The Bill & Melinda Gates Foundation didn’t have Americans in mind when it started pouring money into research on mosquito-borne diseases more than a decade ago. The goal was to save lives and reduce suffering in the developing world, where malaria and other deadly fevers run rampant.
So is it selfish to ask if there’s anything in it for us?
More specifically: Are all these studies ever going to yield a replacement for DEET?
With cautious caveats, many researchers are convinced the answer is finally “yes.”
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Thanks in part to an infusion of cash from the world’s biggest philanthropy, understanding of the mosquito’s astounding sense of smell has advanced rapidly in the past few years. Now, those insights are poised to pay off in the form of better products to block the bloodsuckers’ ability to sniff us out.
“It’s coming,” said Anandasankar Ray
, a neurobiologist at the University of California, Riverside, who leveraged a seed grant from Gates to land federal funding for his studies. “We are on the cusp of making major discoveries.”
Most experts caution that it’s likely to be five years or more before hikers, sportsmen and picnickers can wash their hands of the greasy, DEET-laced lotions and sprays that dominate the market today.
Ray is more optimistic, as befits a man who has already spun off one company, called Olfactor Laboratories. “At least some of these things could be available within a year,” he predicted.
The first might be the Kite Patch, a 2-inch cloth square unveiled by Olfactor this summer. Fasten the chemical-impregnated patch to your clothes, the company claims, and it creates an aerosol shield that renders you invisible to mosquitoes for 48 hours. The technology grew out of Ray’s Gates-funded project, which identified common, nontoxic compounds that can wreak havoc with the mosquito’s ability to detect the carbon dioxide exhaled by potential prey.
“One of the strongest, if not the strongest, attractive cue for mosquitoes and any blood-feeding insect is a turbulent plume of CO2,” Ray said. “That’s how they know a living vertebrate is in the vicinity.”
Before it can be sold in the U.S., the Kite Patch must receive safety certification and undergo independent tests to verify that it works.
Approval can’t come soon enough for the nearly 12,000 fans who donated $557,254 to Kite Patch’s recent crowdfunding campaign. The money will be used for field trials in Uganda, and donors are first in line for patches if the product makes it to market here.
But some scientists caution that a repellent that only shuts down CO2 sensors could run into an obstacle that has confounded many attempts to trick one of mankind’s oldest adversaries. In the female mosquito, evolution has crafted the biological equivalent of a guided missile with multiple methods to lock in on a target and ensure she gets the blood she needs to produce eggs.
“Mosquitoes are smarter than we are,” said Leslie Vosshall
, a neuroscientist at Rockefeller University. “They have other ways to detect us.”
Wisps of carbon dioxide may draw the insects in from afar. But mosquitoes have more than 80 types of odor receptors in their “noses” — which are actually appendages on the head called maxillary palps. Each type is tuned to a specific scent, from the lactic acid in sweat to compounds in breath and the skunky aroma of feet, which many species find irresistible.
Every human has a unique scent signature, which is probably why mosquitoes pester some people but barely buzz others.
No one knows the distance from which a mosquito can catch a whiff of human, but Vosshall’s bedroom at the back of a seventh-floor apartment in New York City isn’t out of range. “They fly up and find us,” she said.
Vosshall was part of a consortium that received a $5 million Gates grant in 2005 to study the mosquito nose, at the same time a group headed by Larry Zwiebel
at Vanderbilt University got $8.5 million.
The foundation has since pulled back from big grants for basic research and doesn’t fund much work on repellent anymore.
But that initial investment kick-started what was really a “fringe field,” Vosshall said.
Scientists now have a much clearer molecular-level picture of mosquito olfaction — and how complicated it is. They’ve developed methods to quickly screen thousands of compounds for repellent-worthiness, and have identified several tantalizing candidates.
“We have a suite of compounds that could really be the next generation in intelligent mosquito — and other insect — repellents,” Zwiebel said.
His prize specimen is a compound called VUAA1, which in preliminary tests appears to be 100,000 times more powerful than DEET.
The compound acts on a key receptor in the mosquito nose called Orco. Over the past few years, researchers discovered that Orco acts as a kind of ring leader for the mosquito sense of smell. Without Orco, none of the odor receptors will function. And Orco seems to play a similar role in all insects.
A chemical that knocks out Orco seemed like the obvious dream repellent, Vosshall said. But when she bred mutant mosquitoes that lacked Orco, they were still attracted to humans — though not as strongly or preferentially as their normal cousins.
VUAA1, which Zwiebel and his team found after screening nearly 120,000 chemicals, takes the opposite tack. Instead of shutting down Orco, it switches all the receptors on at once. The result is a sensory overload that’s kind of like getting on an elevator with someone drenched in perfume, Zwiebel explained.
Something that’s attractive at low levels suddenly becomes repellent — and after you get off the elevator, you can’t smell anything else.
At the U.S. Department of Agriculture’s Mosquito and Fly Research Unit in Gainesville, Fla., Ulrich Bernier and his colleagues also have a lineup of chemicals that repel mosquitoes more effectively and last longer than DEET.
The lab is a successor to the one where USDA scientists developed DEET in collaboration with the military. In the aftermath of World War II, researchers screened hundreds of compounds the old-fashioned way: by having volunteers stick their arms in cages full of hungry mosquitoes.
Bernier still uses the technique, serving as his own guinea pig. But he also relies on computer algorithms to design and synthesize new repellents and lures that can be used to trap mosquitoes.
In addition, he holds the distinction of having participated in a German study that showed beer consumption can make you more attractive to mosquitoes.
“It did get a little tiring,”Bernier recalled. “You had to get up at 8 in the morning and drink hefeweizen.”
Bernier recently applied for a patent on the most promising of his new DEET alternatives. But if the past is any indication, industry’s response will be a yawn.
That’s because it costs up to $200 million to bring a new insect repellent to market. Even though the EPA estimates that one in every three Americans uses DEET annually, repellent sales just don’t justify that kind of investment.
Nor do low-cost repellents for the developing world.
“We were pretty naive to begin with,” Zwiebel said. “The terrible truth is that we could have come up with the most efficacious repellent for (the mosquitoes that transmit malaria), but no one would spend the money to make it and distribute it.”
Repellents aren’t likely to play a pivotal role in eliminating malaria and other disease, so the Gates Foundation is putting its money into more powerful tools such as insecticides, bed nets, drugs and vaccines.
But that doesn’t mean there’s no role for repellents in developing countries. In experiments in Kenya, Ray and his colleagues found that releasing a mix of chemicals that block mosquitoes’ CO2 receptors slashed the number of bloodsuckers that flocked to mock huts.
“If you can drive down the number of bites people get, then it is quite likely you could drive down transmission of disease,” said Ray, who contracted malaria when he was a college student in his native India.
If the only way to get new repellents to the developing world — and to itchy hikers in the U.S. — is to entice drug and chemical companies with the prospect of big profits, Zwiebel thinks he may know how to do it.
“Agriculture is the magic word,” he said.
If a chemical like VUAA1 could be adapted to drive away crop pests, the financial payoff would be enormous. Those margins could subsidize philanthropic projects and make it much more appealing to spin off niche products, he said.
With that possibility in mind, Bayer CropScience is building on Vosshall’s work to develop and test chemicals that interfere with the Orco receptor. Zwiebel is in discussions with some “major players in the field” to explore the commercial application of VUAA1.
The Gates Foundation has kept a hand in as well, he said, hiring a team of business consultants to work with the scientists.
Meanwhile, Vosshall and others are still trying to figure out the old workhorse, DEET. Despite the fact that it dissolves plastic, can be toxic to infants and gives many people the creeps, nothing else works as well or has such a long track record of safety. (The only other repellents endorsed as effective by the EPA are picardin, derived from a chemical in black pepper, and oil of lemon eucalyptus.)
Yet after all these decades, no one is certain how DEET works its magic.
Vosshall believes she’s close to cracking the mystery. Her experiments have shown that mosquitoes robbed of their sense of smell are impervious to DEET. That’s strong evidence that the repellent does act as a cloaking device that prevents mosquitoes from smelling their human prey.
Mosquitoes also seem repulsed by the chemical’s taste, which they detect through taste buds on their feet when they land on DEET-slathered skin.
Vosshall has a project in the works which she hopes will settle the remaining questions. “My feeling is that you can’t improve on current technology unless you understand how the current technology works,” she said.
But she understands the world’s impatience.
“When I go on a trip with my friends and relatives, they say: ‘Leslie, enough talk! When is there going to be a product?’ ”
Sandi Doughton at: 206-464-2491 or firstname.lastname@example.org