Stanford bioengineers close to brewing painkillers without opium from poppies

By Tom Abate

Stanford bioengineer Christina Smolke has been on a decade-long quest to genetically alter yeast to "brew" opioid medicines in stainless steel vats, eliminating the need to raise poppies.

For centuries poppy plants have been grown to provide opium, the compound from which morphine and other important medicines such as oxycodone are derived.

Now bioengineers at Stanford have hacked the DNA of yeast and reprogrammed these simple cells to make opioid-based medicines via a sophisticated extension of the basic brewing process that makes beer.

Led by bioengineering Associate Professor Christina Smolke, the Stanford team has already spent a decade genetically engineering yeast cells to reproduce the biochemistry of poppies, with the ultimate goal of producing opium-based medicines, from start to finish, in fermentation vats.

"We are now very close to replicating the entire opioid production process in a way that eliminates the need to grow poppies, allowing us to reliably manufacture essential medicines while mitigating the potential for diversion to illegal use," said Smolke, who outlines her work in the Aug. 24 edition of Nature Chemical Biology.

In the new report, Smolke and her collaborators, Kate Thodey, a postdoctoral scholar in bioengineering, and Stephanie Galanie, a doctoral student in chemistry, detail how they added five genes from two different organisms to yeast cells. Three of these genes came from the poppy itself, and the others from a bacterium that lives on poppy plant stalks.

This multi-species gene mashup was required to turn yeast into cellular factories that replicate two, now separate processes: how nature produces opium in poppies, and then how pharmacologists use chemical processes to further refine opium derivatives into modern opioid drugs such as hydrocodone.

Morphine is one of three principal painkillers derived from opium. As a class they are called opiates. The other two important opiates are codeine, which has been used as a cough remedy, and thebaine, which is further refined by chemical processes to create higher-value therapeutics such as oxycodone and hydrocodone, better known by brand names such as OxyContin and Vicodin, respectively.

Today, legal poppy farming is restricted to a few countries including Australia, France, Hungary, India, Spain and Turkey supervised by the International Narcotics Control Board, which seeks to prevent opiates like morphine, for instance, from being refined into illegal heroin.

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Stanford bioengineers close to brewing painkillers without opium from poppies