Pubdate: Sat, 27 Jun 2015
Source: Los Angeles Times (CA)
Copyright: 2015 Los Angeles Times
Contact:  http://www.latimes.com/
Details: http://www.mapinc.org/media/248
Author: Eryn Brown

'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.

Allauddin Khan Associated Press 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.

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 proof-of- 
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.
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MAP posted-by: Jay Bergstrom