‘ Home brew’ heroin? Maybe

A dis­cov­ery may lead to safer painkillers, while ad­vanc­ing a per­ilous pos­si­bil­ity

Los Angeles Times - - CALIFORNIA - ERYN BROWN eryn. brown@ latimes. com Twit­ter: @LATeryn­brown

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.

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.

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