The chemical precursors for making morphine and heroin have been produced by genetically-engineered microbes rather than poppy plants for the first time, raising the prospect that the most powerful painkillers known to science could be made from scratch in the lab.
Currently all natural opiates, such as morphine and codeine, are manufactured from poppy plants farmed under licence. Researchers now believe these farms may one day be replaced by industrial vats of genetically engineered yeast fermenting in sugar solution.
However, some scientists have warned that the creation of genetically modified yeast capable of producing morphine precursors could also lead to the illicit “home brewing” of yeast to produce heroin for the illegal drug trade.
Although many modern drugs are made by growing genetically-modified yeast or other microbes in giant fermenters, opiates are a notable exception because of the difficulty of mimicking the elaborate synthetic pathways used by poppy plants in their natural production.
Researchers led by Christina Smolke of Stanford University in California have, however, succeeded in transferring more than 20 genes into the genome of the yeast cell which triggers the production of thebaine or hydrocodone, two chemical precursors of morphine and the other pain-killing opiates, including heroin.
“When we started work a decade ago, many experts thought it would be impossible to engineer yeast to replace the entire farm-to-field process. This is the most complicated chemical synthesis ever engineered in yeast,” Dr Smolke said.
Opiates are the primary drugs used to provide pain relief and palliative care for the terminally ill. About 100,000 hectares of the opium poppy, Papaver somniferum, are currently cultivated under licence around the world for the production of about 800 tons of opiates, mainly thebaine and morphine, for legal, medicinal uses.
The genetically-modified yeast in its present form can only produce minute quantities of opiates. It would need to be genetically engineering still further to boost levels to a point where production would be commercially viable, the researchers said in their study published in the journal, Science.
“This is proof-of-principle, and major hurdles remain before optimisation and scale-up could be achieved,” the researchers said.
It would for example take about 4,400 gallons of the bioengineered yeast to produce a single dose of morphine, but there is nothing in theory to prevent further refinement of the technique now that it has been found to work, Dr Smolke said.
“This is only the beginning. The techniques we developed and demonstrate for opioid pain relievers can be adapted to produce many plant-derived compounds to fight cancers, infectious diseases and chronic conditions such as high blood pressure and arthritis,” she said.
“The molecules we produced and the techniques we developed show that it is possible to make important medicines from scratch using only yeast. If responsibly developed, we can make and fairly provide medicines to all who need them.”
The researchers said there are concerns that the technology could be misused to make yeast for “home brew” opiates, but added that their published findings fall short of providing anyone with the technical know-how to produce heroin in a back kitchen.
Some scientists warned, however, that there will be a great incentive for the illegal drug trade to exploit the technology. “Poppy fields are not readily available to someone in Chicago, whereas yeast can be made available to anyone,” Vincent Marks, a microbiologist at Concordia University in Montreal, told Science.
Dr Smolke said the production of opiate drugs in industrial fermenters could lower costs and allow production to move to anywhere in the world where the drugs are needed, provided proper controls are put in place.
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