Diagnosis remains a major stumbling block in the way of treatment and eradication of several diseases, such as cancer and tuberculosis (TB)—a problem I know all too well, as it concerns my research directly. Early diagnosis has an important impact on patient prognosis and is therefore crucial to the advancement of medical research. Most diagnostic tools rely on the detection of a biomarker that is disease-specific and present in large enough quantities to be easily detectable via quantitative techniques. Ideally, this biomarker should be found in a fluid or matrix that can be obtained from the patient via non-invasive means without using expensive and complex equipment. This is particularly relevant in resource-poor settings where access to state-of-the-art technology is not available.
However, in the case of tuberculosis and certain cancers, the ideal biomarker remains frustratingly elusive. For this reason, certain researchers have had to think outside the box—and outside the lab. Dogs have shown that they can have several uses beyond mere companionship. Guide dogs help millions of visually-impaired people perform daily tasks, while security dogs help police and private companies maintain safety. Dogs are known for their highly acute sense of smell, which enables them to detect explosives and certain drugs. Dogs also have the ability to detect minute disease-specific molecules in patient samples and thus help scientists diagnose certain cancers.
A 2012 study evaluated the abilities of four dogs to detect lung cancer in 220 patients who provided exhalation samples. Some of these patients were diagnosed with lung cancer while others suffered from chronic obstructive pulmonary disease (COPD), an illness often associated with the development of lung cancer. The inclusion of these patients helped to determine that cancer detection by dogs was independent from COPD and other strong odors (tobacco smoke and food) with a specificity of 93% and sensitivity of 71%. This study strongly suggests the existence of a volatile organic compound (VOC) or scent pattern specific to lung cancer that dogs’ noses are strong enough to pick up.
Another study assessed a dog’s ability to detect prostate cancer in patient urine samples. This Belgian Malinois Shepherd underwent 24 months of training before being presented with 66 urine samples, 33 of which came from patients with prostate cancer. To indicate prostate cancer, the dog sat in front of the relevant sample and was rewarded with his ball. The dog was able to correctly identify the cancer samples in 30 of the 33 cases, thus showing 91% specificity and sensitivity. Similar results have been obtained with urine samples from patients with bladder cancer and bandages from patients with breast cancer. In another program, dogs have been trained to sense the onset of their owner’s seizures and warn the patient 15-45 minutes prior to the seizure, thus reducing their occurrence.
Perhaps even more incredible is a study carried out at the University of Otago, New Zealand. It started with the UK-based company Inscentinel, which aimed to train and use bees to detect explosives in airports. Bees can be conditioned to exhibit a proboscis extension reflex in response to smelling certain scents—in the wild, this reflex is a natural reaction to food. While Inscentinel never really took off, Max Suckling and his student Rachael Sagar followed on from the idea and trained bees to recognise three TB signature components that are identifiable in human breath samples: methyl phenylacetate, methyl p-anisate, and methyl nicotinate. These were diluted in methanol and pipetted onto filter paper at a concentration of 10 ng/mL. Insects were placed in Eppendorf tubes with the tip cut off to allow free movement of the head and proboscis, and were presented with various smells. Each time the bee extended its proboscis in response to one of the TB signature compounds, it was rewarded with sucrose.
The results were astounding: the bees could accurately detect all three compounds in human breath samples, with a clear preference for methyl p-anisate. Interestingly, this compound is found in plants such as the Orchidiaceae family and has a jasmine-like fragrance. While these results fascinate both entomologists and TB researchers, no further investigations have developed from this 2011 study.
Through these unconventional studies, researchers have highlighted the importance of creativity in scientific innovation and discovery. While writing successful grant applications to support studies involving animals for diagnostics may prove difficult, the results can be surprisingly positive—as proven by the numerous cancer-detection programs involving dogs.
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