New intuitions for cultured meat

by kyle_fish2 min read5th Oct 202116 comments

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Cultured meat
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A ubiquitous claim in support of cultured meat is that it will be more efficient than animal agriculture because it does not require growing whole animals, only the portions we’re interested in eating. I found this argument seductive when I first encountered the idea of cellular agriculture, and it factored heavily into my decision to spend a few years working in the space. 

I have since come to believe that this argument is misleading and has hindered clear thinking about the prospects of cultured meat as a path to impact. Recent techno-economic (meta)analyses have made a compelling, quantitative case for the staggering difficulty of growing cultured meat. However, I suspect that intuitions about the potential efficiency of producing cuts of meat in isolation will continue to draw altruistic investors and talent to the space unless this notion is straightforwardly debunked. 

To this end, let us consider a futuristic bioreactor for producing cultured meat. This bioreactor requires only dirty water and whole plants as inputs. It has automatic systems for breaking the plants down into usable biomolecules, assembling those molecules into muscle and fat cells, and forming those cells into the complex tissues we love to eat. It has contamination response systems that destroy almost all pathogens, eliminating the need for media or equipment sterilization. It has precise environmental controls and gas exchange systems that keep the internal temperature, pH, and oxygen levels in the ideal range for cell and tissue growth. These systems are good enough, in fact, that these bioreactors do not require special facilities for operation—they can be placed outdoors and subjected to changing weather conditions, and they’ll have no problem making any necessary adjustments on their own. They manage metabolic waste so effectively that they can maintain suitable growth conditions for months or even years on end. And as meat in the bioreactors grows, the reactors expand to accommodate. When they reach full capacity they use energy and matter from the plant inputs to produce new, identical bioreactors that can repeat the whole process.

Nothing I have seen in the cultured meat space suggests that the industry is close to achieving even one of these capabilities. And yet, such bioreactors already exist. They’re called animals, and they are very, very hard to beat.

Producing cultured meat isn’t as simple as making only the parts of an animal that we want to eat. Sure, if we could make a steak by mixing some hay and water in a bucket, that would probably be more efficient than raising a cow. In reality, cultured meat requires unprecedented industrial processes to do almost everything that animals are so miraculously capable of. A few aspects of the living creature can be left out—including, notably, sentience—and others can be reused, but the challenge at hand is much more akin to creating and operating an artificial animal than to growing any one part in isolation. My hope is that these intuitions might inspire impact-motivated funders, scientists, engineers, and entrepreneurs to focus on more promising strategies for displacing conventional meat and ending factory farming.

Thanks to Sofia Davis-Fogel and Kasey Fish for reviewing drafts of this post.


 

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Is anybody working on solving the problem from the other direction, by e.g. genetically modifying chickens so that they don't have brains? ETA: I vaguely recall stories of chickens surviving for weeks with their heads chopped off; people fed them through their open throat. Gruesome, but also  evidence that something like this should be possible.

There's been some discussion over the years of genetically engineering farm animals so they don't experience pain, but I don't know of any efforts to remove sentience entirely. 

If anybody's doing this, I would love to talk to them.

I work in bioprocessing, and overall wasn't that impressed by the Humbird report. The plant Humbird proposes looks nearly exactly like existing bioprocessing plants for biologic drugs. It shouldn't surprise anyone that trying to make (cheap) food isn't possible using plants that are designed to make extremely high value drugs. Let's take insulin, a relatively cheap biologic drug. One unit of insulin (0.035 mg) retails for about $0.30. Let's assume during the fermentation we get 20% cell weight, 10 g insulin/L, and have a 50% downstream yield. This means that we have 1.4 mg of cell mass per unit of insulin, for a cost of ~$0.20 per mg cell mass, which is $200,000 per kg. A reasonable target for cultured meat might be a retail price of $20 / kg. We are talking a 10,000x difference here, so it's clear to me that a cultured meat plant will need to be drastically different than an insulin plant or an antibody plant. To be fair, I'm not exactly sure what the ideal design would be, just that any plant that looks exactly like a biopharma plant (as Humbird assumes) is not feasible.

Keeping things sterile would probably be the hardest element to scale up for culture meat production in my opinion. Equipment/media sterilization is only sufficient if you run a completely closed process. However, keeping your process completely closed is quite difficult, especially if you are using fixed stainless steel equipment. You are eventually going to have to open up your equipment for cleaning and turnover, and you need literal 100% sterility. Even a tiny bacterial contamination will likely spread to contaminate your whole line, since bacteria grow so much faster than animal cells.

Due to these challenges, basically every biopharma plant uses large sterile suites where the rooms have ISO  7/8 quality air. This is really expensive, and was one of the major expenses in the Humbird report. 

However, where all the existing TEAs fail in my opinion is by ignoring single-use materials. It is potentially possible to have a truly closed system using single-use materials (i.e. plastic flowpaths and bioreactors) that are pre-assembled and pre-sterilized. This would allow you to put this process in a plant with more minimal air purification, which drastically reduces your costs. Single-use bioreactors (SUBs) also have drastically lower capital costs compared to stainless steel, something like 70% lower. The downside of course is that your consumables costs as you need to purchase these plastic bioreactors. As of right now, they also don't make 20k L SUBs, the largest I've seen is 6k L. I imagine larger SUBs would be doable if there was sufficient demand.

I wrote a comment in a previous discussion about why I think cultivated meat can be expected to become at least as efficient/cheap as animal-based meat: https://forum.effectivealtruism.org/posts/y8jHKDkhPXApHp2gb/cultured-meat-a-comparison-of-techno-economic-analyses?commentId=MJtLFZya2WqdNADSy

The basic idea is that animals were not evolved to maximize meat production. Just like horses were not evolved to maximize transport efficiency and hence were replaced by cars, plants were not evolved to maximize turning solar energy into electricity and are replaced by more efficient solar panels, pigs were not evolved to maximize insulin production and were replaced by recombinant-DNA yeast,...

I don't think cars, solar panels, and recombinant insulin are analogous technologies here. Cars and solar panels won out because they are completely new approaches to transportation and solar energy capture that are not constrained by the biology of the systems they're replacing. Cultured meat seems severely handicapped by its reliance on the growth of animal cells and tissues. 

Recombinant insulin is still manufactured in biological systems (bacteria and yeast), but they are much simpler than mammalian cells and can efficiently express a protein that is only present in tiny amounts in the pig pancreases it used to be purified from. 

Pigs are ~50% meat by mass, but less than ~0.01% insulin by mass. And animals are pretty well optimized for producing animal bodies with minimal food consumption, so the possible gains are

  • factor of ~2 from not producing the rest of the animal
  • Small factor from turning food into meat more efficiently than evolved animals
  • Small factor from turning energy into food more efficiently than evolved plants
  • Large factor from producing energy more cheaply than we produce crops for animal feed

Cars are not mechanical horses. 

I think this is a bit of a straw-person. It may be true that some commentators overstate the immediate relevance of this consideration, as well as how close companies are to reaping the benefits of this efficiency. However, a more charitable interpretation of the argument is that at scale, support systems will be amortized over a much larger amount of desired output. To give two examples:

  • Animals expend a substantial amount of calories thinking with their brain. This processing will be centralized, and paired down in scope in the computers that run the bioreactors.
  • Animals spend a lot of energy regulating body temperature. Given that bioreactors will be much bigger than animals, they will have a much lower surface area for heat transfer.

(To be clear, I don’t think this category of argument is a major consideration in favor nor against the feasibility of cultured meat. There are arguments pointed in both direction. One disadvantage of bioreactors is that they have to be designed to last decades, have modular components that can be swapped out, etc.)


 

This is a good point. I don't want anyone to write off cultured meat on the basis of my argument alone, but I do want to push us toward much more nuanced conversations. Ideally, discussions of feasibility will include an evaluation of all relevant systems and the ways in which they could improve over animals, weighed against their limitations. I’d refer anyone who is interested in a more rigorous and technical evaluation to the Humbird report.

That said, for me the relevant question isn’t whether it’s strictly possible to make cultured meat competitive in the long run, but whether pursuing cultured meat as a strategy is the best/most cost effective use of money and talent. I think arguments of the style I made can be very helpful for quick comparative evaluations. For example, plant-based meat looks far more promising than cultured meat through this lens, because it is a fundamentally different approach that circumvents many of the limitations of mammalian and avian biology.

I'm pretty confused by your paragraph describing the "futuristic bioreactor". It doesn't seem like we want almost any of those features for cultured meat.

The only parts that seem like they would be needed in are "[...] assembling those molecules into muscle and fat cells, and forming those cells into the complex tissues we love to eat" and "It has precise environmental controls and gas exchange systems that keep the internal temperature, pH, and oxygen levels in the ideal range for cell and tissue growth"

Some (though not all) of the others seem like they might be useful if we were to try and make cultured meat production as decentralizable as current meat production (and far more decentralized than factory farming).

We might not have to replicate the animal systems precisely, but we'd definitely need cheap solutions to the problems of contamination (3rd sentence), sensitivity/robustness (5th sentence), waste management (6th sentence), and scalability (7th and 8th sentences). All of these are currently huge issues for any biomanufacturing.

For the contamination sentence: what's wrong with equipment and media sterilization? Why wouldn't we just grow meat in sterilized equipment in managed facilities? Also, couldn't we just sterlize after the fact?

For the sensitivity / robustness: why does it need to be robust? Can't it just be grown in a special facility? It's not like you can mimic the Doritos production process at home, but that doesn't stop a lot of Doritos being made. Why would the bioreactor need to placed outside?

For waste management: This does seem necessary. But months / years of continual operation don't seem necessary (though more efficient if it can be pulled off). If the bioreactor is shut down and sterilised intermittently, that seems like it would suffice.

For scalability: I believe you that scalability is an issue, but the examples in the 7th and 8th sentences seem unnecessary and unlike any other (roughly) nature-mimicking process we've chosen. Why should the bioreactor need to grow? If the volume needs to change over time, couldn't this be achieved with a piston-like mechanism? In general, we produce things on factory lines, not via creating replicating machines. Useful replicating machines are certainly far beyond our capacity to make de novo (though we can tweak nature's small self-replicating machines)

EDIT: This analysis is probably wrong, see the reply. Leaving post up for context. 

One other comment, related to the Twitter thread that brought me here showing that poultry is 13% efficient at conversion of feed into meat. While this is true, feed costs are a pretty minor cost at least for poultry: NC-Choices-NC-Farm-School-Meat-Chicken-Info-graphic-Breakout.pdf (ncsu.edu)

I'm seeing the cost for conventional feed as $0.89 per lb poultry, compared to total costs of $6.42 per lb, so the feed is only ~14% of the total cost per lb poultry. I suspect that the feed cost is probably far higher for cattle, but that's because cattle are only about 3% efficient in terms of calorie conversion, far less efficient than poultry.

Admittedly, I do agree with your general argument, at least when it comes to poultry. It will be tough to be more than 13% energy efficient for cultured meat. However, the other costs of poultry production are high enough that is still seems reasonable that a cultured meat could still be competitive. 

Hi,

You seem to have a lot of knowledge in bioprocessing, but the figures here aren’t right.


I'm seeing the cost for conventional feed as $0.89 per lb poultry, compared to total costs of $6.42 per lb, so the feed is only ~14% of the total cost per lb poultry. I suspect that the feed cost is probably far higher for cattle, but that's because cattle are only about 3% efficient in terms of calorie conversion, far less efficient than poultry.

Feed costs are 60-70% (cattle probably comes lower at 50% because of larger labor costs).

Feed costs are the largest portion in factory farming, with labor usually being a distant second. 

E.g. See top of these two papers: Effect of feed processing on broiler performance and  Managing Dietary Energy Intake by Broiler Chickens to Reduce Production Costs and Improve Product Quality

 

(This includes amortization for fixed costs such as sheds and equipment).

The dominance of feed costs is true of all factory farming (pork and beef). The root reason is the reduction of other costs (labor, equipment) through scale and genetic selection (with graphic, unbelievable impacts to animal welfare).

Makes sense, thanks for the context!