Welcome to Pluripotent — it’s Thursday, July 2nd, and I’m left to ponder how one actually spends a ‘long holiday weekend’ during a global pandemic. As ever, news tips can be patched through to me via direct message, also feel free to follow me over at @chasepurdy.
NEW YORK — They were strong words coming from someone who prides himself on scientific agnosticism, and it forced a double-take.
Dr. Ricardo San Martin is a chemical engineer, a Good Food Institute grant-recipient, and the director of the Alt Meat Lab at UC Berkeley. His work came to my attention after reading a paragraph tucked in a lengthy Hakai Magazine article about the future of cell-cultured meat. Here’s what it said (bolding by me):
When it comes to cellular agriculture, he is skeptical that it can ever produce cells in volumes that could be useful for food. When the process is scaled up in bioreactors, he explains, the crowded cells overheat and die. Those food-tech start-ups, he claims, are either unaware of the science or deluding themselves and investors. While it’s possible that some new, secret, proprietary technology exists to address this fundamental challenge, he has yet to see proof. That’s why plant- and fungi-based solutions remain the focus at the Alt. Meat Lab.
There are, of course, many scientific hurdles for the makers of cell-cultured meat to overcome before they’re able to produce at scale all the meats people are accustomed to seeing in grocery stores. By now, any close follower of this space has probably read a little about the challenges around liquid medium development. The need for custom-built bioreactors has also started to gain conversational traction. But this issue of cells overheating and dying is something I’d not heard much about. So I asked scientists in the field (three of them in the private sector) about it.
✤ Scientist #1: "This is the first time this has been raised as a dealbreaker."
✤ Scientist #2: "If anything most cells need to be heated up to feel comfortable."
✤ Scientist #3: "Ricardo is probably thinking of fast-growing E. coli cells, which do generate some heat at high densities. But it is not boiling hot. Mammalian cells do not grow that fast. Cooling jackets could be used if needed to cool it down."
✤ Scientist #4 pointed to the production of CHO (Chinese Hamster Ovary) cells, which are manufactured commercially for use in biological and medical research, and in the production of therapeutic proteins. In that process, heat actually has to be added to the system (in some cases with bioreactors as big as 25,000 liters) to keep them at a happy 37°C (98.6°F).
The takeaway was clear. Among them all, the comments made by San Martin generated only confusion.
So I called him up.
Digging in
Right off the bat, San Martin clarified that what Hakai Magazine printed did not reflect what he was attempting to convey to the reporter. The issue isn’t that cells are getting too hot, it’s that after a certain point the liquid around them changes in consistency.
“There's a limitation that's about viscosity,” he says. “Once you reach 25% of volume of fermenter occupied by cells, the viscosity increases dramatically.”
As cells grow in suspension, San Martin says they reach a point—or critical mass—where the liquid medium (which often has a water-like consistency) between the tightly-packed cells starts to heat up causing friction that renders the liquid around the cells to a viscous-like consistency. With the consistency of the liquid changed, it becomes harder to maintain oxygen levels across the medium that the cells need to proliferate.
In other words, San Martin is saying that issues with viscosity might mean that a 25,000-liter bioreactor, like the one where CHO cells can be grown, will have the capacity to create much less meat than a lot of scientists in cultured meat companies would hope—and that amount of meat might not necessarily justify the cost of the production setup.
“This is what I think. And it could be totally irrelevant, I could be proven wrong about this,” he says, emphasizing that he considers himself an agnostic and independent scientist.
Asked if he thinks the issue could be fixed through new bioreactor designs, San Martin says he doesn’t think so, that it isn’t a question about engineering.
“Sometimes nature imposes some limitations,” he adds. “I'm not saying that's the case here, but we have to be careful. If the limitation is imposed by nature, then you're up against a wall.”
But this may not be entirely true—after all, if one considers a cow and its core scientific components, what is it other than a creature built with tightly-packed and warm layers of muscle and fat tissue? I think of Aleph Farms in Israel, which is looking to grow cuts of meat in which cells are grown in tight, structured systems.
“If you were able to reproduce the vascular system, well that's another story,” San Martin says. “You would have to mimic nature fully—and that took millions of years of evolution, you know?”
Line of demarcation
Regarding friction-created viscosity in cell cultured growing in suspension in stirred-tank bioreactors, San Martin says he has personally stood up at a cultured meat conference in 2019 and posed the question to a panel of entrepreneurs.
“Only one, I think, understood what I was saying,” he says. “I don't think they have reached this stage.”
This hits at the inherent tension in the world of cell-cultured meat, a distinct line of demarcation. On one side of that line you have the startup companies who (for good reason) are guarded about their intellectual property. On the other side you have academics who (for good reason) are annoyed by the opacity. Both groups are generally working toward the same aim, but it’s impossible for one group, the academics, to know if the hurdles they’re finding have already been discovered or solved.
As documented in Billion Dollar Burger, San Marino isn’t alone. Dr. Hanna Tuomisto, author of an oft-cited 2011 Oxford University study on cultured meat, has focused much of her research on the environmental impact of this food technology. To get precise data on those measurement, Tuomisto needs to better understand what types of liquid mediums companies are using. But that information is generally kept secret.
“They don’t say what they are doing and they don’t present at conferences, so I’m not completely able to track the progress,” she told me. “I think they are too optimistic.”
In a 2018 interview I also did for the book, I spoke with a cultured meat scientist who’d focused much of their research on cells from a specific species. This person has since gone on to work in one of startup company labs in Silicon Valley, but their comment to me at the time really introduced me to the intellectual divide that exists.
“Sometimes I’m concerned that I’m working really, really hard on something that they’ve already figured out,” they said at the time.
For his part, San Marino can only work with what he does know. And that’s what led to his strongly-worded comment in Hakai Magazine, about how startup entrepreneurs may be “deluding themselves and investors.”
But he can’t know what he doesn’t know, and until the companies prove their ability to overcome the technological hurdles—and some already have been—that veil of mystery separating startup scientists and academic scientists will perpetuate.
In other news…
Billion Dollar Burger was positively reviewed in The Times of London.
Looking ahead toward Series A, Shiok Meats raises $3 million.
A Chinese Communist Party official is calling for a national strategy to lay a regulatory pathway for cell-cultured meat, according to Food Navigator.
Citing food security, Japan is also eying a regulatory pathway for cultured meat, reports The Japan News.
The biggest ranchers’ lobby in the US didn’t like the report issued this week (pdf) by the House Select Committee on the Climate Crisis.
Hickman’s egg farms, which uses prison labor on at least one of its sites, is dealing with Covid-19 infections.
Nearly 30,500 meatpacking workers have now tested positive for Covid-19, FERN reports.
Families of three workers who died of Covid-19 are suing Tyson Foods for allegedly lying about an outbreak, according to The Counter.
That’s all for this week. If you have some extra reading time on your hands this weekend, and are at all interested in the intersection of Pride month and racial justice, check out this story in The Atlantic on how the pandemic and civil unrest changed Pride for the better.