Dr. Jeremy Jon Agresti, CTO of the San Francisco-Based Start-Up Triplebar Bio, Explains How his Company Wants to Increase the Carrying Capacity of Our Planet—and Why Biology Holds the Key to That
The exciting field of synthetic biology combines engineering principles and molecular biology techniques to produce novel biological solutions. At Triplebar Bio, a venture-backed start-up and partner of Global Talent Mentoring, researchers bring decades of expertise and experience to this innovative area. Triplebar Bio is based in California’s San Francisco Bay Area (United States) and works at the interface of biological and engineering sciences to discover microbes that produce a wide range of molecules across the food, agricultural, and pharmaceutical industries.
The name synthetic biology is relatively young, but the concept of what we do is not that young. “Synthetic,” to me, means bringing things together to make something new. To the general public, “synthetic” is associated with “artificial,” such as when we think of synthetic fabrics, but many of the materials in synthetic biology are natural products. The most common way of doing this is to use microbes such as bacteria or fungi, because their genomes are relatively easy to manipulate or breed. The goal is to make something that would be difficult or impossible to create using traditional chemicals for synthesis. The other reason for using synthetic biology might be that it would be destructive or unsustainable to use traditional chemical synthesis, which is usually based around petroleum. So, in synthetic biology, the starting point tends to be an organism that eats something and then, instead of just producing more of that organism, produces some molecule in which we are interested. The organisms often eat sugar, which is a natural product. The sugar comes from a certain plant source, and then we convert that sugar into other useful molecules.
I wouldn’t use the God analogy. But one of the things my company does is to create new biomolecules and the microorganisms to produce them. Even though single-cell organisms such as a bacterium or a fungus, like yeast, are relatively simple biological systems, their metabolism is complex—far too complex for us to design. Science has not advanced to the point where we can sit at a computer to model and predict how even a simple biological system will perform. We’re kind of lucky, though, that biology behaves with a self-optimization process, called evolution. In nature, evolution happens when there are populations of organisms that are all slightly different and with a different chance of survival based on that diversity. At Triplebar Bio, we are able to accelerate the evolutionary process by making larger populations and making the generation time shorter, so that we can make evolution move faster, and in exactly the direction we need it to go. To answer in the spirit of your question, it is kind of like what God did: If you think of all the life—all of that crazy diversity that exists—it is all a product of evolution. This process is super powerful! You can use it for just about any function. That’s our version of synthetic biology. It’s kind of harnessing that natural process of evolution, pushing it in a direction we want to go, and then learning what nature did to solve the problem.
We want to increase the carrying capacity of the planet. The planet can tolerate a certain amount of utilization, and I expect that human population will grow. How do we handle a large population so that it lives in harmony with the earth in a sustainable way? I think that biology holds the key to that. If we are using petroleum as our feedstock to drive systems and produce things such as energy or fertilizer, then we are using a non-renewable source. When we switch to biology, however, there are a couple of advantages. The first advantage is that we are using the sun as the ultimate sustainable source of energy. The sun creates sugar through photosynthesis in plants, and we use that sugar to grow things. Second, biology has this amazing complexity. We can make so many interesting types of molecules through the utilization of biological systems. Our goal is to increase the sustainability of the earth, and biology is the best way to do that.
One of the big areas we are working on is food systems. We want to produce organisms that make nutritional proteins. Such products should have all of the nutrition of the highest quality organic foods, but with a much smaller ecological footprint and produced in a much more sustainable way. We also work in the health sector. Imagine a product that prevents chronic infections. We are also interested in materials, for example, endlessly recyclable plastic that does not degrade with every generation. We can make a big dent in a couple of areas, for example, energy utilization and quality of life for people. We looked into those different areas to see where we can make the biggest impact. Then we evaluated which of the products can make an impact now. That leads to a relatively small list of areas in which to set priorities, and that is what we are working on.
There is a lot of cool science you can do with your creativity. There are many different types of scientists and many different ways to make an impact in science.
As a small company, we don’t completely work alone. It depends on the products, but we often have a partnership with a company in mind that maybe has more expertise in a particular market. Then we handle part of it and they handle another part.
Our collaboration is close in many ways. We work daily with some of the people from The Production Board. We work with them on things from HR and company operations to product and investment strategy, so they are really part of our team in many ways. When The Production Board was setting up this model, they realized that start-up companies have certain things in common, such as administrative and financial issues. The Production Board realized that investors often write checks to get companies started and that a certain fraction of every check goes towards exactly the same purposes across all of these four-person companies they started. The Production Board consolidated the redundant tasks into one central place in order to make much more efficient use of their resources. Start-ups such as Triplebar Bio could then focus on hiring the talents they need to make the products they want. We no longer needed to worry about all of those things. This enabled us to just start working on the problem and start finding solutions.
Yes, it is just like one big company in some ways. That also means we are closer to The Production Board’s other investments. Some of the start-ups are in the same building. So, we interact with them, share resources, and share ideas. Just to give you an example: When COVID-19 started, we didn’t have to work completely independently to figure out what we were going to do to keep people safe. We worked together with these companies and decided about the best practices. That made it much easier to have more minds working on the problems. It’s another advantage. It’s a good network.
There are different stages in product development. After a discovery comes the optimization phase, which is what we are working on right now. Then we have to get the product to the point when it is ready to scale up. Without scaling up, we don’t have much impact. It’s more like a science project, not a product. In five years, we expect to have several products that are being produced at large volumes and are being sold. Meanwhile, there are constantly new products going through the early phase of this process. A typical life cycle of a biological product is probably three to five years from idea to production. You also have to go through regulatory approvals, depending on the market you’re in.
I highlighted him, because he made me seriously consider that I could be a scientist. The funny thing is that I didn’t meet my mentor, Bernie May, until after I finished my undergraduate degree. Even though I have an undergraduate degree in science, it never crossed my mind that I could be a scientist. I think that mentorship has been most effective in my life when the mentor really knew me. A relationship is the foundation. Mentors don’t know some idealized version of me or what they think I should be. They take me at face value. Here is this person. What are his strengths? What are his weaknesses? What are his interests? As a mentee, you trust your mentor more, because they see who you are. It’s different from parental mentorship. Your parents are big fans of yours, no matter what, because they see some idealized version of you, not the real version. Bernie, my mentor at UC Davis, knew me very well and helped me to believe in myself. For me, it was important to hear my mentor say, “Hey, you can do this.” That is what I have needed more than anything throughout my career. My post-doctoral mentor at Harvard University was also very influential, and it was the same thing. He helped me to believe in myself. When I mentor people, formally or informally, I try to think about that. Am I really getting to know them? Who are they? I think the right kind of advice and the right direction comes from that basis.
I don’t know if it’s more important, but I can tell you why it’s important. If you didn’t grow up around scientists, your perception of a scientist was probably formed by movies or books. And if you don’t fit that mold, you may think that you can’t be a scientist. In this case, mentorship becomes even more important. My mentor helped me by saying, “You can be a scientist!” I tend to be a more creative person than a data-driven person. That doesn’t fit into the common model of what a scientist is. But, as it turns out, there is a lot of cool science you can do with your creativity. Then you can choose to surround yourself with people who complement you—those who are more data-driven, more organized, or more of whatever you are missing. The archetype, whatever that really is, is only a fraction of the total. There are many different types of scientists and many different ways to make an impact in science.