Technology to eliminate invasive mosquito vectors raises ethical issues

During a recent webinar conference held by the American Institute of Biological Sciences, researchers discussed scientific advancements made in technology designed to control and possibly eliminate mosquito vectors that harbor invasive arboviruses such as Zika, and the ethical issues of terminating them.

Recent studies have indicated that there is an association between Zika virus infection during pregnancy and adverse outcomes in fetuses, including microcephaly, placental insufficiency, central nervous system injury and fetal death. Local transmission of the virus has spread to 31 countries and territories in Latin America and the Caribbean, and imported cases were reported from every region in the world, according to WHO. While current methods used to contain the Zika epidemic are limited, WHO and the CDC are considering the use of genetically modified mosquitoes to reduce the mosquito population.

“The control of this disease, among other emerging diseases, is a challenge as people routinely travel around the world, global commerce provides increased opportunities for animal vectors to move into new environments, and climate change allows species to invade new habitats, often exposing the people in the colonized area to new pathogens,” Robert Gropp, PhD, interim co-executive director for the American Institute of Biological Sciences, said in a press release. “One line of research to suppress Aedes populations involves a ‘gene drive,’ a genetic construct that once introduced into wild populations is expected to spread rapidly. Such an approach could be designed to bring about a population crash, for example, by distorting the sex ratio in mosquito populations.”

Researchers investigate gene drive technology 

Zach Adelman, PhD

Zach N. Adelman

During the conference, Zach N. Adelman, PhD, of the department of entomology at Virginia Tech, presented research on a gene drive approach that partially transforms female mosquitoes, which feed on humans, to male mosquitoes, which do not feed on humans. The technology involves the Nix gene — a gene recently discovered by Andrew Brantley Hall, a PhD candidate at Virginia Tech, that is only present in male mosquitoes. 

“We were able to do in situ hybridization to mosquito chromosomes and show that this gene was present as a haploid gene,” Adelman said. “It was only on one copy of a chromosome and not two like you’d expect for a gene that was unique to a male chromosome.”

In collaboration with Zhijian Tu, PhD, of the department of biochemistry at Virginia Tech, the researchers conducted a study to determine whether the gene was able to convert male mosquitoes to female mosquitoes. They cloned the Nix gene onto a DNA plasmid and injected it into mosquito embryos to assess whether they all resembled male mosquitoes, or if some remained females.

“After two experiments, it became pretty clear,” Adelman said. “Our injected females had partially turned into males. When we dissected them out, we found that these females actually had testes and male reproductive organs instead of ovaries.”

The researchers hypothesized that an excessive release of the modified male mosquitoes, which would only be capable of producing other male mosquitoes, could reduce and eventually eliminate the female population.

Other research assessing gene drive technologies in the laboratory setting showed that approximately 99% of progenies of two different malaria vectors carried the gene drive construct for multiple generations, Adelman said.

“For Aedes aegypti, there’s no gene drive like this yet, but there’s no reason why it couldn’t work,” he added.

Nongene drive approaches implemented in natural settings

It is unlikely that gene drive technology will be available for regulatory use during the current Zika epidemic, according to Adelman. However, there is another method of disease control involving genetically modified mosquitoes that already has been approved for use in Brazil and may be further assessed in trials in the United States.

The technology was developed by Oxitec, a British genetic engineering company, and has the ability to kill A. aegypti mosquitoes before they reach adulthood. The process involves modifying male mosquitoes with a genetic construct that produces a tetracycline repressible activator, according to Adelman. The males are then released into the wild to mate with wild female mosquitoes. Their progenies, however, do not survive long enough to produce their own eggs.

“The repressor is not present, and this activator can activate its own expression in an infinite loop,” Adelman said. “Accumulation of this protein eventually kills the insects before they’re allowed to grow up.”

The technology was examined during efficacy trials in Brazil, Panama and the Cayman Islands, according to a press release. During the trials, the A. aegypti species declined more than 90%. Oxitec proposed to conduct additional trials in Monroe County, Florida. Preliminary results released by the FDA found the genetically modified mosquitoes had no significant impact on the environment, the release said.

“If that stands, they will allow these trials to go on in Florida this summer,” Adelman said.

In addition to the Zika virus, Adelman said aggressive mosquito control measures can prevent similar endemics with new and unknown arboviruses the mosquitoes may be capable of carrying.

“One of the really strong benefits that I see in reducing or eliminating mosquito populations is what I call ‘fighting the devil you don’t know’,” he said. “Many other viruses have been identified, but they haven’t yet been associated with large-scale disease outbreaks. Having these mosquitoes hang around our house is just a recipe for what’s next. We have Zika now … we had chikungunya … there’s going to be another one. If you can suppress or get rid of those mosquito populations, you’re not just doing yourself a favor for now, but for the future.”

Mosquito extermination raises ethical concerns

Despite these benefits, other experts, including Sahotra Sarkar, PhD, of the department of philosophy at the University of Texas, said there needs to be more public discussion on the ethical issues of intentionally eliminating an entire species.

“Some environmental ethicists argued that if we try to eliminate a species, we are doing something that we really shouldn’t be doing. We are playing God,” Sarkar said during the conference. “This is probably an influential political argument, and it needs to be debated.”

Sarkar raised several questions regarding the efficacy of genetically modified mosquitoes and how much control people would have over the technology if it was used.

“The first question is, if we eliminate A. aegypti, will we eliminate Zika?” Sarkar asked.

He said the virus has been found in at least 10 species of different genera of mosquitoes, including Anopheles, Culex and Mansonia.

“In chikungunya, there has been some recent epidemics in which Aedes albopictus seems to be very seriously involved, Sarkar said. “There is suspicion, but not proof, that this is because of genetic changes in the virus. The same thing could happen in Zika virus.”

Another issue Sarkar mentioned is the lack of knowledge of whether technologies that can be used, if need be, to reverse gene drive will work for A. aegypti.

“The Zika crisis is real and growing, and the technology, if it’s not already there, we’re going to get there very, very soon,” Sarkar concluded. “We cannot avoid this for decades. We need a public discussion.” – by Stephanie Viguers

References:

Hall AB, et al. Science. 2015;doi:10.1126/science.aaa2850.

Oxitec. FDA Publishes Preliminary Finding of No Significant Impact on Oxitec’s Self-limiting Mosquito. http://www.oxitec.com/fda-preliminary-finding-no-significant-impact-oxitecs-self-limiting-mosquito/. Accessed March 16, 2016.

Disclosure: Adelman reports no relevant financial disclosures. Infectious Disease News was unable to confirm other relevant financial disclosures at the time of publication.

During a recent webinar conference held by the American Institute of Biological Sciences, researchers discussed scientific advancements made in technology designed to control and possibly eliminate mosquito vectors that harbor invasive arboviruses such as Zika, and the ethical issues of terminating them.

Recent studies have indicated that there is an association between Zika virus infection during pregnancy and adverse outcomes in fetuses, including microcephaly, placental insufficiency, central nervous system injury and fetal death. Local transmission of the virus has spread to 31 countries and territories in Latin America and the Caribbean, and imported cases were reported from every region in the world, according to WHO. While current methods used to contain the Zika epidemic are limited, WHO and the CDC are considering the use of genetically modified mosquitoes to reduce the mosquito population.

“The control of this disease, among other emerging diseases, is a challenge as people routinely travel around the world, global commerce provides increased opportunities for animal vectors to move into new environments, and climate change allows species to invade new habitats, often exposing the people in the colonized area to new pathogens,” Robert Gropp, PhD, interim co-executive director for the American Institute of Biological Sciences, said in a press release. “One line of research to suppress Aedes populations involves a ‘gene drive,’ a genetic construct that once introduced into wild populations is expected to spread rapidly. Such an approach could be designed to bring about a population crash, for example, by distorting the sex ratio in mosquito populations.”

Researchers investigate gene drive technology 

Zach Adelman, PhD

Zach N. Adelman

During the conference, Zach N. Adelman, PhD, of the department of entomology at Virginia Tech, presented research on a gene drive approach that partially transforms female mosquitoes, which feed on humans, to male mosquitoes, which do not feed on humans. The technology involves the Nix gene — a gene recently discovered by Andrew Brantley Hall, a PhD candidate at Virginia Tech, that is only present in male mosquitoes. 

“We were able to do in situ hybridization to mosquito chromosomes and show that this gene was present as a haploid gene,” Adelman said. “It was only on one copy of a chromosome and not two like you’d expect for a gene that was unique to a male chromosome.”

In collaboration with Zhijian Tu, PhD, of the department of biochemistry at Virginia Tech, the researchers conducted a study to determine whether the gene was able to convert male mosquitoes to female mosquitoes. They cloned the Nix gene onto a DNA plasmid and injected it into mosquito embryos to assess whether they all resembled male mosquitoes, or if some remained females.

“After two experiments, it became pretty clear,” Adelman said. “Our injected females had partially turned into males. When we dissected them out, we found that these females actually had testes and male reproductive organs instead of ovaries.”

The researchers hypothesized that an excessive release of the modified male mosquitoes, which would only be capable of producing other male mosquitoes, could reduce and eventually eliminate the female population.

Other research assessing gene drive technologies in the laboratory setting showed that approximately 99% of progenies of two different malaria vectors carried the gene drive construct for multiple generations, Adelman said.

“For Aedes aegypti, there’s no gene drive like this yet, but there’s no reason why it couldn’t work,” he added.

Nongene drive approaches implemented in natural settings

It is unlikely that gene drive technology will be available for regulatory use during the current Zika epidemic, according to Adelman. However, there is another method of disease control involving genetically modified mosquitoes that already has been approved for use in Brazil and may be further assessed in trials in the United States.

The technology was developed by Oxitec, a British genetic engineering company, and has the ability to kill A. aegypti mosquitoes before they reach adulthood. The process involves modifying male mosquitoes with a genetic construct that produces a tetracycline repressible activator, according to Adelman. The males are then released into the wild to mate with wild female mosquitoes. Their progenies, however, do not survive long enough to produce their own eggs.

“The repressor is not present, and this activator can activate its own expression in an infinite loop,” Adelman said. “Accumulation of this protein eventually kills the insects before they’re allowed to grow up.”

The technology was examined during efficacy trials in Brazil, Panama and the Cayman Islands, according to a press release. During the trials, the A. aegypti species declined more than 90%. Oxitec proposed to conduct additional trials in Monroe County, Florida. Preliminary results released by the FDA found the genetically modified mosquitoes had no significant impact on the environment, the release said.

“If that stands, they will allow these trials to go on in Florida this summer,” Adelman said.

In addition to the Zika virus, Adelman said aggressive mosquito control measures can prevent similar endemics with new and unknown arboviruses the mosquitoes may be capable of carrying.

“One of the really strong benefits that I see in reducing or eliminating mosquito populations is what I call ‘fighting the devil you don’t know’,” he said. “Many other viruses have been identified, but they haven’t yet been associated with large-scale disease outbreaks. Having these mosquitoes hang around our house is just a recipe for what’s next. We have Zika now … we had chikungunya … there’s going to be another one. If you can suppress or get rid of those mosquito populations, you’re not just doing yourself a favor for now, but for the future.”

Mosquito extermination raises ethical concerns

Despite these benefits, other experts, including Sahotra Sarkar, PhD, of the department of philosophy at the University of Texas, said there needs to be more public discussion on the ethical issues of intentionally eliminating an entire species.

“Some environmental ethicists argued that if we try to eliminate a species, we are doing something that we really shouldn’t be doing. We are playing God,” Sarkar said during the conference. “This is probably an influential political argument, and it needs to be debated.”

Sarkar raised several questions regarding the efficacy of genetically modified mosquitoes and how much control people would have over the technology if it was used.

“The first question is, if we eliminate A. aegypti, will we eliminate Zika?” Sarkar asked.

He said the virus has been found in at least 10 species of different genera of mosquitoes, including Anopheles, Culex and Mansonia.

“In chikungunya, there has been some recent epidemics in which Aedes albopictus seems to be very seriously involved, Sarkar said. “There is suspicion, but not proof, that this is because of genetic changes in the virus. The same thing could happen in Zika virus.”

Another issue Sarkar mentioned is the lack of knowledge of whether technologies that can be used, if need be, to reverse gene drive will work for A. aegypti.

“The Zika crisis is real and growing, and the technology, if it’s not already there, we’re going to get there very, very soon,” Sarkar concluded. “We cannot avoid this for decades. We need a public discussion.” – by Stephanie Viguers

References:

Hall AB, et al. Science. 2015;doi:10.1126/science.aaa2850.

Oxitec. FDA Publishes Preliminary Finding of No Significant Impact on Oxitec’s Self-limiting Mosquito. http://www.oxitec.com/fda-preliminary-finding-no-significant-impact-oxitecs-self-limiting-mosquito/. Accessed March 16, 2016.

Disclosure: Adelman reports no relevant financial disclosures. Infectious Disease News was unable to confirm other relevant financial disclosures at the time of publication.

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