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Brewing Bad: New way to create morphine raises concerns over regulation

All over the world, the heavy heads of opium poppies are nodding gracefully in the wind – long stalks dressed in orange or white petals topped by a fright wig of stamens. They fill millions of acres in Afghanistan, Myanmar, Laos and elsewhere. Their payload – the milky opium juice carefully scraped off the seed pods – yields morphine, an excellent painkiller easily refined into heroin.

But very soon the poppy will no longer be the only way to produce heroin’s raw ingredient. It will be possible for drug companies, or drug traffickers, to brew it in yeast genetically modified to turn sugar into morphine.

Almost all of the essential steps had been worked out in the last seven years; a final missing one was published May 25 in the journal Nature Chemical Biology.

“All the elements are in place, but the whole pathway needs to be integrated before a one-pot glucose-to-morphine stream is ready to roll,” said Kenneth A. Oye, a professor of engineering and political science at MIT.

This rapid progress in synthetic biology has set off a debate about how – and whether – to regulate it. Oye and other experts said in a commentary in the journal Nature that drug-regulatory authorities were ill-prepared to control a process that would benefit the heroin trade much more than the prescription painkiller industry. The world should take steps to head that off, they argue, by locking up the bioengineered yeast strains and restricting access to the DNA that would let drug cartels reproduce them.

Other biotech experts counter that raising the specter of fermenting heroin like beer, jokingly known among insiders as “Brewing Bad,” is alarmist and that Oye’s proposed solutions are overkill. Although making small amounts of morphine will soon be feasible, they say, the yeasts are so fragile and the fermentation process so delicate that it is not close to producing salable quantities of heroin.

What is considered one of the last important missing steps, a way to efficiently grow a morphine precursor, (S)-reticuline, in brewer’s yeast, Saccharomyces cerevisiae, was published by scientists from the University of California, Berkeley, and Canada’s Concordia University.

The leader of the Berkeley team, John E. Dueber, said it was not trying to make morphine but 2,500 other alkaloids for which reticuline is a precursor, some of which might become antibiotics or cancer drugs. Nonetheless, he said, since he realized his research has implications for the making of morphine, he sent his draft paper to Oye, suggesting the debate become more public.

Companies are always seeking painkillers that create less addictive euphorias or do not paralyze breathing muscles, and having a predictable process they could tweak would be useful, but they already have a cheap, steady supply of opium from India, Turkey and Australia, where poppies are grown legally by licensed farmers.

Heroin sellers, by contrast, must smuggle raw materials out of lawless Afghanistan, Laos, Myanmar and Mexico. Their supply lines are disrupted when any power – from the Taliban to the U.S. Army – cracks down. Brewing near their customers would save them many costs: farmers, guards, guns, planes, bribes, etc.

One frightening prospect Oye raised was how viciously drug cartels might react if Americans with bioengineering know-how started competing with them. Gunmen from Mexican drug gangs have taken control of many secret marijuana fields in U.S. forests.

His commentary suggested several possible steps to prevent misuse of the technology. For example, the yeasts could be locked in secure laboratories. Or sharing them with other scientists without government permission could be outlawed. Or their DNA could be put on a watch list, as sequences for anthrax and smallpox are, so any attempt to buy them from DNA supply houses would raise flags. Chemically silent DNA “watermarks” could be inserted so stolen yeasts could be traced. Or the strains could be made “wimpier and harder to grow,” Oye said, perhaps by making them require nutrients that were kept secret.