Elliot Swartz Profile picture
Dec 28, 2022 28 tweets 14 min read Read on X
The most comprehensive study to date of #cultivatedmeat production was just published, led by scientists from @believermeats

Much of the data in this paper will likely make up their safety dossier for regulatory approval in the US

What did we learn? 👇

nature.com/articles/s4301…
For context, @believermeats is the 2nd most capitalized #cultivatedmeat company, having raised nearly $400M to date

They recently broke ground on a large production facility in N. Carolina

Cell lines: The company isolated fibroblasts from fertilized chicken embryos from 2 breeds (broiler Ross 308 and Israeli Baladi chickens).

Over time, the fibroblasts spontaneously immortalized, w/ stabilized doubling times of ~20 hrs. Image
Cell lines: The cells were adapted to suspension culture thru a protocol that involves growing them in aggregates, shaking them to adapt to shear stress, dissociating them, and repeating until single cell suspension-adapted clones emerge. ImageImage
Cell lines: Chickens have a lot of chromosomes. The cell lines displayed some karyotypic abnormalities & copy number variations throughout the genome.

Despite this, the cells retain a fibroblast identity. ImageImageImage
Cell lines: They characterize the immortalization of adherent and suspension-adapted cell lines, finding that they occurred without telomerase upregulation but involved downregulation of p53, Myc, and EGFR. ImageImage
Cell lines: The company answered whether immortalization = transformation by analyzing p53 SNVs, DNA repair, abundance of cancer-linked mutations, & tumorigenic potential.

They conclude the cell lines aren't transformed i.e. they are not like cancer cells. ImageImage
Even if the cells were transformed, this is still not a food safety concern. From the FDA's pre-market consultation of UPSIDE Foods cultivated chicken:

Cell lines: They also analyze prion protein & amyloidogenic protein levels, concluding these are normally expressed and pose no risk.

This level of detail goes above and beyond what was seen in UPSIDE Foods' pre-market FDA consultation based on what was shown. Image
Cell lines: Finally, to ensure downstream food safety, the cells tested negative for a panel of chicken pathogens such as Influenza A and New Castle Disease Virus and other microbial contaminants Image
Cell culture: The cells grow in a serum-free media that's relatively simple & can definitely be sourced low-cost.

Generally speaking, fibroblasts are an easy cell type to grow (fewer growth factors needed). The company has previously stated this is an advantage to using them. Image
Cell culture: @believermeats turns fibroblasts into fat by adding food-grade molecules eg phosphatidyl choline & oleic acid (soy lecithin). These molecules induce PPARγ signaling, which regulates adipogenesis. ImageImage
This avoids problems w/ standard fat differentiation protocols that use IBMX & Rosiglitazone, which may not be food-safe as seen in this paper by @mosa_meat

Between these 2 papers, food-safe serum-free fat production has kinda been open-sourced 👍

sciencedirect.com/science/articl…
Cell culture: Impressive data is shown for perfusion growth in a 2L Sartorius bioreactor.

Over 15 days, the company reports cell densities of 108 million cells per mL, equivalent to 36% weight/volume or 360 grams biomass per liter. This is very high. ImageImage
Notice that high amounts of lactate are also produced. If this were able to be captured, it could be a huge opportunity to offset costs and environmental impact.

The Humbird analysis, which is the basis of The Counter article (thecounter.org/lab-grown-cult…), reports a maximum achievable perfusion culture density of 195 g/L.

So do @believermeats higher cell density data invalidate this study? Image
Not quite. To achieve these very high densities, perfusion rate was nearly 20 vessel volumes/day (VVD).

This rate would become very costly as scale increases. Not only would media costs rise, but filter membrane fouling & replacement would become problematic. Image
According to the Humbird study, the largest ATF filters max out at 1000L/day, thus making realistic perfusion rates at scale more like 1-2 VVD rather than 20.

It's thus TBD if @believermeats will be able to maintain cost-effective high cell densities in scaled production. ImageImage
Product: @believermeats blends cultivated fat with extruded soy protein to make cultivated chicken. The paper does not state what percentage of fat is used for the end product. ImageImage
Nutrition: The cultivated chicken has less saturated fat and cholesterol compared to conventional chicken but higher sodium due to the soy protein.

Below, cultured chicken refers to the blended product. Image
Nutrition: Full amino acid and lipid profile compared to conventional chicken.

Images are hard to see (not my fault, that's how it's published) ImageImage
Check out nutritional data from another cultivated chicken product here:
Consumers: In a blind taste test, 67% of potential consumers prefer cultivated chicken to a soy-based analog, suggesting the added animal fat makes a noticeable difference. Image
Consumers: A large proportion of potential consumers rated product attributes highly and said they would be likely to replace conventional meat with cultivated meat. Image
In summary, this is the most comprehensive study of #cultivatedmeat published to date.

It is a very positive signal of transparency that it was led by a prominent company in the industry.

Journalists should be all over this one, IMO.
Many cultivated meat companies, including @believermeats, were founded by leading academics.

In 2022, cultivated meat companies/suppliers led or participated in 12 publications/pre-prints.

Yet people still draw comparisons to Theranos... 😄
In 2023, we are likely to see the completion of more FDA pre-market consultations, which means access to a lot more data like the stuff presented here.

For an overview of the first #cultivatedmeat product cleared by FDA, check my thread here:

"We must ensure that we, as an industry, provide all the scientific data and information to the public. If we do not rise to this challenge, consumers will search and find disinformation from charlatans online. I want to lead this conversation." 👏

proteinreport.org/newswire/hebre…

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More from @elliotswartz

Sep 9
If you asked a room of cell biologists 5 years ago if cell culture media could productively grow cells while costing just $0.63 per liter, you would have been laughed out of it. No longer.

Let's dive into this important study that poses challenges for #cultivatedmeat skeptics: Image
The 1st innovation was developing a way to replace recombinant albumin in serum-free media. Albumin is critical in most serum-free media, but makes up >1/3 of the cost. It's been shown that albumins from plants can functionally replace recombinant animal albumin at low cost: Image
But this study takes it one step further. They show that low-cost, food-grade ingredients such as methylcellulose, cyclodextrin, & antioxidants can individually replace the functions of albumin (shear protection, nutrient carrier, oxidation) in a protein-free manner. Image
Read 20 tweets
Dec 19, 2023
Australian #cultivatedmeat company @itsjustvow's safety info for its product was recently released, making it the 3rd safety dossier available to the public

The product is not yet approved & public comment is open until Feb 5th

Key info in this thread:

vegconomist.com/cultivated-cel…
@itsjustvow Let's start w/ the conclusion from the regulator Food Standards Australia New Zealand (FSANZ), which notes that key safety considerations such as allergenicity, toxicity of inputs, and microbiological risks were low. It is deemed safe to use as an ingredient in food.
Image
Image
@itsjustvow Cells: The cells used for production are an embryonic fibroblast line derived from Japanese quail.

The cells were originally obtained from an unnamed public repository based in Europe and adapted for use in production.
Read 19 tweets
Jun 27, 2023
You probably saw these recent headlines based on a pair of pre-print studies. So is it true?

I spoke to many experts & there are multiple compounding errors w/ the assumptions from these pre-print studies

Read my open letter/critique to the authors:
docs.google.com/document/d/1QY…
Image
The core assumptions that lead to the worst-case scenarios & headlines are not relevant to current or future practices of the industry, despite the claim

Underneath, the findings show that even non-optimized #cultivatedmeat has a lower carbon footprint than conventional beef
In a time where science discourse is polarized & degrading, it's doubly important for journalists to do due diligence, esp. when studies are not peer-reviewed

Unfortunately, a clickbait headline in @newscientist spread around the world w/o anyone questioning the claims
Read 10 tweets
May 9, 2023
The study that this headline is based on is a pre-print, and the claim is based on the authors' assumptions that media inputs require purification analogous to the pharma industry: Image
Unfortunately, the assumption isn't correct.

Data has been shown at conferences for years from media input suppliers that food or even feed-grade ingredients can support animal cell growth without issue, including issues from endotoxins.

ImageImage
The article shares info about our study & assumptions that cultivated meat manufacturers would use primarily food-grade ingredients.

But it doesn't say why: because our assumptions were informed by working w/ over 15 companies involved in the production supply chain. Image
Read 11 tweets
Apr 27, 2023
Didn't have time to read the 150 pages of new information associated with @GOODMeat's FDA pre-market consultation for cultivated chicken?

Key info in this thread.

npr.org/sections/healt…
Let's start with the conclusion. The FDA states, "foods comprised of, or containing, cultured chicken cell material resulting from the production process defined in CCC 000001 are as safe as comparable foods produced by other methods."

So how is it made?
Cells: The cells used for production are a publicly available cell line known as DF-1, which has been in the ATCC cell bank since 1996. The cell line is a chicken fibroblast line obtained from 10 day old embryonic chicken tissue.

This was unexpected!
Read 21 tweets
Feb 14, 2023
Some thoughts on (1) whether immortalized cells for #cultivatedmeat production should be compared to eating cancer (2) whether consuming them would give you cancer & (3) whether long-term studies are needed to ensure the safety of cultivated meat...

bloomberg.com/news/features/…
(1) The article says immortalized cells are precancerous or in some cases cancerous

There are 6 hallmarks of cancer, immortality is 1 of them. Having 1 feature of a complex phenotype doesn't mean it is that type.

You can't equate immortality to cancer.

en.wikipedia.org/wiki/The_Hallm…
(1) Thus, while all cancers are immortalized, not all immortalized cells are cancer. Sorta like how not all rectangles are squares.

To become cancer, a transformation involving the loss of control in various aspects of cell growth & regulation is one event that occurs.
Read 27 tweets

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