Targeting nature’s greatest killer
Scientists use new tools to eradicate mosquito threat
For the second year in a row, molecular biology major Walker Vickery spent his summer internship engaged in the care and feeding of nature’s most prolific killer.
He sprinkled powdered beef liver into trays of water filled with swimming larvae. He fed the females cow’s blood from a nearby slaughterhouse.
Much of the time a hush enveloped the humid white room where he worked, broken only by the barely audible fluttering of a million tiny wings.
In that room, in a nondescript suite of offices at the back of a quiet strip mall, one of the
great battles in modern science is playing out: Man vs. mosquito.
The mosquito, an age-old enemy, carries diseases that kill more than 1 million people a year worldwide. To fight back, scientists have been exploring potent new weapons with the potential to replace pesticides that have harmed humans and the environment.
The scientists Vickery has worked with during his summers at MosquitoMate hope to defeat the insect with an oddly paradoxical idea:
They raise mosquitoes to reduce the mosquito population.
The company rears male mosquitoes infected with Wolbachia, a bacterium that renders them unable to produce offspring. The strategy, which requires annual releases of sterile males into the wild, is being tested in pilot programs on opposite ends of the country — in Fresno, Calif., and the Florida Keys.
“All told, we’re probably producing 500,000 mosquitoes per week,” said Stephen Dobson, founder and CEO of MosquitoMate, which supplies the two pilot studies.
An international project called Eliminate Dengue is much further along than the American programs, focusing on a disease that could infect almost 400 million people a year. Launched more than six years ago, the project has released Wolbachia-infected mosquitoes, male and female, in five countries, including Australia, Indonesia and Brazil, and five more are soon to follow.
By infecting females, the only mosquitoes that bite and transmit disease, the project hopes to purge the insects of the illnesses they can carry: dengue, yellow fever, chikungunya and Zika. Inside the mosquitoes, Wolbachia prevents the viruses from growing and replicating.
Scientists and others debate more controversial methods that would alter a mosquito’s DNA, offering mankind a compelling and potentially troubling bargain.
Using genetic strategies, humans could conceivably wipe out entire species — for example, the 30 to 40 species of Anopheles mosquitoes that carry malaria, which kills half a million people each year.
To save those lives, scientists must make peace with the uneasy fear that meddling with the blueprint for life amounts to “playing God” and risks unintended consequences.
The prospect of ending a disease as ancient and deadly as malaria is not mere wishful thinking, according to Richard Ebright, professor of chemistry and chemical biology at Rutgers University’s Waksman Institute of Microbiology.
“This is something that would take a matter of years and not a matter of decades or centuries,” he said. “But you would have to have public buy-in.”
MOSQUITOES PREDATE US
For as long as there have been humans, there have been mosquitoes biting them.
“We know mosquitoes, or a similar insect, were around and fed on dinosaurs,” said William Reisen, editor of the Journal of Medical Entomology and an emeritus professor at the University of California-Davis. “Certainly they predate humans and most likely have fed on our ancestors.”
The diseases they carry are ancient, too.
Scientists have found the malaria antigen in the desiccated remains of Egyptian mummies 5,200 years old, according to a paper in the journal Transactions of the Royal Society of Tropical Medicine Hygiene.
It wasn’t until 1897 that a British officer working in India demonstrated that the malaria parasite could be transmitted from infected humans to mosquitoes — then spread by the mosquitoes to more humans.
Over the years, humans have drained swamps, installed screen windows, sprayed pesticides and irradiated mosquitoes — all in an effort to fend off the insects and reduce disease.
The estimated 3,500 species of mosquitoes have proved themselves among the hardiest creatures on Earth. Species have been found breeding 14,000 feet up in the Himalayas and 5,000 feet underground in mine shafts.
“Mosquitoes are a natural part of the environment, and to get rid of them, you’re going to have to do something decidedly unnatural,” said Joseph Conlon, technical adviser to the American Mosquito Control Association, a not-for-profit professional association.
NEW STRATEGIES
Recently, scientists have begun exploring new strategies, seeking to kill mosquitoes not by changing their environment but by changing their bodies at the molecular level.
Wolbachia occurs naturally in some insects; the bacterium was discovered in common house mosquitoes, Culex pipiens, in
1924. It took decades before scientists realized its potential to control mosquitoes.
The bacterium works like a lock and key for reproduction. In males, the bacterium locks the paternal chromosomes in their tightly packed ball, unable to unpack and pair up with the female chromosomes. If the female mosquito has the same strain of Wolbachia, the paternal chromosomes are released.
In 2014, Eliminate Dengue conducted a major field trial in Townsville, an Australian city of
180,000 people. For each of the previous 15 years, Townsville had recorded a dengue outbreak. In the three years since the release of the Wolbachia-infected mosquitoes, the city has not experienced an outbreak.
NO TESTING
Despite the spread of the mosquitoes Aedes aegypti and Aedes albopictus through the USA, Wolbachia had never been tested against them in an American city.
In 2013, Aedes aegypti, a disease-carrying invasive species, arrived in the city of Madera, Calif.,
25 miles northwest of Fresno. Once in Fresno, the new invaders found their way into just about anything that held the water they require as a location for laying eggs.
“We were hoping we could eradicate it,” said Steve Mulligan, manager of the Consolidated Mosquito Abatement District, which covers nine cities including Fresno. “We went door to door in the areas it was first found, looking for small containers that could hold water. … We were not able to eliminate the mosquito. In fact, it expanded.”
Of prime concern were the diseases carried by the new mosquito: yellow fever, dengue, chikungunya and a then-little known disease that would soon become front-page news, Zika.
Fresno County had experienced cases of some of these diseases in travelers who’d recently returned from countries where the diseases are common. Until Aedes aegypti, there had never been a local mosquito that could bite those patients and turn a single case of disease into an outbreak.
The year the new mosquito arrived in Fresno, Mulligan and Dobson met at a conference of mosquito experts. Their talks led to Fresno’s pilot study, which began in the spring of 2016.
MosquitoMate shipped infected males overnight to Fresno, and workers released 40,000 mosquitoes a week in a test area of 120 to
130 acres. This went on for five months.
Mulligan said it’s difficult to tell whether the number of mosquitoes is declining.
The district broadened the study this year, releasing the Wolbachia males in two residential areas totaling 500 acres and containing about 700 households. A new collaborator joined the effort, Verily, a sister company to Google that blends science, engineering and medicine.
Verily took the Wolbachia mosquitoes developed by Dobson and automated the rearing process using cameras, machine learning and algorithms to speed the task of separating males from females. The company has released roughly 1 million mosquitoes a week in the Fresno district since mid-July.
Since its appearance, Aedes aegypti has not resulted in any transmission of Zika, dengue, chi- kungunya or yellow fever, said Joe Prado, division manager of community health for Fresno County.
This year, Key West became the second community in the USA to release the Wolbachia mosquitoes raised in Kentucky. The Florida trial ended as scheduled in August, before Hurricane Irma struck the Keys.
The Florida Keys Mosquito Control District went further, proposing the first U.S. use of genetic engineering to curb the mosquito population.
Since 2010, the Florida district and the English biotechnology company Oxitec had discussed a trial using Oxitec’s genetically altered Aedes aegypti.
The male mosquitoes Oxitec planned to release would carry a lethal gene, causing all offspring they produced to die before adulthood.
The plan ran into strong opposition from a group of Florida Keys residents who said the risks and uncertainty outweighed the benefits.
When the public demanded a say in the decision, the district’s five-member board put the issue to a public referendum on Election Day 2016.
Key Haven, the small island selected for the trial, voted in one referendum, the county as a whole in another.
The referendum passed in the county but failed in Key Haven.
NEW QUESTIONS
The new methods of mosquito control raised the possibility of species eradication and with it two questions fundamental to science:
Can we?
If so, should we?
To the first question, it won’t be easy to defeat mosquitoes or the diseases they carry.
“Wolbachia and gene drives might be able to provide permanent replacements and reduce pathogen transmission, but to expect nature not to find a way to prevent extinction may be optimistic,” Reisen said.
Just as mosquitoes developed resistance to the chemicals sprayed on them, they may find ways to defeat a gene drive, said Edward Blumenthal, chairman of biological sciences at Marquette University. Develop a gene drive that impairs fertility, Blumenthal said, and “any mosquito that develops a mutation that allows fertility will out-compete the rest.”
Even getting rid of the mosquito may not eliminate the disease. Killing Anopheles mosquitoes may only force the malaria parasite to find a different host.
The second question — whether scientists should use gene drives to eradicate a species — is thornier still.
True, the insect’s main contribution to the planet seems to be only as food for frogs, waterfowl and migratory songbirds.
But ending a species is no trivial decision. The effort could backfire if a gene drive spreads to an unintended species or disrupts the larger ecosystem.
“The biologist in me says, ‘Preserve everything. We don’t have the right to make the decision to get rid of an entire species,’ ” said Susan Paskewitz, a professor at the University of Wisconsin-Madison and chairman of the Department of Entomology. “The global health specialist in me says, ‘ A half a million people die from malaria, most of them under the age of 5. That’s an awful lot of suffering.’ ”