New bio theses from Compound!
'Human' in a test tube, biohacking, and bio in space
Compound is a thesis-driven and research-centric fund investing in hypotheses of the future. We shared some of our theses last year and have kept adding to it. As we continue to learn and hypothesize about massive value creation in the future, we’d love to hear about your hypotheses for the future and meet founders that are thinking of building in these verticals!
Below are three theses we have about recapitulating human environments in vitro (what I call ‘human in a test tube’), the celestial future of life sciences, and biohacking.
Thesis 1: Humans in a test tube
Concept
Strides in recapitulating more ‘human’ environments in the lab setting will lead to much more predictively valid tests. An enabling technology here could increase the calibre of drugs that enter the clinic.
Longer Description
There’s a groundswell of enthusiasm for laboratory models that better mimic the ‘human’ state. This has played out in a wide array of ex vivo cell culturing companies such as Pear Bio, Oncoprecision, NeuScience, Genoskin, Kiyatec and many more. The ex vivo culturing allows for patients’ cells to be directly tested for drug efficacy, circumventing the proxy research and biomarkers that have been historically used. Ultimately the mecca of biomedical research would be to have an organoid for each human which takes into account each cell type. From this personalized dosing of drugs and maybe even n=1 drugs could be formulated for just you.
In our current system, drugs have been made for large patient populations but the ex vivo companies provide a portal to the future. Between now (drugs for the masses) and the future (drugs for individuals) ex vivo cell culturing companies will lead the way.
Importantly, all of these companies and the ones to come need to be in systems which mimic the human environment e.g. where metabolites, sugars, pH are consistent, not in flux as is the way with our current cell culturing techniques. This can be achieved via perfusion systems which exchanges cell culture media - keeping the nutrients and carbon sources consistent. However perfusion systems are historically lower throughput which leads to issues with replicate numbers and reproducibility. A recent paper by Kang et al., 2023 demonstrates the ability of researchers to now have 3D cell culture models which are much higher throughput and benefit from constant conditions from being inside a perfusion system.
Some perfusion systems are also able to create shear stress which is important for cell phenotypes such as endothelial cell alignment, differentiation of stem cells to endothelial cells and the formation of actin stress fibers. Perfusion culture allows scientists to replicate the blood supply of cancer tumors. There’s also mechanotransduction cultures which can drive pressure forces onto cells since bones, muscles, and skin are all under various pressures throughout our days. Other methods such as ex vivo matrix-collagen-based cultures can recapitulate mouse development at certain stages.
Other thoughts
An issue is that each cell type requires a different environment to recapitulate what it’s like for the cell in vivo. This means a very modular system will need to be built.
A very thorough GTM and specific thoughts on which type of cell culture are most used and most important for recapitulation will be key.
Retrofitting and upgradeability are important considerations for any hardware being built here to allow for mass adoption and modular updating as the field expands.
Comparable Companies
Vitroscope
Emulate Bio
Cherry Biotech
Related Reading
https://www.sciencedirect.com/science/article/pii/S1359644620305274
https://www.biorxiv.org/content/10.1101/2023.03.11.532210v1.full.pdf
https://www.science.org/doi/10.1126/science.aaz5626#:~:text=Human%20choroid%20plexus%20organoids%20provide,development%20of%20neurologically%20relevant%20therapeutics.
Thesis 2: The celestial world of bio in space
Concept
Space provides a unique environment for biomanufacturing and research.
Longer Description
Companies such as Novartis, Merck and Eli Lilly have contracted bio experiments in space since the 2000’s. Due to these experiments and several others, we have a clearer picture of the opportunities of life sciences in space. Findings from the experiments have shown that:
Protein structure characterization works better in space as the formation of the crystal structure is slower leading to higher resolution images
Cell cultures behave more like organs (by growing in 3D) and create opportunities for more predictively valid drug screening in space
Biomanufacturing of complex films (such as retina replacements) work better in space than on earth due to homogenous solutions that aren’t possible in Earth’s gravity. [LambdaVision has even made the process completely autonomous with Space Tango CubeLabs hardware which is specifically designed for use on the International Space Station.]
There could be many other interesting disease modeling, manufacturing, and research use-cases. As these expand there will be increased pressure on the ISS to have more room or even pushes to a public/private Biology Space Station (BSS). Cost is a major deterrent but in a future where space travel becomes significantly and lab automation becomes more commonplace, the age of bio in space will blossom.
Other thoughts
Lab automation of R&D processes (as opposed to CDMO/CMO) will be a bellwether for the field of autonomous labs, and may be where closed loop systems are implemented at scale, first. This is primarily due to personnel constraints of biologist astronauts.
Companies such as Zero-G (which only fly in space and aren’t permanently stationed there) could be ways to conduct shorter term experiments for less money
Partnerships with Blue Origin, SpaceX, and NASA are important signaling while space flights are still infrequent but will be less important as the industry commoditizes
Comparable Companies
Space Tango - CubeLab - standardized hardware platform for R&D on the International Space Station
Firefly Biotech - simulate microgravity on earth and molecular monitoring and remote diagnostic hardware
Yuri Gravity - on earth microgravity and pods for space-based research
Astrogenetix - access to a designated U.S. National Laboratory aboard the International Space Station for research, development and industrial bio-manufacturing processes
M4PM (not for profit) - 3D tumor, organoid and spheroid growth in microgravity to enable the development of space-based personalized Medicine
Leap Biosystems - combine clinical medicine with innovation and disruptive technologies for human space exploration
Related Reading
https://www.biopharmadive.com/news/outer-space-the-final-frontier-of-biopharma-rd/408522/
https://www.the-scientist.com/bio-business/pharma-looks-to-outer-space-to-boost-drug-rd--68183
https://www.synbiobeta.com/read/space-lab-3-0-imagining-the-future-of-science-in-space
Thesis 3: Biohacking the world
Concept
The ease and miniaturization of science is converging with our understanding of human and environmental health. This confluence of new tech and use cases will shift who we consider ‘scientists’ and allow for more citizen scientists or biohackers.
Longer Description
Historically the capital to get a lab up and running and the numbers of people educated in bio was sufficiently low to limit citizen research efforts in bio. However, lab miniaturization and increased efficacy of lab research (<1 week gene editing, gene addition, gene deletions) means that science is much more accessible and impactful. We now understand the causative agents of 10,000+ diseases, with many being discovered each year. This research isn’t only limited to monogenic disease (one gene) but complex diseases too. Moreover the biological toolkit for organisms outside of humans means we use nature’s diversity to solve other problems, besides health and disease. For context, over 200+ organismshave been reported to be edited by CRISPR which opens up tremendous possibilities!
There have been companies (like ODIN - at-home CRISPR kits) and individuals (like Jo Zayner) advocating for citizen scientists and we think this will only continue.
Other Thoughts
We think both centralized labs servicing citizen scientists and individual labs are part of our future. However, decentralized biohacking spaces will be more prominent in the short term with prosumers accounting for most of the spend/innovation
As the field grows, that’s when we envision centralized CRO facilities
Regulations in citizen science will be important to ensure bioweapons won’t become prominent
Comparable Companies
Dangerous things (mostly electronics/implants not molecular )
Related Reading
https://biohackingbrittany.com/