Genetically engineered mosquitoes target deadly dengue fever and Zika
In the Florida Keys this week, newly hatched mosquitoes swarm with wet flower pots, waterlogged spare tires, trash cans and drainage ditches. In six quarters, however, a change is buzzing in the air. Scientists have genetically modified thousands of these mosquitoes and, for the first time in the United States, have made them free to breed.
These genetically modified insects, known by model number OX5034, are a laboratory offshoot of the Aedes aegypti mosquito that transmits dengue, Zika and other infectious diseases. After a decade of public debate and regulatory delays, these bugs are released by a British biotech company called Oxitec.
Using genetic engineering techniques, the company modified male mosquitoes to pass on a gene that causes females to need a pinch of the antibiotic tetracycline in order to survive. Without it, the females that spread the disease die as larvae. The altered, non-biting males seek out wild females to mate and spread the deadly trait to future generations. Gradually, more and more women are dying. The swarms decrease and disappear, without the need for chemical insecticides.
Florida Keys field trial is a key step towards federal approval of the product for modified insects by the United States Environmental Protection Agency, which granted the company a license to use experimental for the test. “It’s a big deal,” says molecular biologist Anthony James of the University of California at Irvine, who is developing bioengineered mosquitoes but is not involved in the project.
It comes as mosquitoes that carry diseases around the world become resistant to chemical insecticides long used to control them and rising temperatures create conditions for them to spread to new areas, according to scientists at Stanford University and the University of Florida, as well as many American public health analysts.
In the Florida Keys, these invasive insects make up only 4% of mosquitoes but are responsible for almost all of the disease’s transmission, according to local mosquito control officials. “We need new tools to fight this mosquito,” says Andrea Leal, executive director of the Florida Keys Mosquito Control District where the test is underway.
Overall, incidence of mosquito-borne dengue fever has been multiplied by 30 in the past 50 years, causing up to 100 million cases of illness per year, due to urbanization, travel and rising temperatures, according to research from the University of Washington and the World Health Organization. The virus is responsible for more than 20,000 deaths per year. Researchers at the University of Oxford in the UK and Harvard University predict that by 2080, the mosquito that transmits the disease will have spread to 159 countries around the world. Zika, which can cause birth defects, infects fewer people, but was epidemic in parts of the Americas about five years ago. So far, dengue is still relatively rare in the United States, with around 70 cases reported in Key Largo, the largest section of the Keys, last year.
“Oxitec is positioned primarily for the decades to come when climate change will make mosquitoes more and more dense and move further north, and you will be more likely to contract a sustained transmission of this type of disease”, explains the biologist. Kevin Esvelt, Director of Sculpting Evolution. from the Massachusetts Institute of Technology, which is developing new gene editing techniques to fight Lyme disease, mosquitoes and other parasites.
More broadly, field testing is a critical moment in the genetic engineering of entire species of disease-carrying insects, or any other sexually reproducing animal or plant in nature. While genetically modified crops are commonplace today, genetically modified insects have not yet been widely introduced everywhere.
“This is a historic project, and it represents an important step for us,” said Gray Frandsen, CEO of Oxitec. “I think more importantly that this is a very big step for the field.”
Oxitec researchers are developing eight species of genetically modified insects in total, including two types of mosquitoes that transmit malaria, as well as worms, moths and flies that attack valuable crops. The company is owned by Radford, Virginia-based venture capital firm Third Security with projects funded by a mix of foundations and corporations.
On May 20, Mr Frandsen announced that the company had embarked on the modification of another creature, a cattle tick responsible for billions of dollars in livestock losses each year, as part of a project funded by a $ 1.3 million grant from the Bill and Melinda Gates Foundation and by Clinglobal, an animal health services company based in Mauritius, an island nation in the Indian Ocean. Like mosquitoes in Florida, the cattle tick has become largely resistant to the chemicals used to control it, even as it spreads to new areas.
In April, the British Wellcome Trust, one of the largest health charitable foundations in the world. gave the company $ 6.8 million to develop ways to unleash the Aedes aegypti mosquitoes more broadly, including a large two-year region-wide pilot project in Brazil, where regulators have already approved their wide use.
Getting approval in the United States, however, is important in building international confidence in the new technology, says Dr. Jones of UC Irvine. “One of the criticisms of Oxitec and the industry in general in other countries is, if this product is so good, why don’t you use it at home? The main thing was to get permission to publish these things in the United States. “
In pest control biological warfare, there is certainly more than one way to attack a mosquito, according to public health officials. In the Florida Keys, authorities have already experimented with a technique using a common parasitic microbe called Wolbachia. When male mosquitoes carrying dengue fever with Wolbachia mate with wild female mosquitoes that do not have Wolbachia, the eggs do not hatch, according to the EPA and the Centers for Disease Control and Prevention.
From the standpoint of basic biology and genetics, however, the mosquito is an elusive target. “They have this incredible resilience in their genome,” says Flaminia Catteruccia of Harvard TH Chan School of Public Health, who helped pioneer mosquito genetic engineering. “What they have shown us time and time again is [that] if we are not very subtle and if we are just trying to kill them, they will find a way out.
Of course, it’s not just mankind tinkering with the molecular biology of Florida mosquitoes. The dengue virus itself genetically modifies them to meet its own needs, researchers at the Johns Hopkins Bloomberg School of Public Health have found.
The virus affects the genes controlling the insect’s immune system, its feeding behavior, and its ability to detect odors, making it hungrier and more likely to bite, according to their research published in the journal PLOS Pathogens. In particular, the dengue virus alters two genes so that the mosquito takes longer to probe a meal, giving the virus enough time to enter the human bloodstream.
Write to Robert Lee Hotz at [email protected]
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