SITNFlash

This month's article covers canines, cancer, and the sense of smell, three topics which have been linked recently in an intriguing new study. After reading this article, we won't be surprised if you are tempted to start calling your dog “Doctor.”

Please see below for an important note regarding the spring 2006 Longwood seminar series.

When one considers how cancer is currently tested for and diagnosed, it is probably thoughts of blood samples and high tech machines with wires and whirring magnets that come to mind. It's unlikely that you think of curiously sniffing canines. However, it is the damp twitching noses of trained pooches that have recently been reported to detect cancer. A research group in San Anslemo , California has reportedly trained 5 dogs to detect cancer in the breath of lung cancer patients with 99% accuracy.

The dogs, borrowed from Guide Dogs for the Blind, were trained as if detecting bombs. That is, they were rewarded for identifying trace amounts of a chemical called n-amyl-acetate, which smells like bananas. Once the dogs had learned to distinguish a particular chemical, their response could then be applied to the detection of unknown chemicals that exist in some samples but not in others. In the actual study, the breath of patients with and without lung cancer was captured in glass tubes. The dogs were led past several samples and sat in front of those samples in which they detected trace amounts of something aberrant. Amazingly, those aberrant samples were largely from the cancer patients.

The concepts upon which the study is based are sound. Cancer cell have long been known to release different amounts of certain chemicals than healthy cells. Normal cells in the body constantly react with oxygen to produce energy and carry out their normal functions. A natural by-product of this energy acquisition is the production of harmful small molecules called free radicals. These molecules can damage proteins, cell membranes, and genes. Part of this process, referred to as “oxidative stress,” results in the release of tiny chemicals called alkanes and benzenes. Cancer cells undergo unrestrained division and ignore all of the normal stop signs and check points. They also use increasing amounts of oxygen to make energy for themselves and, as a result, they produce lots of harmful free-radicals. Thus, cancer cells exude more alkanes and benzenes, which could theoretically be detected, although it is not known if it was these chemicals, or some other biochemical marker, that the dogs were responding to in this study.

Another well-established concept which increases the plausibility of these experiments is the fact that canines have a sense of smell that is estimated to be 1,000 to 100,000 better than that of humans. This superiority of smell is partly a result of dogs having a greater variety of odor receptors in their noses. Individual odor molecules bind to and stimulate receptors in the nose. Nerve cells, or neurons, located in the nose send nerve fibers to a part of the brain called the olfactory bulb. The pattern of neurons that are activated by odors and the combination in which they are received in the olfactory bulb is what allows us to distinguish and interpret smells. In addition to having more diverse smell receptors, dogs also have more neurons connecting their noses to their brains and a greater proportion of their brain devoted to smell. This combination makes it possible for them to discern smells that don't even register on our human odor radar.

Dogs detecting cancer by smell is biologically plausible. However, a good scientist or informed layperson must take a skeptical stance. Peer investigation of the methodology appears clean. It is important that the dog handler and any researchers present in the room were “blind” to whether the tube contained the breath of a healthy individual or one with cancer. This assures that the dogs were not responding to some cue rather than to the smell, as even the nearly undetectable tension of a researcher's hopeful anticipation of a correct response might be sensed. Additionally, it is significant that there is no overt difference between the cancer and control groups other than their lung cancer diagnosis. For example, if all the cancer patients happened to also be smokers, then the dogs could have been detecting whether a person smoked (the major risk factor for lung cancer), not whether a person had cancer. But, in this study such confounding factors were controlled; there was an equal number of smokers in both categories.

While the methodology appears beyond reproach, the accuracy of the dogs is astounding. Studies have been done in the past using canines to detect bladder cancer in urine samples and melanomas on the skin of patients, but never has the accuracy of detection been so high. Some think it's almost too good to be true. In the wake of the discovery of scientific fraud in the high-profile Korean human stem cell publications, the scientific community is appropriately cautious.

The best way to determine the validity of this research is for other research groups to reproduce the results. In science, one never proves anything; scientists just repeatedly fail to disprove an idea until it has been supported enough that it becomes more accepted. As doctors and patients await such checks and balances of scientific discovery, there is plenty to look into in the lab rather than at the dog trainer's. If the dogs are indeed detecting biochemical markers on the breath, scientists are interested in analyzing these breath samples to find the precise mix and levels of chemicals that the dogs were responding to. Such information could be used to create a widespread diagnostic test that you might expect to see at your doctor's office far sooner than you should expect to find Fido there.

Primary Report

“Diagnostic Accuracy of Canine Scent Detection in Early- and Late-Stage Lung and Breast Cancers.”. M. McCulloch et. al Integrative Cancer Therapies. March 2006, Vol 5, No 1. (Limited-time free online access at http://www.sagepub.com/preprint_8435.pdf)

For more information:

“Dogs Excel on Smell Test to Find Cancer” D. McNeil Jr. New York Times January 17, 2006

Society for Neuroscience “Brain Briefing” on Smell and the Olfactory System (http://www.sfn.org/content/Publications/BrainBriefings/smell.html)

National Cancer Institute webpage for cancer information (http://nci.nih.gov/cancertopics)

The 2006 Harvard “mini-med school classes” for the public are unfortunately full. However, you can request to be on the waiting list. More information, as well as videos of the classes, are available online at http://www.hms.harvard.edu/longwood_seminars/ .

The 2006 schedule:

March 1- To Test of Not to Test: Want to Know What's in Your Genes?

March 15- Maintaining Mental Agility: From Brain Aerobics to Repair

April 5- Being Mindful of Your Heart: Pondering Diet, Exercise & Stress

April 26 – Global Health is Local Health: Bad Bugs Can't Read Maps —Co-sponsored by WGBH