GMO mosquitos to combat dengue and chikungunya: Regulatory agencies stretched by rapid advances in recombinant DNA technology
By: Daniël P. Melters, PhD
Juan was admitted to a hospital in Turbaco, just outside Cartagena, Colombia yesterday. He is the third member of his family to be admitted in the last two weeks. His wife and cousin were both diagnosed with chikungunya, which is currently epidemic in most Caribbean nations, including Colombia. Although his symptoms were similar to theirs, they are less severe. After medical testing, it is confirmed he contracted the endemic dengue virus. This is not surprising, as the same mosquito, Aedes aegypti or yellow fever mosquito, transmits both viruses.
On the other side of the Caribbean hope may soon be released. In the Florida Keys, an experimental trial with a new method to combat mosquito-borne diseases is being considered by the U.S. Food and Drug Administration (FDA). The biotech company Oxitec, a spin-off from Oxford University, has developed a genetically modified mosquito that can reduce the number of mosquitos carrying dengue viruses with surgical precision. If the FDA approves the experimental release of hundreds of thousands of GMO mosquitos, it could bring down the number of dengue-carrying mosquitos in the Florida Keys by 80-90%. This anti-mosquito technology is particularly promising for developing nations buckling under the financial and social burden of endemic dengue as it more cost-effective than traditional fumigation.
Mosquitos are responsible for transmitting various human pathogens such as dengue, chikungunya, river valley fever, yellow fever, and malaria – to name a few. Each year, millions of people die as a direct result of such mosquito-borne diseases, mostly in developing nations, including Colombia. About 390 million people are infected with the dengue virus each year and the number is on the rise. This rise can be attributed to both the aggressive nature of its host (A. aegypti) and the increase in the host’s habitat as a consequence of global warming. Although originally from Africa, the principle vector for dengue viruses, A. eagypti, is now endemic throughout the tropical and subtropical Americas.
How do Oxitec’s genetically modified mosquitos reduce the general mosquito population? Their strategy is to only release genetically modified male A. aegypti. These males will mate with females in the wild and pass on a modified gene to their offspring. Mosquitos with this gene require the presence of tetracycline, a broad-spectrum antibiotic, during their development to survive and therefore, they will die before they mature. Furthermore, only female mosquitos bite humans, as they need the amino acid isoleucine from human blood to make their eggs. The risk of any human being bitten by a genetically modified mosquito is negligible.
The major advantage of genetically modified mosquitos over conventional mosquito control measures is the species-specific approach. A. aegypti males will only mate with A. aegypti females. All other insects, including mosquitos that don’t bite humans, will remain unharmed. In contrast, the most commonly used mosquito control method involves large-scale fumigation with insecticides, which kills insects indiscriminately.
The FDA’s decision to consider allowing the Oxitec researchers to release hundreds of thousands of genetically modified male mosquitos has sparked skepticism about the safety and ecological consequences of the proposed release – skepticism that is shared by about 10-20% of the residents of the Florida Keys, according to a recent survey.
One fear is that removal of A. aegypti would be disastrous for the ecosystem, since the ecosystem would lose a pollinator and a food source for many animals. Although this fear might ring true for other species, experts agree that it is unlikely that even losing all of the over 3000 different mosquito species will permanently harm the ecosystem as their niche will most likely be replaced by other insects. Therefore, the potential loss of one mosquito species would have a minimal effect.
Another fear is that removal of A. aegypti will allow more space in the ecosystem for the invasive Asian tiger mosquito (Aedes albopictus) to invade. The Asian tiger mosquito is also capable of transmitting yellow fever, dengue, and chikungunya and has already conquered large parts of Central America and the southern states of the US. To counteract this latter fear, Oxitec is currently developing a genetically modified Asian tiger mosquito by adapting the same principles as the genetically modified A. aegypti.
Thus far, Oxitec has completed three major ecological studies in Brazil, Malaysia, and the Cayman Islands, where they claim an 80-to-90 percent decline in A. aegypti populations over three months. To conduct these studies, Oxitec teamed up with local officials. In April 2014, Brazil’s National Technical Commission for Biosecurity approved the commercial release of genetically modified mosquitos. For the past 5 years, Florida’s Mosquito Control District, which is in charge of mosquito control in the Keys, have been working with Oxitec to get approval from the FDA for similar experimental trials.
Though the fear of genetically modified organisms is not backed by science, the fear itself is still real. After all, an entire food industry has grown around the promotion of not using genetically modified foods. In 1975, the potential for public distrust of recombinant DNA technology (or genetically modifying organisms) was foreseen by scientists. This led Maxine Singer and Paul Berg to organize the Asilomar Conference on Recombinant DNA. At the conference, a group of biologists, lawyers, and physicians discussed the potential biohazards and regulations of biotechnology. They drafted voluntary rules, which still impact regulatory guidelines for biotechnology today.
Regulating the safety of genetically modified crops and pharmaceutical biotechnology products is the domain of the FDA, EPA, and USDA. The EPA and USDA also regulate pesticides and insecticides (under the Federal Insecticide, Fungicide, and Rodenticide Act or FIFRA and through the Animal and Plant Health Inspection Service (APHIS)). Typically, the FDA does not deem it necessary for GMO crops to be approved pre-market, unless the expression of a foreign protein differs significantly in structure, function, or quality from natural plant proteins and is potentially harmful to human health. The FDA has established a voluntary consultation process with GMO crop developers to review the determination of substantial equivalence before the crop is marketed.
The FDA has seemingly created greater hurdles for the approval of genetically modified animals. The review by its Center for Veterinary Medicine of a genetically engineered protein to increase the milk output of dairy cows took some nine years. In the 1990’s the FDA began a review of a genetically engineered Atlantic salmon. In 2012, the agency published a draft Environmental Assessment for the genetically modified salmon with a preliminary finding of no significant impact. As of December 2014, the FDA has not made a formal decision.
In both of these cases, the genetically modified cow and salmon are meant for human consumption. In this regard, the genetically modified mosquito differs greatly. It is intended to reduce the mosquito population and thus prevent mosquitos from biting humans and subsequently transmitting pathogens. Whether this will affect the speed at which the FDA could approve the proposed experimental release in the Florida Keys remains to be seen. A positive development here is the approval by the FDA for the start of clinical trials for genetically modified T lymphocytes to control the number of HIV particles in patients and thus stem the HIV infection.
Mosquito-borne diseases are a great health burden, especially in developing nations, as Juan and his family are experiencing. A cost-effective and precise application to limit the harm caused by mosquitos could potentially benefit billions of people. Yet, the safety of the public and the environment need to be respected and addressed. It is clear that a new era of using genetically modified organisms is here even before society has fully embraced GMO crops. Regulatory agencies now have to catch up to facilitate their safe and effective development. To advance this process, it is imperative that the FDA, Oxitec, and the Mosquito Control District (in this case) clearly and factually communicate with the public about what their course of action is, what the results are, and most importantly what the risks are and how these risks are being mitigated. If the public does not accept GMO mosquitos to combat mosquito-borne disease, the technological advancements for all GMO products will be hampered.