The Fatigue Biomarker Story – Part I

Blog written by John Kalns


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Perhaps one of the more astounding scientific discoveries that I have been involved in is the discovery of the salivary fatigue biomarker. This is part one in the fascinating story about this discovery.

And Our Story Begins…

This story begins 10 years ago when the U.S. Army determined that there was a significant issue at hand concerning fatigue in the Iraq and Afghanistan wars. The problems were: too many soldiers had to work/fight for too many hours; carry too much ammunition, water, and armor; be subjected to 120F heat; and maintain constant vigilance.

Not surprisingly, Army leadership became worried about the situation’s vulnerability to failures caused by fatigue, and they were curious if better analytics could help the issue.

The analytics solution had many components, and one part was getting objective measures of fatigue during combat. The idea was that if fatigue could be measured objectively, then commanding officers could distinguish between which soldiers could be safely deployed and which ones needed to stay home and “catch some Zs”.

The Start of a Long Journey

I wrote a grant proposal to the U.S. Army, proposing that we could identify substances in the body that would be associated with the fatigue state. The proposition was not totally outrageous – there are many physiological adjustments made in response to various stresses. For example, when we get really scared, our bodies initiate a response.

If you get scared enough, your body can release large amounts of small molecules (called neurotransmitters) into your bloodstream. This causes an almost instantaneous increase in vigilance, strength and metabolism, and, most importantly, an almost complete reversal of the fatigue state.

This is called the “fight-or-flight” response, and it can be objectively measured in a number of ways. However, measuring fatigue in a purely objective matter has proven to be a difficult challenge.

The Idea to Collect Saliva Samples

Another really cool and interesting concept was to collect saliva samples instead of blood samples for measuring fatigue markers. From a military operations standpoint, this concept was a great idea. Obtaining blood samples from a soldier during combat is difficult (to say the least), but in comparison, getting saliva samples seems like a pretty simple task.

There are a couple of problems with saliva, though. First, the medical community has been focused on blood since the beginning of time, so research on saliva is thin in comparison to the abundance of research on blood.

Second, mice produce only a small amount of saliva—and getting a saliva sample from a mouse presents difficulties. This is important to consider, since so much biomedical research, including behavioral research in the United States, is conducted on mice. If you’re doing an experimental study on mice, you will typically collect and evaluate blood samples.

Cell Lines… Wait, What?

The third problem is the lack of useful cell lines in salivary glands. You might be wondering what a cell line is, so (without getting too deep into it), cell lines are immortal cells that grow forever in a laboratory. In most instances, cell lines come from cancerous tumors in humans. In the biosciences, cell line experiments are often done before mouse experiments.

Cell line-based experiments can often provide tremendous insight into how things work in the human body. These experiments allow researchers to easily manipulate the genome, send cells chemical messages, and study exactly how cells respond on a variety of levels. Yet while there are cell lines derived from many different organs, there are no cell lines available that mimic the function of the salivary glands. Compared to working with blood, researchers face many challenges when working with saliva.

In my opinion, these advantages are more than offset by the ease with which saliva samples can be taken from people in contexts important to us – in combat, at a sporting/competitive event, at home, etc.

Up Next

Stay tuned because part two of The Fatigue Biomarker Story is coming soon! Check back next week to read the next part of our story!

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