Honeybees: The New Sniffer Dogs?

Honeybees can detect the scent of tuberculosis

Related item in today’s news – “Sniffer dogs detect lung cancer”  http://www.bbc.co.uk/news/health-14557224

Unlike wasps, a large cohort of which recently decided that my bathroom provided the ideal location for a nest-cum-social club, bees are pretty useful*. And now they’ve started expanding their CV beyond the traditional skills of flower pollination and inelegant flight. They’re helping scientists to develop an early-stage diagnostic test for tuberculosis.

David Suckling and Rachael Sagar of The New Zealand Institute for Plant and Food Research recently trained a group of honeybees – Apis mellifera, to give them their official name – to give a signal when they detected the distinctive odour of tuberculosis. They describe their research in the latest issue of Tuberculosis journal.

The story began back in 2009. It was then that Mona Syhre and
Stephen Chambers, two scientists from New Zealand’s University of Otago, discovered that lab-grown cultures of Mycobacterium tuberculosis – the microbe responsible for tuberculosis infection – produced a number of volatile, sweet-smelling chemicals. One of these chemicals was methyl p-anisate, which, curiously, is also produced by some species of orchid. Another, called methyl phenylacetate, is found in Japanese privet, and it has a sweet, jasmine-like smell. Odd as it may seem, the smell of TB is, it would appear, quite floral in nature.

Now, if those same volatile, sweet-smelling chemicals found in lab-grown cultures of M. tuberculosis are also present in the breath of patients with TB, then we’re really on to something. Could these chemicals act as biomarkers in the breath – providing a quick and easy way to diagnose the infection?

The thing is, though, that even if those chemicals are present in the breath of patients with TB, they’re likely to be there at very low levels. The instruments that we typically use to detect volatile chemicals – mass spectrometers, ion mobility spectrometers, or polymer-based electronic noses - may not be sensitive enough.

But the insect world has its very own, ultra-sensitive chemical detector – the bees’ antennae. And, of course, bees are pretty good at detecting the scent of flowers. Could a bee succeed where a £100,000 mass spectrometer could not?

It’s not as unlikely as it may sound. Bees have been lending their talents to science for some time: in fact, they have already been trained to detect explosives and marijuana. So, with this in mind, Suckling and Sagar
decided to see if bees could be trained to indicate the smell of TB. They  went out into the grounds of the institute, and collected thirty honeybees – who, when they set out upon that day’s foraging, presumably had no idea that they were about to participate in ground-breaking research. But that’s what happened.

Suckling and Sagar decided to find out if the bees could be trained to respond to three of the chemicals given off by the Mycobacterium tuberculosis cultures -
methyl p-anisate, methyl phenylacetate and methyl nicotinate.  To that end, the bees were given a crash course in chemical analysis.

First, the bees were placed into a stream of air. Then, the scientists applied a dilute solution of each chemical to a filter paper, and allowed the solution to evaporate into the airstream – so that the volatile chemicals blew over the bees’ antennae. Then, immediately after this exposure to the chemical, a bit of sugar solution was dabbed onto the bees’ antennae. Bees like sugar, of course, and when their antennae detect it, they exhibit a phenomenon called the proboscis extension reflex (PER). They stick their tongue out, in other words.

That reflex – the sticking out of the tongue – is the signal that the scientists are looking for. That’s how the bees can indicate to us that the chemical we’re looking for is, in fact, present.

Finally, the scientists gave the bees a drink of sugar, as a reward for responding to the chemical. And this process of conditioning was repeated
several times, just to be sure that the bees got the message.

But did it work? Could the bees be trained to signal the presence of TB biomarkers? And just how sensitive were the bees’ antennae to very dilute
concentrations of these volatile chemicals?

Well, according to Sucking and Sagar, a proportion of the bees did indeed learn to associate each of the three chemicals with a nice dose of sugar. And, soon enough, these bees were sticking their tongues out as soon as their  antennae picked up traces of each chemical.

Just how sensitive the bees were to these potential biomarkers depended, though, on which chemical they were exposed to. The bees were very good at picking up methyl p-anisate – they could detect this at levels as low as ten picograms. They also responded to very low levels of methyl phenylacetate – around 100 picograms. But they weren’t so good  at detecting methyl nicotinate, needing to be exposed to at least one nanogram of this chemical before they responded with the proboscis extension reflex.

Although Sagar and Suckling believe that there is potential to use trained honeybees as part of TB diagnosis, it’s far too early to say whether this novel research will lead to your GP keeping bees in the surgery. Although these volatile chemicals are produced by lab-grown cultures of Mycobacterium tuberculosis, no-one is certain, yet, whether they are actually present in the breath of TB patients (although a precursor of methyl nicotinate, called nicotinic acid, has been detected). But if they are, and we can detect them, then breath analysis could lead to a cheap, rapid and non-invasive test for a treatable illness that still kills almost two million people each year.

References

Suckling, D., and Sagar, R. (2011).  Honeybees Apis mellifera can detect the scent of Mycobacterium tuberculosis. Tuberculosis 91 (4) pp. 327- 328 doi:10.1016/j.tube.2011.04.008

Syhre, M. et al (2009). The scent of Mycobacterium tuberculosis – Part II: breath. Tuberculosis 89 (4) pp. 263 – 266 doi:10.1016/j.tube.2009.04.003

More about odour-based diagnostics: http://www.guardian.co.uk/science/blog/2011/jan/28/body-odour-dogs-sniff-out-cancer

*Yes, I know that wasps have their place in the natural world, too. But it’s hard to bear that in mind when you are sharing your toilet with two hundred of the poison-arsed feckers.

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