At a university laboratory in Tanzania, an unusual kind of medical research is taking place. Men in white coats watch as rats scurry around glass cages, but these rodents are not test subjects in the latest drug trial. In fact, they're the ones doing the testing, and they're proving rather good at it.
Since 2008, a team of 77 African giant pouched rats have been trained by the Belgian social enterprise Apopo to sniff out the killer infection tuberculosis. They've turned out to be faster and more accurate than local technicians with microscopes.
Tuberculosis kills more people than any other infectious disease apart from HIV, and can be difficult to detect with the outdated techniques used in poorly resourced Tanzanian clinics. As a result, many TB cases are missed.
"The rats got me better. I will always remember them fondly."
- Janet Zakaria, TB patient
The chunky light brown rodents, which have puffy cheeks and are up to 90 centimetres long including their tails, are taught to recognise the odour of mycobacterium tuberculosis in human phlegm or "sputum" samples, and to seek it out in return for a reward.
"In history Hippocrates used smelling to detect some diseases, so it's not something new," says Negussie Beyene, Apopo's TB programme manager in Tanzania.
Sputum samples from TB patients at 25 nearby clinics are taken to Apopo's lab at the Sokoine University of Agriculture in Morogoro every week, and loaded in batches of 10 under small holes in the rats' rectangular glass and steel cages. Today it's the turn of a female called Astrid. "The rat is ready to sniff," Beyene says, and she's off.
Astrid darts from sample to sample, briefly smelling each one, and scratching rapidly with both front paws over any she thinks are infected with TB. The samples have previously been tested at the clinics, and when she flags up a sample that's already known to be positive, she gets mashed banana or peanuts as a reward. If she indicates over a sample that hasn't been flagged up by a clinic, it is marked as "suspect" and re-tested by Apopo's scientists.
A study from 2012 showed when four rats screen each sample the rodents detect the presence of TB in 79.9 percent of cases.
The World Health Organisation says a single technician [with a microscope] can do 25 samples a day. This rat just did 10 samples in a minute.
In comparison, less than 58 percent of positive TB samples are spotted using smear microscopy, the traditional technique for diagnosing tuberculosis where sputum samples are stained so that the TB bacteria show up under a microscope. Undiagnosed TB sufferers can infect up to 15 others a year, and without treatment two-thirds will die.
The rats have already greatly improved outcomes for patients with the infection. So far they have found more than 3,500 cases missed by local clinics, and improved detection rates by more than 30 percent.
Astrid and the rest of Apopo's rats are descendents of wild African pouched rats caught on the slopes of the nearby Uluguru Mountains. The species, cricetomys gambianus, was chosen for its exceptional sense of smell, intelligence, low maintenance costs and long lifespan in captivity. They are also too light to set off landmines, which is what they were originally trained to sniff out.
Training a TB rat takes nine months and begins when the baby rat first opens its eyes at around four-weeks old, says Amanda Mahoney, head of behavioural research at Apopo.
"The trainer will put the young rat in a basket in the front of their bicycle, or let them walk around in the dirt and the grass, or take them on a car journey to get them used to different stimuli and experiences," she says.
After this initial socialisation, the rodents are trained to associate a clicking sound with a reward, and taught they will get a click if they hover over a sample contaminated with the TB bacteria, but not if they pause over others. A rat costs $7,800 to train, but they live for up to eight years and are cheap to keep.
Once qualified, the rats can screen samples extremely quickly. Astrid scampers through her 10 samples, flagging up one suspect case, and stops to give herself a well-earned scratch before going back for her next batch.
"The World Health Organisation says a single technician [with a microscope] can do 25 samples a day," says Beyene. "And this rat just did 10 samples in a minute."
Their speed is particularly useful when large populations need to be screened quickly. "If you have 5,000 inmates in a prison and you want to check whether each prisoner has TB - if you want to check this with a microscope it takes the whole year," says Beyene. "But with the rats you can do it in just a few weeks."
Later this year Apopo will begin research in a Tanzanian prison to see whether the rats could be used as first-line screening tools in large populations, such as those in prisons or refugee camps. The sputum samples identified by the rats will still need to be re-tested by microscopists, but Apopo says the process will be much more efficient as their technicians use more advanced techniques, and only need to check the relatively few samples picked out by the rats.
|Trained rats can test 10 TB samples a minute [Reuters]
Apopo's work is being watched with curiosity by medical researchers. "It is certainly a very interesting, innovative method that justifies further exploration," says Dr Bob Colebunders, professor in tropical diseases at the Institute of Tropical Medicine in Antwerp, Belgium.
"Moreover, the rat training methods developed by Apopo are very interesting because they may also be used for other applications such as the detection of people during earthquakes or the detection of fake drugs," he says.
"We also need to learn more about the smell that is produced by different microbes and how this knowledge could be used to develop new ways to detect these organisms," he adds.
"But certainly additional studies need to be done. It may be difficult to obtain accreditation for the method or to commercialise it because regulatory authorities are not used to this type of test."
Apopo continues to research the rats' techniques and accuracy, and eventually hopes to get accreditation from the World Health Organisation. But in the meantime their operation continues to grow. At the start of 2013 Apopo opened a second TB detection lab, in Mozambique. The rodents are currently screening samples from eight partner clinics, and so far they have picked up 114 TB cases that would otherwise have been missed.
Rats are often seen as dirty, frightening creatures. But as Astrid and the rest of Apopo's "hero rats" continue to save lives, the sight of a pink whiskered nose and a long brown tail may start to provoke a different reaction.
This is certainly true for former TB patient Janet Zakaria, whose illness was repeatedly missed by hospitals before she was diagnosed at Apopo. "The rats got me better," she smiles. "I will always remember them fondly."