The Zika Virus

Genetically modified mosquitoes can protect us from deadly diseases, writes chemistry professor Marc Zimmer.

By Marc Zimmer

he world’s most dangerous animal is not a hippopotamus. It’s not a crocodile, or a lion, or a great white shark. It’s a mosquito.

These tiny critters are vectors of disease, passing devastating and deadly viruses—including Zika—from host to host. How can we stop them? One answer may surprise you: genetically modified mosquitoes.

Zika is not new, but for many decades it remained in the shadow of its older and more common sibling, the Dengue virus. Now, with the recent outbreak of Zika—and its association with a birth defect known as microcephaly—we will have to use everything we have learned about Dengue to control it. That includes releasing genetically modified mosquitoes into impacted areas.

The Zika virus got off to a slow start. The symptoms, which include fever, rash, joint pain and conjunctivitis (pink eye), are typically mild—so mild, in fact, they often go unnoticed. In the 70 years since Zika was first identified in Uganda, less than five cases have been confirmed in that country. However, many people in Uganda have Zika antibodies in their blood, meaning that they were infected but never sick enough to seek treatment. Zika antibodies have also been found in India, Vietnam, Thailand, Indonesia, Malaysia and the Philippines. Yet between 1947 and 2006, there were just 14 confirmed cases worldwide.

In 2007, something changed. Perhaps the Zika virus mutated; suddenly, it was on the move. That year, 50 people were infected on the Micronesian island of Yap. Six years later, thousands fell victim to the virus in French Polynesia, about 5,000 miles away. And now more than 1.5 million people in Brazil appear to have Zika. Not only is the virus spreading more efficiently, but, more alarming, it is also causing microcephaly, a birth defect in which babies’ heads are unusually small and their brains do not develop properly.

Zika is most commonly transmitted by the Aedes aegypti, also known as the “yellow fever mosquito.” This is the same pest primarily responsible for spreading the Dengue virus, characterized by fever, pain in the eyes, a rash, and oral, vaginal and intestinal bleeding. Although Aedes originated in Africa, they are now found in tropical and subtropical areas throughout the world; 40 percent of the world’s population is threatened by Dengue, and it’s a leading cause of illness and death in the tropics and subtropics. Like Zika, there is no treatment or vaccine for Dengue fever.

That these two viruses are primarily transmitted by the same type of mosquito is both good news and bad. On the plus side, in our efforts to fight Dengue, we have learned a lot about controlling Aedes populations that we can now apply to Zika-affected areas.

On the other hand, these are stealthy little creatures. They are smaller and quieter than the mosquitoes typically found in the United States; there is no annoying buzz to warn potential victims. They feed for one-to-two hour periods in the morning and late afternoon, so mosquito netting around bedding provides little protection. They thrive in urban environments; their ideal habitat is close to human homes where they can avoid pesticide spraying. And although Aedes travel less than a mile in their lifetime, humans do travel, and Aedes can pick up viruses from humans and pass them to their offspring.

Controlling and limiting the habitat of these mosquitoes is extremely difficult, as they can lay eggs in a single drop of water. This has led to severe restrictions in several countries: in Singapore, a homeowner can be fined for having Aedes breeding sites, such as a glass of water in the garden; in Malaysia, the home of anyone who contracts Dengue fever and the homes of their neighbors have to be sprayed—inside and out—with pesticides. These insecticides can be harmful to humans, particularly those exposed to them for long periods of time (such as the people doing the spraying) and children. Over time, populations of mosquitoes can also become resistant to pesticides.

Enter the genetically modified fluorescent mosquito.

Created by British biotech company Oxitec, these Aedes mosquitoes are designed with a self-limiting gene that causes their offspring to die in the larval stage. Oxitec breeds these modified mosquitoes by feeding them an antidote that turns the destructive gene off in captivity. The mosquitoes are then sorted according to gender, and, because only pregnant females bite humans (males eat nectar; females need blood to help their eggs develop), the females are killed before the males are released. The released males spend their lives searching for wild females in the area where they were freed. They mate, but all the offspring they produce will have the lethal gene and die.

If enough modified males are released, the entire Aedes population will collapse.

A biologist puts blood on iron plates to feed the females of the nursery that produces genetically modified mosquitoes. The Oxitec laboratory located in Campinas, Brazil, is releasing 250,000 of these mosquitoes to combat Zika. Photo by Victor Moriyama/Getty images

The Oxitec mosquitoes are also modified with a green fluorescent protein gene that produces fluorescent proteins that serve as markers to distinguish them from wild mosquitoes. These fluorescent proteins—which are the subject of my research—glow under a fluorescent microscope or fluorescent light. (This is just one of thousands of practical uses of GFP; it is also being used for everything from tracking the process of bacterial infection to detecting chemical and biological agents planted by terrorists.) Monitoring the ratio of modified vs. wild mosquitoes in traps helps scientists determine if enough modified males have been released to collapse the wild population.

The beauty of the Oxitec technique is that the modified males are only interested in mating with female Aedes mosquitoes, so no other mosquito or insect species is affected. And because male mosquitoes don’t bite and all of their larvae die, humans don’t have to worry about being bitten by the modified mosquitoes. A common concern expressed by opponents of the Oxitec mosquitoes is that the disappearance of the Aedes mosquitoes will have far- reaching effects and unforeseen consequences, since they are part of a complex food web. However, Aedes mosquitoes are an invasive species in all of the areas in which Oxitec is proposing releases. Other opponents simply have a vague fear or dislike of genetically modified organisms in general. In fact, NBC News reported in March that 25 percent of Americans surveyed by the University of Pennsylvania’s Annenberg Public Policy Center thought genetically modified mosquitoes caused Zika. Since these arguments aren’t based on science or facts, they can be harder to overcome.

Thus far, these genetically modified mosquitoes have been released in trials in Dengue-ridden areas of Cayman, Malaysia and Panama, as well as in the Brazilian city of Juazeiro, which has seen an 82 percent reduction in wild mosquito larvae. Recently, Oxitec, in conjunction with Brazilian health authorities, opened a new factory that can produce 4 million of these genetically modified fluorescent mosquitoes each week. With the sudden Zika epidemic, Brazil is hoping to expand its modified mosquito program to several more cities.

Another trial is proposed for Key West, Florida, an area of the U.S. where Aedes mosquitoes are common. Oxitec applied in 2012 for federal approval to release the genetically modified mosquitoes to prevent a Dengue outbreak in the region. The Food and Drug Administration Center for Veterinary Medicine is working with other agencies, including the Centers for Disease Control and Prevention and Environmental Protection Agency, for federal regulation of this project. But these applications take a long time—genetically modified, fast-growing salmon took 16 years to get approval. If the FDA gives the go-ahead for the trial, several million genetically altered mosquitoes would be released up to three times a week in Key Haven, a community with 444 residences.

With the potential for the Zika outbreak to spread, the urgency of the FDA application has certainly increased. And the parameters of the equation have changed. Dengue fever is painful and a Dengue outbreak in Key West will negatively impact tourism in the area, but Zika has permanent, often devastating consequences for babies. To combat Zika, we will have to use all the tools at our disposal.

Marc Zimmer is the Jean C. Tempel ’65 Professor of Chemistry at Connecticut College. Zimmer is the author of Glowing Genes: A Revolution in Biotechnology (Prometheus, 2005) and Illuminating Disease: An Introduction to Green Fluorescent Proteins (Oxford University Press, 2015).