Proof Before Promises

iGEM demonstrates how biology startups can do better

Last week I had the pleasure of serving as a judge for the iGEM Jamboree. Self-billed as the World Expo of Synthetic Biology, iGEM brings together hundreds of teams from around the world, all competing to solve some of the world’s greatest challenges with synthetic biology. Climate change, antibiotic resistance, agriculture, space, art & design are just some of the focus areas that teams can compete in.

While no organization is perfect, there’s a lot to love about iGEM. It provides a pathway for students from high-school to post-grad to enter the world of synthetic biology. Team members bring a wide range of skills to the table, extending far beyond biology into the domains of computer science, design, and hardware.

While developing an impressive solution is great, one of the most fundamental requirements is a demonstration of what iGEM terms “human practices.” This requires teams to demonstrate that they have considered the broader impact and potential risks inherent to their solution, and built safeguards for those concerns into their proposed solution.

Having spent a large portion of my career in startups and developing products from innovations, I can’t help but compare what I see so often from early-stage startups leveraging synthetic biology to iGEM teams.

Here’s a dirty secret: iGEM teams usually have a stronger proof of concept, clearer thinking about risks and mitigation, and have spent way less money. As a result, when I hear a lot of startup founders pitch, I can’t help but think, “…and?!”

A Refreshing Focus on Building a Network of Experts

The Human Practices requirement of iGEM is intended to “ask every team to think deeply and creatively about whether their project is responsible and good for the world.” While this is a lovely sentiment, the real value comes from how it is assessed and the actions teams must take to satisfy this requirement.

In essence, to fully meet the Human Practices requirement teams must talk to a variety of stakeholders, ranging from implementation experts to impacted community members, and demonstrate how those perspectives inform their solution. In the business world we call this user research, and as invaluable as it is a shocking number of deep-tech companies skip it.

To skip it is a mistake. No matter how strong your technology is, it must have market demand and be able to establish market trust to be a successful product. Aspects of venture capital funding can unintentionally skew this further, as many VCs rely on their own assessment rather than consulting with field experts.

This can be costly. Although moving forward with developing a prototype makes for great update emails, it does nothing for market adoption. At last a company is ready to test it’s prototype, but - uh oh - nobody wants to partner to test it in its current form because it lacks key features or design considerations. If a company is lucky, they have enough runway to iterate the prototype according to company needs. But this costs a lot more, in time and money, than having the right understanding of market needs up front.

A Solid Foundation Means Going Further and Faster

No matter what is being built, from buildings, to software, to synthetic biology, the strength of the foundation determines how much can be built without going back and adding reinforcements. A common practice from software is the concession of technical debt; a part of the product is built using an approach that works well enough for the current and immediate future. It is not the ideal way and it will not work as the company grows and gains more users. But, it’s calculated to be an acceptable tradeoff. If the product becomes popular enough to require the change, the company can afford to hire a workforce to make the changes before they break the product.

This concept does not transfer well to biology.

Trying to build a bio-based company with technical debt is like trying to build a skyscraper without a foundation. It will inevitably collapse, and while you don’t know exactly when it usually happens sooner than later. This is the overlooked flaw of Theranos: putting aside whatever your feelings are about Elizabeth Holmes¹, it was never possible to detect everything promised from a blood sample so small. It’s feasible to defy convention, not so much the laws of physics.

What does work, and what iGEM requires of teams, is to robustly demonstrate your foundational data. It’s not enough to say someone else has successfully performed a technique, teams must demonstrate through their data, with appropriate controls and replicates, that they performed the technique. That the premise of their strategy is sound.

Only once that foundation is established is it appropriate to show advancement towards the solution. Teams who defy this paradigm face the consequences in the judging process: a failure to present their data will result in the failure to achieve a medal, much less a coveted prize.

This process handsomely rewards the teams that invest strongly in their foundational work. They are able to achieve a phenomenal amount of progress in a short amount of time precisely because they combine the iterative approach of engineering with protocols that work and data that is interpretable.

Communication: The Golden Ticket to Market Acceptance

One of the most unfortunate myths about genius is the idea that it somehow impairs the ability to communicate with others. This is bullshit. If you cannot find a way to communicate clearly then you either 1) haven’t tried hard enough, or 2) don’t really understand what you’re trying to say.

I’m not saying it’s easy to communicate complex ideas, nor that expert concepts should be explainable to a novice in 30 seconds. But, with effort, a reasonably intelligent person (and certainly a genius) should be able to explain to someone what the point of their work is, why it matters, and how it effects you.

iGEM teams are expected to do this in a 15 minute presentation that introduces their project, the approach, the human impact, and their progress. This presentation is expected to be engaging across a range of knowledge levels, while also convincing the experts in the audience that they really have the data to back up their claims.

Teams also produce a 2 minute version of their presentation.

This is despite the fact that team projects target intractable challenges with impressive ingenuity. Some of the top-performing teams from this year’s competition addressed nylon waste, tattoos for biomarker detection, and combating antibiotic resistance with AI-developed phage therapies. There is nothing easy or simple about explaining these topics.

Teams succeed because the expectation is set. We don’t always hold founders, especially of deep-tech companies, to the same standard. This is a shame because when it comes to effectively recruiting the right team and ultimately bringing the product to market, there is no skill more critical than communication.

The Power of Expectation

I think expectation is the defining feature driving success across all three of these observations. Often, the expectations emphasized to startups are about market size, business model, and speed of scaling. While these are important for the dominant model of venture capital, putting these at the forefront is a distraction; there is no market to worry about if your technology doesn’t have a strong foundation.

While VCs won’t be the ones to drive this change, founders and early employees should insist upon it. Ask critical questions at the next meetup; if the answers don’t impress you, you can express skepticism without being a jerk about it. If the tech foundation isn’t solid, don’t accept the job offer and don’t intro to the investor.

This advice isn’t exclusive to domain experts. It’s reasonable to expect that someone can convey to you, a curious and intelligent person, the general value and principle of how their technology works. If it doesn’t make sense, it’s okay to say so. The right founders will take it as a valuable data point for how they can improve their communication. If they respond by attacking you, you just gained a valuable data point about how much their ego is driving the ship.

Selfishly, this will protect you from investing time, social capital, or financial capital into a weak foundation. More broadly, you’re helping to ensure that bio-based technologies achieve their full potential. This will be the difference between headlines about unbelievable success or scam-filled failure.

Sometimes being unimpressed creates the most optimistic outcome.

1. and please, keep them to yourself