In vivo detox and bioprospecting ancient DNA
New theses from Compound!
Compound is a research and thesis-driven fund investing in frontier tech across AI/ML, robotics, crypto, and bio. We have a public database of areas we’re currently tracking and always adding to it.
Feel free to reach out if your building here or in adjacent verticals - we’d love to speak.
Thesis #1: In vivo detoxification
Concept
Reducing our intake of harmful chemicals can only do so much. Eventually we need to remove the chemicals we’ve ingested and need innovation here.
Longer Description
We are exposed to many products daily (pesticides, phthalates, bisphenols, PFAS) which have been linked to cancer, hormone dyregulation, lower sperm count, and others. However, tools to measure the accumulation of these substances let alone remove them are very limited. I think part of health and longevity should include our bodies being as toxin free as possible. We’ve seen efforts to reduce the amount of PFOS/PFAS remediation with Fixed Earth, BluumBio, Orin Technologies, Allonnia (A Ginkgo Bioworks Company) but think the in vivo remediation could accrue more value. It also dovetails with proactive healthcare which is becoming popularized with the longevity movement.
In order to meaningfully undertake toxin removal, we need to fidelitously measure toxins and their metabolites, understand where they’re accumulating, and ID technologies for removal. Previous work shows that PFAS accumulates mostly in lung tissue, with other forever chemical derivatives enriching in the liver and bone. For inspiration, I tried looking at other toxin removal strategies - developing antibodies which bind the toxin of interest, filtering blood through an affinity column which binds the toxin, carbon nano structures, enzymatic nanoreactors, enzyme discovery, diet have all been found to be able to remediate different toxins.
Other Thoughts
Hard to understand which harmful chemicals to prioritize since we ingest so many.
One could envision a prosumer market entry point as is the case for longevity clinics like Fountain Life, Hudson Health or others such as IV clinics. However, higher risk groups (such as those with kidney disease) could eventually go through clinical trials and insurance reimbursement.
Like longevity drugs, shorter-term endpoints based would need to be used. In places with socialized healthcare systems might have a higher burden of proof - long studies would need to be conducted to calculate the differential quality adjusted life years (QALYs) to demonstrate utility.
Platforms for nanomaterial, enzyme, and/or delivery tech discovery and engineering would be the most compelling from a venture-scale company perspective along with strong views on toxin sequencing.
Related Reading
https://www.epa.gov/pfas/meaningful-and-achievable-steps-you-can-take-reduce-your-risk
https://bmcvetres.biomedcentral.com/articles/10.1186/s12917-014-0255-y
https://www.sciencedirect.com/science/article/pii/S0021925820758205
https://www.theguardian.com/us-news/2019/may/22/toxic-chemicals-everyday-items-us-pesticides-bpa
Thesis #2: Bioprospecting ancient DNA
Concept
Adding a time axis to modern day bioprospecing can create value by elucidating new chemical space for the production of previously unobserved metabolites.
Longer Description
Genome mining (also called bioprospecting) has galvanized many research efforts in industry and academic settings. Indeed, Basecamp Research, Metagenomii, Hexagon Bio, and Enveda are seeded on the premise of massive value creation from natural-derived products. Indeed, 49% of new drugs are derived from nature.
At the same time, there have been increases in the processing analysis of ancient DNA (aDNA) - epitomized by the Nobel Prize in Physiology being awarded to Svante Pääbo last year. He helped reconstruct the Neanderthal genome as well as the Denisovan genome (both extinct hominin species) via methods advances in aDNA.
Despite increasing technological sophistication, the crosstalk between genome mining and aDNA fields could be furthered to mine for products not made on earth in millennia. A recent study (one of few) closed the gap by mining the microbiota of Neanderthals to find new biosynthetic gene clusters (BGCs). They then clone these ancient genes into modern chassis to produce the ‘old’ compound’. Although this metabolic resurrection wasn’t of commercial interest per se, it does prove the possibility.
This is just the tip of the iceberg and think the convergence of these fields with the precipitously decreasing cost of DNA sequencing will lead to the recapitulation of many valuable compounds. Marine sediments, icecaps, soil, and human remains have all been sequenced using aDNA methods.
Other Thoughts
New companies formed here will have tough decisions on where to find aDNA that leads to the highest value creation path. Clear understanding of metabolic requirements and evolutionary pressures will be important in identifying areas to look for the most valuable aDNA. The aDNA could encompass microbial species, extinct plants, and animals.
aDNA processes, depending on the sample, seem to be exceedingly finicky processes - talent scarcity will be important for any company here.
There’s conceptual tension between Generative AI and bioprospecting but they’re both working towards the same goal which is elucidating new chemical space (both small molecule and protein).
Comparable Companies
Resurrecting the Sublime (not really a company but a PoC)
aDNA analysis might eventually be layered into the current companies + new companies will be formed on this premise.
Some groups which look at the evolutionary history of proteins might be able to expand the chemical space but likely not to the level which aDNA would allow.
Related Reading
https://asm.org/Articles/2019/March/Paleomicrobiology-and-Microbial-Ancient-DNA-Get-to
https://ami-journals.onlinelibrary.wiley.com/doi/pdf/10.1111/1462-2920.15913
As always, feel free to reach out (shelby [at] compound [dot] vc) if you’re working on these areas or any in our thesis database - https://compound.vc/thesis.
Very interesting stuff! Thanks for posting.