In the Spring of 2018, I was in the audience of a public Town Hall in the FL Keys discussing the use of innovative mosquito control technologies. I was representing MosquitoMate with their patented Wolbachia male mosquito release technology. Wolbachia utilizes a mechanism known as cytoplasmic incompatibility that can reduce insect populations, in our case the mosquito species Aedes aegypti, a main vector of dengue, Zika, and Yellow Fever. When the Wolbachia bacterium resides inside of the male mosquito, it renders the male sperm incompatible with wild females. As a result, the females’ eggs do not become fertilized and they never hatch (Figure 1). Over time, as female generations mate with the males who possess Wolbachia, the population dwindles. With less biting females around to transmit disease, it is thought that the likelihood of pathogen transmission is less. When I worked on a project like this in Miami, FL, we reduced the population by nearly 80%.
Sterile Insect Technique Technologies
Another company known as Oxitec that utilizes a similar strategy (Figure 2) to MosquitoMate was also present at the meeting. Their technology differs slightly, however, in that the mosquitoes bred in their laboratories are genetically modified with the insertion of a self-limiting gene (known as tTav shown in blue in Figure 2). Under these conditions, tTav blocks the expression of an essential gene (shown in pink in Figure 2) in the mosquito and turns the gene “off.” Thus, with the essential gene “off” the mosquito dies. However, in the presence of the antibiotic tetracycline, the tetracycline stops tTav from blocking the expression of the essential gene and lets it turn “on.” Under these circumstances with the essential gene turned “on,” the mosquito lives.
The only way these Oxitec mosquitoes can survive long-term are in the presence of the antibiotic tetracycline. During male mosquito releases in the environment, when a male mosquito with this self-limiting gene mates with a wild female, the offspring inherit this self-limiting gene. And when these new larvae hatch in the wild where there are no antibiotics in their natural surroundings. The tTav gene is then free to block the expression of the essential gene and the mosquitoes die. This limits the population from growing and has the same effect as the Wolbachia cytoplasmic incompatibility technology. Oxitec has also made their mosquitoes with the gene insertion fluorescent, meaning they can quickly look under a microscope and determine if any captured mosquitoes from the environment are glowing red.
Regulatory and Public Opinion Barriers of mosquito control technologies
But what do technologies like those of MosquitoMate and Oxitec mean for mosquito control? Today, chemical pesticides are the number one method of reducing mosquito populations but are fraught with issues like cost, insecticide resistance, and hurting the environment. This opens the door for innovative science technologies that can mitigate these issues. Male mosquito release technologies (collectively known as Sterile Insect Technique or SIT) do not require any chemical pesticides, they only target one specific mosquito species and leave other animals alone, and male mosquitoes do not bite or feed on blood and so cannot spread any more diseases.
Warranted or not, the Oxitec GMO method is not without points of contention. Although male mosquito releases in the FL Keys were voted down a few years ago, the Oxitec technology is slated to release 750 million mosquitoes in 2021 and 2022 in the FL Keys after receiving EPA approval and community consent. Oxitec also received an Experimental Use Permit (EUP) to release mosquitoes in Harris County outside of Houston, TX. Critics of the technology say that the EPA rushed approval and did not do the proper environmental impact studies associated with releasing millions of mosquitoes in the area. I find this critique invalid: the EPA has been one of the toughest critics (rightfully so as the regulating body of government for pesticides!) of the technology for years.
In the initial EUP application a few years ago, Oxitec was shuttled between different agencies while seeking regulatory approval. Indeed, it has been difficult for governing bodies to classify these innovative technologies. Technologies such as SIT did not “fit” into any known categories at the EPA, and Oxitec’s self-limiting gene technology was initially reviewed under the FDA! The EPA has now created a new class of pesticides for SIT and other microbial pesticides and can be found in the Emerging Technologies Branch under the Biopesticides and Biotechnological Pesticide Products section. In the latest EUP application, over 31,000 public comments both positive and negative) were received to the EPA. To see the EPA comments and documents related to the approval process and release strategy click here.
Final Thoughts
Personally, I am excited to see the technology finally get the approvals necessary to start the releases, and I will be very interested to see how the data pans out. Although Oxitec has performed releases in the Brazil and the Cayman Islands, there is heightened scrutiny with releases in the United States where the potential impact on market capitalization is massive (Oxitec’s parent company is publicly traded Intrexon/Precigen, Inc. Ticker: PGEN). With the potential to reduce the spraying of chemical pesticides, harm to the environment, and substantial costs to controlling vector-borne diseases, it is worthwhile in my opinion and experience to continue our research and study into novel mosquito control strategies and technologies like those of Oxitec’s and SIT.