How Open-Source Synthetic Biology Can Make Medical Solutions More Accessible

My pandemic project was AccessibleGenomics.org. As everyone knows by now, we need to sequence the genetic code of pathogens like SARS-CoV-2 to identify and track their most dangerous variants. In the first months of the pandemic, most developing countries did not have the capacity to sequence the virus.

We built a global team of volunteers, raised some funding from Just One Giant Lab, got donations from suppliers, and organized online training for our partner lab, PGC Mindanao. 10 months after we started, that lab made history: the first sequencing of SARS-CoV-2 enabled by volunteers, and the first on-site sequencing of any organism in Mindanao, Philippines.

I shared my project management lessons learned in this webinar. At the time of writing, we are interviewing labs in Africa and Latin America to see how we can best share what we learned from enabling a rural lab in a developing country to start sequencing.

On the positive side, I was surprised and inspired by all the help we got from the global genomics and open science communities.

On the negative side, I was surprised by what turned out to be the biggest threat to the project. It was not the difficulty of learning sequencing (turned out to be easy for experienced wet lab folks) or getting funding (hard but not impossible). What almost killed the project was the supply chain. Sequencing reagents need to be imported from the US or Europe. This makes them expensive for a lab in the global south. On top of that, we learned that you need to add 30% to 100% to pay gate-keepers, both legal and corrupt ones.

Since we grew up with open-source alternatives, we naturally asked if there are open-source versions of the reagents—affordable ones that allow us to bypass gate-keepers. Not yet, it turns out, but it looks like we are almost there. The answer lies in synthetic biology, a field that is at the cusp of its own open-source revolution.

What is synthetic biology and how will it make our lives better?

Most things that keep us alive are made of atoms strung together to make molecules. Back in our chemistry lab classes, we strung together atoms through simple chemical reactions, resulting in products with characteristics different from their reactants.

There are some valuable materials that are too complex to be made in a chemistry lab, but which we take for granted as products of living organisms. For instance, the food we eat, the air we breath and the medicines we take.

One of the biggest discoveries in the last century was figuring out how living organisms create these complex molecules. We eventually figured out how to engineer this process, particularly in microorganisms, like the bacteria E. coli. This allowed us to make it produce life-saving complex molecules like insulin.

I have two uncles who need to inject themselves with synthesized insulin. I'm sure you also know of people whose lives depend on insulin. Today, approximately 100 million people around the world need insulin. Producing insulin at this scale is a result of synthetic biology.

If you are in IT, you'd know about Unix and its open-source counterpart, Linux. You'd probably also know that over 90% of the world's top 1 million web servers run on Linux. If you are an open-source aficionado, you'd know about Red Hat, a competitor to the likes of HP, IBM, and Oracle that built a huge services business supporting open source instead of proprietary software.

If you are in the field of synthetic biology, or "synbio", you could probably give examples of synbio counterparts of Unix, and of companies like HP and IBM. However, you'll probably be hard-pressed at giving examples of their open-source equivalents in the synbio world. That's because we're still in synbio's pre-open-source phase.

Let's look at previous open-source revolutions to see what might be needed to create open-source synthetic biology.

How did the Open Source revolution happen?

I'm grateful to my parents for getting me and my siblings an encyclopedia in the house where we grew up. Those hardbound books were stacked taller than I was and cost a lot of money. The money my parents paid went to a global business that included expert writers, editors, project managers, printers, and door-to-door salespeople.

If you'd told me that volunteers will build an encyclopedia better than that global business, I would not have believed you. But this is exactly what happened. Wikipedia covers a lot more topics with greater depth than any of those encyclopedias made by hired professionals.

It turns out people are wired to give freely to the community once they are past survival mode. And it turns out Wikipedia was just following the footsteps of the trailblazer, open-source software.

Both Wikipedia and open-source software were enabled by the following:

• An open community collaboratively creating a resource free for the world's use
• A legal framework that protects the freedom of that community's creations
• Broad access to equipment to contribute, in creating that free resource

An open community collaboratively creating a resource free for the world's use

I was a Wikipedia contributor back in 2005 - 2010. I was a combatant in a number of edit wars. I sometimes still visit talk pages to see the story behind a Wikipedia article. Alliances, rivalries, and even friendships were formed in those talk pages.

Whatever our viewpoint on a topic was, we were united by a common goal and a common culture. We wanted well-written articles on topics we cared about. And we tried to abide by the principles of writing from a neutral point of view and assuming the good faith of fellow contributors.

Open-source software projects are also fueled by open communities with a common goal and rules of engagement.

A legal framework that protects the freedom of that community's creations

You'd want the law to be your ally if you want it to protect, or at least to not attack, the goods your community creates.

Copyright law was originally intended to protect creators from copycats. Book authors and software developers also need to feed their kids. The law was intended to make sure they are paid for their work.

What if your kids are already taken care of, and you just want to give away your work? This was a novel situation in the past decades. GNU GPL, Copyleft and Creative Commons were solutions within copyright law that protected not the income of creators, but the freedom of their creations.

Broad access to equipment to contribute to creating that free resource

Prior to the internet, the ability to contribute to projects like Wikipedia or open-source software like Linux was limited to academics in rich countries. Because of the lowering cost of computation, hardware, and software, those of us in the periphery can now contribute to these projects.

Synbio is entering its open-source phase

To see the parallels between software and synbio, let's first look at an example of a company built on proprietary synthetic biology, the counterpart of 80s' HP and IBM. Ginkgo Bioworks is one of the unicorns in the synbio world. They engineer microorganisms for your business, so you could produce valuable molecules. For instance, Ginkgo is engineering E. coli for Cronos Group, a cannabis company, to produce cannabinoids without plants.

Their technology is proprietary, so it is a secret. But we know that they certainly have a wetware stack, a hardware stack, and a software stack.

In synbio, "wetware" is the biological materials that you use for genetic engineering and fabrication, like engineered organisms and chemical reagents. Hardware is the machines that enable the same processes, like liquid handlers and bioreactors. And software are applications that help design these organisms and run the hardware. The collection of these stacks is called a biofoundry.

Open-source software helped democratize access to computing. Similarly, an open-source biofoundry will democratize access to synthetic biology. I'm optimistic. We could already see in synbio the three ingredients that we saw in Wikipedia and in open-source software.

First, an active, collaborative community has formed around synbio to develop and share ideas, resources, and technologies. For instance, the annual and global genetic engineering student competition, iGEM, has been seeding the open-source synthetic biology community for years. This list of companies built by iGEM alumni looks like the synbio counterpart of Y Combinator companies. For example, iGEM alumni are behind Ginkgo Bioworks as well as Just One Giant Lab, the open science platform that funded Project Accessible Genomics.

Second, legal frameworks analogous to GNU GPL and Copyleft have been created for wetware. For instance, wetware under OpenMTA can be legally used both by academic institutions and by third-world entrepreneurs like me who want to produce reagents locally, to lower their costs and bypass rent-seeking or corrupt gate-keepers. Organizations like Open Insulin are using open source to solve the insulin pricing problem in the US. Freegenes, Public Domain Gazette, and Reclone are examples of organizations that distribute or promote free wetware.

Finally, we are seeing in synbio a parallel to the evolution from expensive mainframes to personal computers that democratized contributing to open-source software. For instance, Project Accessible Genomics was only possible because of nanopore sequencing. Just a few years ago, a sequencer would cost more than a car. Today, you can get a MinION sequencer for less than the price of an iPhone. Opentrons has dropped the price of automated pipetting. Bentolab and miniPCR have done the same for core molecular biology lab equipment. (Opentrons and Bentolab are also built by iGEM alumni.)

We are headed in the right direction, but there is still a lot of work to be done.

Let's democratize synthetic biology

How would a low-cost biofoundry look like?

This just happens to be the goal of a 2021 iGEM team called Friendzymes. Like Project Accessible Genomics, the team also got funding from Just One Giant Lab. I've been helping out the team through project management training.

Here's the intro video of the team. They are working on multiple innovations to build a frugal biofoundry. The two I'm most excited about are the following:

• E. coli is the workhorse of synthetic biology. But using it tends to be expensive because you need to literally extract the product out of its guts (purification). What if you could engineer organisms that secrete the product from their cells naturally? The team is looking at Bacillus subtilis and Pichia pastoris as alternatives to E. coli.
• The lab skills you need to do synthetic biology require a lot of experience and wasted reagents. What if you use robots instead, like Opentrons? Then you could do your experiments and processes at scale and share them with other labs, the way 3D printer designs are shared now.

I'm excited about the possibilities that open-source synthetic biology will open for us here in the developing world. It will make molecular biology research much more affordable for our scientists. It will also have an impact on medicine, pathogen biosurveillance and food security.

Let's help Friendzymes by spreading the message of open-source synthetic biology or contributing to their crowdfunding campaign (tax deductible for US donors)!

Thanks to Sam Bhagwat and Dr. Nicole Wheeler for reading and giving feedback on early versions of this article.