Zach Serber is Chief Scientific Officer and Founder of Zymergen, a molecular manufacturing technology company leveraging the power of machine learning, automation, and bioengineering to improve the performance of materials and discover new molecular products that touch every industry – from agriculture to chemicals and materials, to pharmaceuticals, and more.
At Zymergen, Zach is responsible for the company's overall scientific direction. Prior to his work at Zymergen, he was the Director of Biology at Amyris (Emeryville, CA) and served as Principal Investigator on a DARPA contract to develop advanced tools for synthetic biology. Zach has a PhD in biophysics from University of California, San Francisco, an MSc in neuroscience from the University of Edinburgh and a BA from Columbia University.
INDUSTRIAL BIOTECHNOLOGY: What led you to see this unmet need and found Zymergen?
ZACH SERBER: I'm a scientist first and foremost–I trained additionally as a physicist, and I moved more and more over into biology over the course of my career. Prior to founding Zymergen, I was at Amyris where I worked on the artemisinin project as well as on biofuels. I had some success championing the use of liquid-handling robotics and modular molecular biology for doing higher-throughput work.
I left to found Zymergen in 2013 because I saw huge potential around some of the core approaches being employed in the sector. I thought they could be upgraded through the incorporation of algorithms and machine learning, coupled with a business model that took advantage of the exquisite chemistries that can be conducted by cells and enzymes to create products differentiated from those readily made from petroleum starting points. So, I was very much in love with the Amyris notion of displacing petroleum; they went after transportation fuels first and foremost, at least initially. At Zymergen we have a slightly different ambition to displace petroleum–we're going after chemical markets as our first target.
IB: Can you talk about any of your target products?
SERBER: We have a pipeline now of roughly ten products under development at different stages of readiness, and we're launching our first product next year. The products are diverse, but each of them in some way takes advantage of biology as a manufacturing paradigm to create functionality above and beyond what already exists in the marketplace. One of the things I came to believe from my prior experiences in biofuels, is to never expect a green premium. If one shows up, that's wonderful, but one shouldn't ever base one's business around that expectation. So, we've gone after targets where we can create products that have attractive features that are harder or impossible to be made by any other means.
I'm not saying we would never pursue a drop-in chemical under the right circumstances, but our strong bias is to work on targets that are new-to-the-world and advantaged by virtue of being made through biology, in that they have differentiated properties or features that people desire. We are keen on fulfilling unmet market needs through our products–there is really an abundance of these needs because people have traditionally relied only upon petroleum and its native building blocks as starting points.
IB: You talk about engineering biology at a level of predictability, reliability, and performance that was previously unattainable. Can you discuss in more detail what that means and what the implications are for industrial biotechnology?
SERBER: Zymergen is bringing manufacturing-like rigor to the process of strain generation and optimization. Not only do we employ liquid-handling robots, but we also have very thorough deployment of quality-control and quality-assurance steps to ensure that the data we collect relate to genomes changed in the ways we intended, and that the data are accurate and precise. That's the foundation for everything that follows.
The reliability and heights of performance we can attain comes from using those data in accurate and precise ways to inform design strategies that allow us to uncover unexpected sources of improvement through a process we call genome scanning. We look for opportunities in areas of the genome where others wouldn't think to look. Increasingly, these approaches are guided by machine-learning algorithms.
We regard ourselves as pioneers in bringing algorithms and machine learning to solve these complex problems. We really think that this marriage of biology with machine learning is going to be a catalyst for a new bioeconomy and a new industrial revolution. We employ machine learning in different parts of the engineering cycle around optimizing biology: we certainly apply it in the design phase, we use it heavily in error correction, and we adopt it for developing small-scale laboratory models that correlate well with full-scale production assets. Other companies employ algorithms chiefly around enzyme optimization and comparative genomics.
IB: How has the company evolved since it was founded in 2013?
SERBER: We got our start by doing strain optimization for other companies, and we still do that work. But increasingly we are focusing on our own products, as was the plan from the beginning. As a startup, we wanted to work with the incumbents in the sector to gain familiarity with the challenges that they confronted as they try to manufacture products at scale. We also wanted to build industrial credibility and market familiarity, not to mention generate revenue early by working with partners. Generally speaking, we have two classes of partners: those already engaged in biomanufacturing of some sort, who we help improve the economics of their existing processes through optimizing their microbial catalysts; and partners who have little to no familiarity with biomanufacturing who we help innovate ways to stimulate their business through the incorporation of biosolutions. That second line of business has grown over time.
This tactic has also evolved into developing our own products. These products are things we've chosen based upon our own market analyses and insights. As I mentioned before, we are really prioritizing molecules that we might make via biology that are hard or impossible to make through classical synthesis. We are prioritizing performance, where additional molecular complexity or features confer some really striking advantages to the end-use application.
IB: The industrial biotechnology sector has had relatively few commercial successes. With the pace of technology development, to what extent can we shorten commercialization timelines and improve economics to improve outcomes?
SERBER: It is challenging, and our sector has been plagued with more disappointments than it has been inspired by successes. Part of the reason why Zymergen has kept a low profile is because we do firmly believe that the proof is in the pudding. We want to be the catalyst of a turnaround when it comes to industrial biotechnology by bringing products to market. And not just one product, but a steady stream of them. I can say things to try and reassure you that we are on the right track, but ultimately no one is going to believe me until we've done it. So Zymergen has been very much nose-to-the-grindstone, focused on getting it done. In terms of strategy and ways in which I have learned from the past, it is chiefly around choosing the right opportunities. I think our technology is also very good at reducing the risk, expense and timelines associated with developing a product. And those are table stakes, fundamentally, to participating in this sector. But, as important or more important is choosing the right target—making the right molecule that brings the right kind of value—and participating in sectors where the unmet market need is very apparent, the regulatory hurdles are low, and the market pull is very high.
We have a pipeline of ten products, so these opportunities are not extremely rare. If I were to place bets around each of our ten products, I have different degrees of confidence in each, but generally speaking they all fit those fundamental criteria. Part of the point of having a portfolio of course is it that enables you to be off-base from time to time and still be successful in the market.
IB: Zymergen has been successful at raising money, just last year you announced a $400 million Series C round. But along the way did you encounter fatigue in the investment community for this sector?
SERBER: Certainly, back in 2013, when we first were getting started, that was very true. In terms of Zymergen's origin story, we spent all of 2013 not in a laboratory but out talking to the market and trying to understand where we could create value and also trying to raise money to get started. We ended up in a catch-22 where we had clients interested in working with us, but they wanted evidence that we were more than just a couple of folks with a PowerPoint deck. They wanted evidence that we could actually do the work. Conversely the investors were all suffering from the defeats of the biofuels sector and were hesitant to invest again. They wanted evidence that we had commercial traction. Ultimately, we did manage to land our first contract in early 2014 and on the heels of that raised money. It has been a virtuous cycle ever since.
IB: Do you think, from a downstream demand perspective and with consumers demanding more sustainable products, industrial biotechnology is at an inflection point?
SERBER: I have been in this industry for a while, and that has taught me not to build a business with the expectation of a green premium or changing consumer sentiment. However, maybe this is really changing. There certainly does seem to be evidence that sentiment is changing for the better and in ways that are going to favor the bioeconomy. The thing that worries me is that there is a difference between how people respond to surveys and what they will actually pay for in the marketplace. And so I maintain that it is a far safer, more conservative strategy to focus on performance and expect people to pay for that performance than to have people pay more for sustainability. If sustainability as a purchasing motive increases, then certainly Zymergen and many others in the bioeconomy are poised to take advantage of it. But I would caution anyone against relying on it.
IB: When it comes to public perception of gene editing, how do you think industry can avoid repeating past mistakes?
SERBER: I think the most important approach is education and building familiarity. It changes the nature of the conversation when you can demonstrate the good that comes from it. I worked on the artemisinin [malaria treatment] project at Amyris, and the social benefits were so overwhelmingly large that it created a different discussion around the deployment of gene-editing technology. It seems that previous uses of gene editing did themselves and civilization no favors by focusing on traits that didn't bring tangible value that could be realized by the consumer.
IB: Does this question impact what molecules and markets you target?
SERBER: It does, absolutely.
IB: Where do you see Zymergen's technology a decade from now?
SERBER: Zymergen is planning a series of product launches, and I think people will be surprised by the sectors in which we are participating and creating innovative products. My big hope is that in five to ten years, someone seeking solutions for an unmet business need will think about biology first rather than last. Everyone expects biology to heal us and to feed us. Everyone expects biology to participate in healthcare, medicine, and agriculture. But no one much expects biology to be a player in other sectors. The vision of the bioeconomy is based upon a broader reach of biology to make a difference and have impact in other sectors. Currently, if you are in the materials sector and trying to create an innovative product outside of agriculture and medicine, chances are it never even crossed your mind to look at biology for a solution. One sign of success will be that our collective world view on this changes–that we see that biology can bring amazing and creative solutions to many problems.
Ten years from now I expect that the sector will be robust with a solid track record of successes in solving unmet market needs and real-world problems, and that there will be a self-perpetuating cycle where people continue to look to biology for further solutions above and beyond where people look today.
IB: How can policy help make this a reality?
SERBER: I have seen an exporting of the dirtier petroleum-based processes to geographies that are more permissive. These plants keep getting moved around because local governments finally decide that they are too polluting to tolerate. Eventually some of these processes are going to run out of places to hide. We do get interest from the chemical sector that anticipate the end of the road and are already realizing they have to come up with more sustainable, greener solutions to parts of their supply chain that they currently depend upon.
I am all in favor of governments having high standards regarding pollution and avoidance of toxics in their environments. That favors the bioeconomy and the advent of more sustainable, greener, non-toxic solutions.
IB: How do you maintain a culture of innovation at Zymergen?
SERBER: I'll begin by saying that it is absolutely critical to have such a culture, especially in our sector given how much headroom there is and how young our sector is. There is more to be discovered and innovated than has already been discovered or implemented. One way we do this at Zymergen is by fostering a culture that emphasizes collaboration among experts with different backgrounds. While we certainly employ biology, we rely equally heavily on material scientists, application chemists, roboticists, automation engineers, data scientists, machine-learning specialists, microbiologists, and molecular biologists. There's no single technical domain that lords over the others—we really try to foster an equal playing field. One of our hiring criteria is a desire to work with experts in other fields to find solutions together. Our secret sauce is our ability to create innovations through the interactions between these disparate and distinct disciplines that otherwise usually don't interact much with one another. There's a lot of amazing value to be created through that innovation and those interactions, which naturally lends itself to our work. We are trying to solve common problems by coming at it from different technical backgrounds and perspectives. And those conversations are intrinsically innovative and self-perpetuating as well.
