‘ Home brew’ heroin? Maybe
A discovery may lead to safer painkillers, while advancing a perilous possibility
It’s a nightmare scenario: the invention of genetically engineered yeast that would allow people to “home brew” their own highly addictive opioid drugs.
A study published this week in Science brings that possibility a step closer to reality.
Researchers have discovered a long- sought gene in poppies that is crucial to the production of morphine in the plants. Their find could lead to safer and more effective painkillers and other useful poppy- derived compounds.
But it could also smooth the way for people to start producing morphine and its close chemical cousin, heroin, on their own — perhaps even at home, much as hobbyists use yeast to brew beer or make wine.
“There are still some technical challenges, but this is a possible security threat,” said supervisory special agent Edward You of the biological countermeasures unit of the FBI’s Weapons of Mass Destruction Directorate.
Researchers had already cataloged most of the genes driving the multistep process of converting glucose to morphine in poppies. Only one was missing: the gene that directs conversion of a chemical called ( S)- reticuline into another called ( R)- reticuline.
To identify that gene, the team from the University of York in England and Glaxo-SmithKline in Australia introduced random mutations into hundreds of poppy plants. Eventually they found three plants that did not produce morphine but did accumulate ( S)reticuline. That suggested they had altered versions of the gene that allows the crucial conversion to ( R)reticuline to take place.
The three plants all turned out to have mutations in one particular gene, which the scientists later confirmed to be the one they were seeking. They named the gene “STORR,” for ( S)- to ( R)- reticuline.
From a scientific standpoint, STORR is interesting because it’s actually two genes fused together, said senior author and University of York biochemist Ian Graham. That may be part of the reason why it took researchers so long to find it, he noted.
On a practical level, the discovery will help Graham and others find ways to breed poppies to produce anti- cancer agents and designer painkillers.
“Now that we’ve discovered this step we can develop poppy plants and use breeding approaches to make bespoke varieties of poppies that make different molecules,” he said.
Having a handle on STORR also aids efforts to manufacture opiates in yeast, Graham acknowledged.
“The publication of this gene provides the missing link for the production of morphine in yeast — there’s no doubt about it,” he said. “I think it’s only a matter of time before there is a proofof- concept demonstration in yeast that this can happen.”
The prospect that biologists might soon develop morphine- making yeast had people buzzing about “home brew” opiates last month, when a different team of researchers published a study in the journal Nature Chemical Biology that described how they engineered yeast to perform another portion of the process that converts glucose to morphine.
MIT political science professors Kenneth Oye and Chappell Lawson and University of Alberta School of Public Health professor Tania Bubela wrote a response to that study in the journal Nature in which they urged regulators to work preemptively to prevent abuse.
For example, scientists might want to stop short of designing a single strain of yeast to perform the entire conversion, Oye said in an interview, or they might engineer a “DNA watermark” to facilitate tracking.
“Maybe you want to do this in a wimpy yeast strain — one that’s fussy, harder to cultivate,” he said. “But all of these technical steps should be done beforehand. Afterwards, it’s too late.”
Oye, Lawson and Bubela thought the scientists most likely to publish research on the missing step were a team in the Canadian city of Calgary, Alberta. They didn’t know about Graham’s work and certainly didn’t expect the announcement to come barely a month later, Bubela said this week.
“You can see how quickly the technical challenges are being overcome, even faster than we anticipated,” she said, adding that it would be difficult for regulators to keep tabs on all research, all the time. “It speaks to the fact that policymakers need to get ahead of the technology.”
Jeff Comparin, director of the U. S. Drug Enforcement Administration’s research laboratory in Dulles, Va., said that until a specific yeast strain that could make morphine becomes commonly available, his agency “doesn’t perceive an imminent threat.”
But he said the DEA was monitoring research developments, and if heroin producers and traffickers did eventually decide it was worth their while to use the new approach, any heroin produced by yeast- morphine should be easy to distinguish from traditionally sourced varieties.
“We would immediately recognize this type of heroin coming into the market,” he said.
The FBI’s You, whose unit works with scientists to get them thinking about unanticipated outcomes of their work, said he was encouraged that researchers had initiated the conversation in this case.
“It isn’t often that you see scientists proactively calling out something like this. That’s what makes it remarkable,” he said. “We have an opportunity to capture these complications and mitigate them.”
Doing so would safeguard beneficial research efforts, he added.
In the meantime, there’s plenty of work to be done before yeast is synthesizing morphine at any kind of scale, said UC Berkeley bioengineer John Dueber, lead author of the Nature Chemical Biology study, who called the new work a “solid addition to the scientific literature.”
Dueber said he thought the challenge of increasing efficiency and combining everything onto a single yeast strain was “considerable, but I think accomplishable in a few years.”
As part of their experiment, Graham and his team did introduce STORR into yeast to demonstrate that the gene can produce the same enzymatic activity there that it triggers in plants.
The scientist said he wasn’t interested in developing yeast- based production methods for opiates.
But he, too, thought getting regulatory controls in place ahead of time would be a good idea.
RESEARCHERS have found a gene in poppies crucial to producing morphine, which could lead to homemade heroin. But a DEA off icial sees no urgent threat.