Genetic tools for pest, parasite, and disease vector control

This article is part of a series of posts outlining the history and impact of research in experimental organisms. The series is developed in collaboration with the GSA Public Communications and Engagement Committee.

The idea that scientists could create a defensive shield to protect the United States may sound like science fiction, but it’s real, it was begun in the 1960s—and it’s made of insects.

This insect barrier was designed to protect North America from screwworm flies, whose larvae feast on cows and other livestock, inflicting millions of dollars in damage. A screwworm fly-breeding facility along the narrow strip of land connecting North and South America, jointly operated by the United States and Panama, releases sterile male flies across the isthmus at a rate of millions per week. These sterile males mate with female screwworm flies in the wild, ensuring the females produce no living larvae. Perpetual application of this “sterile insect technique” (SIT)—a pesticide-free, genetic method—prevents screwworm fly populations from making their way north from Colombia, keeping North and Central America almost entirely free of a pest that had once been a significant threat in the US south, Mexico, and Central America.

Sterile insect technique—a genetic approach to pest control

The concept of SIT has been around for a long time. During the 1930s and 1940s, scientists working in the United States, the Soviet Union, and Tanzania independently developed the idea of reducing insect numbers by infiltrating the wild populations with lab-raised insects designed to sabotage their reproduction. A main challenge was how to generate large numbers of sterile animals. Research on the fruit fly Drosophila as early as the 1920s showed that X-ray irradiation provided a fast, efficient way to make flies sterile. This finding prompted USDA scientists to test the effects of irradiation on screwworm flies. They found that screwworm flies irradiated in the pupa stage developed into normal-seeming adults, but when untreated females mated with irradiated males, none of the resulting eggs hatched. Scientists now had a feasible way to generate large numbers of sterile male flies.

Screwworm flies are particularly susceptible to control by SIT because females mate only once during their lifespan. Efforts to use SIT to eradicate the screwworm fly began in Florida as early as 1957, spread to other US states and, by the 1970s, continued southward, reaching the narrow and therefore easily covered border of Panama in 2002. Because screwworm flies still live below this border, the need for SIT is ongoing. Every week, millions of sterile males are released along Panama’s southern border, enough to outcompete any fertile males that might try to make their way up from Colombia. Still, in 2016, a screwworm infestation broke out among deer in the Florida Keys. Thanks to shipments of sterile males from the Panama facility, the Florida outbreak was quickly contained. 

SIT has also been used to control some other insect pests, including for the control of crop pests in southern California, northern Mexico, and the Rio Grande Valley in Texas. But traditional SIT has limitations, and modern molecular genetics tools might offer improvements. 

One goal for improvement of SIT is to develop practical and effective methods for control of mosquitoes that transmit disease. Researchers at the University of California, San Diego are using the gene editing technology CRISPR to create sterile male mosquitoes in a targeted fashion, by knocking out specific genes. A system called “precision-guided sterile insect technique” allows the creation of sabotaged eggs that will either hatch sterile males or not hatch at all. Eggs are much hardier than irradiated adult mosquitoes. The hope is that these eggs can be shipped to a destination, sterile males will hatch and mate with wild females, and the mosquito population in that region will be suppressed. 

A harmless nematode helps researchers study a deadly parasite 

Genetic tools are helping researchers control and understand other threats beyond insects. Soil-transmitted parasitic nematodes infect more than one billion people worldwide, often by penetrating the skin of the feet. But these parasites are difficult to rear in the laboratory because they require a living host for some stages of life. Studies conducted on common research organisms—which are innocuous and easily reared in labs—can provide important supplements to study of pests, parasites, and disease vector species like these. The nematode C. elegans, for example, is a cousin to parasitic nematodes, and as such, offers both a source of information and a testing ground for genetic technologies.

Back in the 1960s, Sydney Brenner selected C. elegans as a research organism because it has certain favorable characteristics: a rapid life cycle, small size, and a simple reproductive cycle. Since then, C. elegans has become widely used in laboratories, and it was the first multicellular organism to have its genome completely sequenced. Researchers have fully mapped the tiny worm’s “connectome,” a wiring diagram that shows all its neurons and how they connect. Over the years, sophisticated genetic methods for studying the nematode nervous system have been developed and optimized.

“We have methods for monitoring neural activity, for silencing neurons, for cell-specific labeling of neurons, and also for knocking out genes in Strongyloides,” says Elissa Hallem of UCLA, who studies the parasitic nematode Strongyloides stercoralis. Researchers study the worms’ neurons to learn how they sense the world around them, looking for any avenue to exploit in the pursuit of repelling or exterminating the pests. It is estimated that 30–100 million people are infected with Strongyloides stercoralis around the world. The nematode enters the body through the skin and can travel through the bloodstream, reproducing in the small intestine. Symptoms of a Strongyloides infection include intermittent rash, abdominal pain, or cough. The disease can be life threatening in people with a compromised immune system. 

Hallem and others study S. stercoralis because it is a worldwide health problem, but also because it’s one of the only parasitic nematodes amenable to genetic manipulation in the lab. Even so, it’s fussy and time consuming to work with. Not only does it require an animal host to reproduce, but it’s difficult to establish a stable transgenic line. When new DNA is injected, the parasite generally silences it after one generation unless it’s integrated into the genome. There are tools to insert a transgene into the genome, Hallem says, but the process is inefficient and uptake is generally low. By contrast, C. elegans will continue expressing extra-chromosomal DNA generation after generation. That’s one reason researchers look to C. elegans to suggest starting points for genetic experiments in Strongyloides. 

One active area of investigation is how the worms detect temperature differences and respond to them. As a parasite, Strongyloides needs to infect a host in order to reproduce. The ability to sense the heat of a warm-blooded animal and move toward it is critical for survival. Although C. elegans doesn’t need to find an animal host, it can detect changes in temperature. “C. elegans and Strongyloides have, for the most part, the same set of neurons in the same position throughout the body, and their behaviors are totally different,” Hallem says. In C. elegans, certain proteins on the surface of a particular type of neuron allow the worm to sense temperature changes. By searching the Strongyloides genome for genes in the same family, Hallem’s lab found related genes in that organism likely to be involved in temperature sensing. 

Once they uncovered the candidate genes in Strongyloides, it still wasn’t a simple matter to test the genes’ function. Technical issues around rearing the little worms make it very difficult to establish breeding populations that contain mutated versions of the genes of interest. Again, C. elegans was there for the assist: researchers in Hallem’s lab engineered C. elegans to express the Strongyloides genes, enabling them to study its effect on the temperature-sensing neurons using cheaper and faster methods than would be needed to study genetically modified Strongyloides. Understanding the molecular process underlying the parasites’ heat-seeking capabilities could suggest ways to thwart the process and prevent infection, Hallem says.

Planarians, all but abandoned as a research organism, make a comeback

Planarians, free-living flatworms, enjoyed a brief heyday as a research organism in the 1960s when many laboratories studied their regenerative properties. By the 1990s, however, their popularity had subsided. “When I got interested in studying them, there were just a handful of labs left,” says Phil Newmark of the Morgridge Institute in Madison, WI. “As a postdoc, I went to the University of Barcelona, the only group I knew about that was actively using molecular biology to understand planarian regeneration.” Now, the little flatworms are making a comeback.

Over the last decade or so, researchers working with planarians noticed that they share many features of their biology with parasitic flatworms, called schistosomes, which infect some 200 million people worldwide. When the parasites lay their eggs in the body, they trigger an inflammatory reaction that eventually leads to severe organ damage. A schistosome infection can persist for decades, but not because the eggs hatch into new worms inside the body–schistosomes are just extremely long lived. This extraordinary longevity appears to be related to the type of stem cells that give planarians their regenerative ability, Newmark says. “As we started working on them, we really kind of adopted the toolkit from planarian biology to begin to understand how these parasites operate,” he says. “It’s been really rewarding to see the basic biology of planarians used to help us understand new aspects of the biology of these parasites.”

A major hurdle for controlling schistosomes is that only one drug exists, setting the stage for resistance to emerge. To develop more treatments, researchers are investigating schistosome biology to look for weaknesses that could be exploited with new drugs. Recently, researchers discovered that a gene involved in regeneration in planarians is necessary in schistosomes for digesting their blood meal. Understanding this and other genes involved in the organisms’ fundamental biology could lead to new angles for treating schistosome infections. 

Across a variety of species, research organisms provide anchor points that allow us to understand what might be true of related but harmful species. If the adage “know thy enemy” holds true, then the knowledge we gain from their study might one day help us control a broader range of threats in the future.

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To learn more about how genetics contributes to the control and study of pests, parasites, and disease vector species, visit any of the links below.

1. National Geographic on SIT in the screwworm

2. World Health Organization on SIT in mosquitoes  

3. Rockefeller Institute on a study of how mosquitoes sense us

4. In G3, publication of the genome of the invasive crop pest Drosophila suzukii

5. In G3, analysis in a pathogenic yeast points to potential drug targets

6. VEuPathDB database of eukaryotic pathogen and host information

7. Importance of Vector control