Posts Tagged ‘biotechnology’
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.
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