BBNs Toward Universal Fabricators

A guest post by Ivan Jayapurna

Today’s piece is a guest post by Ivan Jayapurna. Ivan is a Programme Director (PD) at the UK’s Advanced Research + Invention Agency (ARIA). This week marks the launch of his £50m program: Universal Fabricators.

Ivan’s program has some very BBN-shaped pieces of work, and he believes some of his most ambitious applicants might see his call for proposals as their chance to launch a BBN of their own. If that sounds like you, and you can solve the problems Ivan outlines below, reach out to him here. (To learn more about “BBNs,” see this prior FreakTakes post.)

As a bit of context — for those that did not see my interview with ARIA’s founding CEO — ARIA PDs are empowered to fund brand new R&D orgs into existence if it suits their program’s needs. The org covered in the most recent FreakTakes post, Syntato, is a case in point. ARIA’s Programmable Plants work needed a group to build tools to transgenically gene-edit crops. Using its ARIA contract to do just that, Syntato was formed.

Ivan’s program may offer similar opportunities. In our discussions, Ivan was particularly excited about the idea that, at their best, BBNs can be technology-maximizing firms. I hope that a few of your pitches live up to that bar.

Fairchild Semiconductor diffusion area, 1960. The best example of human precision manufacturing is the semiconductor industry. As Ivan puts it, “We’re effectively trying to build a chip fab, but for a much broader range of materials — and using proteins rather than extreme heat and lasers.” Photo from the Computer History Museum Collection, courtesy of National Semiconductor

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Two quick notes.

1. I initially intended this series of BBN-related guest posts to be a weekly series. That was overly ambitious. I get over-eager sometimes, sue me. The new cadence will be two or three pieces a month.

2. In the UK, many have begun to call BBNs “Frontier Research Contractors” (FRCs). Ivan uses that terminology below.

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Universal Fabricators

By: Ivan Jayapurna

Ages of human history are defined by new materials: Stone, Bronze, Iron. However, civilisation-defining materials, from steel to optical fibres, changed the world not at discovery, but only when processes were developed to make them cheap and abundant. Our physical world is still dominated by ancient materials (wood, concrete) and antiquated ones (steel, plastic) built using brute-force heat and pressure. Continued reliance on manufacturing paradigms from the Iron Age and 1900s chemical engineering has trapped us in brittle global supply chains, resource conflicts, and a tiny corner of the total possible materials design space. Despite advances in material synthesis, many desired electromagnetic, thermal, optical, and mechanical properties remain inaccessible.

Mass manufacturing with molecular precision is crucial for state-of-the-art material performance, and proteins represent a uniquely powerful toolkit to achieve this. Yet despite recent breakthroughs in protein engineering (e.g., Alphafold, de novo design, directed evolution, non-canonicals, cell-free synthesis), subsequent investment and applications have primarily been in pharmaceuticals and biocatalysis, leaving the potential of proteins in materials assembly severely underexplored. Today, most protein engineers only design drugs and enzymes. If this programme is successful, they will design next-gen materials across electronics, energy, infrastructure, and more — and proteins will become “universal fabricators.”

As an ARIA programme director, I don’t have a lab of my own. My role is to design the programme, select contractors to fund, and orchestrate them towards the programme’s North Star technical vision. As such, success is almost entirely dependent on the programme’s contractors, who will develop proteins into universal fabricators. I need people and labs that are excited to become universal fabricators. It’s possible that FRCs — or BBNs as they’re also known — could be ideally-suited to do substantial portions of work for this ambitious, engineering-heavy, and radically interdisciplinary programme.

Why FRCs

As Eric has written in a prior FreakTakes piece:

[FRCs] will tend to have ambitious goals that are too engineering-heavy, multidisciplinary, or applied for academia. And they will tend to focus on markets ill-suited to VC — either (a) because these are not billion-dollar markets, or (b) because the financial impact of the work could be massive, but will not be realized within the ~10-year life of a VC fund.

Of course, there are some select academic research groups able to overcome these barriers. Often, these labs are well-funded, highly interdisciplinary, and have worked with ARPA-style agencies before (DARPA, ARPA-H, etc.). These labs have a culture of spinning out companies, allowing for R&D to be distributed between basic scientific research in the main lab and more “engineering-heavy” or “user/product-focused” work in spinouts. However, these labs are few and far between; and where they do exist, their spinouts are often subject to the constraints of venture capital funding.

For example, it is all too common a tale that an exciting materials startup with dreams of building revolutionary platform technologies is pushed by market and investor incentives towards a niche in the pharmaceutical industry, or incremental advancements on existing systems. These are all useful, but tend to fall short of the founder’s original ambitions. For profit-maximising firms this is understandable, but once you narrow in the technical scope to only those markets that fit VC constraints, many lines of societally exciting technical inquiry are lost.

I view FRCs as technology-maximising organizations that seek contract revenue from customers not as the objective to maximize, but as fuel to develop coupled science-engineering breakthroughs. These groups should seek to do work at the edge of the impossible. For that reason, FRC-like groups are a great fit for a programme like ours.

Universal Fabricator FRCs

The majority of our £50m programme will fund a small number (<10) of teams developing proteins into universal fabricators. There are multiple different renditions of what an FRC that could successfully build a universal fabricator could look like. One variant might look something like a team made up of the following archetypes:

• Protein Engineer — Designs the building blocks and interactions on the molecular scale.

• Complex Soft Matter Expert — Manipulates short- and long-range interactions between the building blocks, such that they assemble at the right length scales and time scales.

• Inorganic Materials Mineralization Expert — Programs nucleation and growth of crystalline or amorphous inorganic matter into highly valuable functional materials.

• Process Engineer — Designs reaction environments to create “error-correcting” assembly systems that impose selective pressures for assembly through fields and flows.

No matter how they are structured and composed, these teams should be able to rapidly iterate design-test cycles — quickly going from a sequence, to the design of single molecules, to ensemble design, to field/flow-aligned assembly (liquid → slurry → solid).

To further emphasise, this all-star team is just one vision (mine) of how to design a universal fabricator FRC. We’re looking for creatives with their own takes on team composition, and imaginations that exceed our expectations to fill the white space that sits between:

• Biology and solid-state physics,

• Protein assembly + templated mineralisation (sequence → structure → function) and scalable materials manufacturing (processing → structure → performance)

If successful, I hope these universal fabricators can do the work that defines the next era of human history. I want to read proposals from any team with a vision of how to make that happen.

Protein Production FRCs and Beyond

The programme will likely benefit from other FRC-shaped groups, beyond teams building protein-programmed fabrication platforms. One big challenge that will need to be solved is scaling up protein sequence-to-function design-test cycles. Today, in silico screening and automated assaying is done efficiently at the molecular scale. Scaling this up by many orders of magnitude, to the materials scale, today, would optimistically take months. Ideally, we want to shrink this timeline to under a week, to match the current state-of-art in drug design pipelines.

An FRC focusing on advancing rapid turnaround — large quantity, bespoke, engineered protein production — would likely be one of the most important suppliers for our programme. Specifically, I’m looking for a group to develop a system where, if I give you an arbitrary protein sequence, within a week you can give me enough material to e.g. template the assembly of a magnet large enough to measure (BH)max. Today, this would likely be done by living systems, but it’s conceivable that it could be achieved by drastically improved non-living production systems (e.g., cell free, protein printer). If a group has the capacity and ambition to substantially improve the state-of-the-art, it would be a valuable organisation for us to potentially nucleate into existence.

We expect this service to be exceptionally useful to a variety of customers, beyond the needs and length of our material science programme. In the near-term, we expect that a sustainable inflow of contracts could also be sourced from markets ranging from pharmaceuticals and biocatalysts to food, fibres, and packaging. Contracts like these, in addition to the sizable needs of our own program, would allow for the steady funding required to knock down technical barriers in pursuit of ambitious long-term goals in this space.

These are just two examples of possible FRCs aligned with my programme’s needs. I’d love to read your pitches for more of them. For example, FRC proposals in an area like metrology would be very welcome. Is there an FRC-shaped group that could quickly measure defect-free incorporation of proteins into macroscopic structures?

Call To Adventure

Prior to joining ARIA, I was a researcher trapped at the interface of materials and biotechnology — the only non-healthcare company in a biotech incubator, the only biotechnology in a climate accelerator — as well as between academia and profit-maximising startups. ARIA offered me an alternative, more direct path towards achieving my North Star of ‘Manufacturing Abundance’. Through the Universal Fabricators programme, I hope to open alternative paths for others. If this piece resonated with you, let’s go on this journey together.