A synthetic chemist at Purdue University has built a career working with mind-altering substances that interact with receptors in the brain, but some of his work has had unintended consequences that weigh on him.

"My research wasn't designed to find drugs that could kill people. I really set out to find drugs that could help us understand the brain and maybe find drugs that could treat psychiatric disorders," the chemist, David Nichols, told LiveScience. [Top 10 Controversial Psychiatric Disorders]

Nichols' studies of mind-altering chemicals did not consider their toxicity in humans, but that did not stop at least one entrepreneur from appropriating the research and creating dangerous drugs that are not yet banned by law.

Nichols' story represents a dilemma for scientists, who are left to decide whether to pursue work that could well be misused and cause harm.

Nichols first learned his research was being used to create potentially fatal designer drugs – which create effects like those of illegal drugs while skirting the law – more than a decade ago.

From lab to street

Beginning in 1982, Nichols' lab began working on MDMA — now known on the street as Ecstasy — because this substance and others like it were believed to hold potential for use in psychotherapy. One of the substances the researchers worked on was called MTA, which had a chemical structure similar to MDMA.

Almost 20 years later, Nichols learned from a colleague that MTA had been synthesized outside the lab and sold as tablets called "flatliners." That name was apt, Nichols' observed; by 2002, six deaths had been linked to MTA.

"Because I was the only one working on MTA and publishing on it, I was pretty sure they had picked up the molecule from my work," Nichols told LiveScience in an e-mail.

In an essay today (Jan. 5) in the journal Nature, Nichols writes that knowing that his work — showing that the effects of MTA in rats could be linked to human deaths — left him "with a hollow and depressed feeling for some time."

But he assumed that only a few amateur chemists were behind the designer drugs inspired by his work. This past October, he found out that at least one sophisticated, money-making enterprise was following his work.

In an interview for an Oct. 30 story in the Wall Street Journal, an entrepreneurial European chemist named Nichols' research as an inspiration in his quest for new, psychoactive substances to market.

The newspaper identified the entrepreneur as David Llewellyn, a Scotsman who was a self-described former crack addict. His construction business had gone under, and, looking for income, he turned to the "legal high" business, which is much larger in Europe than in the United States. When the article was published, Llewellyn employed eight people in two labs to whip up the pills and sold his products online. [Read the WSJ article]

The science behind it

Nichols describes his research as having two parts. The first focuses on stimulants that activate dopamine receptors (proteins on brain cells to which the substance dopamine can attach), and could potentially provide treatments for Parkinson's disease and for memory and cognitive decline associated with schizophrenia.

The second and more notorious half focuses on psychedelic drugs. These compounds can cause dramatic shifts in consciousness, and, when he started on this line of research in 1969, Nichols was interested in finding out why.

He now studies how molecules of different psychedelics interact with a particular type of receptor in the brain, which responds to the neurotransmitter serotonin — a substance that regulates many functions, including mood, appetite and sensory perception.

Authorities in Europe continually scramble to identify and ban designer drugs, meaning that entrepreneurs like Llewellyn must come up with new products, according to the Journal. Llewellyn told the newspaper he and his chief chemist search the scientific literature for new ideas, and that they have found Nichols' work especially valuable.

But little work is done to test the toxicity of these substances, according to Nichols. His lab may give a promising substance to rats; however, it doesn't test the effects of prolonged exposure or high doses on rats, or conduct any sort of human testing.

His rat and human studies have shown MTA causes a surge of serotonin release from brain neurons, but without the high associated with Ecstasy. Instead, because MTA also blocks the enzyme that breaks down serotonin, it can lead to "serotonin syndrome," which involves high body temperatures and seizures that can lead to death.

In one case, Nichols said, he and fellow researchers decided not to study a molecule that would likely have a potent Ecstasy-like effect, because of its potential to destroy serotonin neurons in the brain.

The damage the work could have incurred was greater than the possible gain in knowledge, he said.

Moral dilemma

Generally, society has avoided putting any intentional restrictions on research to prevent the results from being used by those with nefarious intent, according to Ruth Faden, director of the Johns Hopkins Berman Institute of Bioethics, who is not involved in Nichols' research.

This is because, in almost all cases, it is impossible to determine whether a piece of scientific knowledge will lead to more evil than good, Faden said.

Beyond that, exercising that judgment could lead to censorship or abuse, she added. [7 Absolutely Evil Medical Experiments]

"Basically, we live with a certain amount of acceptance that any piece of knowledge has some potential to be used toward, if you like, the dark side," Faden said.

While scientists do not generally have the responsibility to anticipate harmful, or just plain evil, uses for their work, when presented with information that it may have immediate, negative consequences, as Nichols was, scientists must use their own judgment as to whether to continue that line of study, Faden said.

The dilemma is agonizing from the standpoint of the individual scientist, but "probably, that is where our best protection lies," she said.

This article was reprinted with permission from LiveScience.

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