Posts Tagged ‘mosquitos’
By: Sarah L Hawes, PhD
Diseases transmitted through contact with an animal carrier, or “vector,” cause over one million deaths annually, many of these in children under the age of five. More numerous, non-fatal cases incur a variety of symptoms ranging from fevers to lesions to lasting organ damage. Vector-borne disease is most commonly contracted from the bite of an infected arthropod, such as a tick or mosquito. Mosquito-borne Zika made recent, regular headlines following a 2015-2016 surge in birth defects among infants born to women bitten during pregnancy. Other big names in vector-borne disease include Malaria, Dengue, Chagas disease, Leishmaniasis, Rocky Mountain spotted fever and Lyme.
Vaccines do not exist for many of these diseases, and the Centers for Disease Control (CDC) Division of Vector-Borne Diseases focuses on “prevention and control strategies that can reach the targeted disease or vector at multiple levels while being mindful of cost-effective delivery that is acceptable to the public, and cognizant of the world’s ecology.” Prevention through reducing human contact with vectors is classically achieved through a combination of physical barriers (i.e. bed nets and clothing), controlling vector habitat near humans (i.e. dumping standing water or mowing tall grass), and reducing vector populations with poisons. For instance, the Presidential Malaria Initiative (PMI), initiated under President Bush in 2005, and expanded under President Obama, reduces vector contact through a complement of educating the public, distributing and encouraging the use of bed nets, and spraying insecticide. Now a 600 million dollar a year program, PMI has been instrumental in preventing several million Malaria-related deaths in the last decade.
But what if a potentially safer, cheaper and more effective solution to reduce human-vector contact exists in the release of Genetically Modified (GM) vector species? Imagine a mosquito engineered to include a new or altered gene to confer disease resistance, sterility, or to otherwise impede disease transmission to humans. Release of GM mosquitos could drastically reduce the need for pesticides, which may be harmful to humans, toxic to off-target species, and have led to pesticide-resistance in heavily-sprayed areas. Health and efficacy aside, it is impossible to overturn or poison every leaf cupping rainwater where mosquitos breed. GM mosquitos could reach and “treat” the same pockets of water as their non-GM counterparts. However, an insect designed to pass on disease resistance to future generations would mean persistence of genetic modifications in the wild, which is worrisome given the possibility of unintended direct effects or further mutation. An elegant alternative is the release of GM vector animals producing non-viable offspring – and this is exactly what biotech company Oxitec has done with mosquitos.
Oxitec’s OX513A mosquitos express a gene that interferes with critical cellular functions in the mosquitos, but this gene is suppressed in captivity by administering the antibiotic tetracycline in the mosquitos’ diet. Release of thousands of non-biting OX513A males into the wild results in a local generation of larvae which, in the absence of tetracycline, die before reaching adulthood. Release of OX513A has proven successful at controlling mosquito populations in several countries since 2009, rapidly reducing local numbers by roughly 90%. Oxitec’s OX513A line may indeed be a safe and effective tool. But who is charged with making this call for OX513A and, moreover for future variations in GM vector release?
Policy governing use of genetically modified organisms must keep pace with globally available biotechnology. Regulatory procedures for the use of GM vector release are determined by country, and there is a high degree of international policy alignment. The Cartagena Protocol on Biosafety is a treaty involving 170 nations currently (the US not included) that governs transport of “living modified organisms resulting from modern biotechnology” with potential to impact environmental or human health. The World Health Organization (WHO) and the Foundation for the National Institutes of Health (FNIH) published the 2014 guidelines for evaluating safety and efficacy of GM mosquitos.
Within the US, the 2017 Update to the Coordinated Framework for the Regulation of Biotechnology was published this January in response to a solicitation by the Executive Office of the President for a cohesive report from the Food and Drug Administration (FDA), Environmental Protection Agency (EPA), and US Department of Agriculture (USDA). Separately, biotech industry has been given fresh guidance on whether to seek FDA or EPA approval (in brief): if your GM product is designed to reduce disease load or spread, including vector population reduction, it requires New Animal Drug approval by FDA; if it is designed to reduce pest population but is un-related to disease, it requires Pesticide Product approval by EPA under the Federal Insecticide, Fungicide, and Rodenticide Act.
Thus, for a biotech company to release GM mosquitos in the US with the intent of curbing the spread of mosquito-borne disease, they must first gain FDA approval. Oxitec gained federal approval to release OX513A in a Florida suburb in August 2015 because of FDA’s “final environmental assessment (EA) and finding of no significant impact (FONSI).” These FDA assessments determined that the Florida ecosystem would not be harmed by eliminating the targeted, invasive Aedes aegypti mosquito. In addition, they affirmed that no method exists for the modified gene carried by OX513A to impact humans or other species. Risks were determined to be negligible, and include the accidental release of a few, disease-free OX513A females. For a human bitten by a rare GM female, there is zero risk of transgene transfer. There is no difference in saliva allergens, and therefore the response to a bite, from GM and non-GM mosquitos. In addition, as many as 3% of OX513A offspring manage to survive to adulthood, presumably by spawning in tetracycline-treated water for livestock. These few surviving offspring will not become a long-term problem because their survival is not a heritable loop-hole; it is instead analogous to a lucky few mosquitos avoiding contact with poison.
Solid scientific understanding of the nature of genetic modifications is key to the creation of good policy surrounding the creation and use of GMOs. In an updated draft of Guidelines For Industry 187 (GFI 187), the FDA advises industry seeking New Animal Drug Approval to include a molecular description of the intentional genetic alteration in animals, method for alteration, description of introduction to the animal, and whether the alteration is stable over time/across generations if heritable, and environmental and food safety assessments. Newer genomic DNA editing techniques such as CRISPR offer improved control over the location, and thus, the effect of genetic revisions. In light of this, the FDA is soliciting feedback from the public on the GFI 187 draft until April 19th, 2017, in part to determine whether certain types of genetic alteration in animals might represent no risk to humans or animals, and thus merit reduced federal regulation.
Following federal clearance, the decision on whether to release GM vectors rests with local government. Currently, lack of agreement among Florida voters has delayed the release of OX315A mosquitos. Similar to when GM mosquito release was first proposed in Florida following a 2009-2010 Dengue outbreak, voter concern today hinges on the perception that GM technology is “unproven and unnatural.” This illustrates both a healthy sense of skepticism in our voters, and the critical need to improve scientific education and outreach in stride with biotechnology and policy. Until we achieve better public understanding of GM organisms, including how they are created, controlled, and vetted, we may miss out on real opportunities to safely and rapidly advance public health.
Have an interesting science policy link? Share it in the comments!
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.