Can you make heroin in your back garden? until recently the answer would have been an unequivocal no. However, independently of each other, two recent articles may change all this. Researchers have genetically engineered strains of yeast that can take simple sugars and produce the molecules necessary for opiates, mimicking how poppies currently do this.
Currently, the only commercial way to produce morphine and other opioid analgesics such as oxycodone is to farm the opium poppy. To attain high enough yields this crop must be grown under highly regulated conditions that are tenable in only a select number of countries. These difficulties make it quite difficult to cultivate illegally, which acts as a minor check on the availability and distribution of opiate-derived drugs; however, difficulty of production may also hinder the production and availability of cheap opiate-derived analgesics. Thus, the development of a novel mechanism for opiates may not be unequivocally good.
The opiate-synthesis pathway is long and non-trivially difficult to emulate given there is no whole genome sequence of the opium poppy, which makes all the enzymes required difficult. The solution was then to find a plant or an insect or even a human model that could be coaxed into producing the desired reactions - so far this does not exist in one organism.
However, Dueber and colleagues show that you can get the half of the way there by having yeast produce an intermediate compound (reticuline). In combination with a similar paper published in April showing how to get the second half, we are now well on our way to producing opiates in yeast.
We should say however, that the authors themselves admit that there will still be a while until these two strains are combined into one, and even then there will still be work to make the fermentation process efficient. However, once these are completed they suggest that anyone with this strain would be just as able to brew their own beer as to make their own morphine.
The benefits for improving the production of opiates are clear - it could lead to more efficient and cheaper painkillers that may indeed have fewer side-effects such as addiction. However, the detriments are also clear - it may make the production of heroin cheap and localised, and in turn make it easier to produce in simpler facilities more widely distributed globally.
In response to these concerns, authors have been discussing the bioethical issues with Kenneth Oye at MIT. It is important to remember that the goal is to create a legal framework for research into these compound producing organisms that preserves important research into drug development while not increasing the risks for a boom in the illegal opium trade. Unfortunately, the current regulatory framework focuses on pathogenic organisms such as smallpox or anthrax, and so are not prepared for these advances.
The regulatory recommendations from these advisers are as follows:
- We could develop a yeast strain that would produce opiates less attractive to criminals (thebaine); or a strain that is artificially difficult to cultivate outwith an industry standard lab, such as is done with E coli; or we could insert a DNA watermark to allow easy identification of strains by law enforcement.
- We should keep the strains under lock and key away from criminals.
My own opinion of these recommendations is that most will not be specific to the current solution and so fail to address the uniqueness presented by this advance in synthetic biology. This is with the exception of having a genetic watermark on the strain, which may be a more honest strategy that accepts the strain will likely be adopted by illicit trade but hopes to allow itself to act retroactively to stop it.
After all of this though we should remember that the researchers themselves are excited scientists that are finding out that we can step outside of what evolution has provided us with and will soon be at a veritable pick and mix for what we can make. The real value of these methods will, they say, not be the more efficient synthesis of things we already have, rather the iterative augmentation of collections of compounds to make new and beneficial compounds in the medical sciences.
Related article : http://www.nature.com/news/drugs-regulate-home-brew-opiates-1.17563
Correspondence & blogpost (this topic) : KSB
Editing : EK
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