Messing up the mosquito's morse code

June 29, 2011 11:36 pm | Updated 11:36 pm IST

HOLY GRAIL: Antimalarial drug candidates are in hot pursuit in medicinal chemistry. Photo: S. Arul Anand

HOLY GRAIL: Antimalarial drug candidates are in hot pursuit in medicinal chemistry. Photo: S. Arul Anand

‘There is more than one way to skin a cat' is a phrase dating back to 1678, which somehow got morphed in the US to become “more ways of killing a cat than choking it with cream”. Either way it means that there are several ways to do something. And if a problem has multiple dimensions, there come several people, each one attempting to find one solution or the other. The ultimate goal is to solve it.

Malaria is a classic ‘cat'. The insect bites you to suck blood for its living. As it does so, the parasite within it, called plasmodium, enters your bloodstream and infects you with the disease.

As malaria kills millions, particularly children, across the world every year, the challenge is to prevent, treat and cure. Global efforts through national, international, governmental and non-governmental agencies are on and the problem is not solved yet. It is indeed one of the Grand Challenges that the Gates Foundation is funding to find a solution.

And there have been more than one way to skin the cat. Some here find drugs to treat the illness. Quinine and artemisinin are two examples, which came from traditional medicine (taken as pills and potions, or as gin and tonic). Antimalarial drug candidates are in hot pursuit in medicinal chemistry and natural products labs in many countries, including India.

Understanding the life cycle of the plasmodium, its movement within the body and arresting the crucial steps in these is a molecular biological route that many are trying to find.

Professor G Padmanaban of IISc Bangalore, and several other scientists in New Delhi, Lucknow and elsewhere are engaged in this effort. Yet others are after the holy grail of vaccines. Dr Chetan Chitnis of ICGEB New Delhi thinks he is very near it.

Other skinners try to kill the messenger and along with it the deadly message, plasmodium, within it. They spray DDT and the like in areas where mosquitoes gather and try to eliminate them. Others use bednets coated with chemicals that repel mosquitoes. Yet others wish to use radio frequency waves to drive them away from an area. Some think neutering (castration is not quite the appropriate word here) male mosquitoes by genetic engineering will soon eliminate the tribe and are working on such birth control techniques. And most of us simply use mosquito repellents as pastes, creams or coils of smoke.

Dr. Ananda Sankar Ray of the University of California, Riverside, is a skinner with a different approach. He wants to blunt the mosquito's nose and stop it from coming near its prey, namely us. The mosquito has a sensory set of neurons called cpA which detects its prey through the pulses of carbon dioxide that the latter exhales in its regular breath.

These pulses activate the mosquito's brain, tracking the insect to fly and land on the prey. Note the ever present CO{-2} in air is not a signal because it does not come in pulses, it is simply a continuous cloud of background The breathing pulse and the puffs of CO{-2} emitted by us are the signal.

As Mark Stopfer writes in his commentary on the Ray paper (both in the 2 June 2011 issue of Nature ), these dashes and dots are the Morse code that spell dinner for the mosquito.

Apart from cpA, there are other sensors in its nose that detect the sweat, and other body odours, directing it to the victim. (This of course explains why some people are more prone to mosquito bites than some others). But if we can disable cpA, we can kill the smell sense (olfactory system) of the mosquito.

How then does one do a “Surpanaka” and hack the mosquito's nose? By swamping the Morse signal of dashes and dots. This is what Ray has been able to do. (Recall though, that in The Ramayana , Lakshmana cut off the nose of Ravana's sister Surpanaka, and thus her amorous intention as well; but Ray only blocks the nose).

Ray's group found that just as plumes of breath generate the on and off pulses in the ‘action potential' of cpA, molecules such as 2-butanone can mimic such signals. These are the mimetic odourants. But some others, for example, 2, 3-butanedione, do an overkill. Rather than pulsing, they generate an ultra-prolonged signal, lasting over a few minutes. Such inhibition of the sensory neuron confuses the mosquito, disorienting it and driving it away.

The group tried this strategy first, releasing mosquitoes into one end of a wind tunnel and checking their behaviour with a mimetic odourant at the other end, and then with the overkill inhibitory odourant.

In the second case the mosquitoes could not reach the other end at all. Next, they tried the same experiment in real life, in Kenyan huts and found the same. Huts that had a whiff of 2, 3- butanedione were rid of mosquitoes.

As Stopfer says, 2, 3-butanedione may not be safe for humans, plus there are other human body odours, so that we need to look at other molecules to bamboozle the mosquito.

It occurred to me that frankincense (olibanum, Dhoop or sambrani ), whose smoke has been used for centuries as an insect repellent, might be worth investigating. It is rich in terpenoids and ketones, some of which might act as safe inhibitory odourants. Any takers?

>dbala@lvpei.org

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