We Make Evolution Move Faster

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.

Triple­bar Bio founder and CTO Dr. Jere­my Jon Agresti earned his PhD in bio­chem­istry at the MRC Lab­o­ra­to­ry of Mol­e­c­u­lar Biol­o­gy in Cam­bridge (Unit­ed King­dom), after which he com­plet­ed his post-doc­tor­al fel­low­ship at Har­vard Uni­ver­si­ty. In an inter­view with Glob­al Tal­ent Men­tor­ing, Dr. Agresti told researcher Elke Krues­mann how his com­pa­ny accel­er­ates the evo­lu­tion­ary process and why encour­age­ment is the foun­da­tion for effec­tive mentoring.

Syn­thet­ic biol­o­gy is a very young field of research. Would you please briefly explain this approach?
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. 
Triple­bar Bio uses biol­o­gy to make some­thing new. I might call what your com­pa­ny is doing “play­ing God.” Would you agree?
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. 
What is the mis­sion of Triple­bar Bio?
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. 
Which spe­cif­ic prob­lems are you and your team work­ing on right now?
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.
Do you need a lot of exper­tise in dif­fer­ent areas?
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. 
Your com­pa­ny is fund­ed by The Pro­duc­tion Board, a ven­ture cap­i­tal firm. How does Triple­bar Bio’s col­lab­o­ra­tion work with them?
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. 
Do you inter­act with the oth­er start-ups that The Pro­duc­tion Board supports?
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. 
Where do you see Triple­bar Bio in five years from now?
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. 
After read­ing your inter­view with The Pro­duc­tion Board, I under­stand that you’ve had great men­tors in dif­fer­ent stages of your life, such as a cer­tain men­tor from the Uni­ver­si­ty of Cal­i­for­nia, Davis. Why was this men­tor so impor­tant to you?
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. 
Do you think that men­tor­ing in sci­ence is even more impor­tant than in oth­er fields?
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. 

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