Venom Double Act

The December edition of Australasian Science will have an unusual occurrence – two articles by me on largely unrelated work from the same team. Professor Glenn King of the University of Queensland Institute of Molecular Biology told me this was a coincidence, rather than an astonishing burst of productivity. One of the papers was ready to be published a year ago, except that the main author went on maternity leave around the time reviewers asked for some modifications.

Nevertheless, both pieces look interesting enough I thought I’d post about them here in combination. King’s team studies venom from invertebrate species and tries to find applications for human problems. Both lines of research have a long way to go, but show potential against truly huge problems.

Dr Maggie Hardy is looking at spider venom, specifically from a species of tarantula. She’s looking for insecticides to replace the ones we have which are either environmentally damaging or producing resistance in target species or, more often, both. Now it is not surprising that spiders would have evolved venoms that kill common insect pests. However, what is unusual about this particular molecule is that it is toxic to certain pests when they eat it on leaves it has been sprayed onto.

This is important. If the toxin needs to be ingested topically it will very likely affect other insects, including important pollinators. Hardy hopes that an orally active insecticide could be sprayed at times when pollinators are off somewhere else, and by the time they are around the impact would be negligible. That remains to be tested, but there is hope.

Short lived species inevitably develop resistance against any toxin, but the interesting thing is that the pathway for resistance against certain existing insecticides actually makes the host more vulnerable to this toxin. Consequently it might be possible to used a spray based on the tarantula venom in alternating years with one of those currently on the market, delaying resistance for a very long time.

The other promising molecule identified by King’s team is more surprising. It is a pain killer from, of all places, the venom of the Chinese red-headed centipede. One of the problems with designing pain killers is that there are multiple pathways by which pain reaches the brain, and many painkillers only work against one of them.

However, according to King, the “Nav1.7 sodium channel sort of sits above all of them acting as an amplifier. It’s like there are multiple strings on an electric guitar with different pick-ups, but without the amplifier the sound never gets heard.” Block the Nav1.7 channel and all pain goes away.

Now there are problems with this – pain is important to our body, stopping us from doing things which are harmful. However, the more immediate issue is that there are 9 sodium channels in the body and molecules that block one of these usually block others. Since one of the channels is essential to the functioning of the heart, and interference with another channel can leave a person paralyzed you really don’t want to be using pain killers that can interfere with the other channels.

“Insects,” King says. “Only have one sodium channel, which is related to all the ones in mammals.” Consequently, the venoms some predators use to subdue insect prey often affect some, but not all, the sodium channels in people. King’s team figured that if they tested enough different species’ venoms they would find something that mainly targetted the Nav1.7 channel, and that might be engineered to reduce the effects on any other channels. Instead they found a molecule that seems to have no affect at all on channels Nav1.1-1.6 and 1.8 and 1.9. None at all. Mice injected with the molecule appear to suffer no pain for about four hours, yet at doses ten times that which produces the analgesic effect their heart rate and blood pressure is unaffected and they can swim fine.

Because the molecule does not relate to the reward centres of the brain King doesn’t expect the addiction issues we see with opiates. He also says (and I admit I don’t understand this at all) that molecules that block ion channels rather than receptors are unlikely to have the tolerance issues one sees where steadily higher doses are needed to achieve the same effect.

Plenty of safety testing remains, but King things the biggest problem is that the kidney clears the molecule too quickly, so new doses would be needed at least every four hours. He hopes drugs could modify this, but frankly if I was suffering some excruciating chronic pain I think that would be the least of my concerns, particularly it if could be taken via pill rather than injection.

We will not need armies of tarantulas or centipedes to give us the drugs required here – in one case we have already modified bacteria to produce it and King thinks this should be possible in the other case as well.

However, we did need a few of the arthropods to get the whole thing started, and Hardy at least has become inexplicably fond of her subjects. She described them as “like little cows, lining up at milking and feeding time, the ideal animal to work with”.

I on the other hand, could not stand to even look directly at the photographs she sent me of the spiders, so here is a red-headed centipede instead.

The photogenic venomous arthropod.

The photogenic venomous arthropod.

The photogenic venomous arthropod.

The photogenic venomous arthropod.

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About Stephen Luntz

I am a science journalist, specialising in Australian and New Zealand research across all fields of science. My book, Forensics, Fossils and Fruitbats: A Field Guide to Australian Scientists is out now through CSIRO Publishing. I am also a professional returning officer for non-government organisations. I'm very politically active, but generally try to restrict this blog to scientific matters.
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One Response to Venom Double Act

  1. Love the centipede’s Salvador Dali mustache.

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