An experimental trial to reduce the number of mosquitoes in a Brazilian town by releasing genetically modified mosquitoes has not gone as planned. Traces of the mutated insects have been detected in the natural population of mosquitoes, which was never supposed to happen.
The deliberate release of 450,000 transgenic mosquitoes in Jacobina, Brazil has resulted in the unintended genetic contamination of the local population of mosquitoes, according to new research published last week in Scientific Reports.
Going into the experimental trial, the British biotech company running the project, Oxitec, assured the public that this wouldn’t happen. Consequently, the incident is raising concerns about the safety of this and similar experiments and our apparent inability to accurately predict the outcomes.
The point of the experiment was to curb the spread of mosquito-borne diseases, such as yellow fever, dengue, chikungunya, and Zika, in the region. To that end, Oxitec turned to OX513A — a proprietary, transgenically modified version of the Aedes aegypti mosquito. To create its mutated mosquito, Oxitec took a lab-grown strain originally sourced from Cuba and genetically mixed it with a strain from Mexico.
The key feature of these bioengineered mosquitoes is a dominant lethal gene that (supposedly) results in infertile offspring, known as the F1 generation.
By releasing the OX513A mosquitoes into the wild, Oxitec hoped to reduce the population of mosquitoes in the area by 90 per cent, while at the same time not affecting the genetic integrity of the target population. The OX513A strain is also equipped with a fluorescent protein gene, allowing for the easy identification of F1 offspring.
Starting in 2013, and for a period of 27 consecutive months, Oxitec released nearly half a million OX513A males into the wild in Jacobina. A Yale research team led by ecologist and evolutionary biologist Jeffrey Powell monitored the progress of this experiment to assess whether the newly introduced mosquitoes were affecting the genes of the target population. Despite Oxitec’s assurances to the contrary, Powell and his colleagues uncovered evidence showing that genetic material from OX513A did in fact trickle to the natural population.
“The claim was that genes from the release strain would not get into the general population because offspring would die,” Powell, the senior author of the new study, said in a press release. “That obviously was not what happened.”
That genetic material from OX513A has bled into the native species does not pose any known health risks to the residents of Jacobina, but it is the “unanticipated outcome that is concerning,” said Powell. “Based largely on laboratory studies, one can predict what the likely outcome of the release of transgenic mosquitoes will be, but genetic studies of the sort we did should be done during and after such releases to determine if something different from the predicted occurred.”
Indeed, lab tests conducted by Oxitec prior to the experiment suggested that around 3 to 4 per cent of F1 offspring would survive into adulthood, but it was presumed these lingering mosquitoes would be too weak to reproduce, rendering them infertile. These predictions, as the new research shows, were wrong.
To conduct the study, Powell and his colleagues studied the genomes of both the local Aedes aegypti population and the OX513A strain prior to the experiment in Jacobina. Genetic sampling was performed six, 12, and 27 to 30 months after the initial release of the modified insects.
The researchers uncovered “clear evidence” showing that portions of the genome from the transgenic strain had “incorporated into the target population,” the authors wrote in the new study. The project resulted in a “significant transfer” of genetic material — an amount the authors described as “not trivial.” Depending on the samples studied, the researchers found that anywhere from 10 to 60 per cent of mosquitoes analysed featured genomes tainted by OX513A.
As the researchers note in the study, the Oxitec scheme worked at first, resulting in a dramatic reduction in the size of the mosquito population. But at the 18-month mark, the population began to recover, returning to nearly pre-release levels. According to the paper, this was on account of a phenomenon known as “mating discrimination,” in which females of the native species began to avoid mating with modified males.
The new evidence also suggests that some members of the F1 generation were not weakened as predicted, with some individuals clearly strong enough to reach adulthood and reproduce. The mosquitoes in Jacobina now feature genetic traits from three distinct mosquito populations (Cuba, Mexico, and local), which is a potentially troubling development.
In nature, the intermingling of traits between different species can sometimes provide an evolutionary boost in a phenomenon known as “hybrid vigour.” In this case, and as the researchers speculate in the new study, the added genetic diversity may have resulted in a more “robust” species, a claim Oxitec denies.
Powell and his team tested the hybrid mosquitoes to determine their susceptibility to infection by Zika and dengue. The researchers found “no significant differences,” as noted in the study, but “this is for just one strain of each virus under laboratory conditions,” and that “under field conditions for other viruses the effects may be different.” It’s also possible that the intermingling of genetic traits might have also introduced entirely new characteristics, such as increased resistance to insecticides, the authors warned in the new paper.
An Oxitec spokesperson told Gizmodo the company is “currently in the process of working with the Nature Research publishers to remove or substantially correct this article, which was found to contain numerous false, speculative and unsubstantiated claims and statements about Oxitec’s mosquito technology.” The spokesperson provided a three-page document detailing Oxitec’s concerns with the research, noting that the new paper did not identify any “negative, deleterious or unanticipated effect to people or the environment from the release of OX513A mosquitoes.”
According to Oxitec, the “OX513A self-limiting gene does not persist in the environment,” and that the “limited 3-5 per cent survival of the OX513A strain means that, within a few generations, these introduced genes are completely eliminated from the environment.”
Oxitec also disputes the researchers’ claim that female mosquitoes began to avoid mating with modified males, saying, “Selective mating has never been observed in any releases of close to 1 billion Oxitec males worldwide. The authors provide no data to support this hypothesis.”
Gizmodo reached out to Powell for comment did not hear back by the time of posting.
German broadcaster Deutsche Welle reports that the news that the Oxitec experiment didn’t go as planned is raising alarms among scientists and environmentalists:
Biologists critical of genetic engineering go one step further with their criticism, among them the Brazilian biologist José Maria Gusman Ferraz: “The release of the mosquitos was carried out hastily without any points having been clarified,” Ferraz told the newspaper Folha de S. Paulo.
The Munich-based research laboratory Testbiotech, which is critical of genetic engineering, accuses Oxitec of having started the field trial without sufficient studies: “Oxitec’s trials have led to a largely uncontrollable situation,” CEO Christoph Then told the German Press Agency, dpa. “This incident must have consequences for the further employment of genetic engineering”, he demanded.
That this project didn’t go as planned is legitimately troubling. The episode demonstrates that releasing genetically modified organisms into the wild can have unintended, unpredictable consequences and that independent scientific monitoring of the outcomes is crucial.