Molecule of the Month: From Nazis to gnats via the Gulf war

Gulf war syndrome, sheep-dipper's flu, and even BSE have recently been linked to organophosphate (OP) insecticides. Their name, somehow redolent of fertilisers with dire warnings on the packet, give rise to suspicion almost immediately.

Yet is it justified? Organophosphates occur naturally, and there are OPs in our body - including that essential of life, DNA, the high-energy molecule ATP, and the natural emulsifier, lecithin. All are molecules with phosphate groups to which organic groups are attached. However, natural OPs generally have one or two organic groups, whereas insecticide OPs have three.

Campaigners against OPs point out that they are related to nerve gases like sarin, although those are not OPs. They do share a common ancestry, though, and attack the same key enzyme, acetylcholinesterase, which is needed to cancel the chemical messenger, acetylcholine, after it has done its job of transmitting a signal across a nerve junction. Nerve gases block the enzyme so effectively that one tiny drop is lethal. OPs seem a lot safer.

But according to Graham Matthews, professor of pest management at Imperial College, London, and author of Pesticide Application Methods (Blackwell, 1992), this does not mean they are safe. "A few people appear to be particularly sensitive to OPs, which span a range of toxicity. Some, such as malathion, are much less toxic and may be used in the home, in shampoos for head lice, or flea collars for cats and dogs, but some that were used in agriculture, such as parathion, are now considered too hazardous and are banned in some countries."

Malathion is widely used by gardeners and farmers, and smells foul because the molecule has two sulphur atoms, a common feature of many synthetic OPs. In the Gulf war it was used to protect Iraqi prisoners of war from mosquitoes. Allied forces, on the other hand, had their sleeping quarters sprayed with less foul-smelling OPs - dimethyl phosphorothionate, diazinon and azamethiphos. The OPs used in sheep-dips - diazinon and propetamphos - have one sulphur atom in the molecule.

Many OPs were first made in Nazi Germany, where Dr Gerhard Schrader led the search for phosphorus-based nerve gases. Some of the compounds his group discovered turned out to be more toxic to insects than to man. Tetraethyl pyrophosphate was one such OP, and for a time after the war it was sold as an insecticide. But some who used it died, and it was withdrawn. Another of Schrader's OPs was parathion - safer and highly effective against mites, aphids and mosquitoes. But it, too, was not safe enough for general use.

When the potency of OPs as insecticides was realised, chemical firms which had researched phosphorus compounds looked again at the molecules they had made. Malathion was originally intended as a flotation agent for mineral separation, but subsequently found to be a safe insecticide; it is still widely used.

Dr Goran Jamal, of the Institute of Neurological Sciences at Glasgow University, is a member of the Government's advisory panel on OPs. Together with the Institute of Occupational Medicine at Edinburgh, he is researching the effects of OPs on humans. "There are three types of response to OPs," he says. "The acute syndrome, which happens within hours of exposure; the intermediate syndrome, which occurs within days, and the delayed response - referred to as organophosphate-induced delayed neuropathy (OPIDN). There is also a chronic syndrome, where there is damage to the nervous system building up over many years."

The acute syndrome manifests itself as sheep-dipper's flu, whereas the intermediate syndrome results in a sudden paralysis of the muscles about three or four days after exposure. The condition lasts for about a month. Dr Jamal is in no doubt that OPs are the cause, and also believes that the chronic syndrome is linked to them too.

The ability to cause degenerative changes in people is associated with the inhibition of another enzyme in nerves, neuropathy target esterase (NTE), and this is now used as a marker to identify harmful OPs. If an OP is shown to inhibit NTE, then it cannot be licensed for use. But Dr Jamal believes this is not an absolute test because it does not spot OPs that produce chronic symptoms.

Among farmers, those on sheep farms are most at risk. MAFF says there are more than 42 million sheep in the UK, all of which must be dipped once a year to control blowflies and scab. Of the thousands who do this job, relatively few have been affected. Those who think they suffer symptoms of OP exposure should contact MAFF's Veterinary Medicines Directorate. A panel set up in 1985 has dealt with 577 such cases.

Dr John Emsley is science writer in residence at Imperial College, London.