“What Questions Should We Be Asking About Cell-Based Meats?” A Fellow Responds.

Last month, Forbes contributor Errol Schweizer published a list of questions about cell-based meat, requesting more information from cell ag stakeholders about issues like growth media, antibiotics, and food safety. Andrew Stout, a PhD candidate in bioengineering at Tufts University, took a stab at answering Schweizer’s questions from his perspective as a cultured meat researcher.

I want to mention a few caveats before starting. This conversation is predicated on the success of cultured meat as a viable food product for mass consumption. I do not hold that assumption, myself. I think there are still a lot of scientific questions we need to answer before we know if this is feasible, at least in the near-term (~5-10 year) and at the scales/product-types we typically talk about.

On a related note, I think a lot of the recent conversation about cultured meat is based on the idea that these products are imminently approaching grocery stores—that we’ll blink and they’ll be here—and so there’s an overly feverish response. I think meaningful mass production is still fairly far away, which I mention to lower the temperature a bit. I’m not saying it’s not important to have conversations now (I think it is!), just throwing in some personal opinion context.

I tried to be unbiased, here, but obviously I am.

– Andrew

Find the original Forbes article here

How will such products be labeled and marketed to consumers on retail shelves and in restaurants and food service?

I use the term cultured meat; however, this will be a decision from regulators in my opinion. My guess is that it will be extremely differentiating at first (very explicitly labeled), and that future labeling (over decades) would change to reflect consumer/public sentiments and our collective understanding of meat’s definition.

What is in the feed stock for the nutrient medium that such products are grown in? The volumes of meat needed to turn a profit for investors will necessitate millions of pounds or gallons of nutrient mix annually. Will the feed stock be derived from cheap, plentiful but chemical-laden byproducts of GMO agriculture, particularly soy and/or corn? Or is there some other readily available supply chain being developed? And what are the environmental and health impacts of these feedstock raw materials?

Not personally sure what this will look like. Currently the main components of media we use in lab (called “DMEM/F12” and purchasable from ThermoFisher) are (by dry weight):
- ~10% amino acids
- ~67% salts (sodium chloride, sodium bicarbonate, and potassium chloride)
- ~20% glucose.
Some groups are working on getting these materials from alternative sources (as in a recent paper by Yuta Okamoto in Tatsuya Shimizu’s lab), though that technology is likely a ways away. In the meantime, I suspect that components such as proteins and sugars will likely come from sources such as soy/corn. Even still, isolating pure amino acids from raw products such as soy at low cost poses a significant technical challenge that the field needs to work on, either by improving extraction techniques or reducing the requirements for highly-pure amino acid extracts (as opposed to more crude protein hydrolysates). I think this is a promising area of research.
Also, I’d like to push back at the loaded tone used to discuss ‘chemical-laden’ corn/soy – is that not the feedstock used in much conventional animal agriculture? And isn’t it the safety of the final product that really matters? My guess is that the health impacts of the feedstock materials will be low or controllable, but that certainly needs to be researched and verified.

What is the “feed” conversion ratio? For every million pounds of cell-based meat produced for consumption, how much feedstock is needed? Feed conversions ratios for live chicken is 1.6:1, meaning 1.6 pounds of feed for 1lb of chicken. Considering the yield of a live chicken is 70%, would this mean that you would need 1.6 pounds of feed for .7 pounds of cultivated meat? Likewise, for a beef cow, the feed ratio is 6:1, 6 pounds of grain to 1 pound of meat. Assuming a 60% yield for live beef, should we assume that 6 pounds of feed would be needed for .6 pounds of cultivated analogous meat? And feed conversion for a healthy, young dairy cow is about 4:1. Would the feedstock requirements for cell-based dairy production be a similar ratio, or will this depend on the specific product line? Would some varieties enable the nutrient uptake to be more efficient, and if so, how and why? And how much acreage per pound of finished product will be necessary to grow such raw materials further upstream?

Super important area of research, I think! A lot of it will come down to our ability to recycle media or extract waste metabolites. These build up in cell culture media and can kill cells unless they are removed. We typically do that in a lab setting by just removing all of the media and replacing it with new stuff (or removing a significant portion and replenishing). Because of that, we often “replace” media that may have high levels of glucose or amino acids, still, but has an accumulation of lactic acid that makes it toxic to cells.
A really important area of research for improving this ratio in cultured meat is to find ways to remove the lactic acid, etc., while keeping the nutrients that cells can use.
Ultimately, though, my answer to your question is: I don’t know, and we need research in this area, and I’m sure that it will change over time. In theory, the fact that energy is not going to non-food processes (e.g. bone growth, neurological activity, breathing, etc.) points towards the possibility for improved nutrient efficiency – where practice meets that theory, though, will be what matters in the end (because it certainly won’t meet it at perfect efficiency).

Will growth hormones be involved in the cultivation of these products, and if so, would the final consumer-facing product contain hormone traces or residue?

Not technically, and most likely. We use growth factors, but those are technically different than growth hormones. For all intents and purposes, though, we can assume they fall under this umbrella (of signaling proteins), in which case: yes. In all likelihood growth factors will be in the product. For instance, we use a protein called FGF (fibroblast growth factor) to grow muscle cells, as it’s very important for doing so. But the important thing to note is that growth factors are present in tissues as well. They are what our bodies naturally use to tell cells to do things, so there’s definitely FGF in any piece of conventional meat, since those tissue are making FGF and have FGF, etc.
An interesting thing to note about these proteins, though, is how quickly they degrade. FGF’s half life in the body is only about 8 hours, and that definitely falls when you cook it and eat it. So, while there may be FGF in the cultured meat upon harvest, there’s likely not going to be much left after aging (as is done to meat), and certainly not after cooking and eating (our stomachs are great at degrading proteins).
- To get in the weeds a little with a fun side note: the technical difference between hormones and growth factors is that hormones are produced in glands, and growth factors are produced in other tissues. For that reason, cultured meat will likely actually have fewer hormones than conventional meat. In a cow, the glands send hormones through the bloodstream to tissues, and those act on those tissues. In the lab, we don’t need to use any hormones to grow our cow cells and so a cultured meat product wouldn’t ever have seen one single hormone.
- That said, the use of “hormone” as a boogie monster here is a bit of an issue, since again hormones are present in all tissues that we eat. Whether or not that matters (in conventional and cultured meat) depends on the levels, I would guess. So I don’t have any issue with actual hormones being used in cultured meat production, I just wanted to point out the fun fact that it’s highly possible cultured meat contains fewer than your grassiest grass-fed cow.
So, in sum: will there be hormones? Maybe not. Will there be growth factors? Probably yes. Will it matter to the consumer? Probably not.

What else is in this growth media and what is the disposal method for the spent media once the protein is extracted? How many gallons or pounds of spent media will be produced per pound of cultivated meat? Will it need to be regulated and handled as a biohazard or will it be compostable or disposable in municipal sewage and waste management systems? Are there other byproducts or waste materials from processing that contain contaminants or biohazards that will need to be mitigated and dealt with?

Other things are vitamins, other proteins (such as the iron-carrying protein transferrin), other minerals (such as selenium at trace levels). Pretty much all stuff that is in blood (since that’s what media is trying to replicate, in essence).
Disposal method is a super great question, and one that the industry will definitely need to figure out. I don’t have any way to start answering it, though (not my area). I believe there have been some numbers put out about liters/kg of meat, but I don’t have those at my fingertips and I’m personally hesitant to trust many of those.
Not familiar enough with biohazard designation, etc., to take a swing here!

How much “poop”, or metabolic waste material, will each pound of cell-based meat produce over the span of cultivation until harvest? What is in it and how will its disposal be managed? Who cleans up the “poop”?

Again, a great question, and again an area for research. Some people may have numbers here, but I don’t. That said, I know that the main waste metabolites are lactic acid and ammonia. Not sure what’s needed for disposal here, though I know they’re useful chemicals in their own way. I like thinking about the possibility of upcycling those waste products, but as with everything we’ll have to see in the real world what the feasibility of that looks like.
For all of these disposal questions, I think they are important issues for regulators to make decisions about — informed by people researching the relevant questions (not me, to be honest).

Are animal derived ingredients, including fetal bovine cells, in the production mix? What about the use of antibiotics in cell cultures to control growth of unwanted microbes? Will antibiotic resistant material remain in the growth media after protein extraction and removal and if so, how will it be dealt with? Will there be antibiotic residue in the final consumer product? And if so, will antibiotic free options be available?

I think this is a reference to fetal bovine serum (FBS)? I don’t know of anybody using fetal bovine cells. For FBS, the answer is no. I believe that JUST’s product they released in Singapore used FBS for production, but I also believe that they and others have since moved to serum-free culture systems. In our lab, we’re working on a serum free media that we just published as a preprint!
I have a Twitter thread about antibiotics here, so I won’t repeat it, but ultimately I would guess no; antibiotic resistant material is unlikely to make it into the product (or at least not in any way that is high as a result of the production process).
- First: I think it’s true that we can feasibly culture these cells at scale without antibiotics.
- Second: if any bacteria do grow, then it becomes really obvious really fast, and that batch would get a big ol’ bucket o bleach (or likely some other better cleaning method that’s just what I do in lab). I definitely envision that antibiotic free options will be available at whatever time-scale (if any) in which any products become truly available for meaningful consumption.

What are the types of molecular scaffolds that such products will be built on and will such ingredients be transparent to consumers? Will they be animal derived, GMO-derived/plant-based or plastic/synthetic? How will they influence the allergenicity of the final product if derived from common allergens such as soy, corn, crustaceans, fungi or insects? How will insect or crustacean derived scaffolding affect Kosher or halal certification?

Scaffolds currently being explored that I know of include:
- Polysaccharides like alginate (from seaweed)
- Chitosan (from mushrooms), mycelium (from mushrooms)
- Cellulose (from plants)
- Various proteins (from corn, soy, wheat, and maybe others?)
I seriously hope anything animal-derived is not included, as that would be antithetical to the aims of the field. Could somebody who doesn’t care about the motivation and just sees dollar signs try to make and sell something using animal-derived components? I guess it’s possible. I’d hope they wouldn’t succeed.
Other options are microbially-produced or bacterially-derived proteins (collagens, hyaluronic acid, others) that are naturally found in the body (though in both of those cases, not animal-derived). I think transparency about the materials would inherently come from ingredients lists, and other needed transparency would largely fall to regulation and policy.
Regarding allergenicity, I think it will depend on the material used. If someone is gluten intolerant and the scaffold is made of gluten (a wheat protein), then they would likely have a reaction,. So, I’d certainly expect regulators to require labeling.
If someone’s allergic to shellfish, I think that often has to do with the protein tropomyosin. So if chitosan is used that’s derived from shellfish rather than mushrooms (not ideal because of the whole animal-derived thing, but for the sake of argument), then I would expect no allergic reaction here, as it’s a totally different part of the animal. That said, you’d obviously want that hypothesis tested (and again I think it’s best to avoid because it’s animal-derived).

Will genetically engineered microorganisms, such as the yeast that produces the soy leghemoglobin (aka heme) used as the colorant and tasty, umami-rich flavor in Impossible® Burgers, have a role in the production process?

I personally expect so and hope so. They’re cool and useful and can make great things (I’m a big Impossible fan). For instance, those growth factors can be produced in engineered bacteria (or engineered plants, so not just microorganisms) and might be essential to make media cost-effective.

What other novel, unintended proteins or byproducts will be present in the finished product? Will these also need to be identified and labeled for consumer transparency?

Needs testing! I don’t have an answer here, but I think it’s an extremely important area of research and one that a lot of people in the field care about answering. The answer could be nothing or it could be something. Time and research will tell.

Will consumers or their family members with food sensitivities/allergies, autoimmune or inflammation issues , or otherwise afflicted with rheumatoid arthritis, Lyme disease or PANDAS be able to safely consume such products? Will there be independent, peer-reviewed, third party research to guide doctors or health care providers on this?

I don’t see any reason why not? No mechanism for this being bad for those people comes to mind (in fact, I think there’s opportunity to engineer cultured meat to have beneficial properties and have done some proof-of-concept research to that fact!). I do expect research to go into this, funded by government, foundations, etc., and yes, I expect it to be third party and peer reviewed.

What is the bioavailability and nutrient density compared to various techniques of animal-based agriculture, ranging from concentrated feedlot beef to Organic, Grassfed or Regenerative beef?

I’m really interested in this question, and would like to do research on it myself. My guess is that initially, bioavailability will be comparable, but nutrient density might be a bit different inherently. This could potentially be overcome at the start with fortification, or it could just be something that the field continues to work on.
I do not think that cultured meat will inherently be “molecularly identical” to conventional meat. For instance, unless you add vitamin B12, there won’t be any (since it’s produced by gut bacteria in cows, not by the cows themselves). On the flip side, there also won’t be trans-fats (also produced by gut bacteria). Lots of room to leverage molecular un-identity to the consumer’s benefit. For what it’s worth, different cuts of steak from different cows are not molecularly identical (and definitely not comparing across those animal ag regimes you mentioned), so I think it’s a bit of a weird goalpost, it’s all about whether it’s healthy.

Will the cell-based analogues be patented and subject to intellectual property protections? And will secrecy and knowledge hoarding enabled by patents and IP protections make these conversations around transparency a moot point?

What types of social equity are being built into the supply chains and organizational structures of cell-based agriculture companies? Who owns, governs and makes decisions? How many companies outside of Asia will have women, people of color and otherwise not cis-hetero white men in charge? What is the distribution and allocation of shares and profits in such companies? Are any pursuing B-Corp certification, open book management, true cost accounting or other progressive corporate models? How many such companies will consider employee ownership or becoming worker cooperatives? Will such companies embrace collective bargaining and unionization efforts, and greater worker input into the labor process and decision making?

Or perhaps the technology should be put into the public sector, especially if research is underwritten by public funds (like previous large scale tech endeavors such as the internet, cellular networks, and LCD technology) in order to ensure that it’s commercialization does not add to the critical levels of inequality, food apartheid, inaccessibility and precarity so common in the food industry. A public sector solution could ensure that all such information can be in the public domain, open sourced and accessible, with patents waived. While the technology intends to challenge the most egregious forms of animal-based agriculture, how will cell-based meat companies improve the living standards and well-being of blue-collar employees in their supply chain? Considering the competition, this should not be a high bar to overcome.

Responding to these last three a little differently since I think they’re outside the scope of me trying to answer field-specific and mostly technical questions. To some degree, though, I think they boil down to: will this technology be developed in a conscientious way and implemented fairly? How will the industry (or government) ensure that it is? I obviously can’t reasonably predict, and I don’t know enough to suggest, so I’ll instead amplify New Harvest (I’ve been biting my tongue about shouting out New Harvest, since I’m super biased there – I’m a research fellow funded by New Harvest – but I can’t bite it any longer. Conflicts of interest front and center: New Harvest is awesome). I also think Mike Selden is sincerely motivated by justice in the field, and that many other people in the field/companies/academia are, as well.

These are some of the many questions we should be asking about this new food technology as it enters the market. Transparency and openness, a clear understanding and mitigation of production externalities, plus justice and equity in business models will be signs that cell-based meat companies are a new breed of food tech. Meanwhile, ethical, meat-averse consumers still have healthy, delicious and compelling alternatives to both cell-based and CAFO meat. But we can hope to cultivate trust and accountability.

(Disclosure: The author is a Board Member of the Non-GMO Project, a non-profit organization that believes that everyone has a right to know what is in their food.)

Counter disclosure: I’m a big fan of GMO technology – sure, it’s a technology that can be misused (as can any technology), but it also has incredible potential, and I think flat out rejection of it is very short-sighted.

You can get in touch with Andrew Stout on Twitter.