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Drugs: Regulate 'home-brew' opiates
Kenneth A. Oye, J. Chappell H. Lawson& Tania Bubela
18 May 2015
The research community and the public require a fast, flexible response to the synthesis of morphine by engineered yeasts, urge Kenneth Oye, Tania Bubela and J. Chappell H. Lawson.
Jerome Sessini/Magnum
Every year, thousands of students from across the world compete to build biological systems from pre-existing parts in a competition organized by the International Genetically Engineered Machine (iGEM) Foundation. Last November, to spark discussion on security and health risks raised by synthetic biology, FBI Special Agent Edward You presented an example: the production of opiates from sugar by yeast (Saccharomyces cerevisiae) that has been genetically modified.
You's hypothetical scenario is becoming a reality. One week after the iGEM competition, two developers of opiate-producing yeast strains approached us, specialists in biotechnology policy. They had results in advance of publication, and requested advice on how they might maximize the benefits of their research while mitigating the risks. Now, published papers by these researchers — John Dueber at the University of California, Berkeley, and his colleagues1, and Vincent Martin of Concordia University in Montreal, Canada, and his colleagues2 — describe all but one step of an engineered yeast pathway that converts glucose to morphine (see 'Brewing bad'). Meanwhile, researchers at the University of Calgary have put in place the final piece3.
Currently, morphine is produced from the opium poppy (Papaver somniferum). By providing a simpler — and more manipulable — means of producing opiates, the yeast research could ultimately lead to cheaper, less addictive, safer and more-effective analgesics. And in generating a drug source that is self-replicating and easy to grow, conceal and distribute, the work could also transform the illicit opiate marketplace to decentralized, localized production. In so doing, it could dramatically increase people's access to opiates.
In recent years, synthetic biologists have produced numerous benign products — antimalarials, scents, flavours, industrial chemicals and fuels — by modifying yeast, bacteria and eukaryotic plants. Opiate synthesis is the first example of synthetic biology facilitating the production of a controlled narcotic; other new production systems for potentially problematic compounds will almost certainly follow.
The synthetic-biology community, in tandem with regulators, needs to be proactive in evaluating the costs and benefits of such dual-use technologies4. Here we lay out the priorities for discussions that are crucial to public health and safety, and to the progress of synthetic biology more broadly. These include restricting engineered yeast strains to licensed facilities and authorized researchers and technicians; reducing the attractiveness of engineered yeast strains in the illicit marketplace; and implementing a regulatory approach that is flexible and responsive to changes in understanding and capabilities.
Complete pathway
The technology to make morphine from glucose using yeast has been seven years in the making. Three groups of researchers introduced genetic components from poppy, beetroot and a soil bacterium into the yeast genome, creating strains that can perform chunks of the glucose-to-morphine pathway1, 2, 5, 6, 7. A fourth group has developed3 a strain that can convert one of the intermediate compounds, (S)-reticuline, into another, (R)-reticuline. With this final step realized, the creation of a single strain of yeast capable of executing the entire pathway is feasible.
In principle, anyone with access to the yeast strain and basic skills in fermentation would be able to grow morphine-producing yeast using a home-brew kit for beer-making. If the modified yeast strain produced 10 grams of morphine, users would need to drink only 1–2 millilitres of the liquid to obtain a standard prescribed dose. (Current strains are not this efficient, but titres in this range and even tenfold higher have been achieved for other commercially relevant metabolic products.)
Although this research is intended to enable synthetic production of opiates for legal pain relief, we perceive several challenges. To be competitive, yeast-based production must be more cost-effective than current systems, more secure and more acceptable to regulators, or provide less addictive, safer products. But most opiates are inexpensive to manufacture, administer and transport.
Advances in breeding high-yield poppies reduced the cost of the main wholesale product, known as concentrate of poppy straw, by 20% between 2001 and 2007 to US$300–$500 per kilogram. The design of more commercially valuable opiates will also require collaboration between synthetic biologists, neuroscientists and medicinal chemists among others, and will involve lengthy and expensive clinical trials. What is more, global supply and demand is tightly regulated to limit potential addiction.
Legal considerations
Various international conventions and national laws are designed to prevent diversion to illegal markets. Countries that manufacture opiates commonly use large, secure industrial facilities. Australia further enhances security by growing a thebaine-rich poppy variety; thebaine is toxic to ingest and is not easily converted into morphine. It is difficult to predict how the main international body, the International Narcotics Control Board (INCB), would react to a new production system for opiates. The INCB is unlikely to slash current opium-production quotas and disrupt current legal opiate-trade patterns to accommodate yeast-based production. This would limit the ability of new producers to enter the market.
Meanwhile, yeast-based opiate synthesis could have a significant effect on illicit markets. Currently, opiates are sold illegally through two main channels. First, prescription pain medications such as oxycodone and hydrocodone are pilfered, prescribed improperly or prescribed legitimately but then sold on illegally by patients. Second, illegally cultivated opium poppies in countries such as Afghanistan, Myanmar, Laos and Mexico are processed into heroin and distributed by criminal networks that sell them at street prices several dozen times the production costs8.
Yeast-based production of opiates could provide an alternative system for current criminal networks, particularly in North America and Europe, where the drugs are in high demand. Because yeast is easy to conceal, grow and transport, criminal syndicates and law-enforcement agencies would have difficulty controlling the distribution of an opiate-producing yeast strain. All told, decentralized and localized production would almost certainly reduce the cost and increase the availability of illegal opiates — substantially worsening a worldwide problem. Globally, more than 16 million people use opiates illegally.
In principle, a home-brew kit for beer-making could be used to make morphine.
continued here http://www.nature.com/news/drugs-regulate-home-brew-opiates-1.17563
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If they can't stop popies from being grown out in the open then they clearly have no chance of stopping this. Well past time to legalize opiates.
Kenneth A. Oye, J. Chappell H. Lawson& Tania Bubela
18 May 2015
The research community and the public require a fast, flexible response to the synthesis of morphine by engineered yeasts, urge Kenneth Oye, Tania Bubela and J. Chappell H. Lawson.
Jerome Sessini/Magnum
Every year, thousands of students from across the world compete to build biological systems from pre-existing parts in a competition organized by the International Genetically Engineered Machine (iGEM) Foundation. Last November, to spark discussion on security and health risks raised by synthetic biology, FBI Special Agent Edward You presented an example: the production of opiates from sugar by yeast (Saccharomyces cerevisiae) that has been genetically modified.
You's hypothetical scenario is becoming a reality. One week after the iGEM competition, two developers of opiate-producing yeast strains approached us, specialists in biotechnology policy. They had results in advance of publication, and requested advice on how they might maximize the benefits of their research while mitigating the risks. Now, published papers by these researchers — John Dueber at the University of California, Berkeley, and his colleagues1, and Vincent Martin of Concordia University in Montreal, Canada, and his colleagues2 — describe all but one step of an engineered yeast pathway that converts glucose to morphine (see 'Brewing bad'). Meanwhile, researchers at the University of Calgary have put in place the final piece3.
Currently, morphine is produced from the opium poppy (Papaver somniferum). By providing a simpler — and more manipulable — means of producing opiates, the yeast research could ultimately lead to cheaper, less addictive, safer and more-effective analgesics. And in generating a drug source that is self-replicating and easy to grow, conceal and distribute, the work could also transform the illicit opiate marketplace to decentralized, localized production. In so doing, it could dramatically increase people's access to opiates.
In recent years, synthetic biologists have produced numerous benign products — antimalarials, scents, flavours, industrial chemicals and fuels — by modifying yeast, bacteria and eukaryotic plants. Opiate synthesis is the first example of synthetic biology facilitating the production of a controlled narcotic; other new production systems for potentially problematic compounds will almost certainly follow.
The synthetic-biology community, in tandem with regulators, needs to be proactive in evaluating the costs and benefits of such dual-use technologies4. Here we lay out the priorities for discussions that are crucial to public health and safety, and to the progress of synthetic biology more broadly. These include restricting engineered yeast strains to licensed facilities and authorized researchers and technicians; reducing the attractiveness of engineered yeast strains in the illicit marketplace; and implementing a regulatory approach that is flexible and responsive to changes in understanding and capabilities.
Complete pathway
The technology to make morphine from glucose using yeast has been seven years in the making. Three groups of researchers introduced genetic components from poppy, beetroot and a soil bacterium into the yeast genome, creating strains that can perform chunks of the glucose-to-morphine pathway1, 2, 5, 6, 7. A fourth group has developed3 a strain that can convert one of the intermediate compounds, (S)-reticuline, into another, (R)-reticuline. With this final step realized, the creation of a single strain of yeast capable of executing the entire pathway is feasible.
In principle, anyone with access to the yeast strain and basic skills in fermentation would be able to grow morphine-producing yeast using a home-brew kit for beer-making. If the modified yeast strain produced 10 grams of morphine, users would need to drink only 1–2 millilitres of the liquid to obtain a standard prescribed dose. (Current strains are not this efficient, but titres in this range and even tenfold higher have been achieved for other commercially relevant metabolic products.)
Although this research is intended to enable synthetic production of opiates for legal pain relief, we perceive several challenges. To be competitive, yeast-based production must be more cost-effective than current systems, more secure and more acceptable to regulators, or provide less addictive, safer products. But most opiates are inexpensive to manufacture, administer and transport.
Advances in breeding high-yield poppies reduced the cost of the main wholesale product, known as concentrate of poppy straw, by 20% between 2001 and 2007 to US$300–$500 per kilogram. The design of more commercially valuable opiates will also require collaboration between synthetic biologists, neuroscientists and medicinal chemists among others, and will involve lengthy and expensive clinical trials. What is more, global supply and demand is tightly regulated to limit potential addiction.
Legal considerations
Various international conventions and national laws are designed to prevent diversion to illegal markets. Countries that manufacture opiates commonly use large, secure industrial facilities. Australia further enhances security by growing a thebaine-rich poppy variety; thebaine is toxic to ingest and is not easily converted into morphine. It is difficult to predict how the main international body, the International Narcotics Control Board (INCB), would react to a new production system for opiates. The INCB is unlikely to slash current opium-production quotas and disrupt current legal opiate-trade patterns to accommodate yeast-based production. This would limit the ability of new producers to enter the market.
Meanwhile, yeast-based opiate synthesis could have a significant effect on illicit markets. Currently, opiates are sold illegally through two main channels. First, prescription pain medications such as oxycodone and hydrocodone are pilfered, prescribed improperly or prescribed legitimately but then sold on illegally by patients. Second, illegally cultivated opium poppies in countries such as Afghanistan, Myanmar, Laos and Mexico are processed into heroin and distributed by criminal networks that sell them at street prices several dozen times the production costs8.
Yeast-based production of opiates could provide an alternative system for current criminal networks, particularly in North America and Europe, where the drugs are in high demand. Because yeast is easy to conceal, grow and transport, criminal syndicates and law-enforcement agencies would have difficulty controlling the distribution of an opiate-producing yeast strain. All told, decentralized and localized production would almost certainly reduce the cost and increase the availability of illegal opiates — substantially worsening a worldwide problem. Globally, more than 16 million people use opiates illegally.
In principle, a home-brew kit for beer-making could be used to make morphine.
continued here http://www.nature.com/news/drugs-regulate-home-brew-opiates-1.17563
......................................................................................
If they can't stop popies from being grown out in the open then they clearly have no chance of stopping this. Well past time to legalize opiates.
That really stung. To be told 'oh, sorry, but we justr don't do those papers' and be forced to accept a grade far inferior to what I deseryved (I don't mean because of some sense of entitlement, but to have my potential kicked to the curb and my earnings devalued like that, I am still to this day, appalled, sickened and disgustred. If I accidentally missed a question, well shit happens, I uln't have missed it, but I should still have been ALLOWED to try and EARN that A+. Because I would have succeeded.