Genetic engineering could stop the spread of mosquito-borne illnesses – but should we use it?

By Lauren Puckett

An epic battle has been growing for decades: Human versus mosquito. Humans attack with poisons, insecticides, vaccinations and medications, but more than one million people worldwide still die from mosquito-borne illnesses every year. 

Today, we have the technology to fight these diseases, and it’s called genetic modification. Gene technologies, developed by mosquito researchers in the lab, have revealed ways to cut off the insect’s power at the source. But which approach is best? And perhaps the more important question: Just because we can genetically modify mosquitoes, should we?

Infographic by Lauren Puckett and Maria Kalaitzandonakes. Source: U.S Centers for Disease Control and Prevention and the World Health Organization.

Infographic by Lauren Puckett and Maria Kalaitzandonakes. Source: U.S Centers for Disease Control and Prevention and the World Health Organization.

Mosquitoes grow in the rice fields of Kenya; breed in moist tire tracks in Brazil; gather in rain gutters in Florida. They’re the transmitters of mosquito-borne illnesses such as malaria, dengue fever, chikungunya, Zika virus, West Nile virus and yellow fever. The mosquitoes pick up infections while taking a blood meal. Flying from one victim to another, they can spread the illness any time their proboscises pierce flesh.

These illnesses affect millions of lives. Dengue causes approximately 22,000 deaths per year, mostly among children, according to the U.S Centers for Disease Control and Prevention. And today, almost half of the world’s population is at risk for malaria, according to the World Health Organization. The Zika virus continues to make headlines, as it’s been connected with the birth defect microcephaly, which causes babies to be born with small heads and potential brain defects, as well as Guillain-Barré syndrome, which can cause respiratory failure and paralysis. Chikungunya has been dealing its own damage as well: in 2015, there were more than 37,000 confirmed cases, just in the Americas. And these aren’t even all the diseases mosquitoes can spread. 

But new developments in genetic engineering could change the game. Researchers working with mosquitoes have discovered ways to snip, stitch and alter mosquito genomes, taking one of several different approaches. One approach is to build resistance within the insect’s genes, essentially giving it a shield against the mosquito-borne illness. This shield would prevent it from spreading the disease to any other host. But other researchers see a different approach: killing the bugs off completely.

“Until the last fifteen years or so, [research with mosquitoes] wasn’t a high priority of funding,” says Anthony James, a mosquito researcher and professor in the School of Biological Sciences and School of Medicine at the University of California-Irvine. “It wasn’t the kind of thing that was on the average consciousness, not just of scientists but of the public. Now everyone’s anxious about what could happen with Zika, so that may be changing things.

“Until very recently these have been the diseases of poor people,” James added. “And you need certain advocates to make change happen.”

And genetic modification can do exactly that.


Building strength or dealing death

James has been working in the area of mosquito research for around 30 years. He’s one of several researchers aiming at mosquito resistance. His lab has discovered a method of gene drive technology to block the spread of malaria in Anopheles mosquitoes.

He and his lab staff make their own antimalarial genes based on antibodies derived from mice. They use the CRISPR-Cas9 system, a revolution in gene technology, to place the genes into the mosquito’s genome. They use a protein called Cas9 to “cut” out a piece of DNA and replace it with a new piece of DNA – in this case, the antimalarial genes. Enzymes then repair the genome, stitching it together. Presto: if all goes well, the bug develops antimalarial resistance. Then, the mosquitoes spread the resistance throughout a population through a gene drive. The idea? Whole populations of annoying but malaria-free pests.

James is not the only researcher tackling this approach. Others implement the resistance strategy with other diseases, such as dengue fever.

But generating a type of resistance in a mosquito doesn’t guarantee it won’t pick up a different virus along the way. For instance, an Aedes aegypti might sport anti-dengue genes, but it could still be susceptible to chikungunya or Zika.

“The mosquitoes will stay where they are,” says Zach Adelman, an associate professor of entomology at Virginia Polytechnic Institute and State University. “The populations would stay high and they could remain biting people. They could still transmit new viruses.”

Adelman instead works towards mosquito extermination in local and regional populations. His lab has developed a gene in mosquitoes called Nix, which makes all larvae develop as male. Even if an embryo is initially female, Nix can transform it into a male.

But this isn’t a question of sexism in mosquitoes; this is about damage control. Since the only mosquitoes that bite humans are female, only females transmit mosquito-borne illnesses. And because only females lay eggs, populations would crash without mothers. Adelman hopes that, using Nix, entire groups of mosquitoes can be wiped out on a local or regional scale.

“We’ve been fighting with all the tools we have in our arsenal to try and kill these mosquitoes, and their numbers are only increasing,” Adelman said. “So we need to do more. The children and the people being affected by these viruses need help.”

British biotechnology company Oxitec is also getting attention for its efforts to eliminate mosquitoes. One of its attack plans is to genetically engineer Aedes aegypti mosquitoes with a lethal, self-limiting gene. The male mosquito passes this gene to a female while mating, and then the mother passes it along to her offspring. The gene then causes the larvae to die. The result: bye, bye, bugs.

However, this doesn’t mean one method of fighting mosquitoes is always better than another. It’s all about context.

“So in places where, for example, you’re only worried about dengue, you don’t want to have to spend a lot of money continually releasing insects. In that case, [building resistance in mosquitoes] is the best approach,” James said.  “But in places where you have multiple viruses circulating and you can afford to continually release, then the type of approach that Dr. Adelman recommended would be good.”


Should we do it?

But wait. Just because this technology exists doesn’t mean everyone is throwing their support behind it. The ethics of genetic modification can be quite tricky.

Alta Charo, a professor of law and bioethics at the University of Wisconsin-Madison, has made studying the ethics of genetic modification one of her research priorities. She says bioethicists often look at the benefit-to-risk ratio: That is, what are the benefits of something versus the risks involved? In the case of killing local or regional mosquito populations, or at least driving down population numbers, she says there’s a relatively high benefit-to-risk ratio. This means the benefits seem to outweigh the risks. However, she said, that doesn’t mean researchers should be gung-ho about sending their gene tech into the wild.

“We know the short-term gain might be significant,” Charo said. “But long-term consequences are much more difficult to assess. An ecosystem is complicated. In most cases, anytime you are going to tinker with an ecosystem in any sort of substantial way, there’s a precautionary principle at work. It’s not one that says ‘You can’t do anything until proven safe.’ But it is one that says ‘You work to have risk minimization and a confidence that the benefits are going to outweigh the risks.’”

Carolyn Plunkett, a research assistant in the Division of Medical Ethics at NYU’s School of Medicine, has spent years researching bioethics, and she has expertise in the area of genetically engineered mosquitoes. She says there are many questions at play, but some of the most important include:

  • What sort of effects might this technology have on the ecosystem?
  • Is there a potential risk to humans?
  • How will the experimentation period be implemented?
  • How will human subjects of the experiment give consent? Will people know if genetically modified mosquitoes are to be released in their backyard in trials, and if so, how would they consent?
  • Are genetically modified mosquitoes safer than pesticides? Are they a better method of attack against illnesses?

Plunkett says this technology needs much more research before it can be implemented in the real world, and that “there’s not really an ethical precedent for this kind of experiment.” Scientists and researchers are being faced with questions and possibilities that they can’t possibly predict.

“The idea of controlling any environment puts a lot of pressure on the people doing it,” Plunkett said.

While she isn’t willing to throw her support behind any one method of genetic modification in mosquitoes, Plunkett endorses a green light for more research. It’s time to take the next steps and see if this technology can really work in the field, on a large scale.

But another concern of critics is the ability to control gene modification technology when it is released into the field. And on top of that: how can we control ourselves from overusing and abusing gene technology?

There are some who think “that the engineering of animals in and of itself is wrong,” Charo said. “There’s a feeling that somehow it’s an act of hubris for humans to take this degree of control and manipulation over their environment. You’ll often hear the phrase ‘playing God.’ As it gets easier to do this, it gets that much more tempting to make more and more changes to more and more animals, just because we can.”

Scientists are already talking about ways to control genetically modified organisms once they are out in the wild. One of the concepts is that of a kill switch or “suicide switch.” This is essentially a piece of genetic code, when worked into a mosquito, that kills the insect if switched on or off.

According to a 2015 article from Gizmodo, many things could trigger this genetic code to “turn on.” For instance, if a mosquito is genetically modified to be dependent on a certain chemical, it won’t survive without that chemical in the wild. The biotechnology company Oxitec is implementing this strategy, making its GM mosquitoes dependent on tetracycline. Unless the bug is saved by this antidote, it will die out in the field. 


Growing interest 

Between 2009 and 2010, Plunkett didn’t just study the ethics of mosquito-borne illnesses – she experienced one. She contracted dengue while spending a year in Honduras. She recovered normally, but the symptoms affected her for 4-5 days.

“You’re on this roller coaster,” Plunkett said. “The symptoms spike at random times. Your body goes from 98 degrees to 104 in fifteen minutes. It’s incredibly painful.”

The Aedes aegypti mosquito spreads multiple mosquito-borne illnesses, including dengue and Zika. Photo by Graham Snodgrass, under Flickr Creative Commons.

The Aedes aegypti mosquito spreads multiple mosquito-borne illnesses, including dengue and Zika. Photo by Graham Snodgrass, under Flickr Creative Commons.

During her time in Honduras, Plunkett witnessed a dengue epidemic. According to a study published by The American Journal of Tropical Medicine and Hygiene, Honduras suffered 66,814 cases of dengue, 3,266 of them severe cases, and 83 deaths in 2010. Around this time, dengue was introduced in Key West, Florida, which Plunkett said propelled some of the initial interest in genetically modified mosquitoes, especially in the U.S.

That initial interest has sparked the wildfire of gene drive technology debate and discussion going on today.

Gene drive technology is “incredibly inexpensive and incredibly powerful. And when you see that, it raises a red flag,” says George Church, a professor of genetics at Harvard Medical School. “But there are procedures by which we make sure things are not risky, and they work pretty well.”

Church is a familiar name in the world of gene technologies. He’s a professor of health sciences and technology at Harvard University and the Massachusetts Institute of Technology. He’s served as Director of the U.S Department of Energy Center on Bioenergy at Harvard and MIT. His numerous awards and accolades have earned him interviews in many prestigious magazines and newspapers, and even a conversation with Stephen Colbert on The Colbert Report.

But, of all the technologies Church has witnessed, CRISPR-Cas9 and gene drives are a couple he finds most exciting. He says this gene technology opens doors for genetic engineering that were previously shut and sealed.

In the fight against mosquito-borne diseases, “vaccines have failed, drugs against the pathogen have failed, and pesticides against the insect vector have failed,” Church said. “In those cases, the core advantage [to gene drives] is that gene drives are inexpensive and extraordinarily specific. Unlike vaccines for humans or immune processes in animals, where we have to deliver each on a case-by-case basis, [gene drives] automatically spread very quickly and they deliver a package.”

That package is the resistance or suppression drive that spreads throughout a species, transforming a mosquito population.

While there are still pros and cons that, at this time, are impossible to know, gene technology is growing both in possibility and in legitimacy. Some day soon, genetic engineering might be one of the strongest weapons we have against the power of mosquito-borne diseases.

“There are people who argue there might be unknown consequences” with genetically modifying mosquitoes, James said. “Yes, but we certainly know one of the known consequences: we wouldn’t have malaria, yellow fever or chikungunya in specific areas.”

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