Tania Bubela discusses the dangers of and need for regulating the production of yeast-based opiates.

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In a May 2015 issue of Nature, two colleagues from MIT and I published a commentary on synthetic biology production of opiates. The commentary was given a catchy title by the journal (Regulate ‘home-brew’ opiates), subsequently translated by Nature News to: “Engineered yeast paves way for home-brew heroin”. The home-brew heroin story rapidly spread to media around the world. It was picked up by outlets from The New York Times and The New Yorker, to national radio stations in Canada, New Zealand and Germany, and to local newspapers and television. It was covered by lay journalists with headlines such as “Scientists: Gangs to have a shot at home-brew heroin” (The Australian) and by experienced science journalists in New Scientist and Scientific American. Here, I reflect on the substance of the original commentary so we can retreat from the alarmist media-coverage and enable discussion to develop a nuanced regulatory response.

An 18th Century Chinese opium den

The commentary arose from Ken Oye (MIT) and my longstanding collaborations on ethical, legal and social issues with two synthetic biology research teams in the US and Canada, respectively. The lead researchers of these teams, John Dueber (University of California, Berkeley) and Vincent Martin (Concordia University, Montreal), sought our input on two impending scientific publications that described the possibility of a synthesis of the biochemical pathway from glucose in yeast to opiates such as codeine, morphine, and heroin. The teams estimate that the approximate 18-step synthetic pathway from glucose to opiates can be assembled in a yeast strain within the next couple of years.

The advent of a yeast-based production system for opiates raises interesting regulatory and ethical questions. In our view, the time to respond is now, before the complete pathway is synthesized in yeast. Of central importance is the question how to develop a flexible and proportionate regulatory response that enables beneficial research and mitigates potential harms. The benefits arise primarily from the first half of the approximate 18-step pathway that produces an intermediate compound from which over 2000 novel molecules can be made, including pain relievers, cough suppressants, anti-inflammatories, anti-cancer compounds, and antibiotics.

The harms emerge from the possible illicit use of yeast-based opiates. If an opiate producing yeast strain were synthesized, it could produce opiates in simple fermentation systems. The fermentation product would require further purification to produce injectable drugs or heroin. The result would be a concentrated liquid, capable of producing effects from very low doses. Once developed and optimized for industrial production-scale, such a yeast strain would be difficult to contain and, in our view, would likely be diverted to illegal production. Currently, illegal opiates are centrally produced and then trafficked across borders. Fermentation production of opiates could, by contrast, be local and widely distributed, as happens now with the production of crystal meth. The technology therefore raises public health concerns as increased availability of opiates at lower costs are associated with higher rates of addiction.

Promoters of yeast-based production of opiates claim that this new system could be more secure than current poppy-based production systems. We disagree. The legal market for opiates is highly regulated internationally, is low-cost and well-developed, and results in little to no diversion to illegal markets. Rather, street drugs like heroin come from illegal crops in Afghanistan, Myanmar, Laos and Mexico. Yeast-based production of opiates would do little to stem illegal markets. Neither would it address the major public health threat from opiates in North America – the illegal diversion and misuse of prescription opioids. A novel production system cannot alter the negative impacts of a consumer-end diversion problem.

Any regulatory response will require coordinated efforts by public health, drug and law-enforcement agencies, internationally. It should aim at controlling the development of the yeast strain and then at mitigating harms if a yeast strain is developed and released (see our Nature commentary for our recommendations). At present, we are heartened by the engagement of the research community. Our Nature commentary has spurred regulatory interest and we look forward to further engagement with the key stakeholders.

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Tania Bubela is Professor and Associate Dean Research, the School of Public Health, University of Alberta. @bubela_tania