BOSTON — Remember LSD, that infamous mind-expanding drug of the 1960s? Some young researchers at Harvard Medical School have cracked open the door to the LSD vault, which had pretty much been locked for more than 40 years.
Jake Wintermute is one of those researchers. He's a metabolic engineer researching pathways to new drugs from those long blacklisted compounds, LSD and especially lysergic acid. "I recently finished my Ph.D. at Harvard Medical School in the department of systems biology. I'm a metabolic engineer and what we do is genetically modify micro-organisms to try to get them to produce molecules, compounds, that are either interesting or valuable," Wintermute explained.
LSD turns out to be both interesting and valuable. But LSD and its close cousin lysergic acid have been under lock and key for decades. They're controlled substances, strictly regulated by both federal and state laws.
"There's real agents in suits with guns and when we get it, we have to sign it out, and there is a two-key mechanism to open the cabinet that has the lysergic acid. They don't mess around," Wintermute said.
"Now the message I have is an old one. It's the simplest and most classic message ever passed on in the world's history. It's those six words: 'Drop out, turn on, then come back and tune it in," Leary said.
Before Leary, researchers in the 1950s were exploring the medical potential of LSD as a possible cure for everything from alcoholism to anxiety and depression.
Leary saw it as a way to reach a deeper level of thinking and inspiration. He became the messiah of LSD. He wanted to turn on the whole world — and on that night in 1967, students packed into Kresge Auditorium at MIT.
"If you take science seriously, and you take the history of science seriously, you'll realize that every great scientist wasn't in it for the commercial pay-off. He was in it to find out what it's all about, what's the nature of energy, what are the many levels of energy, what are the levels of consciousness, how can we map them out and how can we use them," Leary argued.
"And, as he got to know more and more, and to penetrate deeper and deeper into the mysteries of energy around us, he began to...flip out. He began to flip out. Look at Einstein: Einstein did it without LSD," Leary said.
Leary's opponent in the debate was MIT professor Jerome Lettvin. He warned against the loss of judgment that came with LSD, and the risk of "return trips," the repeated episodes that sometimes followed a single dose of LSD.
"Suddenly the colors whirl around, suddenly smells have color, suddenly colors have sounds, and then you're back in the normal world. And what does this smell like clinically, Tim? What does this smell like to you? As a clinician, what is this? If you saw a patient who complained of this, what is it that he would have? What would you diagnose him as?" Lettvin pressed Leary.
Leary: "A visionary mystic."
Lettvin: "[Expletive]! You would diagnose him as a temporal lobe epileptic with an aura. And you know that goddam well!"
Lettvin's sobering message seemed to carry the day in that long-ago debate. Leary was eventually discredited, and the drug locked up by governments around the world. Forgotten was the work of Leary's predecessors, those researchers of the '50s with their hopes for the medical potential of LSD. That's the trail that Jake Wintermute picked up.
His main interest is actually in a close chemical relative to LSD, lysergic acid. Which, he said, can be made both cheaply and quickly using new bioengineering methods.
"But more importantly, a lot of these compounds, they haven't really been developed since the 1950s," Wintermute said. "There are a lot of exciting new drugs that are being developed thanks to these new bioengineering technologies and no one yet has taken up lysergic acid as a kind of promising new precursor and I think a lot of that is because there is this kind of stigma, taboo, when you are working on something that is so illegal or so close to illegal. We presented this work recently at a conference and it was a little bit hard to get people to take it seriously because of the LSD connection."
Wintermute makes it clear that he's not talking about the acid that Timothy Leary dropped.
"These are the kind of drugs, they'll ease your Parkinson's symptoms, they'll cure your migraines, but they won't necessarily get you high, at least in the sort of clinical doses. Particularly the elder dementia treatment, is the one that gets us up in the morning. That's the big market with the aging population," Wintermute said.
It seems like LSD traditionally takes people out of reality and this research is actually about achieving the reverse. Wintermute said the actual mechanism by which the compound works is still somewhat mysterious and has something to do with it acting as a "vasodilator."
He explained the term, "It sort of opens up the blood vessels of the brain, improves the circulation in the brain; the sort of enhanced clarity that people on these drugs can sometimes benefit from comes from that."
New drugs could come from an LSD-related compound — drugs that open up the brain — but not in the manner of Timothy Leary. It's been 40 years but finally we'll have a chance, thanks to Jake Wintermute and others, to see if the hopes of those long-ago researchers of the 1950s will be fulfilled.
On a related note, it turns out that Jake Wintermute's mother was a psychiatric nurse who signed up for an LSD trial back in the early 1960s.
"She tried it. And she liked it. She had the Leary-style experience but she worked in psych wards and she saw the down-side too and she eventually did come to a more Lettvin kind of position about it," Wintermute said.
What does Wintermute's mother think of his research now?
He said, "I think she's proud. I get the occasional wink from Mom."
You can watch the whole mind-blowing Leary-Lettvin LSD debate on WGBH's open vault.
WATCH THE 1967 LEARY-LETTVIN LSD DEBATE