Vagus Nerve Stimulation and the Immune System

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What is the vagus nerve and why is it important for health?

Eric Topol 0:00
All right. Well, I am really thrilled for this new Ground Truths live video to welcome a pioneering neurosurgeon who is the CEO of the Feinstein Institute of Medical Research at Northwell, Dr. Kevin Tracy. Kevin, it's great to have you.
Dr. Kevin Tracey 0:19
It's great to be here, Eric. Thank you for having me on. I'm looking forward to this chat with you.
Eric Topol 0:24
Yeah, well, your work, which has been going on for decades, culminated in this book. A part of it encapsulated in this book, The Great Nerve. If everybody doesn't know what The Great Nerve is, it's the Vegas nerve. Vegas for Latin word for wandering. And this nerve is like the internet throughout the whole body, connecting the brain to everything. And you made a seminal discovery recently. I think it was back in 1986 with baboons, the idea that up till that time, the brain and the immune system were thought to be in different orbits. They weren't connected. They were firewalled. And you came up with experiments, I think, in baboons and tumor necrosis factor. And for the first time, you connected the dots.
Eric Topol 1:12
Is that a fair summary of what happened back then?
Dr. Kevin Tracey 1:16
It is. It is a fair summary of what happened. Back in the 80s, I was part of the team here in a few blocks from where I'm sitting in New York City at Rockefeller and Cornell that identified the biological activity of TNF as a major mediator. He first demonstrated that monoclonal antibodies... targeting TNF could inhibit inflammation. Now, this was published back in Nature in 1987 in a paper I wrote with my colleagues. And this paper was the first description of monoclonal anti-TNF antibodies as having a therapeutic potential. And of course, today, those antibodies have all kinds of commercial names like Humira and Remicade and and they're related ones for IL-1. And we call the whole thing cytokine storm.
Dr. Kevin Tracey 2:08
But back when we were doing this work, what we were actually defining was that TNF is sort of the proximal trigger of a cytokine storm. And today that's treated with these monoclonal antibodies. But the real question that remained is if the body has the ability to produce these molecules, cytokines, TNF, other things, that can cause so much damage through inflammation, then how is it normally controlled? What is it that evolution did over millions of years to put the brakes on inflammation and prevent it from causing damage in most of us who are healthy? And that question led to the discovery of the rule of the vagus nerve acting like the brakes on your car to suppress inflammation.
Eric Topol 2:56
Yeah, so I think this was such a big thing because this inflammatory reflex, as you labeled it, I think, really brought together the pathway in the brain this great nerve, vagus nerve, as a mediator of inflammation throughout the body, which sets up a whole lot of ability to hack into this vagus nerve with vagus nerve stimulation. And so you present in the book many anecdotes. Before I get into that, when you made that discovery back in 86, a lot of people called it a eureka moment. You called it a holy shit moment.
Dr. Kevin Tracey 3:37
So the holy shit moment came in the 1990s. We were specifically addressing the question, might the brain, by sending signals through the vagus nerve, be turning off inflammation? And that came about because of an experiment that produced a big surprise. And you could call it an accident in the lab. we were putting an anti-inflammatory molecule into the brains of mice and rats with the sole purpose of blocking inflammation in the brain in order to reduce the damage of a stroke, an experimental infarct. And that all went as planned.

How did Dr. Kevin Tracey's research connect the brain and immune system?

Dr. Kevin Tracey 4:18
What we hadn't planned is that when we put the anti-inflammatory molecule in the brain, and we had developed this molecule in the lab, so it was an experimental drug, when we... Put this in the brains of these animals, it also turned off inflammation in the body. That was the holy shit moment. Like, how could the brain be sending signals to control the immune system? There was no way in 1998 to explain this. We went into the literature. And I found an old paper, then an old paper, now even older, that had been cited by essentially nobody, that Linda Watkins from Boulder, Colorado, had been studying sickness behavior.

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