NC State University entomologist Maxwell Scott is among a handful of people worldwide with the most thorough understanding of the genetics and lifecycle of the New World screwworm, a blowfly that lays its eggs in wounds or vulnerable spots in livestock, pets, wildlife and humans and feeds on their living tissue. 

Scott’s work has helped identify genes that can be used to develop biology-based solutions to control screwworm that are more effective and less expensive. Through U.S. Department of Agriculture-funded research, his lab team developed a male-only line of screwworms that’s now under review with the U.S. Environmental Protection Agency under the name NovoFly. 

Scott teaches his graduate students about U.S. screwworm suppression efforts that kept the blowfly from spreading from South America up through Mexico and into the U.S. for decades. And on June 3, when USDA experts announced that a case of screwworm had been confirmed in Texas, Scott, who was visiting the Animal and Plant Health Inspection Service (APHIS) in Edinburg, Texas, got a tour of the USDA’s new sterile fly distribution center and equipment a stone’s throw away – right before giving a scheduled presentation on screwworm to ranchers in Houston. 

We asked Scott to provide insight on efforts to eradicate the New World screwworm and explain new genetic approaches to control the parasite.

While you were in Texas a few days ago, you toured some of the new screwworm control facilities there. What did you see?

I had two days in McAllen and I visited the USDA APHIS facility in Edinburg. I went there primarily because we have a new project doing CRISPR and gene editing in Mexican fruit fly, which is a problem there in the Rio Grande Valley. They arranged for me to visit the new distribution center for sterile male screwworm flies, which is walking distance from the lab where the fruit flies are. They were very busy as you might expect because the first cases had just turned up in Texas, and they were being asked to distribute more sterile flies from the center.

The flies are coming up from Panama. That’s the only rearing facility online and they’re shipped as pupae that have been sterilized with radiation. At the distribution center in Texas, they do all the processing to get the flies distributed in the area. They can do it from trucks, such as the ones I saw, and they can also suspend pupal cases from trees and the flies come out of the pupae. I also think they were expecting at least one of the [specialized] planes to come up from Panama or Mexico. These planes are set up to distribute the flies from the air, which is the most efficient way to do it. So it was all new. Looks like a fantastic distribution facility. I was impressed by how quickly they pulled this together, and it seems to be working well.

You also gave a presentation on screwworm to members of a regional cattle association in Houston. How did it go?

Yes, for two days I was in Houston for the Texas and Southwestern Cattle Raisers Association summer meeting. They invited me to come there and speak about screwworm and the male-only lines we’d made. As might be expected, there was a lot of interest in the work we had done and the prospect of using a male-only line for future sterile releases. They seemed happy that I turned up in person.

They’ve had over a year to prepare [since a major outbreak began in Central America in 2025]. So my sense was that the cattle ranchers are ready for this. They’re well prepared and our peer institution, Texas A&M, has been very active working through the Texas AgriLife in educating folks on staying up-to-date with what the treatments are. And at the conference they were distributing [collection and testing] kits because it’s really important that people do disclose if they’ve got infested livestock and collect the maggots and put them in ethanol and send them off for a formal ID.

What’s happened with the male-only screwworm strains that were developed by your lab with USDA funding?

Since the 1950s, what we’ve done is to sterilize screwworm pupae using radiation and then release both males and females. So people just talk about the sterile males because they’re the active component, but the sterile females are there. They don’t help. They’re competing with the fertile females for matings. We know if we release only males that the genetic suppression from releasing the sterile males will be more effective. My lab led the development of male-only strains that carry a gene that is lethal to females but is repressed by adding tetracycline to the diet. So, in the mass rearing factory the population can be expanded by using a diet with added tetracycline, but in the final release generation, omitting tetracycline from the diet causes females to die and only males to be produced. We tested the genetic systems out first at NC State in a blow fly that is related to screwworm. Promising genetic systems were sent to Panama for evaluation in New World screwworm. The initial work in Panama was led by Carolina Concha, a researcher from my lab, with considerable support from USDA-ARS staff. 

At the risk of sounding like one of those late-night TV salesmen, there are more advantages to male-only strains. In 2016, the initial strains of screwworms we made in Panama produced only males. The females died at the pupal stage. But that meant that first they consumed the customized diet for larvae, which is a big cost in rearing them. 

In 2020, we re-engineered the system. It took quite some effort to get this working where the females died right at the beginning of development, so they didn’t consume any diet as larvae. That meant that if you were putting 100,000 eggs on a tray of diet expecting to get 50,000 males and 50,000 females, you could now seed that tray with twice as many eggs, knowing half of them are going to die. You still produce 100,000 flies, but now instead of males and females, you have only males. So you’ve doubled the capacity of the mass rearing facility.

But there’s more. With this fly, the dose of radiation required to sterilize females is really high, probably twice what’s needed for males. If we’re doing a male-only release, we can reduce the radiation, which makes the whole thing easier and produces fitter males, because the radiation takes a toll on the flies. And for this technique to work, the released males have to be fit. They have to compete with fertile males for mates. And so improving their fitness helps improve the overall system. There’s also a biosecurity advantage to these male-only strains if you’ve got a big factory that’s producing millions and millions of flies. With the male-only strains, if any escape, they’re only going to produce males. 

A final advantage of these is that they’re marked with a fluorescent protein. So they’re easy to identify in the field. If you have the right goggles and light, you can see them express red fluorescence because they already carry a marker.

At what point did this male-only strain become ready for EPA review as NovoFly?

About a year ago, the USDA decided to resurrect that strain that was made in 2017. A former postdoctoral researcher with my group, Alex Arp, had been based in Panama and worked there for a couple of years before he was hired as a research geneticist with the USDA ARS. He took the lead on this with a lot of support within the administration. 

The submission to EPA was over 150 pages and it’s to the point now where the first public comment phase is finished. Once the EPA responds to the public comments, then there will be a second public comment period.

To test the strain in the field in Panama, which has not been done, they need regulatory approval from the Panamanian government. Hopefully, they’ll get it because we did receive approval for an earlier field test with radiation-sterilized males. And then if it does well, then it’s potentially something they could consider using in the U.S., pending EPA registration. Even if we had EPA approval, that’s not approval to use it in Mexico. So the process is complex, but I’m glad it’s gotten this far.

You’ve also done research that involves gene drives, which “drive” a trait through the population. What do we know about the effectiveness of gene drives compared to sterile male releases? 

Gene drives are based on non-Mendelian inheritance, the ability to push a trait through the population. You can do the mathematical modeling that [NC State scientists] Fred Gould and Alun Lloyd did, and the models show that far fewer males will need to be released to suppress the population. For the sterile insect technique, you’ve got to release about 10 times as many steriles as wild-type flies that are out there. You need a 10-to-one release ratio and you’ve got to keep doing it. With a gene drive, conservatively we could release one gene drive male for every four that are out there. So, 40 times less would be needed using those estimates. 

What will you work on next?

We have applied for funding to use CRISPR technology to sterilize the males rather than using radiation.

This post was originally published in College of Agriculture and Life Sciences News.