Scientists and startups acknowledge that one of the great challenges for cultivated meat is reaching cost-effective production at scale. Growth factors – the media that enable and promote cell growth and production – are a major part of the costs involved.
An Israeli company called BioBetter believes the solution to cheaper growth factors lies in the tobacco plant. By turning these plants into “natural bioreactors” that grow in an open field, BioBetter says it can bring down the cost of growth factors for cultivated meat — from the normal range of $50,000 – $500,000 per gram to a mere one dollar per gram.
All cultivated meat requires growth factors — the recombinant proteins (those manipulated to contain genetic material from multiple sources), hormones and other components that stimulate cell development and differentiation. These growth factors account for 55% to 95% of the cost of cultivated meat production, according to non-profit the Good Food Institute. They are typically either gathered from livestock or made via fermentation. Both methods are complex and costly, not to mention controversial and borderline unethical: serum extracted from unborn calves — in the process killing them — has been a mainstay for the fledgling industry until recently.
An analysis that ran last year in the now-shuttered publication The Counter noted that a recombinant protein like transferrin can go for $260 per gram; growth factors like TGF-β can cost several million dollars per gram. “The cost of cultivation facilities will always be too burdensome, and the cost of growth media will always be too high, for the economics of cultured meat to make sense,” wrote Joe Fassler, the article’s author.
BioBetter co-founder and CEO Amit Yaari is well aware of these issues.
“When you think about making growth factors with fermentation, one of the major bottlenecks is the CAPEX investment,” he tells AFN. “Fermentation facilities are very, very expensive, costing sometimes hundreds of millions of dollars per facility.”
“There is no way of growing animal-free cultivated meat without using recombinant growth factors,” he continues. “Usually they’re made by fermentation. That means that you have to use a bioreactor just to produce the growth factors. Then you have to purify them, ship them to the cultivated meat company to use them to make the cultivated meat. That’s a very complex process for a product that has to be eventually very efficient and environmentally friendly.”
He says based on current trends for cultivated meat production, the CAPEX needed to produce the amount of growth factors in 10 years will be far too costly. “It will never return the investment because the growth factors will be needed in such huge quantities and at a very low price.”
The BioBetter approach
BioBetter’s process involves turning tobacco plants into bioreactors for the expression of proteins. The company grows these plants in open-field plantations, a method that requires just water, CO2 from the air and sunlight.
Yaari offers a detailed rundown of the process that takes place between plants in the field and sending a growth medium to cultivated meat companies:
- BioBetter inserts gene sequences into the cells of tobacco plants to get those cells to produce growth factors like insulin, transferrin and FGF2.
- To enable rapid and efficient purification, the plants express the growth factor with a CBD tag (Cellulose Binding Domain). The CBD domain strongly and specifically binds cellulose particles.
- As the plants grow, BioBetter tests their ability to express the proteins and chooses the best-performing plants accordingly.
- Once the chosen plants are brought in from the fields, the BioBetter team uses a screw press to extract all the liquid content.
It then applies a proprietary protein extraction and purification process:
- Liquid content gets filtered through a ceramic hollow fiber system Yaari says can handle millions of liters per batch. Large insoluble particles, like dust from the field or bacteria particles, are filtered out.
- “What we get is a liquid that is clear, transparent and holds just the soluble constituents of the plant’s proteins,” he says.
- Cellulose particles are then added, and they “fish-out” the CBD-growth factors that bind them.
- The solution is then filtered a second time on the ceramic hollow fiber system, but this time only the small soluble impurities sift out of the membrane and are discarded. The cellulose particles are too big to pass through the membrane and are retained, with the CBD-factors attached to them.
- Immediately after the second filtration the growth factors are eluted and collected before concentration and drying.
BioBetter’s purification process also removes harmful alkaloids (e.g., nicotine) from the protein.
“Because of the way cultivated meat is manufactured, presence of detectable quantities of alkaloids in the product is highly unlikely,” he says. “Growth factors are used in minute quantities (concentrations of parts per million to parts per billion), and so any carryover from the plants is going to be immensely diluted in the growth media. [Additionally], the cultivated meat product is going to be separated from the growth media, and again remove remnant impurities.”
Yaari stresses that producing recombinant proteins from tobacco plants isn’t a new idea; the pharmaceutical industry has used it for decades.
BioBetter works directly with local farmers in Israel to source its tobacco. It plans to eventually source the raw material from growers all over the world.
If the technology winds up working at scale, it could also play a role in repurposing the tobacco crop, which still provides income for tens of thousands of farmers around the world.
Some additional concerns around tobacco farming include its impact on the environment and potential harm to farmers themselves. The World Health Organization points out that “a tobacco farmer who plants, cultivates and harvests tobacco may absorb as much nicotine as found in 50 cigarettes in a single day.”
BioBetter will have to contend with these and other challenges as it matures its business. The company just raised a $10 million Series A led by Jerusalem Venture Partners. It also plans to expand to a larger pilot plant soon, which will increase its plant-processing capacity to meet its current commissions.
As to the many challenges cultivated meat faces, Yaari seems optimistic, or at least determined.
“[Cheaper growth factors] are necessary for the cellular agriculture vision to become a reality, because it’s not just cultivated meat. It’s leather and milk and eggs and so many things. There is room for many solutions, but you have to make the first step and enable these food-grade growth factors.”