Scientific mindsets clash over GM mozzies

February 2020

At the end of last year, GM-free Scotland reported a study which found a significant presence of offspring of Oxitec's GM 'sterile' male mosquitoes flying around in areas of Brazil where a trial release had been carried out [1]. The object of the trial was to prevent dengue virus by eradicating its mosquito vector. The predicted "barrage of attempts to discredit the scientists and their science which seem to have become routine in response to any biotech-unfriendly research results" duly unfolded.

No surprise there, except that the attack on the study, including a demand for retraction, was led by one of the paper's own co-authors and supported by five of the others.
The complaint seems to be that the published paper was different from the version they had all agreed, although the actual changes haven't been clarified. There's been no suggestion that the data were incorrect and, therefore, no grounds for retraction.

Problems seem to revolve around a perceived use of inflammatory, dramatic language, speculation, and a failure to include a core statement that there are no GM mosquitoes flying over Brazilian North-Eastern skies.

This first complaint seems to have emerged because the media reports of the study were phrased in inflammatory and dramatic terms. However, hyped inaccurate reporting of science in the popular press is not unusual and does not give grounds for retraction.

The second complaint, that of speculation, is interesting. It seems to have emerged from a clash of scientists with a reductionist mindset vs. their colleagues whose view is more holistic.

The researchers who carried out the study were a collaboration of Brazilian scientists led by associate professor Margareth Capurro whose expertise is in biochemistry and molecular biology (DNA), and Yale scientists led by Jeffrey Powell, professor of ecology and evolutionary biology. These two specialist areas of expertise lead to nearly diametrically opposed views of the living world.

In the biochemist/molecular-biologist mindset, organisms exist as 'normal' homogeneous, predominant wildtypes which will vary only when some rare, random mutation arises which happens to be useful. Releasing standard laboratory-bred GM mosquitoes, which are assumed to be sterile and not very robust, into a standard natural population isn't going to introduce any unexpected or problematic genes.

On the other hand, to the ecologist/environmental-biologist, organisms exist as a highly heterogeneous population in which there's always a built-in store-cupboard of useful genes available to come to the fore when required: "enough genetic variation is floating in natural populations for almost all traits to make adaptive evolutionary changes in the absence of any new mutations" (Powell). Floating genetic variation is too wide-ranging and complex to be picked up in laboratory sampling. Releasing batches of 450 thousand mosquitoes derived from parents native to two different countries into a highly diverse natural population in a third country will combine three store-cupboards of useful genes which could be problematic.

The Yale scientists' area of study includes the hybrid vigour known to drive an invasive strain into a native population. Their comment, based on this expertise, that the three-ways hybrid mosquitoes now flying around in Brazil would likely result in a population more robust than the native one due to hybrid vigour was deemed 'speculation' by the Brazilians and was one of their main complaints.

*Note. Interestingly, much the same team of Brazilian scientists published a study in 2015 describing a year-long field trial which released the same GM 'sterile' male mosquitoes, also to reduce the transmission of dengue virus.
The measured final reduction in the mosquito population of 81-95% was hailed, on the basis of specific assumptions and calculation to "likely be sufficient to prevent dengue epidemics in the locality tested".

This may be true, but it's nothing other than speculation based on a model too simple to factor in the natural heterogeneity of either the disease or the vector.

Paradoxically, eight months into the trial, a state of emergency due to dengue epidemic was declared (after which the numbers of GM mosquitoes released were stepped up considerably). The observed early increase in disease while vector numbers were reducing would arise if the GM mosquitoes were selectively removing dengue-resistant sectors of the native population leaving a space for the dengue-carriers to expand into. The danger here is that the capacity for dengue transmission ends up permanently increased in the wild mosquitoes, even while the total population is suppressed.

In the ecologists' view the invaders' genes will inevitably include a diversity of insecticide-resistance and pathogen-supporting traits. The Yale team pointed out these risks and indicate that considerable further testing is needed. However, their warnings were translated by the media into wildly imaginative reports of "super" dengue bugs in mosquitoes which "won't die".

Intriguingly, the scientists' squabble has revealed something Oxitec has been keeping very quiet. About 4% of its 'sterile' male mosquitoes aren't sterile. Apparently, "it was already known that up to 4% of the males escaped the lethal gene and developed into adults. Some degree of mating with the local population with healthy offspring was completely anticipated and poses no surprises" (Capurro). However, in the introduction of the disputed paper, we are informed that some "offspring from matings of (GM mosquitoes) with wild type do survive to adulthood although they are weak and it is not known if they are fertile" (our emphases).

The people in the areas where the GM mozzies have been released certainly weren't told they would be exposed to 4% (that's 18,000 per week) fertile males followed by their possibly weak, possibly healthy, possibly infertile, possibly fertile offspring [2].

Margareth Capurro is leading research into other (non-Oxitec) sterile GM male mosquito schemes for disease control. Bad publicity surrounding the Oxitec version would doubtless rub off on her own-brand novel mozzies.

OUR COMMENT

Indeed, inflammatory, dramatic and wildly inaccurate press reporting, and speculative statements in scientific papers seem to be quite normal and pose no surprises.

There remains the accusation that the Yale team failed to include a core statement that there are no GM mosquitoes flying over Brazil.

True? False? Or, requiring qualification?

How come 4% 'escaped' the lethal gene? It beggars belief that completely unadulterated individuals could leak through a breeding system surrounded by GM mates who couldn't help but pass on their artificial genes. Were they individuals whose GM parents had incomplete, disabled, or non-functioning artificial genes? In such an event, the offspring of GM mosquitoes now flying around in Brazil will have a store-cupboard of GM-induced off-target and epigenetic changes plus bits of man-made DNA in their genome. Since none of these possibilities were tested during the experiment, the demanded 'core statement' that the hybrid mozzies flying around aren't GM would be speculative, misleading and possible untrue.

The only certain aspect of this is that the new strain of mosquitoes now flying around in Brazil are no longer programmed to die out.

Background

[1] GM MOZZIES OUT OF CONTROL? - November 2019
[2] GM MOZZIE ETHICS WANTING - November 2019

SOURCES:

• Jeffrey R. Powell, 2018, Genetic Variation in Insect Vectors: Death of Typology? Insects 9
• Natalia Paternak, Brazilian author asks for retraction of Oxitec mosquito paper, http:revistaquestaodeciencia.com.br/english/, 26.09.19
• Kelly Servick, Dissent splits authors of provocative transgenic mosquito study, Science Magazine, 1.10.19
• Benjamin R. Evans, et al., 2019, Transgenic Aedes aegypti Mosquitoes Transfer Genes into a Natural Population, Nature Scientific Reports
• Danilo O. Carvalho, et al., 2015, Suppression of a Field Population of Aedes aegypti in Brazil by Sustained Release of Transgenic Male Mosquitoes, PLOS Neglected Tropical Diseases
• A sterile line of Aedes aegypti is developed to fight off arbovirosis, www.eurekalert.org, 4.08.18
• Natelie Kofler and others, Genetically modifying mosquitoes to control the spread of disease carries unknown risks, The Conversation, 1.10.19
• Scientific study drawing attention to the risks of GM mosquitoes comes under attack, GM Watch 14.10.19

CC photo James Gathany, USCDCP [CC0]