Author: James Anderson

How is methamphetamine manufactured? National Institute on Drug Abuse NIDA

And companies that sell custom DNA sequences should refuse to supply the genes needed to engineer such strains. Brewing would also be much harder to detect or prevent than the cultivation of drug-yielding plants. Growing cannabis indoors, for instance, requires a lot of electricity to power lights.

Pain-relieving opioids, like morphine or codeine, are important for medical purposes. The drugs have been around for millennia however even today they are still made from poppy flowers, making the production of the drugs dependent on poppy farming. Now, for the first time, researchers from Stanford University have been able to synthesize opioids from yeast cultures grown in the lab, according to a study published today in Science. Synthesising drugs like methamphetamines in small illegal labs, meanwhile, requires not only expertise but also the right chemical ingredients. Cutting off the supply of these chemicals is one of the main strategies of drug enforcement efforts. This would be impossible with homebrew drugs – the only raw material needed is sugar.

Currently, drug makers synthesize this molecule arrangement using a circuitous process that involves creating a mixture and essentially throwing half that mixture out. This new finding may allow drug makers to create this building block in just one step, said David Nagib, the study’s senior author and assistant professor in the Department of Chemistry and Biochemistry at Ohio State. Governments can legislate chemicals–ban a drug, say, a stimulant or a psychedelic–but what happens when chemists make a slightly different version by mixing in a new molecule? The drug becomes, legally, something different, and for as long as it takes the government to catch up on the new substance, the drug can be sold. Power went on a quest to discover just how easy that process was, out-sourcing a version of the stimulant phenmetrazine to a Chinese lab, and in a few weeks, getting the legal version delivered to his door in the United Kingdom.

Until last year, for instance, coca cultivation in Colombia had been declining. But the criminal gangs didn’t vanish; instead, they turned to illegal mining and logging, says Liliana Davalos of Stony Brook University in New York, who has studied the environmental impacts of coca growing. It is a fundamental change that Nagib hopes might make a number of medicines easier to produce. It’s such an iterative process, we have to make our molecule slightly better every day, because in the end you want that masterpiece. And I can tell you that any molecule that becomes a drug is a masterpiece. You can draw from previous understanding in the field, but ultimately you have to invent new ways to create them.”

The artist’s toolkit

By adding a few more enzymes, including one extracted from the opium poppy, the team managed to produce reticuline, an opiate precursor. In a commentary in Nature, Bubela and her co-authors say governments need to act now if they want now to prevent morphine-making yeasts getting into the wrong hands. Some fear that drug use could soar if home-brewing makes drugs easily available.

1. Similarly, scientists can only use a few elements from the periodic table to build drugs.
2. The drug can be easily made in small clandestine laboratories, with relatively inexpensive over-the-counter ingredients such as pseudoephedrine, a common ingredient in cold medications.
3. Caroline Blakemore is a medicinal chemist at Pfizer who helps design small-molecule medicines, which are made through chemical synthesis.
4. Humble fungi and a home-brewing kit could soon do what the combined might of the West failed to – halt the thriving poppy industry in Afghanistan, the source of 80 per cent of the world’s opium.
5. Dueber and his team came up with the ‘recipe’ when they discovered that a certain type of enzyme can turn glucose sugars into morphine, and have for the first time successfully expressed it in a simple form of genetically engineered yeast.

Their discovery, published today in the journal Chem, gives drug makers a crucial building block for creating medicines that, so far, are made with complex processes that result in a lot of waste. Early lab studies showed that an experimental compound originally developed in 2003 to fight the SARS epidemic in China could also potentially be used against SARS-CoV-2. But this prior formula was created as an IV therapy, which meant patients have to be in a hospital or clinic to receive it. Stanford engineers have genetically reprogrammed the cellular machinery of yeast to create microscopic factories that convert sugars and amino acids into plant-based drugs.

Criminal disruption

Pfizer probably has the biggest database of molecular properties in the world on which to build models to help design medicines. But to bring all the knowledge together to create a medicine is an art, which relies on the expertise and courage of our scientists.” “We need to be out in front so that we can mitigate potential abuse.” The aim is not to replace the existing legal supply of opiates, which are made from opium poppies mainly grown in Tasmania, Australia, but to produce novel and innovative forms of opiates, says Kenneth Oye of MIT.

But in this winding journey, scientists will tell you that tapping into creativity, intuition, and outside-the-box thinking is critical to their success. Machine-learning and other technologies are essential tools in drug development today, but human creativity is at the heart of advancing breakthroughs. Methamphetamine production is also an environmental concern; it involves many easily obtained chemicals that are hazardous, such as acetone, anhydrous ammonia (fertilizer), ether, red phosphorus, and lithium. Toxicity from these chemicals can remain in the environment around a methamphetamine production lab long after the lab has been shut down, causing a wide range of damaging effects to health. Environmental Protection Agency has provided guidance on cleanup and remediation of methamphetamine labs.

Just as an artist uses brushes, paints, and other materials to create their works, Blakemore says having a diverse “synthetic toolkit” of these methods, or reactions, is key to building new medicines. Another reason to create drug-producing yeasts, says John D’Auria of Texas Tech University, is for extended crewed space missions. Spacecraft won’t have room to carry every drug that might be needed, but the astronauts could use yeasts to produce them on board as required.

Why do we need drug-producing yeasts?

Researchers want to add opiates to that list because they are part of a family of molecules that may have useful medicinal properties (see box, below). Plant yields of many of these molecules are vanishingly small, and the chemicals are difficult and expensive to make in the lab. Humble fungi and a home-brewing kit could soon do what the combined might of the West failed to – halt the thriving poppy industry in Afghanistan, the source of 80 per cent of the world’s opium. Genetically engineered yeasts could make it easy to produce opiates such as morphine anywhere, cutting out the international drug smugglers and making such drugs cheap and more readily available. Dueber and his team came up with the ‘recipe’ when they discovered that a certain type of enzyme can turn glucose sugars into morphine, and have for the first time successfully expressed it in a simple form of genetically engineered yeast. While their intention was to develop new types of cheaper, more effective, and less addictive painkillers, they say that we should now be prepared for this knowledge to be misused, and figure out how to mitigate that.

Currently, most methamphetamine in the United States is produced by transnational criminal organizations (TCOs) in Mexico.44 This methamphetamine is highly pure, potent, and low in price. The drug can be easily made in small clandestine laboratories, with relatively inexpensive over-the-counter ingredients such as pseudoephedrine, a common ingredient in cold medications. Researchers have been trying to do it for years in order to produce opioids more quickly, or even alter them to be less addictive. But the poppy plant’s chemical processes proved to be surprisingly difficult to replicate in the lab—in the most recent attempt, earlier this year, the researchers only made it two-thirds of the way to a full opioid. Now, publishing in Nature Chemical Biology, the team reports that they’ve found the perfect enzyme for the job. They describe how an enzyme was extracted from the sugar beet (Beta vulgaris), and through a series of genetic modifications, was able to produce the reaction without destroying the l-DOPA molecules.