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BLOG: March 2020

The smell of cancer: will rats be saving human lives?

As far back as 1989, a pair of dermatologists reported in the "Lancet" about a women whose dog wouldn't stop sniffing at a mole on her leg, and once even tried to bite it off. She went on to get a medical checkup, which showed the mole was a malignant melanoma, already a couple of mm thick. It was removed and she suffered no consequences.

Another similar case was reported in the "Lancet" in 2001 by two British doctors. A 66-year old man had his Labrador strangely attracted to a rough patch of skin on his leg, diagnosed as eczema. The dog kept pushing its nose into it, until the man went back to his doctor. The "eczema" turned out to be a basal cell carcinoma, which was quickly removed.

What does cancer smell like? We'll never know, because the concentrations of abnormal gaseous residues of the cancerous cell metabolism are far below our threshold of detection. It wasn't known what was it, specifically, that dogs could smell, but it should belong generally to a group of chemicals called "volatile organic compounds".

We do know that, unlike healthy cell, whose unbelievably complex metabolism takes place in the oxygen-rich environment, cancer cell lives on a comparatively very primitive process of burning glucose under oxygen-deprived conditions. As a result, the cancer cell is acidic, and

its chemical waste is very different than that of a healthy cell.

While it is hard to compare sense of smell between different animals, since they tend to vary in strength with specific smells from one animal to another, it is generally accepted that the number of smell receptors' genes, or OR genes, indicates how strong is the sense. Turns out, rat has 50% more of OR genes than a dog.[1] Knowing that the sense of smell ability increases exponentially with the number of genes - dogs, on the average, have only twice as many as humans - implicates that rats have significantly stronger sense of smell.

Being in addition smaller, easier to handle and cheaper, all make them better a candidate for use as a smell sensor for medical purposes.

We know that rats are already being used to sniff out tuberculosis, as well as land mines, in Africa (so they already are saving human lives, although not from cancer). In either case, what they can smell is known: with TB, it is the tar-smelling chemical waste of the TB-causing bacteria, and with land mines it is the smell of TNT. These rats are simply trained to react to the smell by being rewarded for it with their favored food (they love bananas - and they don't cheat!).

What is now being worked at in Russia, however, is much more sophisticated. They use a microchip as a detector to determine whether bioelectrical impulses generated in rat's brain following its olfactory system (sense of smell) response indicate the presence of "target compounds", or not.

As Fedor Arsenyev, leading researcher of the "Advanced Research Foundation", which developed this so called biohybrid cancer screening technology, says: "Animal has special pre-implanted microelectrodes, which allow to record biorhythms resulting from exposure of its olfactory receptors to cancer markers present in the exhaled air".

In effect, the rat is a sensor used by the chip.

In the first test at a two hospitals in Veliky Novgorod, at the end of November last year, 1073 volunteers went through a very simple procedure of exhaling into a pipe-like device connected to a box with the rat. Test was designed for lung and stomach cancer, and it took only 2-3 minutes per person.

Main intended benefit of the test was to detect cancer in its very early stage, making the chances for recovery much better. Out of 1073 symptom-free participants, 85 (or 8%) were positive, i.e. at a risk of developing cancer. Out of them, 41 accepted follow-up examination using computed tomography of the lungs and fibrogastroduodenoscopy, in order to double check the rat-test result.

It was confirmed in 40% of them for lung cancer, and 20% for stomach (which does not necessarily mean that all others were cancer-free).

Compared to the standard diagnostic tests performance for the Novgorod region, with a 0.8 and 0.4 per 1000 detection rate for the lung and stomach cancer, respectively, the new test is roughly

3-5 times more sensitive.

Apparently, it still has too high false-positive rate, but it is not unreasonable to expect that with further refinements it could be made better in both, sensitivity and accuracy.

The plan is to complete the investigative phase this year, with another experiment with twice as many participants. Potential buyers, if all goes as expected, are the Russian Ministry of Health and the Federal Medical and Biological Agency.


Source: novgorod.ru

[1] Extreme expansion of the olfactory receptor gene repertoire in African elephants and evolutionary dynamics of orthologous gene groups in 13 placental mammals, Niimura et al. 2014



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