Part 1


Dr. Tuszynski: Hi Brian. As you know, I’m a physicist with an interest in biology and medicine, applications of physics concepts, both metaphorical and literal, and one of these concepts that that I find of interest, which exists both in physics and medicine, is the concept of stress. For small stresses, deformations occur which are reversible. For larger stresses deformations become irreversible. Eventually for very large stresses, the object can be broken into pieces. My question to you is whether any of these concepts can be found in medicine and physiology, of course, and whether physics can be useful in understanding these medical concepts and physiological ones?

Dr. Fertig: Sure. Physics and medicine share a rich and powerful intersection, of course, and the chronic activated stress response is the most underrecognized ailment to public health. There are two basic forms of toxic stress – one is cortisol driven. It works on the emotional center of the brain, particularly an area called the amygdala. It drives fear. Anger is rooted in fear. But “chronic fear” doesn’t really exist, it’s imaginary. However, the consequences of chronic fear, anxiety and depression, and the chronic diseases of aging, are not imaginary.

For example, depression portends a 30% increase incidence of acute cardiac events, in the setting of depression as opposed to in non-depressive patients, such as an acute myocardial infarction (“heart attack”) and a 36% increase risk of fatal cardiovascular events (ultimately fatal arrhythmias). One of my favorite quotes by Mark Twain, which I find quite humorous, is “I have suffered much tragedy in my life, most of which never happened.” Very apropos to this topic.

The second type of chronic stress is caused by resistance to cortisol. This is mediated by brain-derived neurotrophic factor (BDNF), which causes phosphorylation of the receptor to cortisol that activates it – so there’s resistance of cortisol. Cortisol works by driving the gene transcription of proteins that create the energy producing machinery, carried in the mitochondria. So, when there is a resistance to cortisol, the result is a loss of oxidative metabolism, and thus the inability to produce energy. This cortisol resistant form of stress, so-called “burnout,” manifests as physical, mental, and emotional exhaustion because you’re not making energy. It’s intuitive and it makes sense.

Also, the fact that it works on the amygdala, which is the fear center of the brain, means that cortisol resistance results in the absence of fear, not afraid of the consequences of giving up. People with burn out often suffer alcohol and drug addiction, divorce, and even suicide. That is the reality of the chronic activated stress response that not only drives the chronic diseases of aging, but these other tragic parts of human life, unfortunately.

Part 2

Dr. Fertig: I recently received an email from a physician and colleague of mine, Lou Amarosa. Lou runs the clinical clerkships of the medical students of Robert Wood, who rotate through the services of medical specialists on staff. He congratulated me on my book and said to me “from one clinician to another, we should heed the advice that we give to our patients, which is: get adequate sleep, maintain a good diet, exercise, and take breaks and vacations from hard work.

Now, let’s talk about that for a minute because all those things are very important to understand when it comes to stress. Take sleep and diet, for instance. They’re pro-inflammatory when you’re not getting an adequate amount of either one. Poor quality sleep and diet leads to a lot of inflammation whereby protein inflammatory cytokines loop back on the brain; that feedback on the brain to reduces the threshold for the perception of stress, which amplifies this chronic activated stress response. Taking respites from work interrupts this persistence of stress. In other words, we must take breaks from the work we thrive on, but which subconsciously impairs our resilience, our wellness, and ultimately the enjoyment of life.

Exercise is also anti-inflammatory. Interestingly, however, is that exercise promotes BDNF production, which begs the question: is BDNF good or bad? Well, it’s both. It’s this notion of hormesis: at moderate levels something is good and, while at low or high levels it is bad. Exercise at moderate levels essentially puts the brakes on the cortisol response by inhibiting the activation of its receptor, and thus provides resilience to the stress fear response. However, if you’re completely negating the effects of cortisol from very high levels of BDNF due to e.g. wildly excessive exercise or other etiology of chronic exaggerated activation of the stress response, that can have tragic effects.

Let me also say that it’s not just exercise that can induce therapeutic levels of BDNF. Studies are showing this effect in other contexts like yoga and mindful meditation. This explains mechanistically the benefits of these behaviors on improving longevity and health span.

While the consequences of both forms of stress (cortisol driven and cortisol resistance) are often reversible, the devastating effects of burnout, including loss of life and broken relationships, are often not, equating to the physical forces of stress that break objects.

You can’t have both vitalizing and toxic stress at the same time. Toxic stress robs us of what makes us uniquely human – empathy, compassion, social awareness and intuition, and love… We can’t have these things if our core values are hardened in the context of chronic stress. So, vitalizing stress is what’s key.

Dr. Tuszynski: It’s been most illuminating. I presume that, based on what you said, quantifying and controlling stress will help a lot of people live better lives, longer lives, and with a higher quality.

Do you have any other suggestions on how one could reduce stress and therefore improve health?

Dr. Fertig: To use a physics analogy, vitalizing stress through social bonding and networking tends to spread stress over a greater mass, preventing or lessening its toxic effects. You know, change is an inescapable hallmark of time, and fear is often associated with change. Human connection and networking, as a collective intelligence, makes it easier to maintain personal expectations such as happiness and fulfillment. In both physiology and society, integration is a hallmark of health while isolation is a disease.

Physiological purpose is inspiring. That we’re motivated not only to survive as individuals, but to help others do so as well. To promote the joys, the opportunities, the health and general welfare of others, which are inextricably entangled to those of our own.

Nothing elevates us more than to become a part of a new system which is greater than the sum of its parts.

This defines physiological purpose at every hierarchical scale – from smaller than the human cell to larger than a human being.

Dr. Tuszynski: I thank you for this most uplifting message, Brian, and I hope that this is to be continued because it’s most interesting to have this dialogue between physics and medicine.

Dr. Fertig: For sure. Thanks Jack, and take care.

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