Pioneers in Bioprocessing: Q&A with Alexi Goranov of SCiFi Foods

Exciting news! Invert is launching a Q&A series, Pioneers in Bioprocessing, to chat with experts in bioprocessing and biotechnology to discuss their work, the potential of the bioeconomy at large, and the personal viewpoints of the individuals who make this work possible.

To lead off the interview series, Invert spoke with Alexi Goranov, Ph.D., VP of R&D at SCiFi Foods. SCiFi Foods is an alternative protein company that aims to create the world’s first cultivated beef, beginning with a burger made of both SCiFi’s beef cells and a proprietary formulation of plant-based ingredients. SCiFi’s hybrid burger aims to remedy the “beef-taste” limitations of plant-based meats while also addressing the significant cost-of-goods issues that currently plague cultured meat start-ups (especially as it relates to cell media and manufacturing sites). Impressively, SCiFi Foods has already managed to reduce their cultivated beef production costs by 1,000-fold through novel cell line research and development initiatives using targeted CRISPR gene editing.

Note: this interview was edited for length and clarity.

To start us off, tell us a bit about your background and how you ended up coming to SCiFi Foods.

My background is in molecular biology and genetics. After coming out of academia, I worked at Zymergen for almost six years as a senior scientist and research director, getting my first exposure to fermentation technology and how important it is for manufacturing goods.

From there, I joined SCiFi Foods. It was an exciting new field to dive into, even knowing full well how challenging and difficult it would be. But it felt nice to know that the goal was to get the cells to do what they want to do (which is to grow), as opposed to making the cells produce things they normally wouldn’t, as is common in the broader synthetic biology space.

In your view, what is the problem with animal agriculture as it stands now?

There are several. The intensity of it, especially in industrial agriculture is very heavy. That’s leading to deforestation and leading to significant greenhouse gas emissions. Animal meat production is responsible for something like 12% to 20% of the greenhouse gases of humanity. So, if all of us care collectively about climate change and want to do something about it, then that is one area where we have a reasonable shot at making a difference. Specifically, beef is the worst offender, especially if you just look at the feed-to-meat efficiency. So, that seemed to be the thing to focus on, and that’s what we are doing at SCiFi Foods.

What would you say makes SCiFi Foods’ approach unique?

I think we’re starting with the end in mind. From our early techno-economic analysis, it became clear that the process needs to be really, really simple.

The first cultivated meat companies started about a decade ago, with the first lab-grown meat burger in 2013. Originally, a lot of folks started with wanting to produce a tissue, which is a lot more expensive and takes longer. We decided to actually do something different by creating a product that is not 100% animal cells. Instead, we use some percentage of beef cells in the product, but it’s mostly plant-based. Three years ago, I would actually say we’re probably the only ones thinking that way. Now, a number of other companies are actually starting to come to the same realization.

In addition, we deploy genetic engineering as well. Though genetically modified foods are a little bit of a touchy subject for some, we do feel that if we really want to give this a shot that was something we had to do. Otherwise, the chance of success would be close to zero, for beef at least.

Can you give us a peek at some specifics of what you’re working on right now at SCiFi Foods?

The R&D work is actually progressing quite fast. We currently have beef suspension cell lines growing without using microcarriers. We also have those cells growing well in a simplified media that lacks various common animal-based media ingredients. Now, the team is really working to figure out how to increase the yields, intensify the bioprocess, and reduce expensive components by leveraging our engineering, media, and testing capabilities.

Recognizing that this is very hard to predict with certainty, when do you think it will be commonplace for people to be grilling burgers from cultured cells?

I’d say at least a couple of years. There are a small handful of companies right now that have the approval to produce. But, I am a little bit skeptical that they can produce at a scale that makes the product easily available, especially to go and purchase at your favorite supermarket. Most likely, they’ll first be available at some restaurants and special events.

In addition to availability, there are multiple other considerations when you decide to sell directly to consumers because of supply, labeling, etc.

Beyond supply and distribution, what are some of the other primary hurdles?

Assuming that everybody gets the regulatory approval, there is also obviously consumer acceptance. For us right now, as far as we understand, the biggest challenge there is taste. I think a lot of people are willing to try cultured meats, but are they going to be return customers? I’m a carnivore. I would not give up meat, but I would like to diversify my diet and have a lesser environmental impact.

“That to me is the question, can cultured meat producers make products that taste similar to animal meats at a low enough cost such that consumers can feel good reaching for a more sustainable meat product?“

What would you say makes cultured meat bioprocesses unique to other biomanufacturing efforts?

There are a lot of unknowns. Everybody knows how to work with common mammalian cells like, CHO and HEK. Though they’re both mammalian, they’re not the same and come with their own little caveats that must be studied and learned for effective application. Over decades, we’ve come to understand these systems very well.

I joke with the R&D team all the time that we are establishing a new model organism. I mean, we literally started with a biopsy from a live, young, and healthy cow and then we isolated different cell types, and then we proceeded to work with them. And yes, you can go read papers about how some primary cells behave from beef culture, but once we start playing with conditions, developing new phenotypes, and the cells start growing well in suspension in internally developed media, it really becomes its own unique system. We are really in uncharted territory, so it starts with basic things.

Tell us a bit about how genetic engineering factors into cultured meat at SCiFi Foods?

It allows us to get the cells in a happier state so that we can start asking them to behave the way that we want them to behave. More specifically, some cells are very, very flexible and can actually adapt and start doing crazy things sometimes very quickly. With many cells from small mammals or chickens, you can immortalize them and put them in suspension with very minimal modification. For example, you have the classical T3T cell lines from mice and a number of new reports from chicken.

For larger mammals, including bovine cells, that’s been trickier. I don’t think many people have succeeded in growing bovine cells in suspension without microcarriers or even immortalizing them very easily. Genetic engineering allows us to introduce several mutations to the cells to very politely nudge them to start adapting and moving in the desired directions.

Importantly, we do not introduce genes from other organisms into our cells, which would make them bona fide transgenic organisms. If we want to do genetic modifications, we either remove a function that already exists or control inherent bovine-specific gene functions. Basically, we stick to the types of changes that can naturally occur in the actual cell. We’re just speeding it up a little bit.

How does cell line and bioprocess development relate to lowering the cost of goods for the production of cultured meat and making scale-up more efficient?

Since we were developing a brand new system, cell line development was particularly important. First, primary cells don’t divide enough times for us to do a full manufacturing production. We had to develop a beef cell line that was able to grow for more than 40 generations (doublings). That means right off the bat we had to develop cell lines that are suitable for longer growth. In addition, we needed cell lines that could grow in suspension and utilize cheaper media.

The bioprocess development work goes hand-in-hand. We all know we need to optimize the process to increase yield and lower costs. This means asking a lot of questions. What’s the optimum temperature? What’s the optimum pH? What’s the cheapest, most effective media? How often do we feed? What process should we use? Should we use perfusion? And so on. You really have to start playing around to find efficiency.

How does the management of all of that bioprocess data play into successful R&D and commercial efforts?

It’s absolutely essential because we need to understand how we make those decisions and what parameters we need to track to make those decisions. Afterwards, we need to be able to go back and ask, “Was that the right decision?”

And the other part is that a lot of data comes out of this. You have basically thousands of lines of online data. If you just see this in a spreadsheet, it doesn’t mean a lot. You need to be able to see trends, look at data graphically, and ideally, compare it to multiple previous runs. I can’t hold all of that data in random spreadsheets with multiple tabs unless it’s some sort of summary.

It’s important to go back and figure this out so that you can start to determine what to fix.

“Keeping data well-collated, accessible, and searchable is absolutely key.”

Another thing that I learned is that complexity is not always better. Sometimes it’s the simplicity and keeping the things you care about at your fingertips that is the most valuable.

Can you just tell us a little bit about your experience with Invert’s bioprocess data management software?

I’ll speak mostly from my own personal view. Basically, when there is a bioreactor going, I live on Invert. I always have a window open. It helps me a lot because I can basically track runs as they’re going in real-time, whether I’m at the office or at work, and I don’t have to ask my team, “Hey, what happened in the run? How does this compare to the previous one?” I can just basically go and pull the trends, the charts, and the KPI summaries.

With Invert, I have pretty much all of the data in the same place and can look at it in an organized way. That allows me to very quickly get a sense of what’s happening, and how things compare, and ask more intelligent questions of my team. Invert also pulls offline data and combines three different platforms right now for us, so I can compare across platforms. It doesn’t matter what we are running; I can actually pull it and start doing comparisons to ask about equivalency in scale-ups and so on.

From my perspective, it’s giving me what I need. It’s keeping it sufficiently simple. It’s easy to access and it’s very easy to select the runs and the various parameters that I need to see.

What would you say are some of the most exciting things happening in biomanufacturing and biotechnology?

One of the more exciting things that I’m paying attention to right now is bioreactor design to see if there is anything groundbreaking that’s going to come out. Even some old technologies are regaining popularity. Everybody, especially investors, is really worried about the cost of manufacturing plants, the cost of bioreactors, CapEx, and cleaning. It’s a huge investment and they are hesitant to make it. In response, there is now the push to make bioreactor manufacturing cheaper and also to make bioreactors cheaper to operate. Unlike biopharmaceutical manufacturers, we are working on producing a commodity where every cent matters.

How do you think we can better grow the bioeconomy as a community?

Two things that are hard to come by: time and money. I would actually say that the government needs to invest even more heavily and support the bioeconomy. They are already, and they are providing some grants. But if you compare it to what is given to other industries, it pales in comparison. There are so many people who are dedicated to the future of this. It’s just a matter of giving us that little bit of financial breathing room to do the magic. That takes a lot of infrastructure and support, which governments are in the best position to supply.

What valuable lessons have you picked up in your career?

Appreciating folks and making sure everybody understands that this is a group effort is key. There is often a tendency for specific recognition, and that often leads to pretty bad outcomes very quickly. Though it’s hard, you want to create unity and an environment where people know that the person next to them has their back. It’s collective failures or collective successes.

The second critical aspect is trusting the technical folks doing the work. They have a better understanding of the challenges and opportunities from a scientific and technical perspective. I spend a lot of time gathering feedback on how things are going and how they would propose we move forward.

Another is having backup plans. I don’t want to underemphasize that.

“Science is difficult to predict, so have multiple contingency strategies for every technical initiative. That is key in R&D. To this day, that’s what gets me out of hot waters every single time.“

So when you’re not working on developing the future of cultured meat, what do you like to do with your free time?

The one hobby that probably takes the most of my time is Bonsai. Well, “hobby” is an understatement, it’s more of an addiction. I have way too many trees in the backyard. At this time of year it’s very busy because it’s the time that you can do almost anything to the tree. I do exhibit them when I find the time to prepare, and I’ve even had trees in national exhibitions. It’s really amazing to think about how I am taking care of trees that are a lot older than me. Some are 100s of years old, and it’s something that I can pass on for somebody else to enjoy.

It’s biology on one hand, but also as a child, I grew up on a farm. So, I was always around plants, taking care of and growing stuff. That comes to me very naturally, and I really enjoy it. I don’t think of it as science. I think of it more as an art.

Huge thank you to Alexi for taking the time to have a great conversation with us. We hope you enjoyed it as much as we did. Thanks for reading and stay tuned for the next edition of Pioneers in Bioprocessing.