Yeast isn’t just for beer and bread — now it makes opiates, too.
A strain of yeast engineered in a lab was able to transform sugar into a pain-killing drug — called hydrocodone — for the first time. And a second strain was able to produce thebaine, an opiate precursor that drug companies use to make oxycodone. The findings, published in Science, could completely change the way drug companies make pain-relieving medicine. Unfortunately, it may also open the door to less positive outcomes, like "home-brewed" heroin.
Yeast transformed sugar into the pain-killing drug hydrocodone
Opiates like heroin and morphine are made from opium poppies grown in places like Australia, Europe, and the Middle East — producing the stuff in a morphine drip is an expensive process that takes over a year. An estimated 5.5. billion people have trouble accessing pain treatments worldwide, partly because of their cost. So scientists have been hoping to drive down costs with yeast-made opiates. But until recently, engineered yeast have only been able to make small quantities of a chemical precursor that, through a number of steps, could be used to make morphine and codeine. That's why today's study is so important; it's the first example of scientists altering yeast's genetic code to successfully transform sugar into an actual opioid painkiller.
"There's this quote from The Martian that goes, 'I'm going to have to science the crap out of this,' or whatever — it's sort of like we engineered the crap out of this," says Christina Smolke, a bioengineer at Stanford University and a co-author of the study. The actual quote from the upcoming Ridley Scott movie is "I'm going to have to science the shit out of this," but you get the gist; Smolke and her team made a lot of changes to yeast's DNA to get to this point. In fact, the strains they produced can make molecules that are normally found in poppy, goldthread, bacteria — and even in rats.
Yeast that make molecules normally found in poppy, goldthread, bacteria — and even in rats
The circles on the left represent the organisms that contributed genes to the bioengineered yeast: California poppy, rat, goldthread, bacteria, and opium poppy. (Stephanie Galanie and Christina Smolke)
In the short term, yeast-made opiates might lead to cheaper drugs. But the true excitement is farther down the road: scientists may be able to use this technology to make more effective pain-killers. "We're not just limited to what happens in nature or what the poppies make," Smolke says. "We can begin to modify these compounds in ways that will, for example, reduce the negative side effects that are associated with these medicines, but still keep the pain relieving properties."
"We're not just limited to what happens in nature."
The two yeast strains aren't anywhere near ready for commercial use. Right now, they make such small quantities of drugs that it would take about 4,400 gallons of engineered yeast to make a single dose of standard pain-relieving medicine. So the next step for researchers is boosting the drug yields — which could take years. And for once, that might actually be a good thing; health officials and scientists will need that time to figure out how to keep these strains from being used to fuel the illegal drug market.
Creating a plan that encourages this line of research while also preventing the illicit use of these yeast strains "is critical," says John Dueber, a bioengineer at the University of California-Berkeley who didn't work on this study, but who has been working on yeast-made opiates. Thomas Binz, head of Biological Safety and Human Genetics in Switzerland's Federal Office of Public Health, agrees. "All facilities or laboratories that want to produce such strains will have to be known to the government," he says, specifying that these are his personal opinions. Binz also thinks that an oversight system for genetically modified organisms or particular DNA sequences will have to be created "to prevent theft." Finally, scientists will have to come up with ways to make it harder for illegal users to produce the strains sustainably.
A plan to keep these strains from fueling the illegal drug market
"All of the technical people that are working on this have tried to limit the risk of home-brewing," says Kenneth Oye, a tech policy expert at MIT who has written about the need for regulation for these kinds of yeast strains. "They're taking this responsibility seriously."
The Stanford researchers acknowledge that their strains could be used to make illegal drugs in the paper; they want to work with outside experts to limit the risk. That said, Smolke doesn't think that risk is very big — at least not right now. In a separate study, her team showed that the strains can’t make opioid compounds under home-brew conditions. In addition, because the laboratory conditions that are needed to make the technique work are so highly specialized, Smolke thinks that even strains that can make more drugs won't be much use to home-brewers.
Already, Smolke and other researchers have founded a company that will license the technology and push toward commercialization. So even though patients won’t be able to get yeast-made opiates right away, the pharmaceutical research and development process has, at least, begun.
A meeting of the International Expert Group of Biosafety and Biosecurity Regulations is set to take place later this month in Berlin, Binz says. "Progress on opiate synthesis in yeast, including built-in security features, will be scheduled on the next meeting."