Dr. Michael D. Gershon is all about the gut. Renowned for his pioneering work on the enteric nervous system and the role of serotonin within it, he’s been respectfully dubbed the “father of neurogastroenterology.” As the author of “The Second Brain: A Groundbreaking New Understanding of Nervous Disorders of the Stomach and Intestine,” he has received widespread academic recognition and made numerous media appearances throughout the years.
The native New Yorker, born on March 3, 1938, studied at Cornell University, where he earned a bachelor’s degree with distinction in 1958, as well as a medical degree in 1963. He then attended Oxford University from 1965 to 1966. “They let me out for good behavior,” says Gershon. “I did my post-doctoral training, came back to Cornell and became a professor. Finally, [Columbia University] chipped me out of Cornell’s woodwork” in 1975. Having acted as the chairman of the school’s Department of Anatomy and Cell Biology until 2006, he is currently enjoying teaching and conducting research at the iconic institution.
Gershon is the recipient of a number of prestigious honors, including the Henry Gray/Lippincott Williams Wilkins Scientific Achievement Award in 2000, being elected as a fellow of the American Association for the Advancement of Science in 2007, and gaining membership in the American Clinical and Climatological Association in 2011. He received an Alumni Award of Distinction from Cornell University in 2012, which was also won by his wife, Dr. Anne Gershon, one year prior. Brain World had the privilege of sitting down and interviewing the famous scientist for its summer issue.
Brain World: What are the origins of neurogastroenterology?
Michael Gershon: The field began at the end of the 19th century, when two British physiologists, [William] Bayliss and [Ernest] Starling, were playing with the intestine of a dog. When they raised the pressure inside the lumen of the intestine, they found that the gut would respond with a stereotypic response — oral contraction and anal relaxation — that was propulsive. They called that the “law of the intestine”; they were very into laws. When they cut all the nerves they could find that went into this piece of gut, the gut continued to do it, so they attributed that activity to the gut’s local nervous mechanism.
They did that because a German scientist [by the] name of Leopold Auerbach previously found a huge number of nerve cells in the gut now referred to as the myenteric plexus (Auerbach’s plexus). Georg Meissner, another German scientist, found a second plexus called the plexus of the submucosa (Meissner’s plexus).
Some 18 years later, Paul Trendelenburg, yet another German scientist, got tuberculosis. That kept him out of the trenches of WWI, but he had to keep busy. So he strung up a guinea-pig gut
in vitro — essentially, a test tube in a nutrient solution — gave it some oxygen and hooked it up to a J-shaped tube. When he blew into the gut through the J-shaped tube, the gut blew back, and what he noticed was that for the gut to blow back, it had to know that he blew into it. That was exactly the same behavior that Bayliss and Starling had seen in intact animals years earlier. And so that established that the gut had a nervous system that could work on its own.
After that, things changed because the autonomic nervous system — the sympathetic and parasympathetic nervous systems — was being discovered. There were two systems, and people knew of two transmitters, so they decided that the enteric nervous system must be parasympathetic. In other words, they thought that the brain or the spinal cord talk to the muscle in the gut to get it to move by working the nerve cells. And they believed the gut’s ability to do it when it was not connected to the brain to be a detail. So it was forgotten.
BW: How did you come to study the gut?
MG: So when I went to the lab of Edith Bülbring in Oxford, back in prehistory, she was working on what enabled the gut to function independently. She had essentially rediscovered what Bayliss, Starling, and Trendelenburg had found earlier, and it became significant. When I got there, I said, “Well, that’s interesting!,” and I decided that I was going to study this nervous system. The idea was that by looking at the gut as a simple nervous system I could understand how a simple nervous system controlled the behavior of its own organ.
BW: So, the gut can work completely independently of the brain?
MG: Yes, it can. Now, an organ such as the heart will beat on its own. So, you can cut off all the nerves and transfer the heart from one person to another. But there’s no integrative behavior in what the heart is doing. It’s not sensing anything and responding to it or changing what it does. It’s automatic, so it just does that for all of your life.
The gut can show many different kinds of behavior; it’s not only this or that. The gut is sometimes propelling, and other times it’s mixing — it lets the chemical reactions for digestion take place. If the gut was propelling like that all the time, then social discourse would become impossible, not to mention you wouldn’t have time to absorb your food. Sometimes, it senses that you ate something you shouldn’t have. Retropulsion and vomiting occur to get rid of it. It teaches you, “Don’t do that again.” Unfortunately, it only uses negative conditioning.
Now, when I say the gut works on its own, and it’s the only organ in the body that can do this, it doesn’t do this all the time without influence from the CNS [central nervous system]. So, for example, when I call NIH [National Institutes of Health] to find out how my latest grant application has done, I become painfully aware of the effect the brain can have on the gut. And that’s a common feeling. This is a two-way street.
It’s also true that stimulating the vagus nerve that connects the brain and the gut — about 90 percent of the fibers in the vagus nerve carry information going upstairs rather than downstairs — is now used to relieve depression, and it’s better than electroconvulsive therapy. It’s been used to relieve epilepsy and has been demonstrated to improve learning and memory in animals and humans.
BW: So, it is possible for the gut to influence emotions and behavior?
MG: Yes, absolutely. Some of the information the gut sends to the brain, which is called “homeostatic” — means it improves balance — is quite beneficial to the workings of the brain because the brain depends on it. And if you cut it off, it’s not so good for the brain because the gut could disturb it.
So, for example, when I was young, we were taught in medical school that there was such a thing as an ulcerative-colitis personality. People with ulcerative colitis [a chronic disease of the large intestine] have hard-driving, Type A personalities; they are obsessive compulsives, perfectionists, and neurotic. And those with Crohn’s disease are very nervous and high-tension people. We now know that these are autoimmune diseases, like rheumatoid arthritis and lupus.
It’s not that the brain is doing something bad to the gut. We think bad thoughts put holes in the colon. What is happening is that the holes in the colon make people think bad thoughts. The personality disorders go away when you take the damn colon out and leave ulcerative colitis.
BW: When you spoke of the two systems and two neurotransmitters earlier, which transmitters were they?
MG: Acetylcholine, and what they thought was epinephrine turned out to be norepinephrine (adrenaline and noradrenaline). Acetylcholine is one of the most important neurotransmitters in the body. It’s the one that makes your skeletal muscles work. The nerve-to-skeletal-muscle junction and 100 percent of the muscle is turned on by acetylcholine. So, that’s critical. Nerve gas blocks the ability of the body to turn off acetylcholine. And it’s deadly, because if you can’t turn it off, your muscles just become flaccid and can’t work.
BW: Can you talk about your work with serotonin?
MG: Serotonin was first known to be a neurotransmitter in the brain. While working with Edith Bülbring, I became aware of the fact that 95 percent of the body’s serotonin is actually found in the gut, not the brain. So, the brain is just a small afterthought in terms of the amount of serotonin that is present in the body.
Brain and gut serotonin are completely different because the blood-brain barrier does not let serotonin go through it. So, all the serotonin that’s in the brain is made there, and all the serotonin the gut puts out into the rest of the body (including the 2 to 3 percent of it found in the blood) is essentially made in the gut.
Now, the serotonin that’s in the brain seems to be involved in everything that makes life worthwhile. For example, it’s important for happiness and in fighting depression. It’s involved in sex, eating, sleeping, and dreaming. I mean, it’s wonderful stuff, but, quantitatively speaking, the gut is where it’s at.
I began looking at what it does there. As it turns out, it’s involved in many, many different kids of things. It’s what I’m now calling a polyfunctioning molecule. The gut has serotonin that is part of the sensing system, and so, when bacteria — and there are plenty of those in your gut — begin to invade, an anti-inflammatory response, which is anti-bacterial, is set up. This is independent of the brain.
However, the inflammation in the gut, which serves to prevent invasion, is potentially damaging to the gut, so the nerve cells in the gut can be collateral damage. But serotonin in the nervous system has a completely different role. Instead of promoting inflammation, it blocks it. And inside the gut, it protects the neurons from inflammation, so if any get killed, it helps make new ones from stem cells. So serotonin acts like the sword and shield of the gut. It also has a number of other functions.
BW: What would happen if serotonin wouldn’t do that?
MG: Animals that have reduced serotonin signaling, turns out, have bacterial overgrowth. It comes charging up out of the colon and the big and small intestine, and, if you monitor that, you see this constant bacterial invasion. They don’t fend off bacteria very well.
But what’s very interesting is that lots of diseases of the brain also affect the gut. For example, Alzheimer’s and Parkinson’s cause problems in the gut. In fact, in Parkinson’s patients, their guts are affected long before they have motor symptoms and can cause them to become profoundly constipated. Similarly, the gut doesn’t function very well in individuals with an autistic spectrum disorders.
There are only a few tens of thousands of serotonin nerve cells in the brain, but they project to many regions of the brain and are necessary for modulating brain function.
BW: How do you study the effects of serotonin in the body?
MG: We now have lots of tools to study it that are very novel. For example, we can look at mice that have no serotonin in the lining of the gut, mice that have no serotonin in the nervous system but have plenty of it in the lining of the gut, and mice that have no serotonin at all — the latter are very unhappy animals. If you eliminate all of the serotonin in the body, you will survive, but you wouldn’t survive very well.