24 June 2002

by Bea Perks, BioMedNet News

Releasing billions of genetically modified insects into the wild is an understandably controversial means of pest control. But a handful of spectacular successes with the technique has prompted a British molecular biologist to focus on finding new ways of taking it from a marginal approach into the mainstream.

Luke Alphey is confident that he has a cleaner, safer, and relatively cheap way to eradicate at least some insect pests, using a method of genetic engineering that should be publicly acceptable. But the effort to take it from a marginal approach into the mainstream is arduous.

Alphey's method relies on releasing into the wild insects that carry within their genomes the seeds of their population's eventual destruction. Historically, this has been an expensive procedure, with a built in element of hit-and-miss. But Alphey, who is a senior research fellow at the University of Oxford's Zoology Department, contends his solution that could improve efficiency and make the system applicable to a broader range of insect pests and geographical locations.

Alphey developed his new technology in Drosophila, and is about to apply it to economically important pests: the medfly, which destroys citrus and coffee crops; pink bollworm, a moth pest of cotton; and Aedes aegypti, the mosquito that transmits Dengue and yellow fever.

His method is based on the tried-and-tested sterile insect technique (SIT) which breeds vast numbers of insects in captivity, sterilizes them, and releases them into the wild to mate with females which will then have no offspring. The net result is a population decrease, and sometimes eradication.

What Alphey proposes is RIDL - release of insects carrying a dominant lethal - whose offspring, if any, would self-destruct. What could be wrong with that idea?

Eradication only happens when there is no immigration into the area, says Chris Curtis, professor of medical entomology at the London School of Hygiene and Tropical Medicine. This was the case in a SIT program in Zanzibar, which succeeded eradicating the tsetse fly there.

"In the case of, for example, malaria mosquitoes in rural Africa, there would inevitably be immigration from village to village," said Curtis. In such situations, traditional insecticide-based methods would also have to be used. (Although he supports the RIDL idea, Curtis' own research focuses on using insecticide-treated bed nets to control malarial mosquitoes.)

Other critics of RIDL don't support it at all. Vocal among them is anti-GM (genetic modification) campaigner Mae Wan Ho, director of the London-based Institute of Science in Society.

"Alphey has glossed over very important safety aspects," said Ho. "Many of the transposons used in insect germline transformation belong to promiscuous superfamilies that are widely distributed in the animal kingdom."

Even when GM insects are disabled by removing transposases, Ho adds, the missing transposases, or their homologs, might be found in other insect genomes.

There is thus, she said, "a dangerous potential for horizontal gene transfer and recombination." Ho says she is "astonished" at the lack of health and ecological considerations given to the approach.

Alphey is well aware that the public perception of GM insects is a potential stumbling block. "Political difficulties" have halted SIT programs in the past, he says. But whereas transgenes in crops could arguably confer a selective advantage and spread through wild-plant populations, he suggests, a lethal mutation, which kills its insect host, would certainly not. Furthermore, he laughed, in contrast with GM crops, "we're not asking anyone to eat them."

But Ho's views are in the minority. There has been mass outcry against the SIT approach, but most arguments are based on the allocation of resources, rather than health and safety.

The major drawback to these approaches is their expense, says Rajinder Saini, principal scientist at the International Centre of Insect Physiology and Ecology (ICIPE) in Nairobi, Kenya. One proposal to eradicate one species of tsetse in 10 million square kilometers, he says, has been estimated to cost $36 billion.

"This staggering amount should be seen within the context of what is required for other diseases like HIV/AIDS, malaria, etc., which are priorities," said Saini.

And past success with the tsetse doesn't necessarily spell success with malarial mosquitoes, he adds. Researchers will have to untangle the poorly understood mating strategies of Anopheles gambiae, the main malaria vector, for the scheme to work, he says. Planning such a scheme may be "presumptuous" at present, he said.

"While we wait for the billions of dollars to be generated for an eradication program ... should we let the poor and their livestock continue to die and continue to live in perpetual poverty?" asked Saini. "Or should we empower the local communities with simple user-friendly tools, which they can adopt and use over sustainable period of time?"

Aphey says he sympathizes with Saini's views. "RIDL can be an extremely useful new approach, both on its own and in synergistic combination with other methods," he said, "but it is not a panacea and will not be the optimum strategy for every pest insect in every region."

He adds, though, that his approach is more ecology-friendly and economical than others suggested in the past. The system is highly species-specific, he says, and reduces the need for polluting insecticides. "It's extremely attractive from an environmental point of view," he said.

For instance, sterilizing insects with irradiation is both expensive and risky - it can cause somatic as well as germline mutations, leaving insects at a competitive disadvantage with their wild-type counterparts, he says. Consequently, about 60 sterilized males have to be released for every wild male.

To get around the problem, Alphey proposes to insert precise dominant lethal mutations into insect DNA. When male insects homozygous for these mutations, breed in the wild, obviously, all their offspring would be doomed heterozygotes.

RIDL's main advantage over SIT is that insects with a dominant lethal last much longer than irradiated ones (which survive only a few days in the wild) and compete more successfully for mates. It works well in Drosophila in the lab, he says.

Transferring the technology to pest species in the wild presents challenges, he says - truly interesting ones to a researcher, more technical than political.

Most insect pests have longer generation times than lab Drosophila, making every experiment 50-100% longer, says Alphey. And, whereas Drosophila can carry out their entire life-cycle in a tiny vial, mosquitoes need several changes of habitat and food supply.

Feeding adult mosquitoes is an art in itself; providing them with the right temperature and carbon dioxide gradients and a skin-like membrane to feed through, not to mention a convenient blood supply. (Alphey uses sheep's blood).

As to the issue of cost, Alphey says that SIT programs, albeit tremendously costly, have already proven cost-effective in terms of improved yields for commercially important crops such as fruit and coffee. His colleage, David Kelly, a medical entomologist in the University of Oxford's zoology department, said this:

"At the moment they're good value programs ... they're cost efficient, but they could be cheaper. By making them cheaper one could also make them applicable in areas where they wouldn't be cost-efficient at present." He added that this could drive the technology into new geographical areas and new pest species.

Kelly has been working with Alphey to apply the technology to Aedes aegypti - a good example, Kelly says, of a species where irradiation was found to be particularly damaging to the insects. Trials in the '70s and '80s came to nothing, "but with the new technology it could work out really well."

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