Nick Milne is a metabolic engineering and fermentation scientist with expertise engineering yeast to produce a range of molecules with pharmaceutical, cosmeceutical and nutraceutical relevance. He has a strong academic and industrial track record with a demonstrated ability to take yeast production platforms from the idea stage to commercial application. He is applying this expertise as the Co-Founder and Chief Science Officer at Octarine Bio
What made you personally want to get involved in this field of research?
For many years I dealt with a handful of mental health issues and ran the gauntlet of different prescription drugs trying to fix it. Most of these drugs did little to improve my symptoms but often came with intolerable side-effects. The whole experience left me with a keen awareness of how inadequate mental-health treatment currently is and the sheer number of people around the world suffering from these illnesses. While my research career took me down a different path (industrial biotechnology) I’d always hoped I could find some way to apply my background to improving mental health, so when I saw some of the early data showing the effectiveness of psilocybin, I convinced my academic supervisor to let me do a small research project on natural psychedelics which was eventually spun-out into Octarine.
What inspired you to create Octarine? What are you looking to accomplish?
The inspiration and endgame for Octarine is to see effective therapies for poorly treated conditions reach patients. Importantly however, we want to make sure that this is done in an equitable and sustainable way. The pharmaceutical industry and the chemicals industry in general are heavily reliant on fossil-fuels to produce all the drugs and various molecules we use in our daily, and this reliance obviously must change as society transitions to a renewable world. In our past lives Nethaji (Octarine CEO and Co-founder) and I have worked to develop and commercialise sustainable, bio-based production processes for a range of molecules used as biofuels, bio-plastics, flavourings and nutraceuticals, so for us sustainable pharmaceuticals was a logical next step.
Your background, specifically, is in metabolic engineering using yeast, how are you using this expertise at Octarine?
The field of metabolic engineering is essentially based around the idea that anything you can do with chemistry, you can do better with biology. So researchers in this field aim to replace chemical processes with better biological alternatives. At Octarine we apply this concept both to drug development and to the production of pharmaceutical drugs. We use biological machinery to produce novel improved derivatives of therapeutic molecules and engineer yeast to produce natural and novel molecules in large scale fermentation. Examples of how we apply this technology include our work on producing cannabinoid derivatives with improved solubility, bioavailability and stability, and our work to transfer the psilocybin biosynthetic machinery from Psilocybe mushrooms into yeast to cost-effectively produce psilocybin by fermentation.
What does De Novo Production mean? What does it mean for Psychedelic Derivatives?
De novo in Latin means “from the beginning”, in metabolic engineering we use this term to describe a biosynthetic production process that starts from the same basic chemical building blocks that a microorganism uses to survive (in the case of yeast this is typically simple sugars like glucose). Our yeast fermentation platform produces a range of psychedelic molecules de novo from glucose, as opposed to other methods which require feeding an engineered microorganism an intermediate of the biosynthetic pathway (e.g. 4-hydroxyindole). Ultimately, this approach to producing psychedelics has 3 main benefits; cost (glucose costs ~$0.5 USD/Kg), sustainability (glucose production is renewable and CO2 neutral), and supply chain stability (glucose is a highly abundant molecule produced all over the world with minimal fluctuations in price and supply).
Why have you chosen Psilocybin to work with?
We don’t only work with psilocybin but aim to produce a range of natural and novel psychedelics (and cannabinoids) for clinical application. That being said, we know more about psilocybin than any other psychedelic, so it makes sense to focus on this molecule (at least initially). From a therapeutic point of view, psilocybin is an attractive candidate since it has a long history of use and has a remarkable safety profile. As the psychedelic therapy industry develops however, we anticipate a need for new molecules with different therapeutic properties which is why we’re using our biological platforms to produce new derivatives of psychedelic molecules.
What kind of therapeutic potential do you see in psychedelics and what kind of impact could that have on healthcare?
Personally, I think the greatest potential of psychedelics is to make mental healthcare more equitable. Today, psychotherapy is arguably the most effective treatment option we have available, but treatments are long (often years), expensive, and resource intensive (often involving 1 on 1 with a psychologist). This ultimately makes treatment inaccessible to many, where even if you can afford the treatment, you’re often faced with long wait times to see a psychologist. Psychedelics used in conjunction with psychotherapy offers the possibility of both increasing the efficacy of treatment and decreasing the treatment length (i.e. from years to days). My hope is that this would make mental health treatment accessible to everyone.
What can people expect to see from Octarine in the future?
We’re building biological production platforms that can produce a range of natural and novel psychedelic and cannabinoid molecules for therapeutic application. Taking a biological approach to this industry allows us the achieve superior production efficiency, but also allows us to produce derivatives inaccessible to synthetic chemistry. In the coming years we will be establishing GMP-grade production processes for these molecules (important for pharmaceutical application), and continuing pre-clinical and clinical development of our most promising molecules. While we aim to commercialize some of this ourselves, some of these production processes and validated therapeutic molecules will be commercialized through partnerships with pharmaceutical companies.
Where do you see the future of Psychedelic Research heading?
From a neurobiology perspective there is a lot that psychedelics could reveal about the human mind and the roots of consciousness, but I’m also really excited to see developments in our understanding of how and why certain species produce psychedelic molecules. Understanding the how (i.e. elucidating biosynthetic pathways to psychedelics) makes these molecules more accessible as therapeutics, while understanding the why (i.e. the evolutionary mechanisms behind psychedelics production) helps us uncover the neurochemical basis for their effects. Also, while western science is now investigating the potential of these molecules, their therapeutic effects and the species that produce them have long been known by indigenous communities. Modern scientific research on psychedelics has been heavily influenced by indigenous knowledge and I look forward to seeing this collaboration model continue to be used in psychedelic research but also hope to see it applied in other areas of science.
What is the most common misconception you hear about Psychedelics?
With all the hype going on with psychedelics at the moment I think its important not to overblow their potential. Psychedelics (particularly on their own) will not be a panacea for mental illness, and it’s important to understand the dominant role that psychotherapy will likely have in these treatments. Psychedelics are very serious molecules which produce intense psychological effects (both good and bad) and over-promoting their therapeutic potential could negatively affect the industry not to mention public health.
From your perspective, what needs to happen to educate the masses about the therapeutic potential of psychedelics?
I think de-scheduling psychedelics will go a long way to convincing the public about their therapeutic potential. Society tends to make the assumption that anything illegal must be bad for you and grouping molecules like psilocybin into the same category as hard drugs like heroin just reinforces that narrative.
Who else is doing important work within psychedelics you think more people should be aware of?
I really want to point out the fantastic research being done by Prof. Dirk Hoffmeister and his research group at the Hans Knöll Institute in Germany. His team elucidated most of the psilocybin biosynthetic pathway in 2017 and since then has greatly contributed to our understand of how and why Psilocybe mushrooms produce indole alkaloids. This kind of fundamental research provides invaluable contributions to the field.