A letter to the EPA: Used tires in Puerto Rico are a public health menace as a principal breeding ground for the Aedes Aegypti mosquito, the vector of Zika virus, Yellow Fever, and Dengue Fever.

Mosquitoes kill more humans than any other animal and were linked to roughly 500,000 deaths in 2015

 

Mosquitoes Are Deadly, So Why Not Kill Them All?

Zika virus’s spread adds urgency to gene editing that could allow scientists to program the insects to die off, but the idea is fraught with quandaries

Guilherme Trivellato of Oxitec releases on Feb. 1 in Piracicaba, Brazil, some Aedes aegypti mosquitoes that have been genetically modified to produce offspring that don’t survive or reproduce. The species spreads at least four viruses that cause major diseases, including Zika.
Guilherme Trivellato of Oxitec releases on Feb. 1 in Piracicaba, Brazil, some Aedes aegypti mosquitoes that have been genetically modified to produce offspring that don’t survive or reproduce. The species spreads at least four viruses that cause major diseases, including Zika. PHOTO: ANDRE PENNER/ASSOCIATED PRESS

The death toll from diseases carried by mosquitoes is so huge that scientists are working on a radical idea. Why not eradicate them?

Mosquitoes kill more humans than any other animal and were linked to roughly 500,000 deaths in 2015, mostly from malaria. For more than a century, humans have used bed nets, screens and insecticides as weapons, but mosquitoes keep coming back. They arenow carrying viruses like Zika and dengue to new parts of the world.

Powerful new gene-editing technologies could allow scientists to program mosquito populations to gradually shrink and die off. Some efforts have gained enough momentum that the possibility of mosquito-species eradication seems tantalizingly real.

“I think it is our moral duty to eliminate this mosquito,” entomologist Zach Adelman says about Aedes aegypti, a species carried afar over centuries by ships from sub-Saharan Africa. It derived from a forest dweller and adapted to thrive among humans, to whom the mosquito spreads at least four viruses that cause major diseases.

Prof. Adelman, a virologist and associate professor of entomology at Texas A&M University, is working to program Aedes aegypti mosquitoes to develop as males.

Eventually, the mosquitoes would run out of mates, crashing the species’ population in places it invaded and “cleaning up a global mess,” he says. Female mosquitoes are the only ones that bite people and transmit viruses.

Purposely engineering a species into extinction—or just diminishing it—is fraught with quandaries. Scientists must weigh the potential impact of removing a species on the environment and food chain. It will take years of more research, testing and regulatory scrutiny before most genetically altered mosquitoes can be released into the wild. And the strategy might not work.

Wiping a species off the face of the earth is “an unfortunate thing to have to do,” saysGregory Kaebnick, a research scholar at the Hastings Center, a bioethics research institute in Garrison, N.Y.

He says humans shouldn’t force a species into extinction to meet their own preferences. “We ought to try not to do it,” says Mr. Kaebnick. One justification, he says, would be to avert a serious public-health threat.

Mosquitoes have an ugly track record of spreading everything from the Zika virus to dengue fever to malaria. Could they be killed off? Here’s a short look at a controversial question.

Out of more than 3,600 mosquito species, only a few dozen transmit viruses and parasites that can sicken or kill humans. Even the killer mosquitoes pollinate plants and are food sources for other animals, though usually not the only staple, entomologists say.

For decades, agricultural officials have used a “sterile insect technique” to eliminate pests that are dangerous to crops or humans. Insects are sterilized with radiation and then released into the wild.

Insects that mate with the sterilized ones produce no offspring, and the populations die off within a few generations. The technique was used to rid the U.S. and a few other countries of the New World screwworm fly, and it is now being used to battle fruit flies.

Imperial College London researchers are refining a system under development for the past several years to drive a self-destructive genetic trait into the Anopheles gambiae mosquito, the major carrier of malaria in sub-Saharan Africa. The trait could eventually shrink the malaria carrier’s population. Malaria kills an estimated 438,000 people a year.

Aedes aegypti is high on the hit list of more scientists now that Zika has spread from Brazil to Miami, spawning an epidemic that has left hundreds of babies with devastating birth defects.

The same type of mosquito caused dengue to proliferate through tropical regions world-wide during the last quarter of the 20th century. The dengue virus infects an estimated 390 million people a year, killing thousands of them.

Aedes aegypti also is a carrier of chikungunya, a crippling disease that causes lasting joint pain, and yellow fever. In Africa, officials are struggling to contain a large outbreak of yellow fever, which can lead to fatal liver disease.

“Aedes aegypti is literally probably the most dangerous animal in the world,” says Omar Akbari, a molecular biologist and assistant professor of entomology at the University of California, Riverside. His conclusion is based on the number of infections to which the mosquito is linked.

Many entomologists say eradicating Aedes aegypti would have a minimal impact on the environment. Such mosquitoes thrive around humans, breeding in water that collects in tires, pipes and plastic containers. Humans are their only source of food.

Zika-carrying mosquitoes aren’t very appealing to other animals as a food source, entomologists say. “They’re so tiny a bat would have to eat thousands of them to equal a couple of moths,” says Michael Doyle, an entomologist and former executive director of the Florida Keys Mosquito Control District, which battled a dengue outbreak several years ago.

Genetic-engineering technologies used by mosquito-fighting scientists include a new tool known as Crispr/Cas9.

With Crispr/Cas9, scientists can use an enzyme to snip DNA and insert changes, then build something called a “gene drive” that makes those changes more likely to be inherited by future generations, altering them. Normally, genes have only a 50% chance of being inherited.

Prof. Adelman and Virginia Tech biochemistry professor Zhijian Tu see a way to do this with genes involved in mosquito reproduction. In a paper published in Science last year, the researchers identified a gene that makes Aedes aegypti mosquitoes male.

“This was the master switch that controls sex,” says Prof. Tu. He and Prof. Adelman were co-authors of the research.

The researchers now are working on a system to program mosquitoes to develop as males. Since only females bite, that change could reduce the ability to spread disease. The researchers aim to then use Crispr/Cas9 to build a gene drive that would spread the change through successive generations.

“If you’re successful, then you end up with all males, and the local population crashes,” says Prof. Tu. Prof. Adelman cautions that a system to target Aedes aegypti would have to be designed to leave the African forest-dwelling mosquito Aedes aegypti formosus intact. That type of mosquito doesn’t threaten human, he says.

Prof. Akbari at UC Riverside is using Crispr/Cas9 to design a gene-drive system that would inactivate a fertility gene in female Aedes aegypti mosquitoes and then pass on the inactivated gene. That would sterilize future generations of females.

He hopes to test the system within the next several months. “We’re working as fast as we can,” Prof. Akbari says.

Using different technology, Oxitec Ltd. has developed what it calls a “self-limiting” Aedes aegypti mosquito, a male genetically modified to produce offspring that don’t survive or reproduce.

In August, the Food and Drug Administration allowed Oxitec to go ahead with a field trial in Key Haven, Fla. Oxitec is a unit of biotechnology firm Intrexon Corp., based in Germantown, Md.

Oxitec’s technology isn’t as powerful as those using gene drive, because the trait isn’t pushed through multiple generations of mosquitoes. As a result, Oxitec’s genetically modified mosquitoes need to be released regularly.

The company says its tests in Brazil, Panama and the Cayman Islands, where the engineered insects are released in a small area, have cut the Aedes aegypti population in those areas by more than 90%.

ENLARGE

In one field trial in a district of Piricicaba, Brazil, cases of dengue fever fell 91% from the same period a year earlier, Oxitec says.

“We focused on Aedes because we saw it as a great unmet need,” says Haydn Perry,Oxitec’s chief executive. “If you look at the statistics, the rise in dengue has been absolutely shocking since the 1970s.”

In June, a committee of the National Academies of Sciences, Engineering and Medicinesaid in a report that organisms modified by gene drive aren’t ready to be released into the wild.

More research is needed on how the modified organisms work and might affect the environment, the report said, concluding that their proposed uses “are based on limited proof-of-concept studies.”

“We need to think through what responsible conduct looks like when you have these tools in your hand,” says James Collins, a professor of natural history and the environment at Arizona State University who is one of the committee’s leaders.

Field trials and releases of genetically modified mosquitoes require regulatory approval and can take years.

In the Florida Keys, Oxitec’s “self-limiting” mosquitoes face opposition from residentswho worry that the insects could harm local ecosystems.

The field trial that got a go-ahead from the FDA will face a nonbinding referendum from voters in Key Haven on Nov. 8. After that, the field trial must be approved by the Florida Keys Mosquito Control District, spokeswoman Beth Ranson says.

Winning consent from the many countries infested with Aedes aegypti for eradication through the use of gene drive will be difficult. That could limit the impact of the mosquito-fighting technique.

“How on earth are we going to manage informed consent and diplomatic agreement?” says Kevin Esvelt, an evolutionary engineer at the Massachusetts Institute of Technology. In 2014, he outlined how using Crispr/Cas9 gene drives could spread genetic traits through wild populations.

Some scientists and foundations say total eradication isn’t necessary. One alternative strategy is to suppress the population of virus-carrying mosquitoes low enough that there are too few left to transmit pathogens from one person to another. That approach could be combined with traditional mosquito-control strategies such as spraying and bed nets.

“We’re not targeting to eliminate mosquitoes. We’re really targeting to eliminate the human diseases,” says Scott Miller, deputy director of the malaria team at the Bill & Melinda Gates Foundation.

In December, researchers at Imperial College reported in the journal Nature Biotechnology that they engineered genetic changes that could make Anopheles gambiae populations plummet. That is the most common carrier of the deadliest form of malaria in sub-Saharan Africa, where the vast majority of cases and deaths occur.

The researchers used Crispr/Cas9 to disrupt genes involved in producing eggs in females, then built a gene drive that passed that trait along to as many as 99.6% of their offspring. As the trait spreads, more females become sterilized, gradually reducing the population, the researchers said.

Imperial College evolutionary geneticist Austin Burt says he and his colleagues are now refining their work.

The Gates Foundation is investing $75 million in the Target Malaria project, partly to help prepare laboratories in Mali, Burkina Faso and Uganda, lay the groundwork to seek regulatory approvals and train staff to conduct field trials. Dr. Miller says release of the engineered mosquitoes into the wild is about a decade away.

Researchers in Australia have developed a way to inject mosquito eggs with a common, naturally occurring bacteria. The eggs need to be injected just once and then pass down the bacteria.

The method is likely to be ready for use far sooner than gene-drive strategies, says Scott O’Neill, director of vector-borne diseases at Australia’s Monash University and head of the mosquito-injection program, called Eliminate Dengue. Large-scale trials are planned in Brazil and Colombia. Financial backers include the Gates Foundation.

Despite the early progress in using gene-editing to conquer the world’s deadliest mosquitoes, many scientists are chastened by history.

A truck sprays the pesticide DDT on Jones Beach, N.Y., in 1945. The push to go after Aedes aegypti mosquitoes with DDT was largely abandoned by the 1970s.
A truck sprays the pesticide DDT on Jones Beach, N.Y., in 1945. The push to go after Aedes aegypti mosquitoes with DDT was largely abandoned by the 1970s. PHOTO: GAMMA-KEYSTONE/GETTY IMAGES

In the 1940s, public-health leaders declared war on Aedes aegypti, going after the insects with aggressive spraying campaigns that included DDT, or dichloro-diphenyl-trichloroethane. By the 1970s, the push was largely abandoned. It succumbed to high costs, feared health risks from DDT, a lack of strong U.S. support and the insect’s resurgence in some areas.

Right now, says Texas A&M’s Prof. Adelman, gene drive seems like “an all-powerful tool that will win the war for us, but that is exactly the sentiment that people felt when things like DDT first came along.
It’s good to be optimistic. But we need to be realistic as well.”

Write to Betsy McKay at betsy.mckay@wsj.com

There are 459 comments.

Mark Nemes

Mark Nemes

Although mosquitoes are a pest and a nuisance, it is asinine to even consider wiping them off the face of the Earth.

Thomas Bundros

Thomas Bundros

If it wasn’t such a tragedy, I would chuckle at the ignorance of the anti-genetic engineering crowd that is opposed to creating males only mosquitos.  Makes you wonder what this group would have thought of when electricity was introduced.

Neoliberal economics and the rise of mosquitoes in Florida…

How foreclosed homes and used tires can threaten public health in the age of Zika.

Microbes and mosquitoes aren’t the only things that can cause the spread of disease. So can human economic activity.

July

Sonia Shah is the author of “Pandemic: Tracking Contagions, From Cholera to Ebola and Beyond.”

With the Zika virus looming just a couple of years after Ebola spread across West Africa, what’s long been obvious to experts should now be clear to the rest of us: We live in an era of emerging pathogens. Between 1940 and 2004, more than 300 infectious diseases either emerged or spread into new places and populations. On Friday, Florida Gov. Rick Scott called a news conference to alert the public to four cases of Zika in South Florida transmitted locally by mosquitoes.

Though we imagine infectious microbes propagating according to their own logic, many are resurging thanks to the unintended consequences of human activity that would seem to have little to do with the biology of microbes, from economics and housing policy to architecture. As these rejuvenated pathogens adapt to the man-made environments that sprawl across the planet, anything from highways to swimming pools can wind up triggering an outbreak.

In a globalized economy, the public health implications of sick people getting on airplanes and spreading germs around the world are obvious. But we’re less used to thinking of things like foreclosed homes, imported tires and decorative bamboo as health risk factors. If we’re going to deal with Zika and the pathogens that will inevitably come after it, we have to start.

Commerce has long provided unexpected opportunities for infectious pathogens to exploit, from the Erie Canal, which slashed the cost of shipping while unwittingly carrying cholera across the country, to the hydropower dams that electrified the South while simultaneously providing succor for scores of malarial mosquitoes. Today, abandoned properties and deteriorating infrastructure, brought on by housing crises and climate change, similarly threaten us with epidemics of mosquito-borne pathogens such as Zika.

Just such an epidemic occurred in 2009, when dengue broke out in Florida. That mosquito-borne disease, which causes joint and bone pain so excruciating that it’s called “breakbone fever” in Latin America and Asia, hadn’t been seen in Florida since 1934. That’s surprising, because the state is surrounded by countries where the disease is endemic, and the mosquitoes that carry the virus, Aedes aegypti, have been established across the Gulf Coast since the 16th century. A few years ago, when I asked Florida Keys mosquito-control expert Lawrence Hribar to explain what had happened, he didn’t point to an invasion of bugs or infected people. He began his explanation with the following: “There were houses in foreclosure.”

The 2008 housing crisis hit Florida hard, Hribar pointed out, and nowhere harder than South Florida, the epicenter of the outbreak. Across the state, more than 380,000 homes had been foreclosed, and many abandoned. That meant a lot of empty swimming pools. Then the rains came. The pools filled with standing water. With nobody home to notice or to let inspectors in, those derelict swimming pools became giant mosquito hatcheries.

It’s not hard to connect the dots between mosquito proliferation and the spread of disease. In 2009, Florida suffered an unprecedented outbreak of dengue. Five percent of the population of Key West was infected, a study by the Centers for Disease Control and Prevention found.

Two years earlier, Bakersfield, Calif., experienced a similar outbreak of mosquito-borne West Nile virus. The spring had been dry, and the birds in which the virus lurks were sparse, so public health authorities predicted that there would be few infections that year. Instead, cases soared. It was only after an aerial survey was conducted that experts realized why: Armies of disease-carrying mosquitoes had colonized scores of swimming pools, hot tubs and ornamental ponds. Their neglect was similarly linked to a housing crisis. The previous year, there was a nearly 300 percent spike in delinquency notices.

Climate disruptions have had a similarly unexpected impact on the spread of mosquito-borne disease. When Hurricane Katrina hit New Orleans in 2005, for example, scores of flooded and abandoned swimming pools were quickly transformed into efficient mosquito breeding grounds. And that expansion of mosquito habitat was followed by a rise in severe cases of West Nile virus in the region the next year.

We’re not conditioned to expect this. Rather, the “built environment” — buildings, waterways and other man-made infrastructure that make up our cities and towns — has long been our way of “improving” on the natural environment. It’s supposed to make us more comfortable, productive and secure. Its modern apotheosis, the air-conditioned suburban home replete with endless lawn and sparkling swimming pool, is the bedrock of the American Dream, a dream sold to millions of people who took out subprime mortgages to achieve it.

The built environment functions as intended only when its components are continuously maintained, often at significant expense in time and resources. That might have been feasible in an era of cheap, abundant energy and easy credit. But not anymore. The housing crisis forced 3.1 million American properties into foreclosure in 2008 alone, leaving behind a rash of abandoned homes and neighborhoods that have yet to be fully re-occupied. Even today, there are more than 1 million abandoned properties across the country, and Florida counts more “zombie closures” than almost every other state. And their neglect amplifies and spreads vectors of disease even more effectively than the wild landscapes they replaced.

The backyard swimming pool perfectly encapsulates the problem. Pools have no natural inflow or outflow of water. Without regular maintenance, such as chemical adulteration and continuous filtration, they can rapidly become incubators of insects and microbes. Blooms of algae appear. Leaves and debris collect on the surface. Impregnated female mosquitoes, searching for water in which to lay their eggs, swoop. And the steep, smooth walls of swimming pools preclude the predators that would feed on their eggs in natural bodies of water.

Neglected swimming pools often go undetected, since pools are frequently surrounded by privacy hedges and high vegetation, obscuring problems from passersby and public health authorities. Even when pools turn green and buggy, satellite images can fail to detect them. And those that are noticed can be difficult to access. In many jurisdictions, by law, when owners aren’t home, swimming pools must be enclosed behind locked gates. That helps prevent accidental drownings, but it also blocks public health workers from treating neglected pools with mosquito-killing chemicals or stocking them with mosquito-eating fish.

That’s not the only way human activity has heightened the disease risk posed by mosquitoes. Thanks to the logic of rapid growth and resource consumption, the United States is home not just to the Culex species that carries West Nile virus, but also to two invasive species of mosquitoes from the genus Aedes, which are carriers of much more deadly diseases such as yellow fever, dengue, chikungunya and Zika.

Neither Aedes aegypti, which hails from Africa, nor Aedes albopictus, from Asia, are native to the United States. But two peculiarly American industries brought them to our shores. The slave trade ferried Aedes aegypti to the New World in the 16th century. These mosquitoes caused repeated epidemics of yellow fever in American cities in the 18th and 19th centuries. Then, in the mid-20th century, another engine of the economy, the automobile, brought Aedes albopictus. More specifically, the trade in used tires, required to service our fleet of vehicles, gave them a lift. Many of these tires were imported from Asia, where albopictus lived in dark, wet tree holes. The tires proved pleasingly similar, and as the tires traveled across the continents, so did albopictus.

In 2001, more albopictus pioneers caught a ride in shipments of a popular decorative plant called lucky bamboo, packaged in standing water for the long voyage from south China to California. The used-tire and lucky bamboo trades have since broadcast albopictus across Europe, Africa and Latin America. They join a smattering of other trades known to have disseminated pathogens throughout the globe. Trade in frogs has been implicated in the spread of a pathogen called chytrid fungus that’s wiping out amphibians; an air shipment of rodents from Ghana introduced a deadly virus called monkeypox into the United States in 2003.

Albopictus pushed aegypti to the edges of its habitat. Unlike aegypti, which thrives in tropical weather and bites humans exclusively, albopictus tolerates temperate areas as well and can bite people or animals, spending its days hiding in green vegetation. Aegypti retreated to the Gulf Coast, concealed in neglected neighborhoods where pockets of stagnant water collect in garbage-strewn lots, and where human blood is easily accessible through the broken window screens of dilapidated homes. Albopictus colonized the leafy suburbs that sprawl across temperate parts of the country, hidden in the high bushes and hedges that surround its gleaming necklace of pools and hot tubs.

Today, 60 percent of the U.S. population is vulnerable to albopictus mosquitoes. A few emerge from my garden every time I walk out my front door in the Baltimore suburbs, awakened by the scent of my exhales, hungry for blood (yes, that’s all it takes). After they bite, they’ll fly off in search of still water to deposit their eggs. In my neighborhood of privacy hedges and lush vegetation, there’s no telling where they’ll land.

For now, there’s little federal funding on tap to finance research and development of new tools to fight Zika, despite months of pleading from the CDC and other agencies. What we do have: an uptick in reported cases of Zika; high-profile athletes pulling out of the 2016 Olympics — which might protect them, but is in no way a meaningful public health response for the rest of us; and a Congress unable to reach consensus on emergency funding to fight the virus. The rest of us are left to slather on mosquito repellent and wait uneasily for the inevitable news of infants born with microcephaly.

There’s more we could do. We could assess the public health implications of our built environment the way we assess its environmental impact — before construction begins. We could empower public health officials to do more than combat outbreaks after the fact, but also help regulate the social and economic conditions that contribute to outbreaks in the first place.

As the strange tales of swimming-pool outbreaks show, housing crises, economic shocks, climate disruptions, and other economic and social factors can affect public health in unexpected ways. Rather than wait for swimming pools to turn into mosquito hatcheries, we could start to address the underlying economic and social drivers that create these and other public health hazards, before epidemics occur.

That would first mean critically acknowledging and assessing our role in bringing about the conditions driving epidemics, whether abandoned homes or neglected neighborhoods, aging infrastructure or trade patterns. And then we would need to enlist a response not just from the biomedical establishment but from all sectors of society, from consumers to banks to builders.

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A letter from the Rubber Manufacturers Association on Puerto Rico’s waste tire problem…

Operacion No mas Llantas Inutiles en Puerto Rico / Operation No More Waste Tires in Puerto Rico
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