Creating a Company Around Genetically Engineered Probiotics: ZBiotics & Zack Abbott, PhD
Evolution of an Idea
While I’ve written about life in a biotech startup and have highlighted the technology of a few biotech companies, I haven’t always dug deeply into how these startups were created. How do you go from nothing more than an idea to a company making products for people? Where do the ideas come from? How do you assemble a company around an idea? How do you fund this?
Zack Abbott, PhD, Co-founder and CEO of ZBiotics
I wanted to learn more about this stage of a startup’s life cycle. To better understand how a company can emerge from the primordial soup of an entrepreneur’s brain, I reached out to Zack Abbott, the co-founder and CEO of ZBiotics, a San Francisco-based startup making genetically engineered probiotic products for consumers.
Zack is a scientist by training, having earned his PhD in microbiology and immunology at the University of Michigan in 2015. But the first flash of the idea that would become ZBiotics occurred before he stepped foot on Michigan’s campus. Prior to grad school, he was working as a lab tech at UC Davis and listened to a lecture on how protein engineering could be used to inhibit HIV infection in a laboratory setting. This idea of creating proteins to affect health intrigued him, but as he looked into this field of biologics, he realized that most of these compounds were being used only in therapeutic areas where the costs made sense – like producing insulin for diabetes or antibody-based drugs for cancer and autoimmune diseases. The process of making the proteins, purifying them, and a host of additional processes made for an expensive endeavor. But it planted the seed of using proteins to help people.
Zack went on to complete his PhD at Michigan, picking up skills related to bacteriology. After graduating, the idea of starting a company was still totally off Zack’s radar. Instead, he took a job at a clinical contract research organization (CRO) in Miami, since he knew that he wasn’t interested in doing a stint as a post doc in academia or working in Big Pharma. He thought that working for a CRO would teach him about how drugs came to market and clinical trial design. During his time at the CRO, he got a sense of the drug development ecosystem, having worked with everyone from individual scientists to huge pharma companies.
It turned out that his time at the CRO would give him more than just a few new skillsets. While at the CRO, several of his coworkers had an idea for a startup and applied for a program at Y Combinator, the famed Silicon Valley startup accelerator. Zack helped his friends put together their application package, getting an initial sense of how to translate an idea into a company. His coworkers’ application was accepted, and they in turn encouraged Zack to take his idea and apply for one of Y Combinator’s fellowship programs.
By now, Zack’s idea had evolved into a concept of using bacteria to produce proteins and harnessing our resident microbiome. Zack decided to apply for the fellowship and honed his thoughts throughout the process, eventually getting accepted and awarded $20,000. While the money was useful, acceptance into the program gave Zack the validation that his idea may be worthwhile. By the time he complete the fellowship, Zack had developed the confidence to start his company around his idea, which had been bouncing around his head for over a decade.
Creating the Product
Now that he had a concept and a company, Zack was ready to jump into the lab and start making…something. At this point Zack had a list of potential products that fit his concept but wasn’t sure where to start. Eventually, he decided to focus on probiotics, the “good bacteria” that can benefit our bodies.
Knowing that he wanted to make a consumer product, he targeted a problem that the general population could understand: feeling bad after drinking too much alcohol. This is due, in part, to the accumulation of acetaldehyde, a toxic byproduct of alcohol that builds up after imbibing. Once consumed, alcohol is broken down into acetaldehyde, which is then further processed into inert compounds.
While this process normally occurs in the liver, our gut microbiome also performs this process. Unfortunately, while the bacteria in the microbiome can convert alcohol into acetaldehyde, they are much less efficient at processing acetaldehyde into inert compounds, leading to the accumulation of acetaldehyde.
This problem was a perfect fit for Zack’s concept of using bacteria to produce a protein to solve a problem. In this case, he would genetically engineer bacteria to express high levels of acetaldehyde dehydrogenase, the protein enzyme responsible for breaking down acetaldehyde. And because the problem occurred in the gut, it made sense to make a probiotic.
Zack and his team decided to use Bacillus subtilis, spore-forming bacteria already found in our microbiome. They then modified the bacteria’s genome so that it expressed high levels of acetaldehyde dehydrogenase. So, consuming these engineered bacteria should increase the overall levels of acetaldehyde dehydrogenase in the gut. As the resident microbiome converts alcohol into acetaldehyde, these engineered bacteria can then complete the chemical assembly line and process the acetaldehyde into inert components. In a sense, these modified bacteria act as mobile hazmat squads, moving through the intestines, sucking up any extra acetaldehyde, and converting it into harmless compounds. ZBiotics believes that their probiotic can therefore reduce the accumulation of the toxic acetaldehyde in the gut following alcohol consumption and prevent people from feeling so lousy after drinking.
Through the design and testing of his product, Zack landed on four guiding principles.
First, he wanted to keep it simple. Biology can be wickedly complex. But sometimes, it can be stupidly simple. Zack wanted to focus on the simple things, so ZBiotics has focused on problems and solutions that were based on a single substrate target (like acetaldehyde) and a single enzyme (like acetaldehyde dehydrogenase).
Second, the engineered bacteria needed to constitutively express the protein of interest. This meant that bacteria were always making more protein, so you didn’t have to worry about having enough protein present at the right time. The bacteria were ready for any substrate that they may encounter.
Third, ZBiotics would prioritize a bioreactor approach. This means that the substrate (such as acetaldehyde) is taken into the bacteria cells for processing by the expressed enzyme (like acetaldehyde dehydrogenase). This contrasts with a biofactory approach where the bacteria would produce the protein and secrete it into the gut. While a biofactory approach could work in theory, bacteria don’t like secreting things. Getting bacteria to efficiently secrete proteins could be done, but it would require complex genetic engineering, violating Zack’s drive for simplicity.
Fourth, the chosen bacterial strain would not seed and colonize the gut. Zack didn’t want to dislodge the existing microbiome, which could lead to unforeseen outcomes. So, his product was designed to be transient; the engineered bacteria do their job as they travel through the gut.
With these principles, Zack and his team at ZBiotics created the world’s first genetically engineered probiotic.
Lessons Learned & Future Directions
But being the first at something isn’t easy, and ZBiotics had to blaze its own path forward, inventing new processes along the way. For example, while manipulating the genome of bacteria relies on basic microbiology techniques, manufacturing an FDA-compliant, genetically engineered probiotic at a consumer scale hadn’t been done before. So, Zack and his team had to invent the whole process.
Zack also had to ensure that there was a market for the company’s products. While modified bacteria and the microbiome could be used in a variety of scientifically sound contexts, Zack’s market research showed that not every application made sense from a commercial perspective.
As he researched his market, Zack also learned how to communicate with potential customers. At first, he tended to overemphasize the science – as scientists often do – while forgetting that scientific minutiae often caused people’s eyes to glaze over. Zack has since learned that if people don’t understand you, it means that you’re not explaining it well. With lots of practice, he has become more relatable, using language that’s easier to understand and taking the time to listen to his audience. For example, while he and his product are proudly GMO, he has also learned to listen to adherents of the anti-GMO movement, understanding their concerns and figuring out ways to empathize with them. As another example, when ZBiotics launched their product, Zack was constantly talking with potential customers at bars, getting their feedback and learning about their excitement and skepticism. Zack continues to solicit feedback from his customers, answering every customer service email so that he can learn more about the people who use his product.
Starting with just a fragment of an idea in his head, Zack eventually created a company after a lot of time and a lot of work. But now, ZBiotics has produced the world’s first genetically engineered probiotic which continues to sell out as soon as batches are made.
While their first product broke new ground, Zack and the company are continuing to develop new innovative products, guided by their principles and their mission to show the power of genetic engineering to improve people’s lives.
Special thanks to:
QIAGEN and Todd Festerling, PhD for sponsoring the blog