Bioengineering the Psychedelics: How Psilocybin, Mescaline and Ibogaine Are Grown

Prof. Jeffrey Gerst, a molecular geneticist at the Weizmann Institute of Science, examines how psilocybin, mescaline and ibogaine are built, by which genes, in which organisms. The course covers the conservation pressure on slow-growing wild sources, the gene clusters behind each compound, and the engineering of yeast and garden plants to produce them without extraction.

Price: $400.00
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Peyote takes seven to ten years to reach harvestable size. Iboga trees take ten or more. The caapi vine, the same. And in the forests of western Cambodia, a rare tree in the cinnamon genus is felled and uprooted for the aromatic oil in its root bark, with roughly ten more trees burned as fuel to distil it. The demand for these compounds is rising faster than the organisms that make them can grow.

Prof. Jeffrey Gerst opens this course with a question we ask constantly of our food and almost never of our medicines: where did this come from, how was it made, who made it, and who benefited? There are only two existing answers. Wild harvesting, which is reaching the limits of what habitats and traditional communities can absorb. And chemical synthesis, which pollutes, strips away the entourage molecules that occur alongside the primary compound in a living organism, and prices access out of reach for most of the world.

This course sets out a third route: moving the biosynthetic pathway rather than the plant. Gerst traces the four-gene cluster that builds psilocybin in Psilocybe mushrooms, sequenced in 2017, and how horizontal gene transfer carried it into more than two hundred fungal species over forty million years. He then shows the method — comparative omics — for finding a pathway nobody has mapped yet, by profiling an organism’s metabolites, sequencing RNA from the tissue that produces most of the compound, and comparing it against a close relative that produces none. That approach has already reconstructed the mescaline pathway in yeast and in plants, and is closing in on the final steps of ibogaine biosynthesis in the Madagascar periwinkle, a plant many people already grow in their gardens.

The closing modules look at rational enzyme design and machine learning as ways to improve yield, and at basil, which makes a compound one biochemical step from the oil currently being extracted from those Southeast Asian forests. Gerst is explicit about the limits of his own argument. This does not replace wild harvesting or traditional cultivation, and it does not settle the question of who benefits. It is a second line of supply, and a set of tools that traditional societies could use themselves, built on four principles he calls ESAU: eco-friendly, sustainable, accessible, and at low user cost.

 

Gerst describes this as a popular science lecture. It assumes no background in molecular biology: the gene names and biochemical steps are there to show how the work is actually done, not to be memorized.

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