As a boy growing up in Covington, Ky., David Nichols played with chemistry sets instead of footballs. By high school, the self-professed "science geek" who made stink bombs for fun recognized his flair for formulas and decided to become a chemist.
Little did he know that the profession that brought him so much happiness would leave him haunted, as drugs he discovered would be misused, causing harm, and even death.
When he started studying for his doctorate in 1969 -- two years after the summer of love -- Nichols was interested in how drugs, such as LSD, acted on the brain.
"It occurred to me: People can take these drugs, and in some people the effects last a moment, but in others it permanently changes them in some way," Nichols said.
Some LSD users have claimed to reach states of superior consciousness and even see God. But others have suffered "bad trips," and even developed permanent psychosis, Nichols said.
"If drugs can change people's perspectives on the world or who they are, they must work in a very fundamental way in the brain," Nichols said.
In the 1980s, Nichols got a research grant to study 3,4-methylenedioxymethamphetamine (MDMA) -- a drug commonly known as ecstasy. At the time, MDMA was being used in psychotherapy.
"When it became clear that it was going to become a controlled substance, I thought maybe we could figure it out how it worked and develop a safe version to allow psychiatrists to continue using it," Nichols said.
To uncover how MDMA worked in the brain, Nichols made analogs -- compounds that were structurally very similar to MDMA, but slightly different. By lopping off pieces of the compound one-by-one, Nichols and colleagues could determine which parts were important for its euphoric effects.
One of the analogs, 4-methylthioamphetamine (MTA), was found to boost the release of the feel-good neurotransmitter serotonin. Certain antidepressants, such as Prozac, improve mood and relieve anxiety by keeping serotonin up in the space between nerve cells. So it was no surprise that, like selective serotonin reuptake inhibitors, MTA also had antidepressant effects in rats.
But after publishing three papers on MTA and its promise in the treatment of mood and anxiety disorders, it emerged that MTA was being made and marketed for a different purpose.
"A colleague told me people were taking MTA tablets called 'flatliners,'" Nichols said.
Flatliners, which were chemically different from MDMA and therefore not considered illicit, were being synthesized by amateur chemists and peddled as "legal highs." At least five people died from taking the drug, Nichols said.
"I was shocked by that," said Nichols, who is now chairman of pharmacology at Purdue University in West Lafayette, Ind. "I had really never thought that people could get killed by something I had worked on."
Nichols knew people were making his compounds, which had never been tested in humans, and selling them as street drugs. The police contacted him asking for samples to use as standards to which drugs seized could be compared. But it really hit home when Scottish drug trader David Llewellyn cited Nichols' work as "especially valuable" to his drug-making business in a 2010 interview with the Wall Street Journal.
"People said, 'You shouldn't be shocked because you knew people were doing this.' But when you see it in print, it's a shock," Nichols said.