Who discovered serotonin? 5 Questions with neuropharmacologist Patricia Whitaker
Whitaker discusses the intertwined histories of LSD, serotonin, and how we understand mental illness.
Serotonin is a rockstar in the neurotransmitter world. You don’t need to be a scientist to know that the “happy” molecule, as it’s known, is involved in regulating our moods. People have tattoos of serotonin’s chemical structure, and there are plenty of serotonin necklaces and earrings available to buy online. So-called classic psychedelics, including LSD and psilocybin, interact with serotonin receptors in the brain.
But Patricia Whitaker, a neuropharmacologist and a professor emeritus at Stony Brook University remembers training as a neuroscientist in the 1970s when serotonin was still novel—only recently understood to be important in how the brain functions. Her career was spent mostly studying the relationship between autism and serotonin, though her 1979 doctoral thesis compared LSD to other psychedelics, such as DMT, ibogaine and psilocybin, examining how they affected serotonin receptors. She and other early neuroscientists saw a connection between serotonin and psychedelic compounds, and believed that understanding serotonin could someday lead to better mental illness treatment options. The Microdose talked to Whitaker about the discovery of serotonin and how the neurotransmitter in many ways gave rise to the modern field of neuroscience.
Who discovered serotonin?
It’s hard to say what discovery means. Let’s say discovery is the moment you give something its name. That would be Maurice Rapport and Irvine Page who discovered serotonin in blood [in 1948]. They worked at the Cleveland Clinic, which was known as a cardiovascular research center. They were focused on the problem of hypertension, or high blood pressure. They knew that when blood vessels were cut, they would spasm and constrict, and they were trying to identify what substance caused that—because they thought maybe that’s why people have high blood pressure. They isolated gallons and gallons of blood, and they found something that caused constriction of blood vessels. They called it serotonin, because sera is serum or blood, and tonin is tension.
At the same time they were doing that, Vittorio Erspamer in Italy was looking at substances in the gut that would cause constriction. He found a substance that he called enteramine. Both Vittorio Erspamer and Irvine Page carried on doing their work for around 10 years before they both realized it was the same thing, when they finally isolated the chemical structure.
Was serotonin ever used to treat high blood pressure? How did serotonin break out of the hypertension box and be understood to be important for the brain?
No, the serotonin that gets in the bloodstream is largely regulated by platelets. If platelets are damaged, if there’s a cut, then the serotonin comes out and constricts blood vessels. It’s only there as a defense mechanism.
The person most responsible for the next step was Betty Twarog, who really thought, let’s look in the brain. At the time, [scientists] were just classifying neurotransmitters. Work with the heart had found adrenaline and acetylcholine—one chemical that sped it up, one that slowed it down. The general attitude was, ‘Why would you need any more?’ In the brain they thought if they found adrenaline and they found acetylcholine, that was enough. Now, we know there’s hundreds of other neurotransmitters.
Betty Twarog was interested in marine animals. If you eat mussels, sometimes you can see there’s a little leg that comes out that attaches to the rock. She was studying what causes it to constrict. When others started talking about serotonin she thought, maybe it’s serotonin. And then she wanted to look for it in the brain, and found it [in the early 1950s]. Everybody, as I said, thought, ‘We don’t need anything more,’ so she had a long, hard time getting her finding published [in 1954].
LSD and serotonin have a similar chemical structure—who noticed that similarity?
D.W. Woolley gets most of the credit for that. He was an amazing guy. By the time he went to Rockefeller University [in 1939] he was blind from diabetes. It is known that he liked to build elaborate visuals in his mind when he couldn’t see. He knew when he was going blind, and he had a couple of years when he traveled across America to really look at things.
The way he did it with LSD is by making a molecular model. When we were undergraduates, we all had kits that you could make models to understand bonds, and that’s what he did. He did it by feeling the LSD model, and feeling the serotonin model.
When you look at LSD, you can see the serotonin molecule when you’re told it’s there. But he must have spent a great deal of time feeling around, because you’d have to find and feel the bonds.
He knew about the effects that LSD could have on the brain, perception, and hallucinations from reading Albert Hoffman’s writing, the inventor of LSD. What did Woolley make of the chemical similarity between LSD and serotonin?
Woolley was interested in diseases that influence agriculture and plants. Like, he worried about this black tongue disease that was in cows. So he developed the idea that there are some little tiny molecules that can cause disease. He wanted to understand why some people got mental illnesses, and he decided—and he was right, of course— that it involved molecules.
It was so completely different from what anybody else thought. Woolley went to international psychiatry symposiums when they’re all still talking about Freud. All the Freudians were like, ‘No, it’s your mother.’
In his book [The Biochemical Bases of Psychoses or the Serotonin Hypothesis about Mental Illness], he really thought it out; he talks about what could serotonin’s role be in schizophrenia. LSD doesn’t cause auditory hallucinations, which is a hallmark of schizophrenia, so maybe serotonin was just one part of schizophrenia. It goes back to his idea that little molecules can do so much, that they can actually make your brain work completely differently. Humphrey Osmond and Albert Hoffman also spent a lot of time taking hallucinogens seeing if they could find out what it was that caused schizophrenia.
All us old serotonin researchers, and I’m in my 70s now, we all joked about getting interested in serotonin because we were so amazed by LSD. I really think that’s true. LSD was a big influence on a lot of research ideas, and what a lot of people thought would be interesting ways to study the brain.
If something could change the brain drastically, the brain must be something that is very finely tuned to function properly—to have the right perception of things, to have the right emotion, to have the right cognition. It must be very, very highly managed. LSD did so many things that at first people thought, well, that’s too many. But now that we know serotonin has so many different receptors and it’s so regulated in so many different ways, it makes sense to have that many effects.
There has been a lot of focus for decades on the role of serotonin deficiency in causing depression. But increasingly people have begun to question that theory of depression. Where do you stand?
Today people throw the word serotonin around, like, ‘Is your serotonin not high enough?’ It’s so annoying how people just write it off, like it’s a boring chemical. But it’s not, it’s so sophisticated in so many ways, in so many brain regions, and developmentally.
I think we got carried away with the SSRIs. Everybody seemed to think you could just take it and that’ll make you better. It’s interesting, it goes along with what I think about psychedelics. I’m a big believer in the role of psychedelics, historically, in religious ceremonies and spirituality. In the same way, you can’t take LSD, MDA, or ayahuasca and all of a sudden believe in God. You can’t take a pill to believe in God, you still have to work at it, study about it, think about it, question yourself.
That’s the same with taking a drug for depression. You can’t take a drug and you’re all better. You still have to work on it, and think about it, do psychotherapy. There isn’t a pill that can change your brain permanently, that quickly.
This interview has been edited and condensed for clarity and length.
