Cell proliferation is one of the few places where “multiply” and “divide” mean the same thing. The hows and whys of clean meat production only get more fascinating from there.
GFI Senior Scientist Dr. Liz Specht took to the stage at the Good Food Conference to give a crash course on clean meat production. In this talk, Dr. Specht walks through a basic framework for what this process will entail once production is scaled to industrial levels.
Clean meat has many environmental and efficiency advantages over conventional meat production. (Plus, have we mentioned there’s no animal slaughter?) In a food system where conventional meat production is deliberately hidden from public view, the ability to transparently show what goes into clean meat production is just one more advantage.
Check out Dr. Specht’s Clean Meat 101 below!!
And/or scroll down to borrow my notes.
First things first, what is clean meat?
Clean meat is genuine animal meat that can replicate the sensory and nutritional profile of conventionally produced meat because it’s composed of the same cell types arranged in the same three-dimensional structure as animal muscle tissue.
Essentially, it has all the same characteristics of conventional meat; it’s just made by growing only the relevant cell types (muscles cells, fat cells, connective tissue) rather than the whole animal. Note, clean meat is also referred to as cell-based meat and cultured meat. Read more about the naming debate here.
Clean meat technology is developing rapidly.
Cell culture technology has long been used in biology research and for medical therapeutics, but only recently have people harnessed it to create food instead of therapies.
Since Professor Mark Post debuted the world’s first clean meat burger in 2013, we’ve seen swift development of the technology and the industry as a whole. Here’s a snapshot of how it has gone down so far:
By now, companies have demonstrated many times over that this process is not only possible but agile. They are developing platforms that can be used to create any number of end products—not just ground beef, not just chicken. The next step is scaling the process and bringing the costs down.
What will this process look like at scale?
The exact production method will vary from company to company depending on what their end product is and what their engineering framework looks like. However, the basic schematic for production will likely be something along these lines:
- Starting cells: First, get some cells. These can be derived from a biopsy of adult animal tissue, which contains some stem cells that are fated to become mature cells of defined cell types. Alternatively, fully mature cells can be coaxed back into a pluripotent state (more on this shortly) where they can grow, divide, and differentiate into different cell types. Another option is to start with a sample of cells in their embryonic state, which are naturally able to proliferate essentially indefinitely and can become any cell type.
- Seed train: Prior to entering full-scale production, the number of cells must be scaled up through a step-wise process called a seed train. This process ensures that the cells are maintained at sufficient cell density to survive: if you went straight from your starting sample into a full-scale production tank, the cells would die off. This is like a prelude to the proliferation that’s coming next.
- Large-scale production: To make a complex product like a chicken breast or a steak, the production will likely consist of a two-phase process: cell proliferation followed by tissue perfusion.
Cell proliferation entails multiplying and dividing the still smallish number of cells from the seed train into a very large number of cells using a bioreactor. The cells are floating freely here: they aren’t yet organized into any particular formation. During this part of the process, we get to capitalize on the biological principle of exponential growth: one cell becomes two, two become four, four become eight, and on and on. As Dr. Mark Post’s company Mosa Meat explains, “it takes 10 weeks to produce one quarter-pound hamburger, but only about 12 weeks to produce 100,000 hamburgers. In comparison, it takes about 18 months to raise a cow for slaughter, from which you would get less than 1500 quarter pounders.”
During tissue perfusion, we induce our newly multitudinous cells to arrange themselves in the desired structure and differentiate into the variety of cell types that make up meat (muscle, fat, connective tissue, etc.).
While the specifics of this process will vary from company to company, depending on production goals and needs, this is the basic setup. Our Clean Meat Industry Mind Map breaks down the core areas where development and technological ingenuity is needed to make this process a reality at scale:
- Supply chain & distribution
- Cell lines
- Cell culture medium
The supply chain & distribution are longer-term priorities. Ultimately, we’ll need to build a supply chain for this industry or adapt materials from neighboring industries such as industrial biotechnology. But first and foremost, we need to optimize the other four areas.
Cell line development
There are a number of different starter cells that we can work from. Pluripotent cells can become any cell type in the body (nerve, bone, muscle, and beyond). Multipotent cells have some options for differentiation but not all. Specialized cells have only one destiny. For example, an adult muscle stem cell can only divide into muscle cells.
In general, cells tend to move from a pluripotent state to a multipotent state to a specialized state as they develop. Companies will choose which cell type they work with based on economic and engineering factors: how easy is it to use a certain cell type to create the desired end product?
Proliferative capacity refers to the number of times cells can divide and reproduce. Pluripotent cells generally have a higher proliferative capacity, while adult muscle stem cells can divide only a handful of times. Since cell division takes advantage of exponential growth, every additional doubling we can get out of the cells makes a tremendous difference for the production process. (Remember that just two weeks of division can make the difference between 10 burgers and 10,000 burgers.)
Additionally, the cells’ stability—their ability to perform in a predictable way, generation after generation, batch after batch—is a key factor in creating a robust, industrial-scale process.
Cell culture medium
In the same way that a chicken needs calories in order to create cellular biomass, cultured cells take in calories and convert them to cellular biomass (i.e., more cells). In clean meat production, those calories come from the cell culture medium. This calorie-rich medium comprises two main parts:
- Basal Medium: relatively inexpensive, run-of-the-mill nutrients like sugars and amino acids. These are the building blocks of the cell.
- Growth Factors: signaling molecules, often proteins, that tell the cell what to do— “float freely, grow, and divide,” “attach to that scaffolding,” “differentiate into a muscle cell!” etc.
So yes, let’s talk about scaffolding! Simply put, this is a 3D support structure to which cells adhere. It’s used to give depth and texture to the final product, be it steak or chicken breast. In addition to providing structure, scaffolding can help guide cell differentiation. For instance, we could potentially use the scaffold to define what the marbling pattern looks like.
Mother nature has a version of scaffolding too. It’s called the extracellular matrix, and it keeps cells organized into tissues. In clean meat production, scaffolds can be designed to break down as cells grow on them so that the cells can then replace the scaffolds with their own material—the aforementioned extracellular matrix. Scaffolds can also be designed to remain integrated into the final product. Again, this is something that will probably vary company by company.
In either case, the scaffold’s porosity (read: sponginess) is a critical element. Nutrients from the cell culture medium must be able to flow through and penetrate even the thickest, deepest portions of the tissue developing on the scaffold.
Also called cultivators by some clean meat companies, bioreactors are where the magic happens. These are the nutrient-rich environments where cell cultures will proliferate and differentiate at scale. Different companies will use different bioreactors, but there are two basic types that will likely be needed:
- Stirred tank bioreactors: These are the bioreactors used to multiply cells in suspension in the proliferation stage. Other industries, like biopharma, already use stirred tank reactors for animal cell culture on a very large scale, so there are good proxies from other fields for what these will look like.
- Tissue perfusion bioreactors: These will be used to scaffold and differentiate cells during—as the name implies—the tissue perfusion stage. Small-scale versions of these are already in use for tissue engineering research, but scaling them to an industrial level is a juicy opportunity for some engineering ingenuity.
The burgeoning clean meat industry has the advantage of being able to build off of groundwork laid by other industries. This is a big part of why clean meat has developed so quickly in the past few years.
The momentum behind clean meat
At the end of 2016, there were only four clean meat companies. Less than two years later, there are over two dozen. Here’s a sample of the competitive landscape.
More companies are in stealth mode or very early formation stages and have not publicly announced themselves. Some companies are beginning to specialize within core competencies like scaffolding or cell adaptation. As the ecosystem gets bigger and bigger, there is growing potential for cross-licensing and collaboration.
Not only are the leading entrepreneurs and companies in the space powering progress, but the expertise of parallel fields is accelerating the speed of development. And even in the absence of widespread government funding, visionary investors are supporting critical exploration and iteration.
Though there is much progress to be made, a groundswell of entrepreneurial and scientific energy is surging through the remaining technical challenges. Scaling clean meat production and creating a more just and sustainable food system is becoming more feasible every day.
GFI is committed to fostering a collaborative ecosystem for clean meat development. In this spirit, we have launched a competitive grant program to close critical gaps in clean meat research. Read more about our competitive grant program here. The deadline for proposals is November 21, 2018.
The header image shows a clean meatball, courtesy of UPSIDE Foods.