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Transgenic Mosquitoes: A Circumspect Assessment of Fitness

February 11, 2010 - 00:35 -- Mark Benedict

The James Gang at UC Irvine has made a useful contribution to the question of whether or not transgenic mosquitoes are fit.

In the paper “Comparative fitness assessment of Anopheles stephensi transgenic lines receptive to site-specific integration,” (Insect Molecular Biology), Amenya et al. describe measurements of the fitness of four transgenic lines of transgenic Anopheles stephensi which contain insertions of phiC31-attP docking sites. Production of such strains is a good accomplishment in itself since these strains will allow reproducible comparison of expression of effectors or other transgenes in the same chromosomal milieus.

Why would anyone want to know the relative fitness of transgenic lines that are not going to be released? Numerous manuscripts have reported fitness of transgenic mosquitoes using various methods, but many of these have left me asking, “So what? These strains are not going to be released.” There is justification however: there was concern circulating that transgenesis itself – regardless of the transgene or insertion site – might negatively affect fitness. This manuscript, like several that have preceded it, suggest that if this is the case, clear evidence has been hiding. The authors report fitness of the transgenics that was not generally different from the host strain.

What I really appreciate about this manuscript is that the authors understood the context for asking this question. It was not field release or persistence in the environment. It was simply a question of whether these particular strains were less fit than the laboratory colony from which they were developed. Which would one choose as a subject for insertion of effectors? This is good science, good methods and – as evidence of a maturing field - appropriate significance was attached to the results. Fitness, as measured in the laboratory, is of limited value to predict behavior in field releases. Moreover, evolutionary fitness of the first transgenics that will be released, sterile mosquitoes, is zero. What is needed in those situations is mating competitiveness and dispersal.

If strain fitness loss (due e.g. to bottlenecks or inbreeding) is observed, persistence of their transgenes in the environment still might occur, but only if adventitious deleterious alleles in the strain are not tightly linked to the transgene: otherwise they will be lost by recombination. Those of us who advocate exploring the use of transgenic mosquitoes for disease control must consider that loss of fitness is both an advantage - to provide self-limiting characteristics for biosafety – and a defect which might reduce spread – reducing its power. As I have argued elsewhere in a related blog, the importance of these counter-balancing forces will depend on the application and stage of testing.

Given the fact that transgenic strains will begin expanded field and semi-field testing during 2010-11, we may begin to know for a fact whether transgenic mosquitoes will satisfy the measures of fitness that matter most in public health – cost, effectiveness and public acceptance.

Comments

Usa Lek-Uthai's picture
Submitted by Usa Lek-Uthai on

Transgenic mosquito (TM) research is an ideal for vector control strategy, Friends of mind have done a lot about TM, they started since the egg stage..till TM were developed with white eyes and red eyes mosquitos '(vector and non vector)comparison groups, finally the results from their studies could not be allowed to launch R2P (Research to Practice) in the community (affect to the agricultural control):(( what would u suggust to do?...if the country is a small island and the ethical committee accept this trial program!
Usa

Usa Lek-Uthai,
Mahidol University,
Bangkok, Thailand

Mark Benedict's picture
Submitted by Mark Benedict on

No, R2P is not easy. This is why most in the field propose an incremental approach in which very small, safe and well-defined steps be taken. Without knowing any details of the effort you describe, I cannot say anything about whether the scientific program was sound nor whether the ethics committee made the right recommendation.

A slow and careful approach is the proper way to proceed though: an overly ambitious but premature effort will diminish confidence that the science is ready for R2P. It is possible that the ethical committee did exactly what they should: ensure that public health interventions are safe and sound.