TechBio: a new stack for a new biology

How can we produce and supply enough safe and nutritious food in a sustainable way to a population which is expected to exceed 9 billion? How can we keep global warming under 1.5C, or even 2C, whilst petrochemistry provides most of the energy and materials this rising population requires? How can we outwit diseases that have so far outwitted us and continue to meaningfully extend human healthspan and lifespan? Most of the key questions facing us, most of them requiring urgent answers, hinge on our understanding and use of biology.

It is perhaps a lucky coincidence that both are accelerating like never before. An ever increasing community of life scientists, leveraging technologies that were completely out of reach just until recently, is causing the rate of innovation in biology to outpace Moore’s law. Cheap genomic sequencing and novel gene-editing methods, alongside other recent advances in DNA synthesis and transcriptomics and the increasing adoption of AI, are starting to make biology data-driven, programmable, and scalable. Companies like Solugen, Perfect Day and Moderna are some of the first to use this new, software-like quality of biology to drive forward new products of “the bioeconomy”. We expect bioeconomy companies to become some of the world’s most valuable in the next 30 years.

As players within the bioeconomy specialise, tools and services that have developed in isolation over the past few decades are becoming components of an exciting new “stack” to serve this community and make it more efficient. Here, we present a view of this stack, using the product development “lab-to-market” process, inspired by our knowledge of software products, as a framework.

It should be noted that many of the companies mentioned currently span multiple layers: for example, Moderna’s COVID vaccines currently span all layers of our stack. These vertically integrated propositions have also attracted the vast majority of VC funding so far, and are likely to continue doing so. As markets turn to synbio and the stack’s technologies mature, we think players that are focused on horizontal layers will continue to emerge alongside today’s vertically integrated companies. These companies will focus on infrastructure, adopt licensing and partnership models and benefit from avoiding the additional burden often incurred by serving end markets.

Stack layers

We’ve included a small selection of company examples for each layer (note that we’ve prioritised European companies, even when earlier stage), but have collated an initial database of other companies & tools here. We’d love to enlist your help to add the many companies and tools we’re sure we don’t know and make this a resource for the amazing bio + tech community.

End Products Layer

McKinsey estimates that 60% of the world’s physical inputs could be made with biology, representing USD$2-$4 trillion in annual direct economic potential in agriculture, materials & energy, consumer products, and health/pharma. In the end products layer, companies are developing end products in these categories, for businesses and consumers. Today, product development infrastructure is still an important part of these companies. Example companies include:

• Solugen, which uses bespoke-to-enzyme reactor systems to produce an array of specialty chemicals.

• Perfect Day, which uses precision fermentation to make whey protein powder which is molecularly identical to the one made with cow’s milk.

• Moderna, which has built a machine to design and produce mRNA therapeutic candidates at massive scale.

• Meatable, which is bringing lab-grown meat to market.

• Origin Bio, which is redefining how to use fermentation to produce high value chemicals.

Many other companies are emerging to finally bring to market products that have notoriously been hard to develop, from biofuels to bioplastics. The tech bio stack can hopefully help them overcome some of the challenges that have in the past led to failure in these fields.

Regulatory Layer

The regulatory layer is naturally most relevant to healthcare and foods. The FDA/EMA/regional food and health authorities are the gatekeepers for any novel therapy that hopes to make it onto market and exist to protect patients (they also play a huge role on novel food products coming onto market - again with consumer health at the center). Within this layer of the stack, new tech tools are helping companies successfully navigate the different steps of the regulatory process, from trial design, to recruitment, to working with regulatory bodies. Example companies include:

• myTomorrows, which helps to solve the trial recruitment puzzle by pooling patients with unmet clinical needs to grant them access to medicines in development.

• Sano Genetics, which allows consumers to contribute their DNA data to clinical research.

• Scarlet, which is building a new type of regulator that is able to handle continuous reviews of products such as health SaaS or digital therapeutics.

• Qualio, a modern alternative to paper-based quality management systems that allows companies to bring life science products to market more quickly.

• Apheris, which allows for the creation of “data ecosystems” in healthcare and beyond, that respect data privacy whilst allowing for data sharing.

Manufacturing Layer

All of tomorrow’s biotech companies developing novel applications and products will have similar challenges in scaling up manufacturing and distribution. Take mRNA vaccines as an example: once the COVID-19 vaccines were ready, Pfizer and Moderna had to build factories and distribution systems from scratch. Scaling up biology is not as simple as scaling up a piece of software, as the complexity scales almost exponentially with capacity. There is no AWS or even TSMC for biology yet, that can take an organism design and scale it almost infinitely, and even biomanufacturing capacity is becoming a bottleneck as the key bioreactor manufacturers have months of delays. Within this layer of the stack, companies old and new are developing solutions that are AWS or TSMC-like. Example companies include:

• Culture Biosciences, which allows scientists to design, monitor, and analyze high-throughput bioreactor experiments in the cloud from their laptop.

• Stamm Bio, which facilitates the implementation of cell growth systems with a novel bioreactor design.

• Unicorn Bio, which is working to scale adherence based biomanufacturing - particularly important for lab grown meat.

• FabricNano, which is using enzyme immobilisation to enable drop in biocatalysts for bio-based commodity chemical manufacturing.

• Ori Biotech, which has built a manufacturing platform for cell and gene therapies.

• Automata, which is helping to automate production lines for life science products.

Product Development Layer

We think of the product development layer as all the tools scientists use to read, write and engineer biology whilst imagining new bio-based products and applications. This layer can range from screening and reading technologies like NGS, transcriptomics, proteomics, single-cell screening, to novel tools and techniques, like directed evolution and CRISPR, to computer-aided design like AlphaFold and Rosetta. We even think of lab-scale automation as a key enabling technology to speed up product development. Within this layer of the stack, companies are allowing scientists to treat biology as an engineering discipline, moving from pure discovery to “design, build and test” cycles. Example companies include:

• Cradle Bio, which is building software infrastructure for molecular design.

• Latch Bio, an open-source toolchain that any bioprogrammer can use to define serverless bioinformatics workflows with plain python.

• Benchling, a unified R&D cloud-based platform, including design tools for DNA, oligonucleotides, and AA sequences.

• Zafrens, which works at the cutting edge of biology, chemistry and engineering to build single-cell multi-omics tools.

• Oxford Nanopore, which has developed technology for nanopore sequencing.

Raw Materials Layer

It’s hard to overstate how huge a shift has happened over the past decade in the availability and speed of sourcing of the fundamental building blocks of biology. DNA can now be quickly synthesized at bench scale or even delivered directly to the lab, which in turn is the backbone of synthesizing proteins and microbes with specific functions (more on design later). There has also been a proliferation of research around induced pluripotent stem cells as the starting point for many research projects and applications, as we are learning how to effectively manipulate and reprogram them. Within this layer of the stack, more and more novel technologies will emerge that will provide companies with better components and materials to develop their products at speed and scale. Example companies include:

• Twist Bioscience, a silicon-based DNA Synthesis platform that provides “raw materials” including genes, oligo pools, antibodies and more.

• Nuclera, which offers on-demand gene to protein synthesis in a desktop bioprinter that can be put in any lab.

• Codexis, a protein engineering company that develops enzymes for pharmaceutical, food and medical applications.

• Core Biogenesis, which uses plants as biofactories to scale the production of high-value bioproducts such as growth factors.

• Bit Bio, which combines synthetic and stem cell biology to produce batches of human cells with precision and at scale.

Research Funding, Review and Dissemination

The emergence of a technology stack is fundamentally redefining the capital requirements to build biotech companies (similar to the effect AWS and the software stack played on tech companies). At the same time, there is renewed interest in the VC ecosystem to unlock funding opportunities for early-stage research beyond the traditional academic routes or life sciences funds. More recently, several alternative models are popping up, like the Arc Institute or even funnelling crypto profits into early-stage research like VitaDAO and the Decentralised Science movement.

Basic research has been mainly driven by academic institutions, with the goal of advancing humanity’s knowledge. While the peer-review process does have its flaws, it remains the gold standard for young and experienced researchers alike. The emergence of open access platforms like bioRxiv, where scientists can upload their preprints before they hit the journals, and Sci-Hub, which aims to open up papers behind paywalls, are paving the way for a more collaborative and open communication layer between scientists. We would love to see more technology disrupt peer review or dissemination.

Final thoughts

The emergence of this “stack” goes hand in hand with the rise of bio-platforms. We are seeing companies that both vertically integrate, using their platforms to produce end products in house, while also unbundling the stack, by offering their platform to the development of other companies. Now that a stack exists, new bio companies are free to focus on developing their core capabilities while leveraging other platforms where they are weakest.  We’re positive that the future of biology will not just be built by monolithic giants but by nimble platforms, fueling their growth via cross-pollination and collaboration. As tech investors, we come to this stack humble about our lack of depth in biology, excited to contribute our experience in engineering, and thrilled to help build the bio-solutions the future needs.