[aerosmile]

It would take about 30 mins to do so diligently. I took about 5 mins and skimmed it top to bottom. What I found is a lot of statements that didn’t have any amount of humility or recognition that not all of science has been invented yet. It sounds like you took a deeper stab at it. What did I miss?

[cycrutchfield]

Then it would have been preferable if you had started your original post with “I haven’t read the article fully, but…”

It’s a good read. Don’t be lazy.

[tacticalmook]

> when GFI held an invite-only video call on the future of cultivated meat ... San Martin kept pressing. In his view, the science is essentially settled: Cultivated meat won’t be economically viable until companies can make cells grow beyond certain widely recognized biological limits. Higher cell density means more meat per batch, which in turn means the number of bioreactors can fall, and the size of the clean room can shrink.

“I’m not saying no one knows how to do it,” San Martin remembered saying. “I’m saying if someone knows, can you please share it with us?”

... “You can play with the numbers as much as you want, but unless you see the fermenters growing the cells at scale, then it’s just a very theoretical scenario,” he told me. “We don’t get straight answers from the companies. They don’t have to share with us, because we are a university—what’s the point of sharing with us? But it would be nice to know that someone has done it at scale, not in a little shaker. At scale. No one has ever published something saying we can do this at scale at this many cells per ml, and we do it using this trick and this trick.”

What’s more likely, then, is that companies are still struggling with an inherent, widely documented challenge: the cells’ tendency to limit their own growth. Like all living things, animal cells in culture excrete waste.

... Even the legendarily efficient and versatile Chinese hamster ovary cells—an immortalized cell line which has benefitted from more than 60 years of constant research and development—is “probably not efficient enough for low-cost production of bulk cell mass,” according to Humbird.

Maybe cell lines optimized specifically for food production will fare better in time. Still, the cell density issue is one of the most intractable problems this emerging industry will face. Considering that the pharmaceutical industry has already likely spent billions[link] on this very challenge[link]—sums that make the total investment seen in cell meat look like a drop in the bucket—solving it would be a stunning accomplishment.

> Eat Just is preparing to open a large-scale cultivated meat plant in Doha, Qatar, in partnership with two state-backed organizations ... And yet when I spoke to Eat Just’s CEO, Josh Tetrick, he readily admitted that there are still many unknowns—including reckoning with the same challenges Humbird outlines in his report. ... “A number of significant engineering challenges will need to be accomplished,” Tetrick said, with a bluntness that surprised me. “We have a high-quality engineering team. We have sufficient capital to be able to get after this. We understand what the challenges are, and if we’re successful in handling these challenges, we’ll put ourselves in a place where we can do this. And if we don’t, then we won’t. I think that’s just the reality of it.”

If we don’t, then we won’t. I wasn’t sure I’d ever heard a CEO so readily admit that a promised product—in this case, one that Eat Just has raised hundreds of millions of dollars to produce in the last six months alone—might simply not be possible.

... Tetrick said that the Doha facility will need to be a large facility, and that the company defines “large” as being able to produce 10 million pounds of meat a year. That’s only about two-thirds of the output of Humbird’s hypothetical facilities, and less than half of GFI’s. But those facilities are projections; they don’t yet exist. There has never been a facility on earth that can produce cultured animal cells at that kind of volume—not in biopharma, and not anywhere.

... According to Renninger, there’s a reason why the biopharmaceutical industry’s largest bioreactors for animal cell culture tend to peak at about 25,000 liters.

“It’s not so much that it’s just never been done. It’s that it’s never been done because it doesn’t make sense,” he said. “It’s never been done because you can’t. You’re just going to be producing vats of contaminated meat over and over again.”

... Sterility isn’t the only challenge that becomes more grave at larger production volumes. Bigger bioreactors all also struggle to provide all of the cells with the same amount of nutrients and oxygen. The only solution is to stir the cells more rapidly, or blow more oxygen in—but both of these approaches can be fatal. Because they lack a rigid cell wall, animal cells are prone to “shear stress”; they’re fragile little things that can are easily torn apart by rising air bubbles, cell-to-cell collisions, and rotating impellers. This need for increased stirring and oxygen has historically put practical limits on bioreactor size—a problem that remains unsolved at scales well below what Tetrick envisions.

> Eat Just ... wants to use smaller perfusion reactors that cycle out waste material, and it has developed a novel process that also allows for protein and other nutrients to be cycled back in. This approach is one factor that helps to cut down the volume of media needed, leading to what sound like impressive results: $18 to produce a pound of cultured chicken, according to a press representative.

That's the lowest real-world figure I heard in the course of reporting this story. It could also easily translate into a price of more than $30 dollars per pound at retail—and may never go any lower. In a 2019 podcast interview, Future Meat’s chief science officer, Yaakov Nahmias, admitted that, given the company’s process, there aren’t really additional economies of scale to capture. For the foreseeable future, that’s more or less how much Future Meat’s products are going to cost.

... Working with small, perfusion reactors means putting hard limits on the size of a facility; their smaller size means many more bioreactors are needed overall, which means more capital expenditure costs and a larger clean room.

That may be why, in the 2019 podcast, Nahmias said he didn’t see large-scale facilities in cultured meat’s future.

... [He] went on to imagine a scenario where farmers and ranchers pivot away from livestock and instead take on their own bioreactors, cranking out several thousand pounds of cultivated meat each year (and, I assume, paying a license fee to Future Meat for use of its tech). Others can debate whether or not that approach is practically feasible, though sterility control and the lack of specialized training would seem to be major obstacles. The larger problem is economic. Without scale and centralization, cultured meat will be no different from any other food production method: expensive.

... We already have a food system where people with enough means can pay for meat from “happy” animals. Cultured meat on a smaller scale would likely only extend that logic. Namely, that if you’re rich enough, you can pay to know that your meat didn’t die a painful death

... Based on his experience on the board of the Global Alliance for Livestock Medicines, a Gates Foundation-funded nonprofit that supports people in Africa, India, and Nepal who rely livestock for their livelihood, Wood feels that the solutions proposed by cultured meat advocates are hopelessly out of touch with the needs of the developing world.

“These are not solutions for these people,” he said. “So in this whole debate around the future of food, we’re ending up with solutions that fit wealthy, middle-class people who want more options. I’ve got nothing against it, but don’t pretend it’s going to solve world food. That’s the thing I find most offensive.”

[tacticalmook]

While overly wordy and negative, most of the premises of dissent seem to be well founded. The article's own summary:

> *For cultured meat to move the needle on climate, a sequence of as-yet-unforeseen breakthroughs will still be necessary. We’ll need to train cells to behave in ways that no cells have behaved before. We’ll need to engineer bioreactors that defy widely accepted principles of chemistry and physics. We’ll need to build an entirely new nutrient supply chain using sustainable agricultural practices, inventing forms of bulk amino acid production that are cheap, precise, and safe. Investors will need to care less about money. Germs will have to more or less behave. It will be work worthy of many Nobel prizes—certainly for science, possibly for peace. And this expensive, fragile, infinitely complex puzzle will need to come together in the next 10 years.*

More snippets below

Note that GFI refers to the optimistic analysis/factory proposal and Humbird is the author of the pessimistic analysis commissioned by Open Philanthropy.

> The single, hypothetical facility described by GFI would require nearly a third of <the entire capacity of the biopharmaceutical industry today>, just to make [.0002, or one-fiftieth of one percent, of the 100 billion pounds of meat produced in the U.S. each year.]

... If cultured protein is going to be even 10 percent of the world’s meat supply by 2030, we will need 4,000 factories like the one GFI envisions, according to an analysis[link] by the trade publication Food Navigator. To meet that deadline, building at a rate of one mega-facility a day would be too slow.

Each of those facilities would also come with a heart-stopping price tag: a minimum of $1.8 trillion, according to Food Navigator.

> Humbird’s analysis ... represent the lowest prices companies can expect. ... The final product would be a single-cell slurry, a mix of 30 percent animal cells and 70 percent water, suitable only for ground-meat-style products like burgers and nuggets. With markups ... [this] becomes $40 at the grocery store—or a $100 quarter-pounder at a restaurant. Anything resembling a steak would require additional production processes, introduce new engineering challenges, and ultimately contribute additional expense.

... “The requirements for return on investment need to be set much lower than common practice in commercially motivated investments,” the authors [of GFI] write. ... It will likely need public [subsidies] or philanthropic support to be competitive.

> In cell culture, sterility is paramount. Animal cells “grow so slowly that if we get any bacteria in a culture—well, then we’ve just got a bacteria culture,” Humbird said. ... "The culture has no immune system. If there’s virus particles in there that can infect the cells, they will. And generally, the cells just die, and then there’s no product anymore. You just dump it.”

... It may not matter if governments end up allowing cultured meat facilities to produce at food-grade specs, critics say—cells are so intensely vulnerable that they’ll likely need protection to survive.

... According to Humbird’s report, those economics will likely one day limit the practical size of cultured meat facilities: They can only be big enough to house a sweet spot of two dozen 20,000-liter bioreactors, or 96 smaller perfusion reactors. Any larger, and the clean room expenses start to offset any benefits from adding more reactors. The construction costs grow faster than the production costs drop.

For comparison, GFI’s hypothetical plant would have 130 fed-batch reactors and 430 perfusion reactors—a facility that could easily cost over a billion dollars if Humbird’s specs and prices prove to be accurate.

> In Humbird’s projection, the cost of amino [acids] alone ends up adding about $8 per pound of meat produced—already much more than the average cost of a pound of ground beef. GFI’s study, on the other hand, reports that the cost of aminos may eventually be as low as 40 cents per kilo.

Why the discrepancy? ... the price figures for macronutrients are largely based on a specific amino acid protein powder that sells for $400 a ton on ... Alibaba.com. That source ... is not likely not suitable for cell culture. ... Because they’re not intended for human consumption, they may include heavy metals, arsenic, organic toxins, and so on. ... foreign substances that aren’t consumed by the cells—or that don’t kill them outright—likely end up inside the cells.

Currently, global production of individual amino acids is far too low to support cultured meat production, even at a modest scale. ... “There can be no cultured meat scale-up without concomitant and dramatic scale-up of amino acid production,” Humbird’s report concludes.