RA&RM of Living Modified Mosquitoes

As in the Netherlands we have as yet only encountered mosquito issues in our risk assessment for contained use, I have not a lot of expertise in the environmental risk assessment and management of GM mosquitos (or arthopods in general). Therefore, I can only give some general comments to the initial outline of the guidance document on mosquitos.

I think that a section on ethical, legal and societal issues is not within the scope of what the AHTEG should take into consideration. Still, it would be important and appropriate to give a brief overview of the issue involved. This could however best be done in the way we have solved this in the Roadmap, in a last paragraph on ‘related issues’.

As to scope, I think that we should probably focus on all mosquitos causing human disease, but, for identifying issues and adverse effects, you could probably go wider. In the suggested readings, for instance, there is already provided a document on GM arthropods in crop protection, that looks quite useful.

In the list of topics to consider, I am not sure what ‘analysis strategy’ means. Is this the ‘strategy of the risk analysis’ or the ‘risk analysis of strategies’? In both cases, I think this topic should be up-front, after a section on scope and scale, but before the adverse effects.
Could you please provide some comments of what this section would cover.

Thank you all for your very helpfull inputs to the development of the guidance document.

Risk assessment of LM mosquitoes is indeed a challange, even if only for its unlikeness to any other living modified organisms that we have had some experience so far. So, any contribution from the forum members are very much wellcome!

I appreciate the coments given on the issue of "informed consent". I agree with the argument that, if an informed consent is required, one individual can halt the whole process. This brings about the issue raised by Hans on the appropriatedness of a section on ethical, legal and societal issues. It has been agreed that these issues are not in the scope of the ATHEG. However, we are dealing with a completly different issue than that of LM crop plants (mosquitoes born disease and move about, etc.). Additionally, considerable support is given in the literature to the idea that the release of LM mosquitoes will require careful evaluation from an ethical perspective, particularly if the application has unknown efficacy. It is also argued that the involvement of key stakeholders in the early stages may determine success or faillure. For these we have included this topic in the draft outline and wish to have a good discussion with the forum members. 

Eliana

I wish to comment on the informed consent issue :

I agree that the community should be informed of potential trials and their outcomes, however individual informed consent seems inappropriate for several reasons outlined below.  I also wish to draw the groups attention to a specific guidance document already in existance for consent in community based research.


How can informed consent be practically obtained for everyone in an areawide experiment ?  This is not a standard to which previous releases of mosquitoes have been held or indeed other public health interventions  e.g fluoride in water, biological control, insecticide spraying for vector control. How can the abilty to withdraw from an area-wide trial be implemented ? Anyone potentially entering the program area would need to be fully informed and informed consent obtained.  Furthermore that individual, with whatever motivation, could shut the program down on a whim.  This is neither practical or desirable.  Therefore there should be other mechanisms for community based research.  One of these is described in CIOMS/ WHO (1993) International guidelines for ethical review of epidemiological studies  -
“”where research is undertaken on a community basis …… individual consent on a person to person basis  may not be feasible and the ultimate decision to undertake research will rest with the public health authority in consultation with the research ethics committee.  The committee  should satisfy itself that it is permissible to proceed without individual consent and the investigator or sponsor has made adequate arrangements to protect the safety of the research subjects and maintain confidentiality". 
The guidelines also state that all possible means should be used to inform the community concerned of the aims of the research, the advantages expected from it and possible hazards.

These appear to be a more appropriate set of ethical standards that trials with genetically modified  mosquitoes could be considered under.

Greenpeace welcomes the opportunity to comment on the AHTEG and, in particular GE mosquitoes

Greenpeace is opposed to the release of genetically engineered (GE) insects in the same way that it is opposed to the releases of any genetically engineered organism.  Once released to the environment, there can be no recall.  This is especially obvious with flying insects such as mosquitoes.  The genetic engineering approach is unlikely to succeed, as there are so many unknown or poorly understood ecological and genetic parameters.  For example, if a GE mosquito is planned to be resistant to one malarial-inducing parasite (the worst kind) but it is not known how this would affect the infection and transmission of other malarial-inducing parasites or other diseases transmitted to humans by the mosquitoes.  If there were any unintended or unexpected affects from the GE mosquitoes, it would impossible to recall them.

The diseases spread by mosquitoes are serious and pose very complex problems.  It is unlikely that one technique will provide a magic “silver bullet”. There is no full understanding of the methodology nor the implications of genetically engineered mosquitoes.  Other approaches being developed, such as vaccines, low technology methods to reduce biting frequency.  Why divert funds away from these projects developing such a risky technology?

Regarding LMM recall:

- Many LMMs that are under development carry modifications that are self-limiting, in the sense that they have an inherent tendency to disappear from a population unless they are continually released. Sterile males are a clear example. For these LMMs the issue of recall does not arise because they will disappear of their own accord if releases are stopped.

- Even for self-sustaining modifications that are expected to spread though a target population, it may be possible to recall the modification (Burt 2003 Proc Roy Soc Lond B 270:921-928; Chen et al. 2007 Science 316:597-600).

Austin Burt

Dr. Cotter has understandably given attention only to the most distant and speculative strategy of transgenic mosquitoes, gene drive systems. These have been given much popular news coverage which often seeks the most exciting stories. I generally agree with her that at this time, they also pose the most speculative risk and will therefore require the most testing (see posting #1223). That is why many in the community that is developing these technologies favor population suppression strategies as the first transgenic methods to be employed. One of the advantages of these systems is that because the released mosquitoes are sexually sterile and have a very short lifespan, there is nothing to recall.

The investment in transgenic vector technologies to reduce or eliminate vector-borne disease transmission is miniscule and has yielded usable products in a very short time compared to development of malaria vaccines. Is either a silver bullet? Of course not. Are they worth the investment? This will only be known if safety and efficacy testing of the technologies is allowed to proceed.

To oppose the release of transgenic organisms without appreciating their diverse properties ("in the same way") may deny those for whom existing technologies are *not* adequate the opportunity to decide for themselves which of the various approaches are desirable.