Bioengineering advances raise fears of 'home-brew heroin'

The Daily Mirror carries the alarming headline that, “Heroin made in home-brew beer kits could create epidemic of hard drug abuse”. It says scientists are “calling for urgent action to prevent criminal gangs gaining access to [this] new technology” following the results of a study involving genetically modified yeast.

This study did not actually produce heroin, but an important intermediate chemical in a pathway that produces benzylisoquinoline alkaloids (BIAs). BIAs are a group of plant-derived chemicals that include opioids, such as morphine.

BIAs have previously been made from similar intermediate chemicals in genetically engineered yeast. Researchers hope that by joining these two parts of the pathway, they will get yeast that can produce BIAs from scratch. This could be cheaper and easier than current production methods, which often still involve extraction from plants.

But because morphine can be refined into heroin using standard chemical techniques and yeast can be grown at home, this has led to concerns about the potential misuse of this discovery.

So, will this lead to a rash of “Breaking Bad”-style heroin labs in criminals’ garages and spare rooms? We doubt it – at least in the near future. A strain that can produce morphine has not yet been made and would need to be specially genetically engineered to do this, not just using unmodified home-brewing yeast available off the shelf.

Still, it may be worth raising awareness about the potential need for regulation of opioid-producing strains. 

Where did the story come from?

The study was carried out by researchers from the University of California and Concordia University in Canada.

It was funded by the US Department of Energy, the US National Science Foundation, the US Department of Defense, Genome Canada, Genome Quebec, and a Canada Research Chair.

The study was published in the peer-reviewed journal, Nature Chemical Biology. It is open access, meaning it can be read online for free.

The Daily Mirror’s reporting takes a sensationalist angle – the picture caption, for example, reads: “Home-brewed heroin is on the rise, scientists warn”. No heroin was made in this study, and complete opioid-producing strains of yeast have not been made yet – home-brewing heroin from yeast is not yet possible, much less on the rise.

The possibility of home-brewing comes from a commentary on the article in Nature, which discusses the findings of this and related studies. This commentary also discusses the potential legal implications, and the ways that risks could be reduced. For example, scientists could only produce yeast strains that make weaker opioids. But they acknowledge that the risk of criminals making opiate-producing yeast strains themselves is low.

The Guardian and BBC News take a slightly more restrained approach, suggesting that home-brew heroin may be a problem in the future but it certainly is not an issue now. The BBC also points out that producing medicines in microbes is not a new thing. 

What kind of research was this?

This laboratory research studied whether a group of chemicals called benzylisoquinoline alkaloids (BIAs) could be produced in yeast. BIAs include a range of chemicals used as drug treatments in humans. This includes opioids used for pain relief, as well as antibiotics and muscle relaxants.

Opioids are among the oldest drugs first identified as being produced naturally by opium poppies. Morphine is an opioid derived from poppies, and it and other derivatives or man-made versions of opioids are used to treat pain.

Opioids also produce euphoria and can be addictive. The illegal drug heroin is an opiate that can be produced by refining morphine to make it more powerful.

The researchers say many of these compounds are still made from plants such as the opium poppy, as they are chemically very complex and therefore difficult and expensive to make from scratch in the lab.

However, now we know much more about how the chemicals are made in plants, it may be possible to genetically engineer microbes in the lab to produce these chemicals in industrial quantities.

The researchers say the yeast S. cerevisiae – sometimes known as baker’s or brewer’s yeast – has been used to produce BIAs in the lab from intermediate chemicals in the BIA production pathway. The earlier steps in the pathway have not yet been managed in yeast, although they have in bacteria.

In this study, the researchers wanted to see if they could produce the intermediate chemical (S)-reticuline in yeast. This has been tried before, but was not successful. 

What did the research involve?

The researchers knew they needed one particular type of protein called a tyrosine hydroxylase, which would work in yeast to perform the first step in the process of making (S)-reticuline.

They developed a system to allow them to quickly screen a large group of known tyrosine hydroxylases to identify one that would work in yeast. The tyrosine hydroxylase is needed to produce the intermediate chemical dopamine.

The researchers then needed other proteins that convert dopamine and another chemical already present in yeast into another intermediate chemical, and then carry out the other chemical steps needed to form (S)-reticuline. They identified proteins they needed for these stages from the opium poppy and the Californian poppy.

Finally, they genetically engineered yeast cells to produce tyrosine hydroxylase and all of the other proteins needed, and tested whether the yeasts were able to produce (S)-reticuline.  

What were the basic results?

The researchers were able to identify tyrosine hydroxylase from the sugar beet that worked in yeast, allowing them to produce the intermediate chemical dopamine. They used genetic engineering to make a version of this protein in yeast that worked even better than the original one.

They were also able to produce the other proteins they needed in yeast. A yeast strain producing all of these proteins was able to produce (S)-reticuline, the chemical intermediate needed in the production of opioids. 

How did the researchers interpret the results?

The researchers concluded that coupling their work with the work already done, and improving on the yield of the process, “will enable low-cost production of many high-value BIAs”.

They say that, “Because of the potential for illicit use of these products, including morphine and its derivatives [such as heroin], it is critical that appropriate policies for controlling such strains be established so that we garner the considerable benefits while minimising the potential for abuse.” 

Conclusion

This laboratory study has successfully managed to produce an important intermediate chemical in the pathway that produces benzylisoquinoline alkaloids (BIAs), a group of plant-derived chemicals that include opioids.

BIAs such as morphine have previously been made from similar intermediate chemicals in genetically engineered yeast, but this is the first time the earlier stages have been completed successfully in yeast. The researchers hope that by joining these two parts of the pathways, they will get yeast that can produce BIAs from scratch.

This study has not completed this final step, however. Researchers will need to test this before they know that it will be successful. They acknowledge that further optimisation of their method to produce more of the intermediate chemical is needed before it could be used to produce BIAs.

This study has generated media coverage speculating about the possibility of “home-brew heroin” creating an “epidemic of hard drug use”. But the researchers did not produce heroin or any other opioid, only an intermediate chemical. These yeasts have been specially genetically engineered, and the experiments are not the sort of thing most people are going to be able to easily replicate in their garage.

While the likelihood of such strains being successfully made for criminal use seems very small, at least in the short to medium term, criminals can be resourceful. Considering the potential implications of this research and whether policies are needed, both nationally and internationally, may be prudent.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

Home-brewed heroin? Scientists create yeast that can make sugar into opiates. The Guardian, May 18 2015

‘Home-brewed morphine’ made possible. BBC News, May 19 2015

Heroin made in home-brew beer kits could create epidemic of hard drug abuse. Daily Mirror, May 18 2015

Links To Science

DeLoache WC, Russ ZN, Narcross L, et al. An enzyme-coupled biosensor enables (S)-reticuline production in yeast from glucose. Nature Chemical Biology. Published online May 18 2015