Hormonal Bind for Bad Insects

Article excerpt

In the 1960s, Harvard University insect biologist Carroll Williams informed the world that only 0.1% of insects were pests. The remaining species were innocuous, even beneficial to humans.

Williams made his point in response to the emerging problems of indiscriminate pesticide use. Chlorinated insecticides such as dieldren and heptachlor, and organophosphates such as parathion had promised to revolutionise crop protection, but in two decades had caused environmental contamination, residues in humans and animals and pesticide resistance.

As a means of reducing these harmful side-effects, and protecting the innocent insect species, Williams suggested developing a new generation of pest-specific insecticides based on the chemistry of the insect's own hormones.

Nearly 40 years on, scientists at CSIRO Molecular Science, in collaboration with DuPont and Melbourne's Biomolecular Research Institute, have adapted Carroll Williams' idea. They have embarked on a project to develop new insecticides that target the receptor for the insect steroid hormone ecdysone.

By targeting the ecdysone receptor the scientists intend to overcome a previously unforeseen problem with hormone-based insecticides.

`A major problem with Carroll Williams' approach is that insects have a system of breaking down their own hormones once they have performed their regulatory function,' CSIRO molecular biologist Dr Ron Hill says. `We're trying to develop new chemistries that will interact with the insect ecdysone receptor, but can't be broken down by the insect's catabolic systems.'

Ecdysone and its receptor help to control insect growth and development. Normally, the concentration of ecdysone rises and falls many times during the insect's life cycle. When the hormone binds its receptor in the nucleus of the cell, it activates genes that regulate metamorphosis, reproduction and moulting. Synthetic molecules that interact with the receptor, but resist catabolism, will switch on the genes controlling these events at the wrong time.

`So the insects will moult prematurely or they'll undergo metamorphosis ahead of time, causing major disruption to their orderly process of development,' Hill says.

And according to CSIRO organic chemist Dr Paul Savage, the targetted control such as synthetic molecules offer will ensure greater environmental friendliness.

`Some of the pesticides used in the past were very dirty and very nasty, because they were broad spectrum and tended to hit biochemical pathways that many organisms have,' he says. `The benefit of this approach is that it targets a receptor in moulting invertebrates that is absent from humans, birds, fish and so on. So toxicity will be limited to the targetted pest species.'

Signals and crystals

Hill and Savage are tackling the project in two ways with the help of CSIRO molecular biologist Dr Gary Hannan and protein chemist Dr Lloyd Graham.

The first approach tests the interaction of natural or synthetic molecules with the receptor in cultured cells. …