By David N. Leff

Along about the time of the Civil War in the U.S., slaves sang a song called ¿Jimmy Crackcorn¿ with this first verse:

When I was young I used to wait

On Massa, and give him his plate,

And pass the bottle when he got dry,

And brush away the Blue-Tail Fly.

That infamous, bluish insect was, in fact, the screwworm fly (Cochliomyia hominivorax), which laid its parasitic larvae in open wounds or nostrils of cattle, and bored into the living tissues of mammals, in which they inflicted injury or death. Nowadays, one refers to C. hominivorax in the past tense, because half a century ago an ingenious strategy more or less wiped out the screwworm fly¿s livestock scourge throughout the U.S. and Mexico.

¿Edward Knipling originated the idea of releasing sterile insects to control the screwworm fly,¿ molecular geneticist Dean Thomas, at the Zoology Department of the University of Oxford, England, recalled. ¿It was an important agricultural pest in the Southern states of the U.S. He succeeded in its total eradication from North America and Mexico ¿ later, from Libya in the 1980s.¿

Knipling, a research entomologist at the U.S. Department of Agriculture after World War II, reasoned that persistently spraying vast numbers of live, sterilized male flies in infested areas of the South would eventually reduce the screwworm population to nearly nil.

¿His screwworm fly program,¿ Thomas continued, ¿produced about 50 million male flies a week, sterilized by irradiation, at a large factory in Florida. These flies were collected in small paper bags, and 20 airplanes flew daily flights to the area where they wanted to control the pest. The bags were thrown out of the aircraft, and dispersed over a large area. That¿s pretty much the way they still do SIT [sterile insect technique] today.¿

Molecular geneticist Luke Alphey heads the laboratory at Oxford in which Thomas is a graduate student. ¿As I learned about the genetic SIT technique,¿ Alphey told BioWorld Today, ¿and the existing sex selection mechanisms, I realized that the transgenic procedures I was familiar with in Drosophila melanogaster, the fruit fly, could potentially be used to get around many of the problems that were evident with the existing technology.¿

Alphey is senior author, and Thomas first author, of a paper in the March 31, 2000, issue of Science. Its title, ¿Insect population control using a dominant, repressible, lethal genetic system,¿ describes their SIT work in Drosophila.

Nobody Bothers To Control Drosophila

¿Our main challenge now,¿ Alphey observed, ¿is to get this system into an agricultural-pest insect or human disease vector ¿ as opposed to the fruit fly, which we work on because it¿s harmless, and consequently nobody cares about controlling it. So we need to translate this technology into insects of commercial or medical significance.

¿The two harmful insects we¿re focusing on initially,¿ he continued, ¿are the Mediterranean fruit fly (Ceratitis capitata), Med fly¿ for short ¿ a very important agricultural pest ¿ and the yellow fever mosquito (Aedes aegypti). But that¿s just because we know how to grow them and raise them in the lab.¿

Thomas pointed out, ¿A big problem with dispersing sterile insects to control insect pests ¿is that it¿s counterproductive to release both sexes. In the screwworm, for instance, it didn¿t really matter if you released both males and females, because both had an effect on cattle, and cattle aren¿t as important as people.

¿But you can¿t really disperse both male and female mosquitoes,¿ he added, ¿because it¿s the female mosquito that takes the blood meal. So you can¿t, for instance, release 50 million sterile females, which would increase transmission of the disease you¿re trying to prevent. And Med flies, by the same token,¿ Thomas went on, ¿will still try to lay their eggs in fruit, and cause the types of damage that you¿re trying to control.

¿Releasing males instead could theoretically take care of these mosquitoes,¿ Thomas suggested. ¿In theory, SIT could now be used for the control of mosquito populations. We¿ve already begun experiments in Aedes aegypti, the mosquito vector of yellow fever, and Ceratitis capitata, the Med fly. We¿ve begun to make transgenic insects; it¿s coming along and looks promising.¿

To which Alphey added, ¿These trials show a degree of success, without being near to something you could actually use in the field. The indications are that most of the key components we have tested will work, but we haven¿t got them functioning efficiently enough, and at a level where we could even think of any kind of field use. So it looks as though it¿s going to work, but not without some tinkering.

¿The theoretical idea,¿ he explained, ¿is to construct a strain of flies that are homozygous for ¿ that is, have two copies of ¿ a dominant, female-specific lethal gene or genetic system. You can¿t raise a strain of flies of this type in a factory or lab, because all the females die. You have to repress the sex-specific gene in the factory, and you want whatever you¿re using as the repressor to be very specific, and unavailable to the wild insects under any reasonable circumstances. An ideal solution would be a chemical additive to their diet that they wouldn¿t come across in the wild. For this we used the antibiotic tetracycline.¿

No Tetracycline On The Menu; No Live Females

¿It represses the lethality, so we can raise the strain in the factory. We then withdraw the chemical additive from the last insect generation, so this dominant female-specific lethal effect would kick in, all the females would die, and we would end up with a population of males only.

¿That in itself is a big deal,¿ Alphey pointed out, ¿because it¿s an efficient genetic sex-selection mechanism. In a conventional SIT program, you would take those males sterilized by irradiation and release them. So this would be a step forward, because you would effectively separate out the males from the females, a very difficult thing to do on a factory scale.

¿Actually, we are suggesting that one can use this strain as a control agent without having to irradiate it. Clearly, irradiating insects to the point of sterility is likely to have adverse effects, and make them less good at competing for mates, in terms of a SIT control program.¿

The university has patents pending on this novel SIT method, but is not in touch with any biotech or pharma companies. ¿However, I¿m not saying,¿ Alphey concluded, ¿that we wouldn¿t be interested.¿