Whenever journalists, futurists and ethicists come up with Top Ten lists of ways the human race will bring about its own demise, an entry for “synthetic biology” inevitably edges up in the rankings. Pundits love to cite the example of how this technology might let smallpox be turned into an unstoppable weapon by marshaling the capabilities of this emerging technology.
So far, this type of doomsday scenario has come nowhere close. In fact, borrowing an enzyme from one organism and repurposing it for a new use in another—as if one were transferring a part between two used cars—has so far only shown its benign side. Synthetic biology has already demonstrated new ways to make anti-malarial medicine, scents, flavors, industrial chemicals and such.
The honeymoon for any new technology does not last forever. One of the first instances of the possible dark side of synthetic biology just appeared online in Nature Chemical Biology. Researchers from the University of California at Berkeley and Concordia University in Montreal have just reported on a means to coax yeast to make the chemical, reticuline, a critical intermediate step in producing morphine and other opiates.
Combining reticuline with other parts of the manufacturing process, already demoed in separate laboratories, would enable the making of opiates in yeast—no poppies required. All that is needed is to feed spoonfuls of sugar to the engineered microbe. Putting all of this together into an integrated morphine-making machine has yet to be done. But all the steps are now in place. “This sort of metabolic engineering optimization is fairly straightforward,” says George Church, a professor of genetics at Harvard Medical School, and one of the pioneers of synthetic biology. “Once the recipe is published, it becomes very easy to reproduce it—something that many amateur garage labs could do.”
The paper is more than a technical tour de force. The researchers also went to extra lengths to anticipate unavoidable questions about the risks of a home-brew opiate kit. Before going to press, John Dueber of Berkeley and Vincent Martin of Concordia, the lead researchers in the study, contacted two political scientists from MIT and a professor of public health from the University of Alberta, all experts in technology policy, to provide analysis and commentary about ways to ensure the technology does not fall into the wrong hands.
In an accompanying online comment in Nature, Kenneth Oye and Chappell Lawson of MIT and Tania Bubela from the University of Alberta issued a call for establishing a regulatory framework that goes beyond existing rules for anthrax, smallpox and other pathogenic bacteria and viruses. “You really want to control this before it gets out,” Bubela says. “Once the barn door is open and it’s unbolted, it’s a lot harder to control.” To prevent illict use, they advocate measures such as making yeast strains with a DNA watermark that could be identified by law-enforcement.
The yeast could also be engineered so that an additional nutrient has to be added for the production process to proceed. Screening could be instituted for DNA sequences that might be ordered from commercial outfits to engineer opiate-producing yeast. Microbes could be stored in biosecurity facilities and the U.S. Controlled Substance Act could be extended to encompass yeast that produce opium.
The publications will likely lead to prolonged debate about bioengineered narcotics and also force a larger look at synthetic biology in general. Christina Smolke, a Stanford researcher who has also labored on opiate production in yeast, took issue with the idea that a new regulatory scheme should be immediately brought up for consideration. Making opiates from yeast “will require very specialized and highly controlled fermentation conditions, which are not readily accessible to nonspecialists,” she says. “In fact, it is more likely that a person could more easily access morphine by dumping a bunch of poppy seeds in their home brew (or tea).” Smolke agrees that careful discussion of risks and ensuing regulatory issues are needed, but does not see the assertive urgency reflected in the commentary. “This should ideally not be led with a sensationalist, inflammatory approach that is not grounded in accurate representations of the technical capabilities.”
Hank Greely, a bioethicst from Stanford, endorsed the commentary’s call to action, but added that a new technology to manipulate genes—CRISPR/Cas9—may make it relatively easy for a criminal syndicate to engineer an opiate-producing yeast strain. He also thinks that regulators may be slow to give their nod to the new technology. “It seems to me entirely possible that the only uses of this discovery will be illicit,” he says.
The publication, he says, also illustrates the need to revamp the existing regulatory infrastructure to accommodate new technologies that may soon range the gamut from preventing disease transmission to bringing back extinct animals. "We need to think hard about new regulatory systems—national and international—that don't foreclose the potential benefits of engineering life, but that provide some protection against its risks - from environmental damage to new waves of drug abuse."
What drives Dueber and Martin’s research is not the novelty of cranking out opiates in modified beer-making equipment. Feeding in sugar at one end of the pathway and collecting the valued reticuline at the other will enable them to find new ways of making more than just morphine and its cousins. A ready source of reticuline can be used to explore new leads for anti-cancer, antibiotics, among others.
Their research exemplifies a new trend that is advancing biotechnology into the realm of synthetic biology, moving beyond inserting a single gene into an organism and making single proteins. Engineering entire chemical pathways into yeast and other biomanufacturing systems—borrowing molecules from different organisms to facilitate each step of the process—is what inspires researchers whose wish is to harvest the nascent power of synthetic biology.