Prescription pain medicine addiction has become prevalent and widespread with several areas in the U.S. calling it a public health crisis. Opiates include prescription pain medicines, such as Vicodin, OxyContin, or fentanyl. The surge in opiate drug addiction can be traced to changes in the increase in prescriptions for opiate drugs beginning in the 1990s. Now headlines tout the possibility of a “home-brewed heroin.”
If we unpack the headline, it turns out this “home-brewed” heroin is not exactly here yet. Scientists have replicated all of the metabolic processes that opium poppies use to turn glucose into morphine. They have replicated parts of this process in yeast strains in an effort to make less addictive pain medicines as well as other analgesics. This synthesis of cellular processes is called synthetic biology. By way of a quick review, synthetic biology involves creating the digital DNA code to make proteins, the internal machinery of a cell, in the lab. Yeast and e.coli are simple organisms and are often used to insert the DNA in a cell fitted with the necessary equipment to replicate and express the DNA. Craig Venter, in his book on synthetic biology, Life at the Speed of Light, calls DNA the software and yeast provides the hardware. Scientists want to tweak the software to make tailor-made drugs.
Synthetic biology overlaps with genetic engineering, but where it differs is that synthetic biology allows scientists to replicate an entire cellular pathway within an organism, such as yeast, as opposed to inserting or deleting mutations in a DNA strand and then inserting it in a cell.
The metabolic pathway reported in Nature (See the Nature News article) is the first part of the glucose-to-morphine pathway. The second part of the pathway, as well as a reaction that links the two parts, was recently reported by other research groups. All of these parts have been demonstrated separately in various yeast strains. If scientists were to combine these parts in one yeast strain, then theoretically, they would be able to convert glucose to morphine. This has not been done yet, but will likely occur soon.
The process for making morphine from glucose is complex (it’s approximately eighteen steps), and because scientists do not know the whole genome for the opium poppy, they have had difficulty identifying the enzymes that catalyze each step in the reaction pathway. To overcome this hurdle, scientists turned to enzymes in other organisms to that catalyze similar reactions. The most recent research that identifies the first half of the morphine pathway used an enzyme from sugar beets that scientists mutated to ensure that it produced the product they needed without unwanted byproducts.
The question remains, are we at a point where people can brew their own synthetic morphine? The short answer is no, not yet.
First, all of the steps have not been combined into a yeast strain. While this may be the next step in making synthetic morphine in the lab, it will need to be tested, and it may not work at first. Once scientists succeed at creating a yeast strain that can accomplish all of the steps, the process will need to be refined and optimized.
Secondly, in order for someone to brew their own morphine, he would have to acquire the yeast strain containing the synthetic DNA. This would mean acquiring the yeast from someone who not only knows the DNA code, but also has a PCR machine or some way to make synthetic DNA and then incorporate it into yeast.
Lastly, even if someone did acquire the yeast strain, according to Christine Smolke of Stanford University whose lab has made a semi-synthetic opioid using yeast, in an interview with Wired, said that the fermentation process would require specialized equipment and conditions that would be difficult to do outside a laboratory. It would also not produce enough morphine to make it cost effective.
While we are not at the point of worrying about home-brewed liquid morphine, the authors of the study were concerned about future consequences of their research. One of the motivations for designing the synthetic pathway is to tweak it to make less addictive pain medicine or to make medicines for other uses. This same ability to tweak the morphine-producing pathway could also be used for nefarious purposes.
The authors of the study sought ethical guidance from biotechnology-policy specialists Kenneth Oye, of MIT and Tania Bubela, of the University of Alberta. They published an article in Nature with Chappell Lawson, also from MIT, that came out in tandem with the research article. Oye, Bubela, and Chappell delineate the ethical and legal considerations for such research and provide four broad areas that should be considered:
- Engineering – The yeast strains could be engineered to make them less appealing to criminals and more difficult to cultivate outside of a laboratory setting, similar to biocontainment practices with e. coli.
- Screening – Since the DNA sequence would need to be ordered from a lab, there could be a screening process in place that flags orders of opiate-producing yeast strains
- Security – They could employ biosecurity measures, such as watermarking yeast made from certain labs and background checks on people working with the strains.
- Regulation – Opium is a globally controlled substance. The laws that apply to opium could be extended to cover opiate-producing yeast strains.
Overall, the headlines are a little misleading in that we are not yet on the cusp of people brewing their own morphine. However, the authors should be commended for considering the consequences of publishing their research and seeking ethical guidance. It is a good example of pre-emptively considering the hazards and consequences of technological advancement rather than responding to a crisis.
For more information, see my article in Salvo 31, “Dying to Feel Good: Modern Self-Realization & the Painkiller Addiction Epidemic“