On March 31 2021, PLOS Computational Biology introduced a new journal requirement: mandated code sharing. If the research process included the creation…
As a synthetic biology enthusiast, I am fascinated by the power of the biological tools that are being developed to solve the very immediate and practical problems that our society is facing today. Synthetic biology was born in an academic environment but was readily embraced by industry, with an impressive number of start-ups having been created in the past few years. The industrial advancements in the field are just as impressive as the research developed by the more theoretically oriented academia, and for this reason, I have started a series of interviews with people that are at the core of the synbio industry and can give us insights from their different perspectives.
I also encourage interested synbio people and companies that would like to share their stories with us to get in touch! In our next post, we could be speaking about you!
Christina Agapakis, creative director of Ginkgo
This time, I had the honour to interview Dr. Christina Agapakis, creative director of Ginkgo Bioworks. Christina is an inspiring person, in so many ways. She defines herself as a synthetic biologist, as this is her background, but her life and interests soon brought her to expand her horizons. Her story is most peculiar and started to intertwine with Ginkgo since her time as a graduate student at Harvard. While her PhD was coming to an end, the founders of Ginkgo were wrapping up their time at MIT and starting their company. The founders were part of her same, at the time small, synthetic biology community: they were attending the same conferences, valued the same vision. However, Christina’s interest at the time was shifting away from the bench. As some of us scientists experience, myself included, there comes a point at which science at the bench starts to become too narrow. You end up working on such a specific scientific problem (for instance, the engineering of a single enzyme, part of a specific metabolic pathway, which is in reality part of an increasingly complex biological system) that you tend to forget about the bigger picture. This is when Christina started to use writing, “As a way to get out of the bubble of my own particular experiment.” Writing helped her ground her scientific work, and understand it as part of a bigger picture, which in her case was biofuel production.
“The more I was writing, the more I was connecting to people outside of this very small thing that I was working on. I was seeing people that were asking really exciting questions, helping to shape a vision for what synthetic biology should be.”
In this context, she started to get excited about a particular question: What is the best way to design biology? Looking for an answer, she began collaborating increasingly with people in the design industry who were asking that kind of question and, “Making really compelling objects and stories about the future of biotechnology.” During her postdoc, she continued to work on biofuels, enzymes and microbes, but also worked with the UCLA Art|Science Lab. While a postdoc, she also worked with the Art Center College of Designs, connecting to artists and designers and thinking about bigger questions such as, “What are creative ways that we can see a different future for these technologies, and communicate it?”
When ready to move back to Boston, she found herself “in the right place at the right time.” Ginkgo was growing fast, and they were starting to see the need for the kind of communication and vision she had been developing. She was able to reconnect with the founders and find a way to work together with them to build a role within the company through which they could be thinking creatively about how to communicate better what the future of biotechnology could look like.
Ginkgo Bioworks: the organism company in Q&A
“Ginkgo Bioworks is the organism company. We design custom microbes for customers across multiple markets. We build our foundries to scale the process of organism engineering using software and hardware automation. Organism engineers at Ginkgo learn from nature to develop new organisms that replace technology with biology.”
Daniela: Could you tell us about the history of Ginkgo Bioworks? The founders, the people, the vision.
Christina: The history of Ginkgo starts very early in the history of synthetic biology. In the early ‘90s, Tom Knight was a Professor at MIT in computer science and he started to ask a really provocative question: what is the next thing that is going to be interesting to program—after computers? His answer was something really unexpected at the time – engineers should be looking to DNA for the future of programming. Synthetic biology as a field came out of his early work trying to learn biology as a computer scientist and engineer; a community that built up around the idea of making biology easier to engineer.
Ginkgo was funded in 2008 when he left MIT with four graduate students who had just finished: Jason Kelly, Reshma Shetty, Barry Canton and Austin Che. At that point, synthetic biology had grown as a community, and there was a need to create a company that could drive the scale to deliver on building an engineering discipline and making biology easier to engineer. Their vision corresponded to what would then become the foundry here at Ginkgo: a set of automated tools for engineering biology that can effectively scale as the technology gets better and the company grows. The company is built on this vision that biology is an awesome and powerful substrate for design and that we need powerful tools to be able to work effectively with biology.
Daniela: How many people work for Ginkgo? Which kind of people?
Christina: We are 120 people currently, and the team is mostly composed of scientists and engineers. Even for the approximate 20% that aren’t working in the foundry, taking care of management, operations and business development, a lot of us have backgrounds in science and engineering. I focus on communication and partnerships, for example, but I have a PhD in synthetic biology. Across the team you’ll find chemists and chemical engineers, computer scientists, biological engineers, software engineers, computational biologists, and so on. As our team grows, there are a lot more opportunities for people coming from different backgrounds because this field is so interdisciplinary.
Daniela: Could you comment on your approach to enzyme engineering: how do you make it fast enough to be industrially interesting?
Christina: For us a big focus is on building those automated tools to make the high-throughput screening faster, cheaper and more accessible, so that we can approach more targets and industrially relevant projects. The technology used in our foundry, coupled with the decreasing cost of DNA synthesis means that it is possible to design and screen many different prototype pathways and many enzyme variants, to hone in on the best designs. For a given enzyme for a particular project, we might screen 500 versions per enzyme, and this is usually done by a metagenomics screening approach, which can then be iterated: we find the best hit, and then we repeat the metagenomic screen, or we use that as the query for further searches. Or we might start with a metagenomic screen and then do a mutagenic screen where we are actually mutating targets on the active site (more targeted mutagenesis). For example in a recent project, there were three enzymes that needed to be modulated and tested, and for two of them, we screened about 500-1,000 for each one, for the third one we did some screening and then mutagenesis and then screened a library of the order of twenty thousand. Over six months we were able to improve the function of the pathway 20 fold. This is the kind of scale where we are at now, and we are also trying to improve our throughput and capacity. And that’s also coupled to computational tools to narrow the design space upfront.
Daniela: High throughput is a synonym of big data. How do you deal with this side of your business?
Christina: We have an amazing team of software engineers, computational biologists and bioinformaticians that are doing great work getting insights from that data we gather and building the tools necessary to analyse the data.
Daniela: Who contacts you for help? Who are your clients?
Christina: The majority of our work is customer focused. We work with companies that want to find ways that biology can solve problems in their supply chains, manufacturing or sustainability. We work with flavor and fragrance houses, for example Robertet, companies that produce food and nutritional ingredients, like Ajinomoto, Cargill, and ADM, and others across a number of industrial and consumer good sectors.
Daniela: So basically a customer would come to you and ask you: could you do this for us?’
Christina: That conversation and that process with a customer are very interesting and very complicated. Rarely will a customer come to us with an exact specification like, ”We want an organism that can do x, y, z.” It’s much more of a design process in which we develop a technical project together. We go back and forth to understand the gaps our customers have in their supply chains, and the challenges they are experiencing. There are a lot of ways where we can find biological solutions. Some other times, customers might come to us for help with a specific module. For instance, they might ask us if we can help them make a specific target to improve productivity; this is the simplest type of conversation. We then try to understand if this is a good target for us based on our tools and we proceed by making a business plan. There are also cases that are a bit more open-ended: we start with a customer looking across their portfolio and their challenges, and we are able to work with them to find places where the target and the market make sense for our technology.
Daniela: Rose oil from yeast is one of your success story. Can you tell us more?
This project is a very interesting one, and it is still ongoing. On the business side, the story is intriguing. A huge high-speed train being built will pass straight through the fields in France where they grow roses for Chanel perfume. Agricultural products, in general, are under pressure, but if there were a way to produce these compounds in a cultured way, this would release some of the market strain. That’s where the emphasis of our work lies. On the scientific side: a rose makes hundreds of different compounds that combine to make the smell the rose, and that can vary in different seasons or if grown in different places; all of these factors are important in creating that bouquet. We were excited about the idea of how biotechnology might be able to create another kind of unique experience of the scent of a rose. It is going to be different than what you can grow on the ground, but it could be another addition to the pallet of the perfumes industry, another kind of product.
Daniela: I am curious: what about Ginkgo’s logo? And the name?
Christina: Ginkgo is a very interesting plant. It’s a living fossil, the only member of the phylum that survives, and
there are fossils of ginkgo leaves from the Jurassic period. It has a very ancient evolutionary history, and it survived for a long time because of its association with humans. Monks in China helped to preserve and maintain the trees over many years. Ginkgo trees spread out of China, and now they can be found in almost every city. That kind of uniqueness among this phylum, and its fascinating evolutionary history is what inspired the founders. The logo is the ginkgo leave inside the gear: our company is a place where biology and engineering meet.
Daniela: Your vision of the synthetic biology field: will it really bring us “where no one else has gone before”?
Christina: I see biology as the driving force here: the most powerful thing. I am sitting here in the office, and I am looking out at a vacant lot in an industrial part of the city, but there are still plants thriving and growing and finding a way even in this kind of neglected and forgotten place: living things growing themselves out of dirt. If you look at them closely, you see something incredibly powerful. Just think about photosynthesis happening in each cell of these plants, and you can go down super deep and see these kinds of things that biology is doing all the time around us and that we take for granted. For me, the power of this revolution is to no longer take biology for granted. To see it for what it is: the most incredible technology that we can imagine. What if in the future thanks to this technology you smash your iPhone screen, and it heals itself? Biology can heal itself. What if we could recognize the most amazing computer is actually inside of us, and we are walking around with it in our head every day. I think that learning how to respect and value this and draw from the power of biology for human technology is where the real power of the field resides.
A special thanks to Jordyn Lee, Senior Associate Bateman Group for putting me in contact with Christina and for providing the pictures through Ginkgo BioWorks.