Is Cultivated Meat for Real?—Asterisk

@tags:: #lit✍/📰️article/highlights
@links:: cultivated meat,
@ref:: Is Cultivated Meat for Real?—Asterisk
@author:: asteriskmag.com

=this.file.name

Book cover of "Is Cultivated Meat for Real?—Asterisk"

Reference

Notes

The Challenges of Cultivated Meat Are Real

Quote

In 2020, David Humbird published a techno-economic model that took a critical eye to the technology. There were, he noted, some massive technical challenges. His critique was popularized in a 2021 piece in The Counter. The challenges he identified — which include fundamental cost barriers for input materials, challenges in scaling production processes, difficulty maintaining sterility at large scales, and constraints set by investors — make a convincing case against The Dream of cultivated meat being feasible within the next 5 to 10 years.
- No location available
-

The Prices of Input Materials

Quote

The manufacturing of cultivated meat requires three inputs:1. Starter cells, often stem cells of some type. 2. Nutrients that the cells need to duplicate and turn into the relevant tissue types. These include sugars, fats, minerals, and amino acids.3. Signaling molecules that tell the cells how to behave, called “growth factors.” Unlike many types of microbes, animal cells don’t multiply by default. GFs’ presence in animal cells’ environment gives them the cue to multiply or turn into different tissue types.
- No location available
-
- [note::Make this into an Excalidraw diagram]

Quote

(highlight:: Early economic analyses pointed to GFs as the costliest input to cultivated meat,
1
but Humbird deemphasizes this as a long-term bottleneck, and I agree. GFs are expensive now, but GF production via precision fermentation is easily scalable. Bulk purchases often yield massive drops in unit price. The supporting industries that produce the relevant GFs at massive scales don’t exist yet, but they should be able to grow at least as quickly as cultivated meat itself. Companies can also modify the starter cells to require lower concentrations of GFs or to forgo them entirely.Put another way, GFs carry information, which is fundamentally easier to manipulate than mass. There are unlikely to be long-term thermodynamic or biochemical limits on getting information to cells.)
- No location available
-

Quote

This same is not true for amino acids. Amino acids are the fundamental building block of the proteins in meat; cells can’t be engineered to need less. In Humbird’s model, amino acids alone may constitute $7 to $8 per pound of cultivated meat (although there is by no means a consensus about this). They also have to be pure enough to avoid negatively affecting the cell culture, which adds to the price. Absent new breakthroughs, it’s possible that price floors on bulk amino acids could be a fundamental bottleneck on the price of cultivated meat.
- No location available
-

Scaling Up the Manufacturing Process

Quote

Manufacturing cultivated meat happens in two stages: proliferation and differentiation. During proliferation, the starter cells continually divide to create more cells until there’s a sufficient quantity of “cell slurry” — a mass of cells mixed in a liquid. During differentiation, cells in the slurry transform into the desired tissue type, like muscle or fat.
- No location available
-

Quote

For the proliferation stage, the most common is a “stirred tank” process, where materials are mixed in a container of liquid, which is stirred to ensure a homogeneous distribution of cells, nutrients, and GFs. This type of process has a long history of use in other industries, like biopharmaceutical manufacturing. While cultivated meat would likely require substantially larger tanks in the long term, the basic procedure is well understood.
- No location available
- cell proliferation, cultivating meat,

Quote

The differentiation stage is more complicated. Since large-scale cell differentiation isn’t a challenge other industries face, cultivated meat companies have to design new processes. UPSIDE Foods distributes cell slurry onto a “sheet” where cells adhere to some substrate and turn into tissue. Alternatively, Mosa Meat has developed a novel culture vessel where muscle cells grow in a ring around a central pole and are then sliced off when fully formed.
- No location available
-

Maintaining Sterility at Scale

Quote

External microbes carried in by humans or present in the input materials can also thrive. Since bacteria tend to duplicate much faster than mammalian cells, a single microbe can contaminate an entire batch of product. This makes cleaning a critical aspect of the manufacturing process.This problem gets worse as scales increase. A bigger batch means a longer, more complex process with more materials — and a higher risk of contamination. To make matters worse, a larger contamination means more material goes to waste, leading to a larger financial impact. There are well-established procedures for maintaining a sterile environment for large-scale cell culture, but they require expensive and complex facility upgrades and cleaning procedures. They’ve also never been tested at the relevant scales. Wasted materials from contamination will need to be priced in to the total cost of the final product, meaning that maintaining sterility will be a major engineering focus of the industry as it matures.
- No location available
- alternative proteins, sterilization,

Massive Capital Investments

Quote

Technological development in the physical world requires substantial capital, capital flows to things that investors think will succeed, and firms demonstrate potential for success through technological development. This is what I’ll call the “virtuous cycle of capital deployment.” Technology firms solicit funding from investors and promise certain milestones. Whether or not the investors invest is a function of how well firms have performed in the past, the financial situation of the investors, and the vibes of the investment environment.The virtuous cycle can break if one of its parts slows down. If technology firms don’t hit their promised milestones, investors may start to lose faith. On the other hand, if there’s an economic downturn that causes investors to tighten their belts, money for speculative research and development or large capital projects can dry up. But a major technological breakthrough or a new funder (say, a government with sustainability goals) can catalyze a new flurry of investments.
- No location available
-

Quote

Different investors are more suitable for different stages in a technology’s lifecycle. Right now, venture capitalists are the primary funders of cultivated meat, since their risk tolerance is high and the technology is unproven. As the technology matures and investments become less risky, investors with lower risk tolerance but much larger checkbooks — such as governments, public equity markets, and debt markets — may enter the scene.
- No location available
-

Quote

Many milestones exist between now and The Dream of cultivated meat becoming a reality. First, companies have to develop scalable processes and demonstrate them in pilot plants. Regulatory agencies then need to certify that these processes yield products that are safe to eat. Then the long road of scaling and cost reduction begins. Companies will need to build and operationalize larger and larger facilities to increase production capacity, and invest in further R&D to lower costs, all the while demonstrating that there is consumer demand.
- No location available
-

The Goals Were Overly Ambitious

Quote

Cultivated meat is a capital-intensive industrial manufacturing technology that aims to produce high-volume, low-margin products. Industrial animal farming, the incumbent technology, is fully commoditized and has had decades to lower costs through scaling, optimization, consolidation, vertical integration, and R&D. However, these structural challenges are not unique. Other technologies have faced similarly daunting prospects, and some have even succeeded, albeit over many decades of slow, steady progress. Looking at how their stories played out can help us understand the path forward for cultivated meat.Solar energy, now heralded as one of the most notable success stories of clean tech, is a particularly useful comparison.
- No location available
-

The Limits of Techno-economic Modeling

Cell Density and Alternative Processes

Quote

In “adherent” proliferation processes, cells are secured onto a substrate so they remain stationary, and liquid is circulated through the substrate to deliver nutrients and remove waste — similar to how blood flows in an animal’s body. Adherent processes can achieve massively higher cell densities than stirred tank systems, one of the core bottlenecks in Humbird’s analysis. It’s easy to see why: A liquid containing cells and nutrients becomes harder to mix effectively as it gets thicker and less viscous. However, if cells are kept stationary, they can be packed very tightly, as they are in natural tissue.
- No location available
-

Quote

One reason these systems could be underexplored is that cultured meat is ultimately solving a different problem than the industries that precede it. In biopharmaceutical production, cells produce the end product, but for cultivated meat, cells are the end product. If a producer needs to extract a drug from the cell culture, it may be easier with everything loosely floating in a liquid, rather than trapped in a dense matrix of cells.The problem with adherent systems is that it’s difficult to find comparable examples. Operationalizing and scaling up a new bioreactor system is massively more challenging when nothing is known about how cells might behave in the new environment.
- No location available
-

Cell Size

Quote

One avenue to scalability that’s unique to cultivated meat is increasing the size of each cell. Even after the number of cells in a batch is set in the proliferation phase, more mass can be added during the differentiation phase. Fat cells in particular vary by orders of magnitude in volume and could likely be grown much larger than seen in nature. Fat will likely be critical to hybrid products, since fat carries many of the important flavor compounds we associate with meat.Humbird’s TEM underweights the potential impact of cell size, since it only considers the proliferation phase. His rationale is likely that if cell slurry can’t be produced at comparable costs to meat, then neither can fully differentiated tissue. However, if significant mass is gained during the differentiation phase, this could be a critical aspect of the total cost competitiveness of the product. Since differentiation processes differ across companies, the possibility is difficult to model.
- No location available
-

Genetic Engineering

Quote

Until recently, one might have thought that any sort of explicit genetic tinkering would have been a regulatory non-starter. This would make it much more difficult to achieve the metabolic efficiencies and other desirable cell traits that Humbird views as necessary (but insufficient) for cost-competitive cultivated meat. Fortunately, UPSIDE Foods’ recent FDA approval included the use of genetic engineering to make cells overexpress a particularly helpful protein. This is a positive sign for the industry. It frees up companies to pursue a host of research directions to make cells more efficient and more suitable for large-scale cell culture.
- No location available
-

Amino Acids

Quote

Currently, cell culture media is made by combining each individual amino acid one by one. But this isn’t how animals get amino acids in nature. Rather, animals eat food, and then break down proteins into the constituent amino acids via digestion.Technologies that mimic this process could help lower the cost of cultivated meat in the long term. Humbird explicitly mentions soy hydrolysates as a potentially promising solution. With this technology, soy (the main source of protein for livestock) is broken down in a chemical reaction with water and added to media as a single composite ingredient. This is a novel technology with its own host of challenges, but with a longer time horizon for cultivated meat, it isn’t out of the picture (just as our highly optimized system of growing corn and soy for animal feed developed alongside industrial animal agriculture).
- No location available
-

Quote

Another avenue to decrease the cost of amino acids is to decrease the percentage of them in the final product by focusing on fat. Since fat cells have more lipids and fewer amino acids than muscle cells, they could be cheaper to produce at large scales. This could be an important factor in the cost competitiveness of hybrid products, which can primarily get amino acids from plant-based components.
- No location available
-

A Bet Worth Making

Quote

A longer time scale will come as a disappointment to those who bought into the early, more optimistic projections for cultured meat. But in the fight for animal welfare, there is no silver bullet. Plant-based meat has shown tremendous promise and has the potential to undercut conventional meat on price in the longer term, but it’s unclear whether consumer demand will be there. Traditional advocacy has had some major wins (a third of egg-laying hens in the U.S. are now cage-free), but social change is hard to steer and even more difficult to predict. Given how little we can truly know about how the future will play out, I believe we need to maintain a diversified portfolio of bets across cultivated, plant-based, and traditional advocacy and social change.
- No location available
-


dg-publish: true
created: 2024-07-01
modified: 2024-07-01
title: Is Cultivated Meat for Real?—Asterisk
source: hypothesis

@tags:: #lit✍/📰️article/highlights
@links:: cultivated meat,
@ref:: Is Cultivated Meat for Real?—Asterisk
@author:: asteriskmag.com

=this.file.name

Book cover of "Is Cultivated Meat for Real?—Asterisk"

Reference

Notes

The Challenges of Cultivated Meat Are Real

Quote

In 2020, David Humbird published a techno-economic model that took a critical eye to the technology. There were, he noted, some massive technical challenges. His critique was popularized in a 2021 piece in The Counter. The challenges he identified — which include fundamental cost barriers for input materials, challenges in scaling production processes, difficulty maintaining sterility at large scales, and constraints set by investors — make a convincing case against The Dream of cultivated meat being feasible within the next 5 to 10 years.
- No location available
-

The Prices of Input Materials

Quote

The manufacturing of cultivated meat requires three inputs:1. Starter cells, often stem cells of some type. 2. Nutrients that the cells need to duplicate and turn into the relevant tissue types. These include sugars, fats, minerals, and amino acids.3. Signaling molecules that tell the cells how to behave, called “growth factors.” Unlike many types of microbes, animal cells don’t multiply by default. GFs’ presence in animal cells’ environment gives them the cue to multiply or turn into different tissue types.
- No location available
-
- [note::Make this into an Excalidraw diagram]

Quote

(highlight:: Early economic analyses pointed to GFs as the costliest input to cultivated meat,
1
but Humbird deemphasizes this as a long-term bottleneck, and I agree. GFs are expensive now, but GF production via precision fermentation is easily scalable. Bulk purchases often yield massive drops in unit price. The supporting industries that produce the relevant GFs at massive scales don’t exist yet, but they should be able to grow at least as quickly as cultivated meat itself. Companies can also modify the starter cells to require lower concentrations of GFs or to forgo them entirely.Put another way, GFs carry information, which is fundamentally easier to manipulate than mass. There are unlikely to be long-term thermodynamic or biochemical limits on getting information to cells.)
- No location available
-

Quote

This same is not true for amino acids. Amino acids are the fundamental building block of the proteins in meat; cells can’t be engineered to need less. In Humbird’s model, amino acids alone may constitute $7 to $8 per pound of cultivated meat (although there is by no means a consensus about this). They also have to be pure enough to avoid negatively affecting the cell culture, which adds to the price. Absent new breakthroughs, it’s possible that price floors on bulk amino acids could be a fundamental bottleneck on the price of cultivated meat.
- No location available
-

Scaling Up the Manufacturing Process

Quote

Manufacturing cultivated meat happens in two stages: proliferation and differentiation. During proliferation, the starter cells continually divide to create more cells until there’s a sufficient quantity of “cell slurry” — a mass of cells mixed in a liquid. During differentiation, cells in the slurry transform into the desired tissue type, like muscle or fat.
- No location available
-

Quote

For the proliferation stage, the most common is a “stirred tank” process, where materials are mixed in a container of liquid, which is stirred to ensure a homogeneous distribution of cells, nutrients, and GFs. This type of process has a long history of use in other industries, like biopharmaceutical manufacturing. While cultivated meat would likely require substantially larger tanks in the long term, the basic procedure is well understood.
- No location available
- cell proliferation, cultivating meat,

Quote

The differentiation stage is more complicated. Since large-scale cell differentiation isn’t a challenge other industries face, cultivated meat companies have to design new processes. UPSIDE Foods distributes cell slurry onto a “sheet” where cells adhere to some substrate and turn into tissue. Alternatively, Mosa Meat has developed a novel culture vessel where muscle cells grow in a ring around a central pole and are then sliced off when fully formed.
- No location available
-

Maintaining Sterility at Scale

Quote

External microbes carried in by humans or present in the input materials can also thrive. Since bacteria tend to duplicate much faster than mammalian cells, a single microbe can contaminate an entire batch of product. This makes cleaning a critical aspect of the manufacturing process.This problem gets worse as scales increase. A bigger batch means a longer, more complex process with more materials — and a higher risk of contamination. To make matters worse, a larger contamination means more material goes to waste, leading to a larger financial impact. There are well-established procedures for maintaining a sterile environment for large-scale cell culture, but they require expensive and complex facility upgrades and cleaning procedures. They’ve also never been tested at the relevant scales. Wasted materials from contamination will need to be priced in to the total cost of the final product, meaning that maintaining sterility will be a major engineering focus of the industry as it matures.
- No location available
- alternative proteins, sterilization,

Massive Capital Investments

Quote

Technological development in the physical world requires substantial capital, capital flows to things that investors think will succeed, and firms demonstrate potential for success through technological development. This is what I’ll call the “virtuous cycle of capital deployment.” Technology firms solicit funding from investors and promise certain milestones. Whether or not the investors invest is a function of how well firms have performed in the past, the financial situation of the investors, and the vibes of the investment environment.The virtuous cycle can break if one of its parts slows down. If technology firms don’t hit their promised milestones, investors may start to lose faith. On the other hand, if there’s an economic downturn that causes investors to tighten their belts, money for speculative research and development or large capital projects can dry up. But a major technological breakthrough or a new funder (say, a government with sustainability goals) can catalyze a new flurry of investments.
- No location available
-

Quote

Different investors are more suitable for different stages in a technology’s lifecycle. Right now, venture capitalists are the primary funders of cultivated meat, since their risk tolerance is high and the technology is unproven. As the technology matures and investments become less risky, investors with lower risk tolerance but much larger checkbooks — such as governments, public equity markets, and debt markets — may enter the scene.
- No location available
-

Quote

Many milestones exist between now and The Dream of cultivated meat becoming a reality. First, companies have to develop scalable processes and demonstrate them in pilot plants. Regulatory agencies then need to certify that these processes yield products that are safe to eat. Then the long road of scaling and cost reduction begins. Companies will need to build and operationalize larger and larger facilities to increase production capacity, and invest in further R&D to lower costs, all the while demonstrating that there is consumer demand.
- No location available
-

The Goals Were Overly Ambitious

Quote

Cultivated meat is a capital-intensive industrial manufacturing technology that aims to produce high-volume, low-margin products. Industrial animal farming, the incumbent technology, is fully commoditized and has had decades to lower costs through scaling, optimization, consolidation, vertical integration, and R&D. However, these structural challenges are not unique. Other technologies have faced similarly daunting prospects, and some have even succeeded, albeit over many decades of slow, steady progress. Looking at how their stories played out can help us understand the path forward for cultivated meat.Solar energy, now heralded as one of the most notable success stories of clean tech, is a particularly useful comparison.
- No location available
-

The Limits of Techno-economic Modeling

Cell Density and Alternative Processes

Quote

In “adherent” proliferation processes, cells are secured onto a substrate so they remain stationary, and liquid is circulated through the substrate to deliver nutrients and remove waste — similar to how blood flows in an animal’s body. Adherent processes can achieve massively higher cell densities than stirred tank systems, one of the core bottlenecks in Humbird’s analysis. It’s easy to see why: A liquid containing cells and nutrients becomes harder to mix effectively as it gets thicker and less viscous. However, if cells are kept stationary, they can be packed very tightly, as they are in natural tissue.
- No location available
-

Quote

One reason these systems could be underexplored is that cultured meat is ultimately solving a different problem than the industries that precede it. In biopharmaceutical production, cells produce the end product, but for cultivated meat, cells are the end product. If a producer needs to extract a drug from the cell culture, it may be easier with everything loosely floating in a liquid, rather than trapped in a dense matrix of cells.The problem with adherent systems is that it’s difficult to find comparable examples. Operationalizing and scaling up a new bioreactor system is massively more challenging when nothing is known about how cells might behave in the new environment.
- No location available
-

Cell Size

Quote

One avenue to scalability that’s unique to cultivated meat is increasing the size of each cell. Even after the number of cells in a batch is set in the proliferation phase, more mass can be added during the differentiation phase. Fat cells in particular vary by orders of magnitude in volume and could likely be grown much larger than seen in nature. Fat will likely be critical to hybrid products, since fat carries many of the important flavor compounds we associate with meat.Humbird’s TEM underweights the potential impact of cell size, since it only considers the proliferation phase. His rationale is likely that if cell slurry can’t be produced at comparable costs to meat, then neither can fully differentiated tissue. However, if significant mass is gained during the differentiation phase, this could be a critical aspect of the total cost competitiveness of the product. Since differentiation processes differ across companies, the possibility is difficult to model.
- No location available
-

Genetic Engineering

Quote

Until recently, one might have thought that any sort of explicit genetic tinkering would have been a regulatory non-starter. This would make it much more difficult to achieve the metabolic efficiencies and other desirable cell traits that Humbird views as necessary (but insufficient) for cost-competitive cultivated meat. Fortunately, UPSIDE Foods’ recent FDA approval included the use of genetic engineering to make cells overexpress a particularly helpful protein. This is a positive sign for the industry. It frees up companies to pursue a host of research directions to make cells more efficient and more suitable for large-scale cell culture.
- No location available
-

Amino Acids

Quote

Currently, cell culture media is made by combining each individual amino acid one by one. But this isn’t how animals get amino acids in nature. Rather, animals eat food, and then break down proteins into the constituent amino acids via digestion.Technologies that mimic this process could help lower the cost of cultivated meat in the long term. Humbird explicitly mentions soy hydrolysates as a potentially promising solution. With this technology, soy (the main source of protein for livestock) is broken down in a chemical reaction with water and added to media as a single composite ingredient. This is a novel technology with its own host of challenges, but with a longer time horizon for cultivated meat, it isn’t out of the picture (just as our highly optimized system of growing corn and soy for animal feed developed alongside industrial animal agriculture).
- No location available
-

Quote

Another avenue to decrease the cost of amino acids is to decrease the percentage of them in the final product by focusing on fat. Since fat cells have more lipids and fewer amino acids than muscle cells, they could be cheaper to produce at large scales. This could be an important factor in the cost competitiveness of hybrid products, which can primarily get amino acids from plant-based components.
- No location available
-

A Bet Worth Making

Quote

A longer time scale will come as a disappointment to those who bought into the early, more optimistic projections for cultured meat. But in the fight for animal welfare, there is no silver bullet. Plant-based meat has shown tremendous promise and has the potential to undercut conventional meat on price in the longer term, but it’s unclear whether consumer demand will be there. Traditional advocacy has had some major wins (a third of egg-laying hens in the U.S. are now cage-free), but social change is hard to steer and even more difficult to predict. Given how little we can truly know about how the future will play out, I believe we need to maintain a diversified portfolio of bets across cultivated, plant-based, and traditional advocacy and social change.
- No location available
-