GMM technologies offer several theoretical advantages over conventional vector control strategies. They may reach mosquito populations and mosquito larval breeding sites that have traditionally been the hardest and most expensive to access by exploiting the natural behaviour of mosquitoes to mate and seek sites for egg laying. For example, GMMs would be well suited to urban settings, where current control measures are largely ineffective due to the wide availability of cryptic mosquito larval breeding sites. Additionally, GMMs may reach outdoor and day-.‐biting mosquitoes that often escape control methods such as bed nets and indoor insecticide spraying. The modification could be made highly specific for the target mosquito species, which would avoid ecological and environmental hazards associated with commonly used broad-.‐spectrum insecticides. GMMs could provide continuous protection in situations where other disease control methods have been interrupted, and prevent the reintroduction of the pathogen after successful elimination efforts. It is important also to note that GMM technologies could be used in ways that are compatible with other disease control methods and could be incorporated into integrated vector management programmes.”(from WHO/TDR, FNIH (2014) The Guidance Framework for testing genetically modified mosquitoes: World Health Organization.)

What’s the basic approach?

“A phased testing pathway is recommended, in which new GMM strategies move from the laboratory, to testing in more natural environments under confined conditions, and finally to open release trials, with each transition dependent upon satisfactory demonstration of efficacy and safety. When GMM are incorporated into national or regional vector control programmes, the need for ongoing case-.‐specific monitoring of effectiveness and safety should be considered to ensure acceptable quality and performance standards and to inform any necessary management responses.” (from WHO/TDR, FNIH (2014) The Guidance Framework for testing genetically modified mosquitoes: World Health Organization)

Another example of a GMM (larva) used in laboratory studies in which the nervous tissue and some muscles (broad bands running the length of the body) are expressing a green fluorescent protein

Another example of a GMM (larva) used in laboratory studies in which the nervous tissue (series of diamond-shaped tissue in each segment) and some muscles (broad bands running the length of the body) are expressing a green fluorescent protein.  From the author’s laboratory

The document contains a nice aggregation of various genetic strategies that have been discussed among scientists for some time and then puts all of that in a broader risk assessment context.

This will be a helpful document, particularly to countries whose biotechnology regulatory structure is less robust and where new mosquito control strategies are most needed. WHO’s guidance should be welcomed.

 

 

 

WHO/TDR, FNIH (2014) The Guidance Framework for testing genetically modified mosquitoes: World Health Organization ISBN 978 92 4 150748 6

 

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