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Animal Product Alternatives

  • Portfolio Area: Alternatives to Animal Products
  • Focus Area: Farm Animal Welfare
  • Portfolio Area: Other Scientific Research Areas
  • Focus Area: Scientific Research
  • Content Type: Cause Investigations
  • Content Type: Medium Investigations
  • Content Type: Research Reports

Table of Contents

    Published: December 13, 2015

    This is a writeup of a medium investigation, a brief look at an area that we use to decide how to prioritize further research.

    In a nutshell

    • What is the problem? More than eight billion land animals are raised for human consumption each year in factory farms in the U.S. alone. These animals are typically raised under conditions that are painful, stressful, and unsanitary. Chickens account for a large share of the animals affected. Currently, there are no alternatives to meat, dairy, or eggs that have succeeded in displacing a large fraction of the market for animal-based foods.
    • What are possible interventions? Successfully developing animal-free foods that are taste- and cost-competitive with animal-based foods might prevent much of this suffering. A for-profit investor could invest in companies developing plant-based alternatives to animal-based foods (such as Hampton Creek and Beyond Meat); cultured egg and dairy products (such as Clara Foods and Muufri); plant-based foods that use bioengineering to mimic the taste and texture of meat (such as Impossible Foods); or cultured meat products (such as Modern Meadow, though Modern Meadow is developing a novel, ‘meat-based’ product that is not a direct substitute for traditional meat). A philanthropic funder could support academic work aimed at developing cultured ground meat or meat with a more complex structure (such as steak or chicken breasts) in hopes of bringing the products closer to development and making them more attractive to profit-motivated investors. Our impression is that developing cultured egg whites will be substantially easier than developing ground meat, which (in turn) will be substantially easier than developing meat with complex structure (such as steak or chicken breasts). Based on cost analyses, comparisons with tissue engineering and biofuels, and discussion with scientists who have experience with cell cultures and tissue engineering, we currently see developing cost-competitive cultured muscle tissue products as extremely challenging, and we have been unable to find any concrete paths forward that seem likely to achieve that goal. We have not closely investigated the challenges associated with creating plant-based alternatives to animal products.
    • Who else is working on this? There are well-funded companies developing plant-based alternatives to animal-based foods. The largest potential gaps in this field seem to be for cultured meat and cultured eggs. There are no companies developing cultured meat as a replacement for animal-based foods (though Modern Meadow makes cultured leather and “steak chips”); this problem receives little attention from governments and philanthropy (we estimate < $6M in funding in the last 15 years), and much of the work is unlikely to be done by people in neighboring fields (such as tissue engineering). Because we do not see a concrete path that could lead to commercially viable cultured meat in the short term, we would guess that cultured meat is also a poor fit for profit-motivated investors. We are aware of only one company developing cultured egg whites (Clara Foods), and it has received approximately $1.7 million in funding.

    1. What is the problem?

    See our overview of factory farming for more detail.

    2. What are possible interventions?

    2.1 Overview and general issues

    It seems to us that if there were plant-based or cultured alternatives to meat and eggs that were cost- and taste-competitive with animal-based foods, it could greatly reduce the amount of meat and eggs produced, and thereby greatly reduce pain and suffering of animals produced for food.

    There are a variety of possible routes to developing high-quality alternatives to animal-based foods, including:

    • Plant-based alternatives that simulate the taste and function of animal-based ingredients. For example, Hampton Creek and Beyond Meat are companies working in this space (see below).
    • Fermentation (yeast-based production) of ingredients originally from animals using synthetic biology. For example, Clara Foods puts the genes coding for egg white proteins in chickens into yeast so that the yeast can produce the same proteins in fermentation processes.1 Muufri is taking a similar approach for milk.2
    • Various types of engineered muscle tissue (aka “cultured meat”). This approach involves growing muscle cells from animals in cell cultures, and forming the cells into tissues that can be eaten. Different versions of this approach include:
      • Millimeter-scale muscle strands grown in the lab, (hereafter “ground meat”) which are similar to muscle from an animal and might be used to replace ground meat. For example, Professor Mark Post is working on developing cheap animal-free cell culture media3 (i.e., liquids that provide the chemical environment and nutrients for animal cells to grow in the lab), incorporating separately-grown fat tissue into the ground meat product to improve the product’s taste,4 and working on overall manufacturing scale-up.5
      • Large whole pieces of cultured muscle tissue (hereafter “slab meat” in contrast with ground meat). For example, Amit Gefen, funded by Modern Agricultural Foundation, is exploring the feasibility of making a whole piece of chicken meat, such as a chicken breast.6 We have not investigated what technical strategies they are considering.
      • Novel meat-based products that would not directly substitute for conventional meat, such as Modern Meadow’s “steak chips.”7

    Our investigation focused on cultured meat and yeast-based production of egg whites, rather than other possibilities listed above, because:

    • There are a number of well-funded companies pursuing plant-based alternatives (see ‘Private companies’ under ‘Who else is working on this’?).
    • There are many more chickens producing eggs than there are cows producing milk,8 so we guessed that the “fermentation” work focusing on eggs would be more promising than the “fermentation” work focusing on milk.

    Within our investigation of cultured meat, we focused primarily on ground beef (rather than slab meat or ground chicken or pork) because:

    • Work on cultured ground beef seems to be more developed than work on cultured ground chicken or pork.9
    • The market for ground beef is much larger than the market for ground pork or chicken (more on this below).
    • Our understanding is that progress toward cultured ground beef would be relatively transferable to cultured meat from other animals. Mark Post suggested that work on ground meat is highly transferable between species, noting that he was able to transfer from mice to pork and from pork to beef in his lab in roughly six months in each case.10 Other researchers also reported that the same (or a similar) protocol for culturing muscle cells has worked for multiple species, including mice, rats, and chickens.11
    • Apart from an ongoing feasibility study by Amit Gefen (see above), we are not aware of anyone trying to make cultured slab meat. Moreover, we would guess that progress on ground meat would also help with developing slab meat because some of the challenges are shared (e.g., finding a low-cost, animal-free media to feed the cell culture).

    We found limited evidence on the question of whether the public would buy cultured animal products and did not pursue the issue further.

    2.2 Cultured ground meat

    2.2.1 Potential impact of taste- and cost-competitive cultured meat

    In 2014, ground beef accounted for 43.3% of total beef sales,12 but for other animals, ground meat accounted for a much smaller portion of the total meat market. For example:

    • Chicken breasts made up 56% of the market for chicken in the U.S. in 2014, and ground chicken only claimed 1% of the market.13
    • Ground lamb was only 6.2% of the market for lamb in 2014.14
    • Ground pork was only 1.9% of the market for pork in 2014.15

    We would therefore guess that the market for a cultured ground beef product would be much larger than the market for a cultured ground chicken/pork product.

    It is possible that displacing a large fraction of the markets for these other types of meat (such as chicken) would require developing cultured slab meat. If so, that would make the value of successfully developing cultured slab meat much greater than the value of successfully developing cultured ground meat because a very large fraction of all land-based farm animals are chickens.16

    2.2.2 What is the state of the art for making cultured meat?

    Our understanding is that Mark Post’s cultured beef hamburger represents the state of the art for cultured meat.17 The main steps in his process are as follows:18

    1. Extraction of satellite cells, which are skeletal muscle stem cells, from a muscle sample of an animal taken using a needle biopsy.19
    2. Proliferation phase to grow large numbers of cells from an initial batch by encouraging the cells to divide, producing copies of themselves.20
    3. Differentiation of the muscle precursor cells into mature muscle cells. Growing or “conditioning” the cells in the right mechanical environments (attached to scaffold) that allow them to “get exercise” by contracting against structures that offer resistance. The muscle cell contraction boosts protein production in the cells and increases their size.21
    4. Harvesting the muscle strands and combining them with color, flavor and texture enhancers, such as separately grown fat tissue.22

    As discussed above, our understanding is that the process for making cultured ground meat from other species is/would be similar.

    The process for making the “steak chips” that Modern Meadow is pursuing similarly begins with harvesting and growing muscle cells, however the final steps to process the product are different. The first step is a biopsy to harvest muscle cells from a cow and then create large quantities from that sample by growing them in the lab and allowing them to divide and produce more cells like themselves. After growing the cells, the next step is to harvest them by separating the cells from the liquid they are grown in (cell culture media). The final step is to combine the cells with pectin and flavorings (e.g., teriyaki or BBQ) and use a food dehydrator to make them into chips.23 We would guess that the technical challenges involved with making the steak chips are probably simpler than the challenges involved with making ground meat because making ground meat still involves making small chunks of tissue, whereas steak chips could conceivably be made without establishing much (if any) tissue structure. However the manufacturing scale-up challenges associated with cost-effectively producing a large number of cells still remain.24

    Methods for making slab meat are currently unknown.25 Here it would seem important not only to have a process for growing and flavoring cells, but also to have a way of generating the (potentially complex) three-dimensional structure associated with non-ground meat.

    2.2.3 Interventions to reduce cost and scale-up production of ground meat

    In 2013 it was reported to have cost Mark Post $325,000 to make a single hamburger with cultured ground beef in a university research lab.26 We do not have a detailed understanding of the costs for Mark Post’s prototype. However, major sources of cost for large-scale manufacturing in tissue engineering include the cost of cell culture media, facilities, maintaining sterile conditions in the facilities, and skilled labor.27 Obstacles to decreasing costs include lack of knowledge of how to make cheap animal-free media (researchers don’t know what ingredients would work), how to cheaply and efficiently grow muscle cells on scaffolding, and how to harvest and process this cultured tissue at massive scales. Researchers also don’t know how to grow cells quickly in culture – academic scientists have estimated one month to grow one batch of meat in a bioreactor.28 Longer production times increase the cost of production and increase the risk that any given batch is contaminated.29

    In order to decrease the cost, a funder could support lab work aimed at:

    • Cheap animal-free media that supports muscle cell growth. Cell culture medium is the liquid that provides the chemical environment and nutrients needed for animal cells to grow in the lab – it is the liquid surrounding the cells in the Petri dish. Standard cell culture media for muscle cells contains fetal bovine serum (extracted from the blood of cow fetuses), which is not suitable for cultured meat production focused on reducing animal agriculture because it is likely that one or more cow fetuses would be required to make 1 kg of meat.30 Currently there are commercial animal-free media formulations that do not contain fetal bovine serum, but we’ve been told these are expensive and may not encourage high growth rates of muscle cells because current animal-free media formulations have not been optimized for cultured meat production. Hence, finding a cheap animal-free liquid medium to grow the cells in is essential to making cultured meat commercially viable.31 Developing a cheap animal-free medium would likely involve guided trial and error of many combinations of potential ingredients that could support good muscle cell differentiation and growth.32
    • Established cell lines. When doing research experiments to improve cultured meat development, a researcher must have animal cells to work with. If each researcher uses cells harvested from a different animal, it may be difficult to get reproducible and comparable results across multiple labs, slowing progress in the field because it is harder for separate researchers to build on each other’s work. An “established cell line” is a standard lineage of cells that are capable of proliferating indefinitely (whereas normal mammalian cells can only divide a limited number of times).33 While established stem cell lines exist for humans and mice, they do not exist for agricultural animals such as cows and chickens. Nicholas Genovese is currently working on this. Established cell lines may also be used to form the starting material for manufacturing-level production, reducing the need to continually harvest from animals.34
    • Efficient scaffolding designs for ground meat. To develop tissue structure and protein production similar to that of muscles in an animal, muscle cells grown in the lab need to grow on structures (aka “scaffolds”) that mimic the mechanical environment they would experience in an animal. Currently there are at least two main approaches for scaffolding for ground meat or processed meat products: growing tissue in thin sheets (e.g., Modern Meadow) or growing cells and tissues on scaffolds (e.g., velcro) in lab-scale dishes and bioreactors (e.g., Mark Post).35 We do not have a detailed understanding of the imperfections of current approaches to scaffolding, but a number of people we spoke with suggested that improved scaffolding could reduce the costs of producing cultured meat,36 and some people working in the stem cell industry have reported that optimizing scaffolding design made their process substantially more efficient (although we have not closely examined this claim).37 Developing improved scaffolding might involve varying the shapes and sizes of scaffolds and/or the scaffolding materials used, and testing which most improve cell culture growth rates (without introducing other issues).
    • Developing efficient methods of harvesting and assembling a large number of muscle cells from the scaffold/bioreactor into the final meat product; e.g., perhaps design scaffolding that dissolves or is edible and can be incorporated into part of the product. We are not aware of any existing process for this and have a limited understanding of what challenges might be involved.
    • Methods to maintain sterility at lower cost. Preventing or minimizing microbial contamination is important because other organisms like bacteria grow faster than mammalian cells and could quickly consume a bioreactor, ruining an expensive batch of muscle cells. Maintaining sterile manufacturing conditions is expensive because expensive fans and filters are needed to keep contaminants out.38 The current tissue engineering industry is already able to create sterile conditions, however maintaining sterility contributes significantly to the high cost of production.39 We have a limited understanding of potential methods for reducing these costs.
    • Optimization of bioreactor operating conditions. Cells are grown in vessels called “bioreactors,” which control temperature, replenishment, and circulation of the cell culture media, oxygenation, and other conditions that promote cell growth. According to Mark Post, cultured meat has only been grown in small bioreactors (~5L) so far, but will need to be grown in much larger bioreactors if production will be scaled up (~25,000L). Bioreactors will need to be optimized for this larger scale of production.40 Industrial scale-up is a non-trivial engineering challenge requiring significant resources, because the systems are expensive to build and test. However, the biotech and tissue engineering industry are currently working on bioreactor designs and scale-up that may be relatively transferrable to cultured meat production. Our understanding is that scaling-up is one of the most common modes of failure in industries such as synthetic biology which also involve large scale bioreactors.41 Our understanding is that this work would involve designing new bioreactors and testing them for improvements in metrics like cell growth rates and contamination rates.42

    2.2.4 Issues associated with taste and consumer acceptance

    People who tasted Mark Post’s burger said it tasted “close to meat,” but that it was “not that juicy,” had a somewhat unusual texture, and that the lack of fat was noticeable.43 In addition, cultured meat is currently missing some cell types and chemicals found in conventional meat, including blood and connective tissue.44 We would guess that it may be necessary to find the appropriate ratios and arrangements of these ingredients in order to replicate the texture and flavor of natural meat.

    Potential paths to improving the taste and texture of cultured meat include:

    • Trying different scaffold designs and media formulations, and testing the taste and texture of the results.
    • Culturing fat cells and experimenting with incorporating them into the meat. Mark Post is currently working to improve the quality of the cultured meat by adding fat into the burger.45
    • Adding flavor enhancers, an approach which is likely already widespread in both ground and whole slab conventional meat production as evidenced by the USDA regulations on labeling of flavor enhancers in meat and poultry.46

    Other approaches (which we have considered less and may be more speculative and challenging) include:47

    • Experimenting with different ratios and arrangements of connective tissue (e.g., fat, collagen), muscle cells, and blood.

    2.2.5 Possible approaches that are not, to our knowledge, being pursued within cultured meat research

    We are not aware of anyone pursuing the following approaches to cultured meat:

    • Hybrid plant-based and animal-cell-based approaches: These approaches would involve mixing plant-based and animal-cell-based food, and could potentially offer both better flavor/texture than pure plant-based approaches and lower cost than pure animal-based approaches. Plant-based approaches (e.g., Hampton Creek for egg products) are typically significantly cheaper than animal-based food products; however, the challenge has been in producing a plant-based product that tastes like it came from an animal.48 Developers could explore the minimum amount of animal-based product needed to provide a realistic meat-like flavor and texture, when combined with plant-based ingredients.
    • GMO approaches for cultured meat. Mark Post and Modern Meadow are not pursuing genetically modified approaches to cultured meat.49 According to Mark Post, his decision on this is driven by concerns about lower market adoption.50 However, we would guess that allowing genetic modifications of the muscle cells could help make manufacturing scale-up of cell culture more efficient, as it has in synthetic biological fermentation. For example, we would guess that GMO muscle cells might be made to reproduce faster, significantly reducing manufacturing times (and thus costs).

    2.2.6 Will it be possible to make cultured meat cost-competitive with conventional meat?

    Some estimates of the possible future costs of cultured meat are below:

    ESTIMATE BY: COST OF CULTURED MEAT (USD) ASSUMED MANUFACTURING VOLUME YEAR
    Vandenburgh $5M / kg51 Small-scale production in laboratories52 200453
    Exmoor €3300 – 3500 / tonne

    (€3.3 – 3.5 / kg)

    Scaled-up to large volume 2008
    Van der Weele and Tramper €391 / kg assuming typical media cost of €50,000 / m³. One estimate of the lowest possible cost of media is €1,000 per m³, but we do not know what this estimate is based on. Plugging this assumption into Van der Weele’s model would imply that €8 of media is needed for 1 kg of meat.54 Scaled-up to large volume55 2014

     

    The Exmoor estimate seems very optimistic to us. For example it assumed $0 cost for growth factors in media,56 but it could be one of the more expensive components.57 Note that the cost of production of beef at the time was ~€3600/tonne. 58 The study notes that cell culture media cost €7000-8000/tonne, and needed to reach < €350/ tonne for commercial viability.59 Isha Datar, now the Executive Director of New Harvest, said this estimate was preliminary and “could be largely inaccurate.”60

    We are highly uncertain about the eventual cost per kg of cultured meat, and have not closely examined the above cost estimates. However, none of these estimates suggest a cost competitive with that of conventional meat.

    The Van der Weele and Tramper estimate is based on back of the envelope calculations by academic researchers. They argue that even if we reduce the price of animal-free medium to what they believe is its lowest possible cost—€1 per liter—it will be insufficient to make cultured meat cost-competitive with conventional meat.61 Van de Weele and Tramper do not explain why €1/L is the lowest possible cost of animal-free medium, but their claim that a cost of less than €1/L is required seems correct to us because meat costs a few dollars per pound, and we would guess that a minimum of a few liters of serum-free media would be required to produce 1 kg of meat.

    For reasons explained below, it seems to us that it will be extremely challenging to get the cost of animal-free media this low. Currently, a major cost of animal-free media is the cytokines (cell-signaling molecules) that encourage cell proliferation.62 Two approaches to reducing the cost of cytokines include:

    • Trying to find small molecule replacements for cytokines. While inexpensive small molecule replacements for some cytokines have been discovered, we were told that it has proven challenging to find replacements for others, and we would need to replace all the expensive cytokines used in order to get costs below €1/L. We are not aware of how many cytokines would need to be replaced, but would guess that manufacturers of animal-free media could answer this question.
    • Trying to culture genetically engineered yeast cells (or other host organisms) to produce cytokines through fermentation. We have a limited understanding of this approach.

    Steve Oh, a scientist who has worked on decreasing the cost of animal-free media, told us that it would be extremely challenging to get the cost of animal-free media below ~€1/L through either of these approaches.63 Even if the cytokines could be produced at zero cost, we would guess that that would not suffice to bring the cost of animal-free media below €1/L because, as of 2006, “basal medium,” a sort of medium without cytokines, still cost $1-4/L.64 We have not closely investigated the feasibility of decreasing the cost of the basal medium, but it may be challenging because many of its ingredients sound like commodities (based on a first-glance review of the list of major ingredients).65

    2.2.7 How long will it be before it is possible to make cultured meat cost- and taste-competitive with conventional meat?

    We have seen only a couple of informed estimates of how long it might take to make cultured meat cost- and taste-competitive with conventional meat. Mark Post estimated 7-10 years,66 and a scientist in the tissue engineering field said that cost-competitive cultured meat would be very unlikely to be available in the next 10-15 years, absent a major technological breakthrough.67 We have a very limited understanding of what these estimates are based on.

    We are highly uncertain on this topic because we believe there is essentially no industrial data around cost of scaling up cell production to these levels. Many non-trivial unknowns may exist associated with a new endeavor like this, making it very challenging to accurately predict the costs. For example, synthetic biology company Amyris (described more below) took longer to scale up biofuel production than anticipated.68

    One way to consider likely future cost reductions is to compare cultured meat with progress in the closest industry analogues we’ve been able to identify in tissue engineering and synthetic biology:

    • Organogenesis (a tissue engineering company) was founded in 1985 and had its first skin graft product, Apligraf, approved in 1998.69 Their product, Apligraf, is a wound care patch (75 mm diameter circular disc that is 0.75 mm thick), is functionally similar to skin, and is used to cover wounds and speed up the healing process in patients with certain leg and foot ulcers.70 Manufacturing Apligraf is similar to manufacturing cultured meat because it involves culturing multiple cell types and combining them with collagen and other chemicals into a tissue substitute.71 Unlike cultured meat, there is much lower cost pressure on medical products, and Apligraf had to pass FDA regulatory approval. We have a limited understanding of the state of their program in 1985, but it was early-stage academic research, and the early years of the company were heavily research-based.72 The product volume required for that product is much lower than for meat (making for a less challenging scale-up problem) and the cost pressure is much lower (they can charge a premium for high-value medical product, rather than competing with a commodity like conventional meat). Since then, they have further reduced the real cost of their skin grafts by roughly a factor of three.73 Based on rough back of the envelope calculations, we would guess that the manufacturing cost of Apligraf is on the order $90,000/kg.74
    • The synthetic biofuel company Amyris was founded in 200375 and started fuel production in Dec 2012.76 We would guess that at founding, Amyris was mainly based on early stage academic work and had done little work in manufacturing scale-up.77 Moreover, we would guess that biofuel may be a simpler product than cultured meat because the final product, a liquid biofuel, does not require cells or three-dimensional tissues.78 Despite $700M investment in the company, Amyris has not been able to compete on cost with conventional fuels.79

    Judging on the basis of the above two examples, the challenges involved in dramatically reducing the cost of animal-free media, and our holistic assessment of the challenges involved in reducing the cost of cultured meat, discussion with scientists who have experience with cell cultures and tissue engineering, we currently see developing cost-competitive cultured meat products as extremely challenging, and we have been unable to find any concrete paths forward that seem likely to achieve that goal.

    2.3 Cultured slab meat

    We investigated cultured slab meat less closely because it seems more challenging and we are not aware of anyone who is working on it now, except for a group doing a feasibility study on chicken (see below).

    Slab meat poses additional challenges because it would likely require cell cultures with multiple types of tissues that grow in appropriate complex formations.80 In addition to the interventions listed above—which would largely help with the development of cultured slab meat as well—a philanthropist interested in accelerating the development of cultured slab meat could support:

    • The development of scaffold/bioreactor designs able to feed and support thick three-dimensional structures of cells. Thicker multi-layer tissue structures may require vascular systems to deliver nutrients deep within the tissue.81
    • Feasibility analysis of slab meat, e.g., as Amit Gefen is doing for chicken.
    • There may also be approaches involving self-assembly and 3D-printing, however we have not closely considered these possibilities and would guess that they would be difficult to implement in the near future.82

    We would guess that developing cost-competitive cultured slab meat is a challenge in the same rough ballpark of difficulty as developing transplant organs in vitro because both would likely require growing large, complex, multi-layered 3D structures and vascular systems. We would guess that cultured slab meat would be technically easier to achieve without cost constraints (since it would not be necessary to fully replicate as many natural functions), but also that price pressure on in vitro organs would be much lower.

    2.4 Cultured egg whites

    2.4.1 Potential impact of taste- and cost-competitive cultured egg whites

    In 1996, approximately 12% of the total eggs produced in the U.S. went towards making processed egg whites,83 out of the 65 billion eggs produced in the U.S. overall.84 In 2014, the number of eggs produced in the U.S. had risen to 100 billion.85 We would guess that the development of cultured egg whites that were cost- and taste-competitive with traditional egg whites would significantly reduce the amount of eggs produced.

    2.4.2 What methodology is currently used to make cultured egg whites?

    We are only aware of one company developing cultured egg whites: Clara Foods. Clara Foods is a biotechnology company founded in 2015 working on developing cultured egg whites. It is still in development stages. Its process involves:

    • Putting genes for chicken egg white proteins into yeast cells using genetic engineering techniques.
    • Growing the yeast cells that produce the egg white proteins in a fermentation process.
    • Letting the yeast produce the egg white proteins.
    • Separating the egg white proteins from the yeast through a purification process.86

    Clara Foods is working on protein purification methods to efficiently extract the egg white proteins from the “soup” of yeast fermentation.87 Their founders have created a prototype to demonstrate that only a subset of egg white proteins are needed to functionally substitute for egg whites. To make the prototype, they extracted a subset of proteins from real egg whites and showed that it was possible to make meringues using this subset of proteins. All of these steps are aimed at making the cultured egg whites cost competitive with conventional egg whites.88

    2.4.3 Will it be possible to make cultured egg whites cost-competitive with conventional egg whites?

    Our understanding is that the main hurdle for cultured egg whites is in achieving scaled-up manufacturing that is cost-competitive with conventionally farmed eggs. We would guess that it will be significantly easier to meet this challenge with cultured egg whites than with cultured meat because:

    • Cultured egg white protein production is more similar to already demonstrated industrial biotech processes (e.g., synthetic patchouli).89
    • Rather than producing tissues (which are arrangements of entire cells), producing egg whites likely only requires manufacturing a small number of proteins (which is much simpler).90

    2.5 Plant based alternatives

    We did not closely investigate this topic because our impression is that work in this area is well-funded. See below.

    3. Who else is working on this?

    3.1 Private companies

    Key Companies Developing Alternatives to Animal-Based Foods

    COMPANY PRODUCTS IN DEVELOPMENT CELLS / GENES FROM ANIMALS? MAINLY PLANT BASED DIRECT SUBSTITUTE FOR CONVENTIONAL ANIMAL PRODUCTS FUNDING
    Modern Meadow Leather, possibly steak chips91 Yes (cells)92 No No $10.4M93
    Breakout Labs,94 ARTIS Ventures, Francoise Marga, Healthy Ventures, Horizons Ventures, Interplay Ventures (Partner: Mark Peter Davis), Karoly Jakab, Iconiq Capital, Sequoia Capital95
    Clara Foods Egg white produced by yeast via synthetic biology96 Yes (genes)97 No98 Yes99 $1.7M100
    David Friedberg, Gary Hirshberg, Ali and Hadi Partovi, Scott Banister, SOSventures101
    Impossible Foods Plant-based meat and cheese alternatives using bioengineering techniques to combine select plant proteins and molecules to replicate the experience of animal-based foods.102 No Yes103 Yes104 $183M
    Bill Gates, Horizons Ventures, Jung-Ju (Jay) Kim, Khosla Ventures, UBS, Viking Global Investors105
    Beyond Meat Extruded plant-based chicken substitute106 No107 Yes108 Yes109 Undisclosed amount, completed Series D in 2014.
    Bill Gates, DNS Capital, Kleiner Perkins Caulfield & Byers, Obvious Ventures, S2G Ventures110
    Muufri Milk produced by yeast via synthetic biology111 Yes (genes)112 Some plant-based fats113 Yes114 $2M + $30k
    SOS Ventures, Horizon Ventures115
    Hampton Creek Plant-based versions of products containing eggs, such as mayonnaise, cookie dough, scrambled egg mixture (in development)116 No117 Yes118 Yes119 $120M
    Ali and Hadi Partovi, Ash Patel, Brian Meehan, OS Fund, Collaborative Fund, Demis Hassabis, Eduardo Saverin, Far East Organization, Founders Fund, Horizon Ventures, Jean Piggozzi, Jerry Yang, AME Cloud Ventures, Jessica Powell, Kat Taylor, Khosla Ventures, Marc Benioff, Mustafa Suleyman, Scott Bannister, Tao Capital Parters, Tom Steyers’ Eagle Cliff, Uni-President Enterprises Corporation, Velos Partners, WP Global Partners120, Bill Gates 121

    3.2 Academic researchers and non-profit organizations

    Key Academic Groups Developing Alternatives to Animal-based Foods

    RESEARCHER WORK APPROACH DEVELOPING MEAT/EGG ALTERNATIVE?
    Mark Post Cheaper animal-free cell culture media, adding fat to cultured meat to improve taste122 Cultured animal tissue123 Yes124
    Nicholas Genovese Establishing new lab in stem cell biology for meat production125 Developing stem cell lineages for cultured meat126 Yes127
    Amit Gefen Feasibility study on making whole cultured chicken meat Cultured animal tissue128 Feasibility study129

    3.3 Potential gaps in the field

    Plant-based alternatives appear relatively well-funded (see ‘Key Companies Developing Alternatives to Animal-Based Foods’).

    We see cultured meat and cultured eggs as the largest potential gaps in the field. To our knowledge, Clara Foods is the only organization working on a cultured egg product (egg whites specifically), and it has received about $1.7M in funding since they were founded in 2015 (see ‘Key Companies Developing Alternatives to Animal-Based Foods’).

    Cultured meat also receives a limited amount of funding (we estimate <$6M over the last 15 years),130 though it has a longer history and a larger number of people involved. We discuss it in more detail in the following section.

    3.4 Cultured meat

    3.4.1 Current activity

    We are aware of only one company working on cultured meat today: Modern Meadow. As noted in the table ‘Key Companies Developing Alternatives to Animal-Based Foods’, they are currently focused on leather and possibly steak chips, which would not translate immediately into alternatives to meat. However, we would guess that there could be substantial overlap in research and development pathways (such as developing less expensive animal-free media, finding low-cost methods of maintaining sterility, and optimizing bioreactor operating conditions) but perhaps less overlap related to scaffolding.

    There are a few academic groups worldwide working on cultured meat,131 but our understanding is that very limited grant funding is available for cultured meat132 and others we spoke with suggested that the work is considered fringe by the academic community.133 Mark Post has talked about how his family was disappointed when he switched his research to cultured meat.134 Among the limited amount of work on cultured meat, beef is receiving more attention than chicken or pork as seen in the tables ‘Key Companies Developing Alternatives to Animal-Based Foods’ and ‘Key Academic Groups Developing Alternatives to Animal-based Foods’.

    New Harvest is a small non-profit that makes seed grants to entrepreneurs and academics working on cultured animal products.135 In 2013, their annual expenditures were about $60,000.136

    Mark Post plans to start a company focused on commercial production of cultured meat, in hopes of replacing conventional ground beef.137

    3.4.2 Past activity

    There has been work on cultured meat at least since Willem van Eelen began promoting research efforts in the late 90s.138. Other past projects include:

    • In 2002, NASA funded Prof. Morris Benjaminson of Touro College to culture goldfish muscle tissue.139 This was very preliminary work – he took samples from animals and showed that their size increased after growing in a dish, in order to investigate the potential of culturing meat for human consumption in space.140
    • As an art project in 2003, Oron Catts cultured frog muscle cells into a small “steak” which was eaten in public (four of eight tasters spat it out).141
    • Vladimir Mironov performed research on cultured meat (although his U.S. lab closed) and collaborated with Nicholas Genovese who is continuing work on cultured meat.142
    • Mark Post began work on cultured meat in 2008. His work stems academically from early cultured meat proponent Willem van Eelen.143
    • In 2010, a startup company called Mokshagundum Biotechnologies was interested in making genetically modified meat by harnessing tumor-growth-promoting gene, but we found no record of this company since then.144
    • In 2013, Singularity University produced a startup team called LifeStock aimed at producing animal-free meat, specifically focused on the scaffolding component.145 However, we have not found recent activity (2014 and onwards) mentioning LifeStock, and the website listed on their Facebook page does not appear to be active.146

    There have been at least four symposia/workshops on cultured meat since 2008:

    • The first cultured meat symposium was held in 2008 in Norway.147
    • In 2011, there was a workshop by the European Science Foundation held in Gothenburg, Sweden, with 25 attendees.148
    • In 2012, a panel on tissue engineered nutrition was held at the TERMIS (Tissue Engineering and Regenerative Medicine Int’l Society) conference in Vienna.149
    • In May 2015, New Harvest and the IndieBio accelerator hosted an event in San Francisco called “Edible Bioeconomy”, convening those involved with the development and promotion of animal product alternatives.150
    • There is also a symposium planned for the fall of 2015, the “First International Symposium on Cultured Meat”, focused on discussing tissue engineering for cultured meat, which is organized in association with Maastricht University and New Harvest.151

    3.4.3 Related work in tissue engineering

    Over $4.5B of capital investment went toward tissue engineering efforts worldwide between 1990 and 2002, and over 90% of the investment came from the private sector.152 Tissue engineering efforts focus on many of the same challenges facing cultured meat: developing scaffolds,153 scale-up, and tools to accelerate the research.154 However, we would guess that some of the challenges associated with making cultured meat cost- and taste-competitive with cultured meat are unlikely to be addressed by people working in tissue engineering unless they are done specifically for manufacturing cultured meat. Two such examples include:

    • Creating extremely low-cost animal-free media: Tissue engineers in the medical field already have incentives to use animal-free media because it improves reproducibility.155 Our understanding is that cell media is a significant cost for tissue engineering companies,156 but because the prices of tissue engineering products are much higher than the price of meat,157 we would guess that tissue engineering companies may not be incentivized to lower costs of animal-free media to the levels that would be required for cultured meat to be commercially viable.
    • Scaling up production of cultured meat to vast quantities: The volume of tissue production required for biomedical applications (such as skin grafts and organ replacements) is significantly lower than the volume required for meat.158 We would therefore guess that they will not need to develop as large-scale production facilities as may be required for mass-produced cultured meat in the near future.

    3.4.4 Availability of funding from for-profit investors

    Our impression is that venture capitalists generally seek investments that could provide a significant return within several years.159 However, as discussed under above, we would guess that it will take longer than that for cultured meat to become cost- and taste-competitive with natural meat. One potential goal of philanthropic funding would be to allow work to progress without expectations of a near-term return on investment in hopes of de-risking cultured meat to the point where a profit-motivated investor would be willing to finance further development.

    4. Our process

    We initially decided to investigate the cause of alternatives to animal-based foods because:

    • We believe that, for someone who cares about the welfare of farm animals, the treatment of animals in industrial agriculture is an extremely important problem. For more detail, see our overview of industrial animal agriculture.
    • It seems to us that if there were plant-based or cultured alternatives to meat and eggs that were cost- and taste-competitive with animal-based foods, it could greatly reduce the amount of meat and eggs produced, and thereby greatly reduce pain and suffering of animals in industrial agriculture.
    • The area seemed unlikely to get financial support from traditional sources that support research and development in the life sciences.

    We spoke with 8 individuals with knowledge of the field, including:

    • Isha Datar, Executive Director, New Harvest
    • Mark Post, Professor of Vascular Physiology and Chair of Physiology, Maastricht University
    • A scientist with 18 years experience in the tissue engineering industry
    • Five individuals who spoke with us off-the-record.

    In addition to these conversations, we also reviewed documents that were shared with us and had some additional informal conversations.

    Nick Beckstead wrote this page in consultation with an Open Philanthropy Project scientific advisor who has experience with cell cultures and biotechnology.

    5. Questions for further investigation

    We have not deeply explored this field, and many important questions remain unanswered by our investigation.

    Among other topics, our further research on this cause might address:

    • How quickly and in what directions are commercial and academic tissue engineering advancing? How transferable might this work be to cultured meat?
    • If funded, what is the potential impact of additional academic research in cultured meat?
    • Is it possible to make a realistic cost model in which cultured meat/egg products are cost-competitive with traditional meat/eggs? What advances would be needed to put such a model into practice?
    • How long will it take to develop cost- and taste-competitive cultured meat/eggs?
    • How could additional funding advance the development of cultured egg whites?
    • What could be done to advance the development of cultured slab meat? How much more challenging would it be to develop cultured slab meat in comparison with cultured ground meat?
    • Would the public buy cultured animal products?

    6. Sources

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    Angel.co company profile, Muufri Source (archive)
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    Apligraf Medicare Product and Related Procedure Payment, 2015 Source (archive)
    Apligraf website, What is Apligraf Source (archive)
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    Biofuels Digest 2011, Amyris opens first commercial facility Source (archive)
    Bloomberg 2013, Modern Meadow Makes Leather and Meat Without Killing Animals Source (archive)
    Breakout Labs portfolio company page, Modern Meadow Source (archive)
    BusinessWire 2013, Beyond Meat Completes Largest Financing Round to Date Source (archive)
    Category share of beef sales in the United States in 2014, by cut type Source (archive)
    Category share of chicken sales in the United States in 2014, by cut type Source (archive)
    CBInsights company profile, Modern Meadow Source (archive)
    CNN 2009, Lab meat Source (archive)
    Crunchbase company profile, Hampton Creek Source (archive)
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    Danoviz and Yablonka-Reuveni 2012, Skeletal Muscle Satellite Cells: Background and Methods for Isolation and Analysis in a Primary Culture System Source (archive)
    Datar and Betti 2010, Possibilities for an in vitro meat production system Source (archive)
    DFJ Portfolio Source (archive)
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    Economist 2011. Global Livestock Counts Source (archive)
    Edelman et al. 2004, In vitro cultured meat production Source (archive)
    Exmoor In Vitro Meat Consortium Preliminary Economics Study, March 2008 Source (archive)
    Fast Company 2012, THE RISE AND FALL OF THE COMPANY THAT WAS GOING TO HAVE US ALL USING BIOFUELS Source (archive)
    Fastcoexist 2013, Lifestock: The Newest Player In The Growing Lab-Made-Meat Industry Source (archive)
    First International Symposium on Cultured Meat, 2015 Source (archive)
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    FoodProcessing.Com.Au 2015, Producing Egg Whites Without Chickens Source (archive)
    Forbes 2014, Bill Gates-Backed Food Startup Hampton Creek Source
    Forbes 2014, Yum! Petri-Dish Beef Is like “Jerky Melting in Your Mouth” Source
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    Genetic Engineering & Biotechnology News 2015, Biopharma Demand Is Driving the Cell Culture Market Source (archive)
    GiveWell’s non-verbatim summary of a conversation with a scientist with 18 years experience in the tissue engineering industry, April 23, 2015 Source
    GiveWell’s non-verbatim summary of a conversation with Isha Datar, March 10, 2015 and July 24, 2015 Source
    GiveWell’s non-verbatim summary of a conversation with Mark Post, March 24, 2015 Source
    GiveWell’s non-verbatim summary of a conversation with Steve Oh, October 7, 2015 Source
    Gizomodo 2011, The first lab-grown hamburger will cost $345,000 Source (archive)
    Guardian 2012, Fake meat Source (archive)
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    Hunsberger et al. 2015, Manufacturing Road Map for Tissue Engineering and Regenerative Medicine Technologies Source (archive)
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    Jochems et al., The use of fetal bovine serum: ethical or scientific problem? Source (archive)
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    New Harvest 2014, World’s First In Vitro Meat Symposium Source (archive)
    New Harvest 2015, Edible Bioeconomy Event–Recap Source (archive)
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    Post 2012, Cultured meat from stem cells Source (archive)
    Post 2014, An alternative animal protein source: cultured beef Source (archive)
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    Q+A with Modern Meadow CEO, Andras Forgacs Source (archive)
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    The CrunchBase pages we archived are covered under the Creative Commons license.

    Expand Footnotes Collapse Footnotes

    1.“From the onset, Clara was founded on a fundamental belief that we can cultivate a better and safer food system using technology,” said CEO Arturo Elizondo. The start-up describes the process of creating the animal-free egg white as being “similar to brewing beer or wine. However, instead of using yeast to convert sugar into alcohol, our yeast is specialised to convert chicken DNA into egg white proteins.” @FoodProcessing.Com.Au 2015, Producing Egg Whites Without Chickens@.

    2.“Biohackers Ryan Pandya and Perumal Gandhi are working on crafting a plant-based concoction that’s nearly identical in makeup to what’s found in grocery milk.

    To achieve this, they’ve gone so far as modifying sunflower oil so that it can take on a structural composition similar to milk fats, substituted lactose with galactose, a nearly indistinguishable sugar, and culturing yeast to release casein, a natural animal milk protein. If successful, the process they’ve developed could someday be used to churn out a wide range of dairy products, such as cheese, butter and yogurt.

    The duo, both with bioengineering backgrounds, are the co-founders of Muufri, a San Francisco-based start-up that hopes to fashion the idea of lab-brewed milk as a more humane alternative for consumers.” @Washington Post 2014, Man-made cow’s milk@.

    3.“The team is attempting to change the culture conditions in the lab to remove all animal products, most significantly fetal bovine serum (FBS). Developing an animal-free medium is very challenging because skeletal muscle and satellite cells are particularly dependent on serum.” @GiveWell’s non-verbatim summary of a conversation with Mark Post, March 24, 2015@.

    4.“The team is working to enhance the quality of cultured meat, at a small-scale level of production, in two ways:

    • Achieving an optimal protein content level by changing the culture and feeding conditions
    • Adding fat tissue to the product which would be added to the skeletal muscle tissue to create a true meat ‘mimic’ ”

    @GiveWell’s non-verbatim summary of a conversation with Mark Post, March 24, 2015@.

    5.“To begin to make its meat product commercially viable, Professor Post’s team hopes to scale production to the capacity of a 25,000-liter bioreactor.” @GiveWell’s non-verbatim summary of a conversation with Mark Post, March 24, 2015@.

    6.“The Modern Agriculture Foundation – a nonprofit organization founded in early 2014 in Israel – is launching a world-wide pioneering project in the study field of cultured meat, focused exclusively on chicken meat. The project will start on January 2015 headed by Professor Amit Gefen from Tel Aviv University, one of the world’s leading experts in Tissue Engineering.

    The project team will be conducting a feasibility study for the production of cultured chicken breast meat that will be published and shared with the general public. During the course of the project, the challenges of production of cultured chicken breast meat will be mapped and potential solutions, along with the implications of their realization (methodology, time and cost), will be examined and described.” @Modern Agriculture Foundation Press Release, Jan 2015@.

    7.“But you’ve also been making batches of snacks you are calling ‘steak chips’ made from cow muscle cells, with flavors like teriyaki and shiitake mushroom. You didn’t bring any. When will they be ready?

    We’re doing private tastings but are still are refining the recipe and developing ways to scale production. We have to think about whether this is the project we take to market. We hope steak chips will be available commercially within five years, and eventually competitive with high-end snack foods like kale chips, but it depends on regulatory process and scaling the manufacturing.” @MIT Technology Review 2014 on Modern Meadow@.

    8.This is something we believe based on previous reading and currently unpublished work. For a standard presentation of this point, see the table presented in @Galef 2011@.

    9.We are aware of Mark Post’s prototype ground burger (discussed in ‘What is the state of art for making cultured meat’), but no comparable prototype for ground chicken/pork.

    10.“Work on cultured meat is relatively easy to transfer from one animal to another. Professor Post’s team began with mice before moving to pork and finally beef. The team needed about six months to optimize culture conditions for each new animal.” @GiveWell’s non-verbatim summary of a conversation with Mark Post, March 24, 2015@.

    11.Note that reference numbers 12, 62, and 46 in the original reference refer to experimental work in other species using this protocol. “This procedure can be performed in any tissue culture facility, using wildtype and mutant mouse muscles of various ages (12), and is suitable for satellite cell isolation from rat (62) and chicken (46) muscles.” @Danoviz and Yablonka-Reuveni 2012, Skeletal Muscle Satellite Cells: Background and Methods for Isolation and Analysis in a Primary Culture System@.

    12.@2014 Consumer Perishables Databook@, p. 24, see pie chart.

    13.@Category share of chicken sales in the United States in 2014, by cut type@. The information is in the table displayed, but most of the information is behind a paywall.

    @2014 Consumer Perishables Databook@, p. 28, see pie chart.

    14.@2014 Consumer Perishables Databook@, p. 32, see pie chart.

    15.@2014 Consumer Perishables Databook@, p. 34, see pie chart.

    16.“THE world’s average stock of chickens is almost 19 billion, or three per person, according to statistics from the UN’s Food and Agriculture Organisation. Cattle are the next most populous breed of farm animal at 1.4 billion, with sheep and pigs not far behind at around 1 billion.” @Economist 2011. Global Livestock Counts@.

    17.This is based on many hours of reading and talking to people about this topic, and asking about what work represents the state of the art.

    18.“The stem cell technology to produce cultured beef requires four steps (Fig. 1): (1) harvesting of stem cells, (2) expansion of stem cell numbers, (3) differentiation of stem cells into skeletal muscle cells and fibers, and (4) assembly into the final meat product.” @Post 2014, An alternative animal protein source: cultured beef@.

    19.“Skeletal muscle-specific stem cells, so-called satellite cells, are harvested from a small piece of bovine muscle tissue (e.g., taken through a biopsy needle). A needle biopsy is a harmless and small procedure that requires little resources, other than some labor. The subsequent mechanical and enzymatic digestion steps to isolate the satellite cells also mainly cost labor and very little material or energy.” @Post 2014, An alternative animal protein source: cultured beef@.

    20.“Culturing of skeletal muscle cells from satellite cells can be separated into two phases with distinct goals: the proliferation phase and the differentiation phase. The challenges in optimizing culture conditions for large-scale skeletal muscle growth are therefore also different for these two phases. In the proliferation phase the goal is to obtain the maximum number of cells from the starting batch of cells, i.e. to maximize the number of doublings. As a result of the theoretical power of 2 relationship between number of doublings and number of cells, moving from 20 to 30 doublings makes a tremendous difference when, in fact 30 doublings give a thousand-fold higher yield. With the current isolation and culturing methods for satellite cells 20 doublings can be achieved. Higher doubling numbers have generally been obtained by delaying differentiation, therefore much attention has focused on the mechanisms that determine differentiation. A major improvement in maintaining the replicative capacity of satellite cells indeed resulted from a combination of mild enzymatic treatment and trituration of remaining skeletal muscle fibrils during harvesting according to Collins et al. (2005). Once harvested, the concept is to recreate the stem cell niche as closely as possible to retain the stem cell behavior of the satellite cells (Boonen & Post, 2008). For instance, success has been achieved with changing the elasticity of the substrate on which the satellite cells are cultured (Gilbert et al., 2010).” @Post 2012, Cultured meat from stem cells@.

    21.“After having produced sufficient cells, the next goal is to differentiate them into skeletal muscle cells and coerce them into maximum protein production i.e. to undergo hypertrophy. For satellite cells, this process occurs almost naturally with very little adjustment to culture conditions. The cells will merge, form myotubes, and will start to express early stage skeletal muscle markers such as MyoD, myogenin and embryonic isoforms of muscle myosin heavy chain. The cues for subsequent hypertrophy are a mix of metabolic, biochemical and mechanical stimuli. It appears that mechanical stimuli are extremely important in triggering protein synthesis and protein organization into contractile units. The latter gives the muscle its typical striated microscopic morphology. Usually, these cells are cast in a collagen-like gel or onto a temporary biodegradable scaffold. In both conditions the cell constructs or bio-artificial muscles (BAMs) are anchored (e.g. Velcro™ or silk wires) to the culture dish to simulate tendons. Differentiation therefore takes places in a tissue engineering construct.” @Post 2012, Cultured meat from stem cells@.

    22.“Fibers can be harvested and assembled into a patty together with separately grown fat tissue.” @Post 2014, An alternative animal protein source: cultured beef@.

    23.“And one thing we’ve come up with is a savory snack chip concept, something we call ‘steak chips.’ We don’t know if it’s a product yet, but it’s an example of the sorts of things we can do. And the way you make steak chips is you take cells from an animal, a cow for example, without harming the animal — it’s a biopsy of muscle cells — and then you grow them in a cell culture medium. Expanding number of cells from millions to billions. This is a process that’s similar to culturing lactobasilis [sic] if you’re making yogurt or culturing yeast if you’re making beer, it’s basically growing cells. Except in this case it’s a different kind of cells. Once we have billions of muscle cells, we separate the cells from the culture medium, we mix in some pectin, derived from citrus or apples (it’s used to congeal jam), and then we’d add flavors and spices. So we’ve been experimenting with an Asian teriyaki sauce and a poblano barbecue sauce. So we take this flavored muscle or meat concoction and we bake it in a food dehydrator to make chips and you end up with this crispy, savory snack that people have described as beef jerky that’s crunchy.” @Q+A with Modern Meadow CEO, Andras Forgacs@.

    24.“ ‘Efficiency will be the critical hurdle,’ says Andras Forgacs. ‘As we scale up, we need to make sure we can produce a high-quality product at a price the market will accept.’” @Bloomberg 2013, Modern Meadow Makes Leather and Meat Without Killing Animals@.

    25.Based on materials from conversations not documented in public notes.

    26.“And the burger was created at phenomenal cost — 250,000 euros, or about $325,000, provided by a donor who so far has remained anonymous. Large-scale manufacturing of cultured meat that could sit side by side with conventional meat in a supermarket and compete with it in price is at the very least a long way off.” @New York Times 2013, Building a $325,000 Burger@.

    27.“Cultured meat is likely to be a very expensive product. An analogy is the cost to manufacture a six-pack of beer. The actual beer is the cheapest component. The price is significantly increased by the cost of the bottles, packaging, distribution, manufacturing and overhead costs. The same holds true for tissue engineering. The necessary infrastructure is much more expensive than the cells themselves. More significant costs include:

    • Employing the necessary skilled technicians, quality, regulatory and manufacturing staff
    • Maintaining sterile environments and lab spaces, especially cleanrooms, which use expensive fans and filters to maintain very low levels of air contamination
    • Sterile disposable plastic ware
    • Necessary supplements and cell media.”

    @GiveWell’s non-verbatim summary of a conversation with a scientist with 18 years experience in the tissue engineering industry, April 23, 2015@.

    28.“Box 1. Technical and economic aspects of cultured-meat production The diameter of animal cells is generally between 10 and 20 μm. This means that the volume of one cell is on the order of 10⁻¹⁵ m³ , corresponding roughly to 10⁻¹² kg/cell. If we assume that everybody in the world will eat 25–30 grams of cultured meat per person per day (10 kg/year), and if we further assume that in 2050 there will be 10 billion people, 10¹¹ kg of cultured meat would be needed per year. In other words, we need to produce 10²³ cells per year. The doubling time of animal cells is generally on the order of 2–3 days (one day is fast for an animal cell), which means that it takes minimally 2–3 weeks to grow cells from the lowest inoculum density of about 5 x 10¹¹ cells/ m³ to the still challengingly high density [15] of about 128 x 10¹² cells/ m³ in eight doublings. One run in a 20 m³ bioreactor, the largest size used for animal-cell cultivation today, will therefore take about 1 month, including all steps (cleaning, filling, sterilization, and so on). To be on the safe side, we assume that 10 runs per year would be executed with this bioreactor, yielding 2.56 x 10¹⁶ cells in total per year, which corresponds to 25,600 kg cultured meat per year per bioreactor, assuming no losses. Given these assumptions, a bioreactor of 20 m³ can thus supply the meat demand (10 kg per person per year) of 2,560 people, a small village. One should realize that this can only be done in an ultramodern factory under Good Laboratory Practice (GLP) and Good Manufacturing Practice (GMP), or International Organization for Standardization (ISO) norms conditions, needing at least three to four highly educated and well-trained technical employees. In the Netherlands, the price of minced meat is not much more than €5 per kg; in other words, 25,600 kg of meat would only earn €128,000 per year, hardly enough to pay the salary of one ‘butcher’ and his/her assistant. Growth medium is also a cost-determining factor, certainly for growing stem cells. A price of €50,000 for 1 m³ of defined medium is not extreme. Per run, at least 20 m³ of medium is needed, corresponding to €1 million. This equates to a cost of €391 per kg of cultured meat. A price of €1,000 per m³ is considered to be the absolute minimum for growth medium. In that case, the medium costs for 1 kg of cultured meat would be €8; and this price accounts for only the growth medium.” @Van der Weele and Tramper 2014, Cultured Meat: every village its own factory?@.

    29.Based on a scientific advisor’s prior knowledge of cell culture.

    30.Based on the following rough back of the envelope calculation. If the cell culture media contains 10% serum, then 100 L of fetal bovine serum FBS is needed to make 1000 L (approximately 1 tonne) of media, which produces about 193 kg of meat, according to analysis by the company Exmoor. Source: “Assume 10% serum or serum mimic in media.” and “Hence 193kg wet weight in vitro meat can be produced per tonne of media.” @Exmoor In Vitro Meat Consortium Preliminary Economics Study, March 2008@. So roughly 0.5 L of serum is needed to make 1 kg of meat. A single cow fetus can produce 150-550 ml of serum, depending on its age. Source: “A bovine fetus of 3 months yields about 150 ml of raw FBS, at 6 months 350 ml and at 9 months (near-term) 550 ml.” @Jochems et al., The use of fetal bovine serum: ethical or scientific problem?@. Thus 1-3 (or more) cow fetuses may be required to make 1 kg of meat, compared with harvesting many kilograms of meat directly from a single cow.

    31.“Developing animal-free cell media

    Media is the substance that feeds cultured cells. Standard media contains fetal bovine serum and is harvested from cow fetuses. Standard media is basically a by-product of other processes and works well in cell culture. However, because it comes from cow fetuses it isn’t standardized across batches. Animal-free media is more consistent and allows more standardized experiments. Dr. Post used animal-free media towards the end of his hamburger production. However, producing this animal-free media is very expensive and time intensive. Also, currently available animal-free media may not be the most efficient for promoting high cell growth.

    The challenge is to make animal-free media affordable, scalable, and high performing (optimized for cell growth). It is possible there may be one media needed for promoting high cell growth that would be switched to a second media for differentiating the earlier stage cells into muscle fibers. This would be attractive to all kinds of research that uses cellular culture (e.g., organ regeneration). Marketing and selling animal-free media could help finance other cultured meat research.” @GiveWell’s non-verbatim summary of a conversation with Isha Datar, March 10, 2015 and July 24, 2015@.

    32.Based on a scientific advisor’s prior experience with tissue engineering.

    33.Based on a scientific advisor’s experience with cell cultures and academic research.

    34.“Developing cell lines

    • Stem cells – Most work on stem cells has focused on human and model organism cell lines, which have very few agricultural applications. Cell lines from different species behave in different ways. Once agricultural animal stem cells lines are established and their behavior is better understood, it will be possible to reproduce them on a mass scale. Stem cells must be directed to become muscle cells. Dr. Genovese is working on this. When stable cell lines are established, it would be possible to produce cultured meat without ever collecting cells from animals again.
    • Myosatellite cells – Myosatellite cells are more mature than stem cells – they are already destined to become muscle cells. Research on myosatellite cells is still in its early stages. Dr. Post and Modern Meadow are collecting tissue from recently slaughtered animals to explore ways to create myosatellite cell lines. It is possible to collect myosatellite cells from live animals via a biopsy (with applied anesthetic).

    Note that cell lines are useful not only as a source for the cultured meat cells, but as a research tool. Using well-understood and well-established cell lines would allow researchers to conduct more reproducible research, furthering our understanding of how to optimize conditions for cell growth, differentiation, and formation into fibers and tissues.” @GiveWell’s non-verbatim summary of a conversation with Isha Datar, March 10, 2015 and July 24, 2015@.

    35.Our understanding is based on a conversation with Isha Datar, a scientific advisor’s prior knowledge of the field of tissue engineering, and other informal conversations. “Creating scaffolds with large surface areas – Modern Meadow is working on growing cells on thin sheets over a large surface area. Mark Post is working on scaffolds that involve beads and noodle-like strings. This is the ‘ground beef’ approach.” @GiveWell’s non-verbatim summary of a conversation with Isha Datar, March 10, 2015 and July 24, 2015@.

    36.For example, “Scaffolds are the structures on which muscle cells would be grown; they are important because muscle cells need to be attached to something in order to grow. In addition, cell cultures that lack veins and arteries can only grow about 0.5 millimeters before the bottom cells begin to die because they aren’t exposed to the growth media. Mark Post developed scaffolding approaches to make his burger, but these scaffold designs are inefficient and labor-intensive to use at scale because they were intended only for academic prototype use. At this stage, developing successful scaffolds would have broad applications for cell culturing beyond cultured meat development.

    There are currently two approaches:

    • Creating scaffolds with large surface areas – Modern Meadow is working on growing cells on thin sheets over a large surface area. Mark Post is working on scaffolds that involve beads and noodle-like strings. This is the “ground beef” approach.
    • Creating vasculature – This could either be a scaffold made that resembles a vascular system, or growing a vascular system within the tissue. This approach has the potential to yield thick tissues. It is the “steak” approach.

    When designing a scaffold, researchers need to determine if the scaffold will stay with the final product, or if it will be removed and reusable.” @GiveWell’s non-verbatim summary of a conversation with Isha Datar, March 10, 2015 and July 24, 2015@.

    37.“Zami Aberman, chairman and CEO of Pluristem Therapeutics, a developer of placenta-based stem cell products also presented positive data on how its PLX (PLacental eXpanded) cells are being used in orthopaedics to help improve muscle repair post hip replacement surgery. … Aberman agreed that having the right technology is crucial. ‘Our progress with cell therapy in the beginning was so slow because we did not have the tools to scale up. When you grow stem cells in 2D instead of 3D they change their expression properties and we have had to develop a 3D bioreactor process to produce stem cells which are effective.’ Aberman continued: ‘We now culture our stem cells in bioreactors using a 3D polystyrene and polypropylene scaffold to which stem cells can adhere to and have found this is around 70 times more efficient than 2D culturing. We can produce 30 doses of 300 x 106 cells per run from a five liter bioreactor and 150 doses of 300 x 106 cells from a 25 liter bioreactor so we can scale up our process.’ Courtney also predicted that the cost of reagents and media for the culturing and production of stem cells has to become lower and these cell culture products should be designed to deliver consistent results in automated systems.” @Genetic Engineering & Biotechnology News 2014, Driving Down the Cost of Stem Cell Manufacturing@.

    38.Based on a scientific advisor’s prior knowledge of cell cultures and tissue engineering.

    39.“Cultured meat is likely to be a very expensive product. An analogy is the cost to manufacture a six-pack of beer. The actual beer is the cheapest component. The price is significantly increased by the cost of the bottles, packaging, distribution, manufacturing and overhead costs. The same holds true for tissue engineering. The necessary infrastructure is much more expensive than the cells themselves. More significant costs include:

    • Employing the necessary skilled technicians, quality, regulatory and manufacturing staff
    • Maintaining sterile environments and lab spaces, especially cleanrooms, which use expensive fans and filters to maintain very low levels of air contamination”

    @GiveWell’s non-verbatim summary of a conversation with a scientist with 18 years experience in the tissue engineering industry, April 23, 2015@.

    40.Based partly on a scientific advisor’s prior knowledge about tissue engineering and partly on comments by Mark Post: “For the production of the prototype hamburger, we used traditional 10-layer cell factories, but it is evident that, for the production of large quantities of cells, fermenter-type setups, such as the 25,000 L tank described earlier, are the only realistic alternatives to date. In order to grow adherent cells in those tanks, either a floating surface needs to be offered or cells need to grow in aggregates suspended in the culture medium (for review see Ref. 8). In our hands, satellite cells can be grown on commercially available microcarriers as well as in aggregates, but both approaches still need further optimization (unpublished data). Published data on stem cell production in a microcarrier system are currently limited to tank sizes of 5 L or less, so there is considerable work ahead to bring this production to scale.” @Post 2014, An alternative animal protein source: cultured beef@.

    41.Based on a scientific advisor’s background knowledge about synthetic biology start-ups.

    42.Based on a scientific advisor’s background knowledge about cell cultures.

    43.“The cultured beef burger, made from 20,000 tiny strands of meat grown in a laboratory dish from a cow’s stem cells, was cooked in front of an invited audience and served to nutritional scientist Hanni Rutzler and author Josh Schonwald.

    ‘I was expecting the texture to be more soft, there’s really a bite to it….It’s close to meat. It’s not that juicy but the consistency is perfect. I missed salt and pepper,’ said Ms Rutzler.

    ‘The surface of the meat was crunchy, but not typically crunchy. It was more like the surface of bread or cake,’ she added.[…]

    ‘The texture, the mouth feel, has a feel like meat. The absence is the feel of fat. There is a leanness to it. But the bite feels like a conventional hamburger,’ said Mr Schonwald.” @Independent 2013, Lab meat taste test@.

    44.Based on materials from conversations not documented in public notes.

    45.“The team is working to enhance the quality of cultured meat, at a small-scale level of production, in two ways:

    • Achieving an optimal protein content level by changing the culture and feeding conditions.
    • Adding fat tissue to the product which would be added to the skeletal muscle tissue to create a true meat ‘mimic.’”

    @GiveWell’s non-verbatim summary of a conversation with Mark Post, March 24, 2015@.

    46.“What Federal regulation defines what can be listed as a natural flavoring on the meat and poultry label?

    On March 1, 1990, FSIS published the final rule, Ingredients That May Be Designated as Natural Flavors, Natural Flavorings, Flavors, or Flavorings When Used in Meat or Poultry Products. The rule did the following:

      • Defined the ingredients, i.e., spices, spice extractives, and essential oils, that may be declared as ‘natural flavors’ or ‘flavors’ on meat and poultry labels.
      • Required more specific listing of certain ingredients. Substances such as dried beef stock, autolyzed yeast, and hydrolyzed proteins must be listed on the label by their common or usual names because their purpose is not just for flavor. They are flavor enhancers, emulsifiers, stabilizers, and binders.
      • Required that the specific source of hydrolyzed protein be indicated on the label, for example, ‘hydrolyzed soy protein’ or ‘hydrolyzed whey protein.’”

    @USDA, Natural flavorings on meat and poultry labels@.

    47.Ideas brainstormed by a scientific advisor.

    48.This is an impression we formed based on conversations that were not documented in public notes.

    49.“Do you make genetically modified meat?

    No, we do not make genetically modified foods. At Modern Meadow, we source our cells naturally and provide a nurturing environment for them to grow and create the purest, most high quality animal products.” @Modern Meadow FAQ@.

    50.“So far Professor Post has not used genetic modification to improve the quality of the meat, to avoid the risk of negative public reception. This is due to his belief that any use of genetic engineering of muscle cells would turn public sentiment against the project.” @GiveWell’s non-verbatim summary of a conversation with Mark Post, March 24, 2015@.

    51.“The costs of cultured meat are unknown. Vandenburgh has estimated that to produce cultured meat using present technology would cost approximately $5 million per kilogram (Brown University, personal communication, 20 February 2004). This estimate is based on the costs of producing functional skeletal muscle tissue in laboratories on a small scale. Presumably the costs would be orders of magnitude lower if one used a suspended cell culture technique, and mass produced the cultured meat in industrial bioreactors. Advances in the technical aspects of cultured meat production will greatly improve efficiency and lower costs significantly. Theoretically, cultured meat could afford higher resource and labor efficiencies, which could translate into lower costs, if cultured meat were produced at scale with an affordable medium. In any case, it is unlikely that cultured meat will soon compete with conventional meat in ordinary markets. However, there are technologies now found in virtually every household – computers, the internet, Velcro, freeze-dried foods – that originally cost too much for mass acceptance. They found their first applications in space and defense projects. Only after reductions in cost by several orders of magnitude were they mass-produced. This could be true of cultured meat, as well.” @Edelman et al. 2004, In vitro cultured meat production@.

    52.“The costs of cultured meat are unknown. Vandenburgh has estimated that to produce cultured meat using present technology would cost approximately $5 million per kilogram (Brown University, personal communication, 20 February 2004). This estimate is based on the costs of producing functional skeletal muscle tissue in laboratories on a small scale. Presumably the costs would be orders of magnitude lower if one used a suspended cell culture technique, and mass produced the cultured meat in industrial bioreactors.” @Edelman et al. 2004, In vitro cultured meat production@.

    53.“Vandenburgh has estimated that to produce cultured meat using present technology would cost approximately $5 million per kilogram (Brown University, personal communication, 20 February 2004).” @Edelman et al. 2004, In vitro cultured meat production@.

    54.“Box 1. Technical and economic aspects of cultured-meat production The diameter of animal cells is generally between 10 and 20 μm. This means that the volume of one cell is on the order of 10⁻¹⁵ m³ , corresponding roughly to 10⁻¹² kg/cell. If we assume that everybody in the world will eat 25–30 grams of cultured meat per person per day (10 kg/year), and if we further assume that in 2050 there will be 10 billion people, 10¹¹ kg of cultured meat would be needed per year. In other words, we need to produce 10²³ cells per year. The doubling time of animal cells is generally on the order of 2–3 days (one day is fast for an animal cell), which means that it takes minimally 2–3 weeks to grow cells from the lowest inoculum density of about 5 x 10¹¹ cells/ m³ to the still challengingly high density [15] of about 128 x 10¹² cells/ m³ in eight doublings. One run in a 20 m³ bioreactor, the largest size used for animal-cell cultivation today, will therefore take about 1 month, including all steps (cleaning, filling, sterilization, and so on). To be on the safe side, we assume that 10 runs per year would be executed with this bioreactor, yielding 2.56 x 10¹⁶ cells in total per year, which corresponds to 25,600 kg cultured meat per year per bioreactor, assuming no losses. Given these assumptions, a bioreactor of 20 m³ can thus supply the meat demand (10 kg per person per year) of 2,560 people, a small village. One should realize that this can only be done in an ultramodern factory under Good Laboratory Practice (GLP) and Good Manufacturing Practice (GMP), or International Organization for Standardization (ISO) norms conditions, needing at least three to four highly educated and well-trained technical employees. In the Netherlands, the price of minced meat is not much more than €5 per kg; in other words, 25,600 kg of meat would only earn €128,000 per year, hardly enough to pay the salary of one ‘butcher’ and his/her assistant. Growth medium is also a cost-determining factor, certainly for growing stem cells. A price of €50,000 for 1 m³ of defined medium is not extreme. Per run, at least 20 m³ of medium is needed, corresponding to €1 million. This equates to a cost of €391 per kg of cultured meat. A price of €1,000 per m³ is considered to be the absolute minimum for growth medium. In that case, the medium costs for 1 kg of cultured meat would be €8; and this price accounts for only the growth medium.” @Van der Weele and Tramper 2014, Cultured Meat: every village its own factory?@.

    55.“One run in a 20 m³ bioreactor, the largest size used for animal-cell cultivation today, will therefore take about 1 month, including all steps (cleaning, filling, sterilization, and so on).” @Van der Weele and Tramper 2014, Cultured Meat: every village its own factory?@.

    56.See Media Cost Assumptions table on page 11. “Growth factors, Cost: 0, Negligible cost for raw materials. Make on site in small scale bioreactors.” @Exmoor In Vitro Meat Consortium Preliminary Economics Study, March 2008@.

    57.Based on a scientific advisor’s prior knowledge of tissue engineering.

    58.See Graph 1 In Vitro Meat – Suspension & 3D Matrix. @Exmoor In Vitro Meat Consortium Preliminary Economics Study, March 2008@.

    59.“Media prices and quantities. Prices for commercially available media in small quantities and suitable for biopharmaceutical applications are in the region of Euro 7000 – 8000 / tonne. This price reflects the fact that the current market is not designed to produce media in the large quantities required for a global in vitro meat industry. Prices will fall if large quantities are produced. It is not realistic to consider buying in re-cycled media because the quantities are not available and the quality would be variable (requiring local analysis and make up). Media within an in vitro meat plant would be re-cycled however. In vitro meat production requires large quantities of media costing less than say Euro 350 / tonne. This may require production to be co-located with the in vitro meat plant and further development of both the recipe and the process plant will be required. A possible recipe at this cost is given in appendix 2. It has been assumed that about 193kg (wet weight) of in vitro meat can be made per tonne of media. The assumptions behind this calculation are in appendix 2.” @Exmoor In Vitro Meat Consortium Preliminary Economics Study, March 2008@.

    60.“A preliminary economics study reviewing the financial viability of in vitro grown meat estimated the cost of manufacturing to be Euro 3500/ton, but note that because such technology has not yet been developed, this estimation could be largely inaccurate (eXmoor Pharma Concepts, 2008).” @Datar and Betti 2010, Possibilities for an in vitro meat production system@.

    61.“Growth medium is generally an important cost-determining factor. A price of €1 per liter for growth medium would bring the price of a minced-meat type of product within the price range of conventional minced meat, but this is when only the price of medium is considered (Box 1). This is already an ambitious goal, but not enough to make cultured meat competitive with conventional meat. For that, an order-of-magnitude increase in the price of the latter would be needed.” @Van der Weele and Tramper 2014, Cultured Meat: every village its own factory?@.

    62.“Currently, a major cost of animal-free media is the cytokines (cell-signaling molecules) that encourage cell proliferation.” @GiveWell’s non-verbatim summary of a conversation with Steve Oh, October 7, 2015@.

    63.“Dr. Oh is aware of two kinds of approaches to reducing the cost of cytokines:

    1. Finding small molecule replacements for cytokines. While inexpensive small molecule replacements for a few cytokines (such as BMP4) have been discovered, it has proven challenging to find replacements for others (such as bFGF). Essentially all cell cultures need bFGF to grow. In Dr. Oh’s lab, researchers grow embryonic stem cells and then find small molecules that induce them to become particular types of muscle cells. But once the stem cells are differentiated, they are unable to produce any additional cells without bFGF. At sufficient densities, these cells may be able to produce their own cytokines, but Dr. Oh has not investigated this possibility.
    2. Engineering host organisms that produce cytokines through synthetic biology.<//strong> This approach could involve using bioengineering techniques to put genes for cytokines into host cells, producing cytokines from the host cells, and then extracting the cytokines from the cell culture. A potential challenge with this approach is that some growth factors (e.g. VEGF) need glycosylation to work, and it may be hard to produce such growth factors using fermentation. Dr. Oh does not know of a host organism that could produce all the necessary growth factors.

    In Dr. Oh’s opinion, it is very unlikely that these approaches would succeed in decreasing the cost of animal-free media below $1/L.” @GiveWell’s non-verbatim summary of a conversation with Steve Oh, October 7, 2015@.

    64.“Basal medium (without serum or serum substitute) costs about $1-$4 per liter in quantity and prepared from components, and from $4-$10 per liter in preformulated powder or supplied in solution.” @Hochfeld 2006@, p. 218.

    65.Wikipedia lists the ingredients in basal medium as follows:

    “An undefined medium (also known as a basal or complex medium) is a medium that contains:

    • a carbon source such as glucose for bacterial growth
      water
    • various salts needed for bacterial growth
    • a source of amino acids and nitrogen (e.g., beef, yeast extract)”

    @Wikipedia Growth Medium page 2015@

    66.“Expected timeline for development Professor Post believes that cultured meat can be produced commercially at scale in five to seven years. Though the product has not yet been perfected, it would be 4 marketable within three to four years if production were scaled up to the necessary level. Regulatory approval would take another two to three years. At that point, the product would still be very expensive. However, after further refinement of the culture conditions, the cost of the product would likely be competitive within another three to five years (i.e., seven to ten years from now).” @GiveWell’s non-verbatim summary of a conversation with Mark Post, March 24, 2015@.

    67.“Without a major technological breakthrough, it seems very unlikely that cost-competitive cultured meat will be available in the next 10-15 years.

    It is already possible to make a football field size of 2mm thick meat. That technological hurdle is done, which means the product is maybe 70% of the way there in terms of technical risk. However, in order to have a viable business, it needs to be 95% of the way there. The additional 20-30% comes from making gains in manufacturing, which is doable in the long term. The target product profile will also matter. It is likely more difficult to manufacture thick pieces of cultured meat because of the mass transport challenges.” @GiveWell’s non-verbatim summary of a conversation with a scientist with 18 years experience in the tissue engineering industry, April 23, 2015@.

    68.“To hear it from Renninger, Melo’s promise is the tragic misstep of Amyris’s young and turbulent life. In his view, the company’s problems are not problems of technology but problems arising from the pitiless expectations of Wall Street. ‘We were chasing that number,’ Renninger says of the 50 million liters. Amyris would have to meet the quotas Melo had presented or lose credibility. Coming from the petroleum industry, Melo saw those volumes as laughably small. But this was a failure of comprehension. Amyris was not an oil company, and it still didn’t have a full-scale plant. ‘The regret is not realizing how hard it was to get the scale up,’ says Melo now. He soon discovered it would take a lot longer for a fermentation and manufacturing system to work than his team had estimated.

    The company opened on the Nasdaq on September 28, 2010, at $16 a share. A 100-million-liter-a-year plant in Sao Martinho was still years from completion. To meet Melo’s goals, the company had to rent a hangar in rural Sao Paulo from an animal-feed producer called Biomin and installed two 200,000-liter stainless-steel fermenters, each the size of a two-story house. The plant, which began running in June 2011, was beset with problems. Sometimes the process worked as it had in the California labs. Other times, the enormous tanks frothed with the carcasses of exploded yeast cells.” @Fast Company 2012, THE RISE AND FALL OF THE COMPANY THAT WAS GOING TO HAVE US ALL USING BIOFUELS@.

    69.“Having pioneered the field, Organogenesis Inc. is a commercial leader in regenerative medicine, focused in the areas of bio-active wound healing and soft tissue regeneration. …

    The company was originally founded in 1985 as a spin-off of technology developed at the Massachusetts Institute of Technology (MIT). … 1998: First FDA approval of a living, allogeneic, cell based product (Apligraf® approved for the treatment of venous leg ulcers).” @Organogenesis company profile@.

    70.“Apligraf is living cell based product for chronic venous leg ulcers and diabetic foot ulcers. Apligraf is supplied as a living, bi-layered skin substitute. Like human skin, Apligraf consists of living cells and structural proteins. The lower dermal layer combines bovine type 1 collagen and human fibroblasts (dermal cells), which produce additional matrix proteins. The upper epidermal layer is formed by promoting human keratinocytes (epidermal cells) first to multiply and then to differentiate to replicate the architecture of the human epidermis. Unlike human skin, Apligraf does not contain melanocytes, Langerhans’ cells, macrophages, and lymphocytes, or other structures such as blood vessels, hair follicles or sweat glands.

    Apligraf is supplied as a circular disc approximately 75 mm in diameter and 0.75 mm thick.” @Apligraf website, What is Apligraf@.

    71.“Keratinocytes and fibroblasts are cultured and expanded under separate conditions.” @Apligraf website, How is it Made@.

    72.“Tissue regeneration specialist company Organogenesis Inc. was one of the first biotech companies formed. Incorporated in 1985, the company was originally a spin-off from a research program at MIT. For the first 10-15 years, Organogenesis was heavily research based, but then gradually moved into development. The company’s flagship product is Apligraf–a living, bilayered skin construct with two FDA-approved indications: diabetic foot ulcers and venous leg ulcers.” @MacKay 2006, Bioactive wound healing, bioaesthetics and biosurgery@.

    73.Based on materials from conversation not documented in public notes.

    74.As stated above, Apligraf is a wound care patch that is a 75 mm diameter circular disc that is 0.75 mm thick. A scientist with 18 years of experience in the tissue engineering industry told us that this much Apligraf costs hundreds of dollars to produce. For purposes of this calculation—which is only an order of magnitude calculation—we’ll assume it costs $300. These numbers imply that Apligraf costs $300 for ~3.3 mL of material. If we approximate the density of Apligraf as 1 kg/L (guessing that it is comparable to water), then this is ~3.3g of material. That would imply a cost of about $90,000/kg.

    “A hockey-puck sized piece of Apligraf takes three weeks to manufacture and costs hundreds of dollars.” @GiveWell’s non-verbatim summary of a conversation with a scientist with 18 years experience in the tissue engineering industry, April 23, 2015@.

    75.“Founded in 2003 in the San Francisco Bay Area by a group of scientists at the University of California, Berkeley, Amyris uses breakthrough science and an innovative business model to address some of our planet’s most daunting problems.” @Amyris company history@.

    76.“The Amyris-Total renewable fuel was produced using engineered microorganisms that convert plant sugars into Biofene®, Amyris’s brand of renewable farnesene, a long-chain, branched hydrocarbon. In December 2012, Amyris began commercial production of Biofene at its industrial-scale production facility in southeastern Brazil.” @Amyris 2013, Amyris and Total Announce Successful Demonstration Flight With Renewable Jet Fuel During Paris Air Show@.

    77.“Amyris Biotechnologies (see Box 1) is harnessing that power to train Escherichia coli, via molecular biology, to make artemisinin, a very effective antimalarial agent but one that is expensive on an industrial scale to harvest, extract and purify from its wormwood plant source.

    The company is built on technology from Keasling’s lab to genetically modify microbes to produce a class of compounds known as terpenoids1, a starting point for a number of possible therapeutics and industrial chemicals (Figure 1), says Amyris president Kinkead Reiling. Synthetically producing artemisinin by genetic engineering and fermentation and scaling up the production to a commercial level will be the company’s starting point to expand into synthesis of other compounds, he says.” @Nature Bioentrepreneur 2005, Commercializing synthetic biology@.

    78.“Amyris feeds sugar cane syrup into three dedicated 200,000 liter fermentors containing Amyris proprietary yeast. The yeast digest the syrup feedstock and produce farnesene, which is then separated and purified.” @Biofuels Digest 2011, Amyris opens first commercial facility@.

    79.“Amyris, a company that uses synthetic biology to make alternatives to conventional petroleum products, recently decided to wind down its biofuels business, which sells ethanol and reformulated gasoline, and focus on selling higher-value products such as cosmetics. Now it’s clear why.

    Details about Amyris were disclosed during the company’s earnings call last night. They show just how far the company is from making biofuel profitably.

    Shortly after it was founded, Amyris had set out to make biofuel using genetically modified organisms and simple chemistry to turn sugar into a type of oil that’s similar to diesel. It had some success making bio-derived biodiesel for buses in Brazil. But the chemicals produced by the company’s microörganisms can be used for other things as well, such as moisturizers and fragrances, that sell for higher prices.

    Last night, the company said the average selling price for all its products is $7.70 per liter, or $29 per gallon, far higher than the price for petroleum-based diesel. (In Brazil, diesel costs about $1 per liter. Amyris says it can sell its diesel-replacement for niche markets that command prices much higher than $1 a liter.)

    The average price—which is propped up by the price it can charge for moisturizer—is higher than what Amyris sells bio-derived biodiesel for. (It didn’t disclose the exact price for the fuel.) But even $7.70 per liter isn’t enough for the company to break even.” @Technology Review 2012, Why Amyris is Focusing on Moisturizers, Not Fuel, for Now@.

    80.Based on a scientific advisor’s prior knowledge of tissue engineering.

    81.Based on a scientific advisor’s prior knowledge of tissue engineering.

    82.Based on a scientific advisor’s prior knowledge of tissue engineering.

    83.Based on the following back of the envelope calculation, with all quotes from @USDA, Egg Products Processing and Distribution Module@:

      • Fraction of total eggs produced in the US that go toward making processed egg whites = [(Total number of egg whites processed) / (Total number of eggs processed)] x (Fraction of total eggs produced that end up being processed) = (7.58 billion / 17 billion) x 27% ~= 12%
      • Total number of egg whites processed = (total weight of egg white processed) / (weight per egg white) = 5.21 x 10⁸ lbs. / 0.06875 lbs. = 7.58 billion egg whites
        • Total weight of egg whites processed = 5.21 x 10⁸ lbs. (from Figure C-3, p. 119)
        • Weight per egg white = 0.55 x 2 oz. = 1.1 oz. = 0.06875 lbs.
          • Egg is 55% albumen by weight (“An egg is 55% albumen and 45% yolk by volume or weight.” p. 122)
          • The mean weight of an egg is approximately 2 oz. since the mean weight of a dozen eggs is approximately 24 oz. (Figure C-4, p. 123).
      • Total number of eggs processed = 27% billion eggs (“The eggs products industry processed 17 billion eggs or 27% of the U.S. production of eggs in 1996”, p. 115)
      • Fraction of total eggs produced that end up being processed = 27% (“The eggs products industry processed 17 billion eggs or 27% of the U.S. production of eggs in 1996”, p. 115)

    84.“Annual egg production

    6.47 X 10¹⁰” @USDA, Egg Products Processing and Distribution Module@ from Figure C-1, p. 116.

    85.“U.S. Value of Egg Production Up 17 Percent

    Value of all egg production in 2014 was $10.2 billion, up 17 percent from $8.68 billion in 2013. Egg production totaled 99.8 billion eggs, up 2 percent from 97.6 billion eggs produced in 2013.” @U.S. Poultry & Egg Association 2015, economic data@

    86.Based on conversations from Clara Foods presentations and discussions at IndieBio Demo Day 2015 not documented in public notes.

    87.Based on conversations from Clara Foods presentations and discussions at IndieBio Demo Day 2015.

    88.Based on conversations from Clara Foods presentations and discussions at IndieBio Demo Day 2015.

    89.Based on a scientific advisor’s prior knowledge of tissue engineering and the synthetic biology industry.

    90.Based on conversations from Clara Foods presentations and discussions at IndieBio Demo Day 2015 not documented in public notes.

    91.“Can you tell us a little about what Modern Meadow is working on?

    Modern Meadow is a 3-year-old company that is focused on producing animal products in a fundamentally different way. So rather than having to raise, slaughter and transport animals, we’re making animal products from cells that are grown. We’re making materials, such as leather, and we’re also making foods — animal protein foods. … To focus on food part — again, materials are coming out first, but to comment a little about what we’re doing in food, we’re developing a way to produce animal protein without having to kill animals. And one thing we’ve come up with is a savory snack chip concept, something we call ‘steak chips.’ We don’t know if it’s a product yet, but it’s an example of the sorts of things we can do. And the way you make steak chips is you take cells from an animal, a cow for example, without harming the animal — it’s a biopsy of muscle cells — and then you grow them in a cell culture medium. Expanding number of cells from millions to billions.” @Q+A with Modern Meadow CEO, Andras Forgacs@.

    92.“And one thing we’ve come up with is a savory snack chip concept, something we call ‘steak chips.’ We don’t know if it’s a product yet, but it’s an example of the sorts of things we can do. And the way you make steak chips is you take cells from an animal, a cow for example, without harming the animal — it’s a biopsy of muscle cells — and then you grow them in a cell culture medium. Expanding number of cells from millions to billions.” @Q+A with Modern Meadow CEO, Andras Forgacs@.

    93.In the table, Total Funding for Modern Meadow is $10.4M. @CBInsights company profile, Modern Meadow@.

    94.“Modern Meadow funded by Breakout Labs June 2012” @Breakout Labs portfolio company page, Modern Meadow@.

    95.Investors are listed in the Funding Round table. @Crunchbase company profile, Modern Meadow@.

    96.“ ‘From the onset, Clara was founded on a fundamental belief that we can cultivate a better and safer food system using technology,’ said CEO Arturo Elizondo. The start-up describes the process of creating the animal-free egg white as being ‘similar to brewing beer or wine. However, instead of using yeast to convert sugar into alcohol, our yeast is specialised to convert chicken DNA into egg white proteins.’”@FoodProcessing.Com.Au 2015, Producing Egg Whites Without Chickens@.

    97.“ ‘From the onset, Clara was founded on a fundamental belief that we can cultivate a better and safer food system using technology,’ said CEO Arturo Elizondo. The start-up describes the process of creating the animal-free egg white as being ‘similar to brewing beer or wine. However, instead of using yeast to convert sugar into alcohol, our yeast is specialised to convert chicken DNA into egg white proteins.’”@FoodProcessing.Com.Au 2015, Producing Egg Whites Without Chickens@.

    98.“ ‘From the onset, Clara was founded on a fundamental belief that we can cultivate a better and safer food system using technology,’ said CEO Arturo Elizondo. The start-up describes the process of creating the animal-free egg white as being ‘similar to brewing beer or wine. However, instead of using yeast to convert sugar into alcohol, our yeast is specialised to convert chicken DNA into egg white proteins.’” @FoodProcessing.Com.Au 2015, Producing Egg Whites Without Chickens@.

    99.“Founders Arturo Elizondo, David Anchel and Isha Datar ginned up a wild experiment inside biotech accelerator IndieBio this summer to produce a genetically identical, lab-grown egg white liquid using a proprietary batch of manipulated yeast.

    If Clara Foods can get this idea to scale, it could significantly reduce the cost and time spent raising chickens, procuring eggs and then separating the egg whites.” @Techcrunch 2015, Clara Foods Cooks Up $1.7M in Funding@.

    100.“Biotech startup Clara Foods announced the close of $1.7 million in seed funding from David Friedberg, Gary Hirshberg, Ali and Hadi Partovi, Scott Banister, and SOS Ventures today.” @Techcrunch 2015, Clara Foods Cooks Up $1.7M in Funding@.

    101.“Biotech startup Clara Foods announced the close of $1.7 million in seed funding from David Friedberg, Gary Hirshberg, Ali and Hadi Partovi, Scott Banister, and SOS Ventures today.” @Techcrunch 2015, Clara Foods Cooks Up $1.7M in Funding@.

    102.“Impossible Foods is developing a new generation of delicious and sustainable meats and cheeses made entirely from plants. Our mission is to give people the enjoyment of food that comes from animals without the health and environmental drawbacks.

    We look at animal products at the molecular level, then select specific proteins and nutrients from greens, seeds, and grains to recreate the wonderfully complex experience of meat and dairy products. For thousands of years we’ve relied on animals to transform plants into meat, milk, cheese and eggs. Impossible Foods has found a better way to make the foods you love, directly from plants.” @Impossible Foods website@.

    103.“Impossible Foods is developing a new generation of delicious and sustainable meats and cheeses made entirely from plants. Our mission is to give people the enjoyment of food that comes from animals without the health and environmental drawbacks.

    We look at animal products at the molecular level, then select specific proteins and nutrients from greens, seeds, and grains to recreate the wonderfully complex experience of meat and dairy products. For thousands of years we’ve relied on animals to transform plants into meat, milk, cheese and eggs. Impossible Foods has found a better way to make the foods you love, directly from plants.” @Impossible Foods website@.

    104.“Impossible Foods is developing a new generation of delicious and sustainable meats and cheeses made entirely from plants. Our mission is to give people the enjoyment of food that comes from animals without the health and environmental drawbacks.

    We look at animal products at the molecular level, then select specific proteins and nutrients from greens, seeds, and grains to recreate the wonderfully complex experience of meat and dairy products. For thousands of years we’ve relied on animals to transform plants into meat, milk, cheese and eggs. Impossible Foods has found a better way to make the foods you love, directly from plants.” @Impossible Foods website@.

    105.@Crunchbase company profile, Impossible Foods Investors@, see table.

    106.“If Brown could get folks to eat less meat, he could help the climate and animals.

    Problem was, Brown didn’t know how. So he started looking for partners and reading academic papers on meat analogs. That’s how he found food scientists Fu-hung Hsieh and Harold Huff, both at the University of Missouri. They were tackling the texture problem and had made considerable progress toward developing an extrusion process that could actually mimic meat fibers. Brown paid Missouri a visit, and after some back and forth he formed Beyond Meat in 2009. Brown was CEO, Hsieh and Huff were scientific consultants, and the university was a partner.” @Wired 2013, Alton Brown on the End of Meat as We Know It@.

    107.“ ‘Meat is actually just the combination of amino acids, fats, water, carbohydrates and trace minerals,’ said Ethan Brown, CEO and Beyond Meat co-founder. ‘These things are available in the plant kingdom, and we combine them in a way that re-creates the same sensory experience for consumers without having to rely on the animal to produce it. We believe this is the meat of the future and the way to feed a growing world population cost effectively with minimal environmental impact and use of natural resources.’” @BusinessWire 2013, Beyond Meat Completes Largest Financing Round to Date@.

    108.“ ‘Meat is actually just the combination of amino acids, fats, water, carbohydrates and trace minerals,’ said Ethan Brown, CEO and Beyond Meat co-founder. ‘These things are available in the plant kingdom, and we combine them in a way that re-creates the same sensory experience for consumers without having to rely on the animal to produce it. We believe this is the meat of the future and the way to feed a growing world population cost effectively with minimal environmental impact and use of natural resources.’” @BusinessWire 2013, Beyond Meat Completes Largest Financing Round to Date@.

    109.“ ‘Meat is actually just the combination of amino acids, fats, water, carbohydrates and trace minerals,’ said Ethan Brown, CEO and Beyond Meat co-founder. ‘These things are available in the plant kingdom, and we combine them in a way that re-creates the same sensory experience for consumers without having to rely on the animal to produce it. We believe this is the meat of the future and the way to feed a growing world population cost effectively with minimal environmental impact and use of natural resources.’” @BusinessWire 2013, Beyond Meat Completes Largest Financing Round to Date@.

    110.“Beyond Meat®, the first company to re-create meat from plants, has completed its Series D financing round, its largest to date. By making meat from plant-based sources, privately held Beyond Meat, based in El Segundo, California, is dedicated to improving human health, positively impacting climate change, conserving natural resources and respecting animal welfare. New investors include DNS Capital, representing the business interests of Gigi Pritzker Pucker and Michael Pucker; Taiwan’s Tsai Family, through its family office, WTT Investment; and S2G Ventures. Existing investors Kleiner Perkins Caufield & Byers, The Obvious Corporation (founded by Evan Williams and Biz Stone), Bill Gates, Morgan Creek Capital and Seth Goldman (founder of Honest Tea) also participated in the round.” @BusinessWire 2013, Beyond Meat Completes Largest Financing Round to Date@.

    111.“Making milk, while complicated in its own way, is nonetheless much simpler than growing meat.

    ‘If you look at all the components, less than 20 make milk milk—give it the taste, structure, color you expect when you drink milk,’ Pandya says.

    Muufri will contain only those essential proteins, fats, minerals, and sugars. Pandya and Gandhi’s plan is to insert DNA sequences from cattle into yeast cells, grow the cultures at a controlled temperature and the right concentrations, and harvest milk proteins after a few days. The process is extremely safe, says Gandhi: It’s the same one used to manufacture insulin and other medicines.

    Although the proteins in Muufri milk come from yeast, the fats come from vegetables and are tweaked at the molecular level to mirror the structure and flavor of milk fats. Minerals, like calcium and potassium, and sugars are purchased separately and added to the mix. Once the composition is fine-tuned, the ingredients emulse naturally into milk.” @National Geographic 2014, Meat grown in a lab@.

    112.“Making milk, while complicated in its own way, is nonetheless much simpler than growing meat.

    ‘If you look at all the components, less than 20 make milk milk—give it the taste, structure, color you expect when you drink milk,’ Pandya says.

    Muufri will contain only those essential proteins, fats, minerals, and sugars. Pandya and Gandhi’s plan is to insert DNA sequences from cattle into yeast cells, grow the cultures at a controlled temperature and the right concentrations, and harvest milk proteins after a few days. The process is extremely safe, says Gandhi: It’s the same one used to manufacture insulin and other medicines.

    Although the proteins in Muufri milk come from yeast, the fats come from vegetables and are tweaked at the molecular level to mirror the structure and flavor of milk fats. Minerals, like calcium and potassium, and sugars are purchased separately and added to the mix. Once the composition is fine-tuned, the ingredients emulse naturally into milk.” @National Geographic 2014, Meat grown in a lab@.

    113.“Although the proteins in Muufri milk come from yeast, the fats come from vegetables and are tweaked at the molecular level to mirror the structure and flavor of milk fats. Minerals, like calcium and potassium, and sugars are purchased separately and added to the mix. Once the composition is fine-tuned, the ingredients emulse naturally into milk.” @National Geographic 2014, Meat grown in a lab@.

    114.“ ‘If we want the world to change its diet from a product that isn’t sustainable to something that is, it has to be identical [to], or better than, the original product,’ Gandhi says. ‘The world will not switch from milk from a cow to the plant-based milks. But if our cow-less milk is identical and priced right, they just might.’” @National Geographic 2014, Meat grown in a lab@.

    115.Muufri Funding listed in Funding section as a $2M round by Horizon Ventures and a $30K round by SOS Ventures. @Angel.co company profile, Muufri@.

    116.“The startup has succeeded in landing its plant-based ‘mayo’ and cookie dough in Walmart and Whole Foods stores all over the U.S., and it’s considered international expansion.” and photo caption “Above: Scrambled eggs, Hampton Creek style, courtesy of research and development chef Ben Roche.” @VentureBeat 2014, Hampton Creek’s data scientists team up with chefs to find the holy grail of plant proteins@.

    117.“At Facebook and LinkedIn, data scientists analyze site usage and develop features that take user information into consideration. Inside the cramped office of Hampton Creek, a 3-year-old San Francisco startup, data scientists are doing something wholly different, and arguably more impactful.

    They’re weeding out billions of proteins from hundreds of thousands of plants to figure out what could form the basis of a vegan equivalent of an egg.” @VentureBeat 2014, Hampton Creek’s data scientists team up with chefs to find the holy grail of plant proteins@.

    118.“At Facebook and LinkedIn, data scientists analyze site usage and develop features that take user information into consideration. Inside the cramped office of Hampton Creek, a 3-year-old San Francisco startup, data scientists are doing something wholly different, and arguably more impactful.

    They’re weeding out billions of proteins from hundreds of thousands of plants to figure out what could form the basis of a vegan equivalent of an egg.” @VentureBeat 2014, Hampton Creek’s data scientists team up with chefs to find the holy grail of plant proteins@.

    119.“What they’re cooking, though, isn’t even an egg. It’s a top-secret plant protein prototype with three ingredients that these chefs and a crew of biochemists and data analysts are coaxing through the R&D phase before launching it as a food product. Dubbed Just Scramble, it’s on schedule to debut in the food-service sector at the end of this year. And in case there is any doubt: This eggless innovation is being designed to compete against and even outperform the humble egg.

    Just Scramble is being hatched by Hampton Creek.” @Washington Post 2014, Can this company do better than the egg?@.

    120.See Funding section for amounts and investors participating in each round of funding for Hampton Creek. @Crunchbase company profile, Hampton Creek@.

    121.“…Hampton Creek, which is backed by some of the world’s richest men including Bill Gates and Li Ka-shing, is a lot further along in its quest to replace eggs in all foods.” @Forbes 2014, Bill Gates-Backed Food Startup Hampton Creek@.

    122.“Quality improvements

    The team is working to enhance the quality of cultured meat, at a small-scale level of production, in three ways:

    • Achieving an optimal protein content level by changing the culture and feeding conditions
    • Adding fat tissue to the product which would be added to the skeletal muscle tissue to create a true meat ‘mimic’
    • Elimination of animal products

    The team is attempting to change the culture conditions in the lab to remove all animal products, most significantly fetal bovine serum (FBS). Developing an animal-free medium is very challenging because skeletal muscle and satellite cells are particularly dependent on serum. Professor Post’s team is also working on a synthetic replacement for bovine collagen, another animal product that is important for cell and tissue organization. Removing these products is necessary in order to eventually secure regulatory approval and ensure that the meat can be produced sustainably, without infringing on animal welfare.” @GiveWell’s non-verbatim summary of a conversation with Mark Post, March 24, 2015@.

    123.“Quality improvements

    The team is working to enhance the quality of cultured meat, at a small-scale level of production, in three ways:

    • Achieving an optimal protein content level by changing the culture and feeding conditions
    • Adding fat tissue to the product which would be added to the skeletal muscle tissue to create a true meat ‘mimic’
    • Elimination of animal products

    The team is attempting to change the culture conditions in the lab to remove all animal products, most significantly fetal bovine serum (FBS). Developing an animal-free medium is very challenging because skeletal muscle and satellite cells are particularly dependent on serum. Professor Post’s team is also working on a synthetic replacement for bovine collagen, another animal product that is important for cell and tissue organization. Removing these products is necessary in order to eventually secure regulatory approval and ensure that the meat can be produced sustainably, without infringing on animal welfare.” @GiveWell’s non-verbatim summary of a conversation with Mark Post, March 24, 2015@.

    124.“To begin to make its meat product commercially viable, Professor Post’s team hopes to scale production to the capacity of a 25,000-liter bioreactor.” @GiveWell’s non-verbatim summary of a conversation with Mark Post, March 24, 2015@.

    125.“Dr. Nicholas Genovese, a visiting scholar at the University of Missouri, has recently joined the first academic lab in the United States dedicated to cultured meat. The lab can accommodate four scientists and Dr. Genovese is the first hire.” @GiveWell’s non-verbatim summary of a conversation with Isha Datar, March 10, 2015 and July 24, 2015@.

    126.“Nicholas Genovese, PhD – Research Summary

    As a visiting scholar at the University of Missouri, I am currently developing methods for in vitro specification of ungulate pluripotent stem cells toward differentiated tissue lineages. Potential applications for this research include cultured meat production systems, model systems for regenerative medicine and basic livestock developmental biology.” @IEET 2014, Interview with Nicholas Genovese@.

    127.“Nicholas Genovese, PhD – Research Summary

    As a visiting scholar at the University of Missouri, I am currently developing methods for in vitro specification of ungulate pluripotent stem cells toward differentiated tissue lineages. Potential applications for this research include cultured meat production systems, model systems for regenerative medicine and basic livestock developmental biology.” @IEET 2014, Interview with Nicholas Genovese@.

    128.“The Modern Agriculture Foundation – a nonprofit organization founded in early 2014 in Israel – is launching a world-wide pioneering project in the study field of cultured meat, focused exclusively on chicken meat. The project will start on January 2015 headed by Professor Amit Gefen from Tel Aviv University, one of the world’s leading experts in Tissue Engineering.

    The project team will be conducting a feasibility study for the production of cultured chicken breast meat that will be published and shared with the general public. During the course of the project, the challenges of production of cultured chicken breast meat will be mapped and potential solutions, along with the implications of their realization (methodology, time and cost), will be examined and described.” @Modern Agriculture Foundation Press Release, Jan 2015@.

    129.“The Modern Agriculture Foundation – a nonprofit organization founded in early 2014 in Israel – is launching a world-wide pioneering project in the study field of cultured meat, focused exclusively on chicken meat. The project will start on January 2015 headed by Professor Amit Gefen from Tel Aviv University, one of the world’s leading experts in Tissue Engineering.

    The project team will be conducting a feasibility study for the production of cultured chicken breast meat that will be published and shared with the general public. During the course of the project, the challenges of production of cultured chicken breast meat will be mapped and potential solutions, along with the implications of their realization (methodology, time and cost), will be examined and described.” @Modern Agriculture Foundation Press Release, Jan 2015@.

    130.We looked for sources of funding, and the largest we found included $1M for Mark Post’s burger prototype and 2M euros or $4M from the Dutch government (conflicting reports as shown in quotes below). We are not aware of any other past grants of this size.

      • “ ‘Some people think this is science fiction,’ Sergey Brin, founder of Google and the single donor who provided funding (nearly $1 million thus far) for Post’s research, said, but he sees it as an achievable goal.” @Verge 2013, Lab meat@.
      • “Professor Mark Post of Maastricht University in the Netherlands, who had led the 5-year research effort funded by Mr Brin, accepted that the burger was still work in progress and that he needed to find a way of adding fatty tissue to the cultured beef to make it more palatable.” @Independent 2013, Lab meat taste test@.
      • “The Netherlands’ Government has also invested around $4 million in Dutch research into in-vitro meat production.” @CNN 2009, Lab meat@.

    131.“Currently there is slightly more research being conducted on cultured meat in academia than in industry. Apart from Professor Post’s five-person team working on muscle tissue engineering, small research groups throughout the world are working on cultured meat, including a team in Israel that is attempting to develop chicken and another team in Queensland, Australia, that is developing cultured fish. Interest in cultured meat seems to be growing among academic researchers.” @GiveWell’s non-verbatim summary of a conversation with Mark Post, March 24, 2015@.

    132.“There is no dedicated funding for the field of cultured meat.” @GiveWell’s non-verbatim summary of a conversation with Isha Datar, March 10, 2015 and July 24, 2015@.

    133.Based on materials from conversations not documented in public notes.

    134.“Post, who is a vascular biologist and a surgeon, also has a doctorate in pulmonary pharmacology. His area of expertise is angiogenesis—the growth of new blood vessels. Until recently, he had dedicated himself to creating arteries that could replace and repair those in a diseased human heart. Like many of his colleagues, he was reluctant to shift from biomedicine to the meat project. ‘I am a scientist, and my family always respected me for that,’ he said. ‘When I started basically spending my time trying to make the beginning of a hamburger, they would give me a pitiful look, as if to say, You have completely degraded yourself.’” @New Yorker 2011, Test-tube burgers@.

    135.“New Harvest is a strategic grant-making organization devoted to kickstarting an industry of animal products made without animals. These technologies use cell cultures to replace substances conventionally obtained from animals. In the past year New Harvest has broadened its work beyond cultured meat to include cultured milk, eggs, and more. New Harvest would like to kick start a new industry around these new technologies to make animal agriculture obsolete. To further these goals and populate the new industry with more players, New Harvest supports academic research and entrepreneurship by issuing seed research grants of up to $50k.” @GiveWell’s non-verbatim summary of a conversation with Isha Datar, March 10, 2015 and July 24, 2015@.

    136. “From January 1 to December 31, 2013, New Harvest spent a total of $58,115.03

    • $50,000.04 on the Executive Director’s salary
    • $2,647.50 on web development
    • $4437.14 on travel expenses
    • $1030.35 on miscellaneous expenses (Network for Good subscription, printing, etc.)”

    @New Harvest Expenditures@.

    137. “Professor Post is starting a company to achieve scale-up at this level, which would not be possible from within the university.” @GiveWell’s non-verbatim summary of a conversation with Mark Post, March 24, 2015@.

    138. “While most of his career was spent in medical and public health pursuits, van Eelen continued to think about the potential for meat to be industrially produced without the conventional raising and slaughter of animals. In the 1990s he entered into partnerships to create a cultured meat process, and while the resulting laboratory work was unsuccessful, towards the end of the decade van Eelen did file several patents for cultured meat techniques in the Netherlands and the United States. Beginning in 2000, van Eelen, then in his 70s, organized a consortium of Dutch researchers and helped them to obtain grant funding from the Dutch Ministry of Economic Affairs – with additional help from a consortium of food companies and universities. This led to four years of research, between 2005 and 2009, and while progress was never fast enough for van Eelen’s taste, it did produce not only very high-quality scientific work, but also the seeds of later projects, including Mark Post’s very well known work on the 2013 hamburger, funded by Sergey Brin.” @New Harvest 2015, Willem Van Eelen obituary@.

    139. “In 2002, NASA took a passing interest in the idea and funded Morris Benjaminson at Touro College, New York, to investigate making meat from muscle cells as a way to feed astronauts on deep space journeys.

    Dr Benjaminson removed a sample of cells from the muscle of a goldfish and managed to grow it outside the fish’s body. The fillet was marinated in garlic, lemon, pepper and olive oil and deep-fried. A panel of testers inspected the fillet and said it smelt and looked just like the real thing, but they weren’t allowed to eat it because of US laws prohibiting consumption of experimental products.

    Unfortunately, NASA decided there were easier and cheaper ways to feed astronauts, and stopped funding Dr Benjaminson.” @BBC 2011, Grow your own meat@.

    140. “Our purpose was to establish the feasibility of an in vitro muscle protein production system (MPPS) for the fabrication of surrogate muscle protein constructs as food products for Space travelers. In the experimental treatments, we cultivated the adult dorsal abdominal skeletal muscle mass of Carassius (Gold fish). An ATCC fish fibroblast cell line was used for tissue engineering investigations. No antibiotics were used during any phase of the research. Our four treatments produced these results: a low contamination rate, self-healing, cell proliferation, a tissue engineered construct of non-homologous co-cultured cells with explants, an increase in tissue size in homologous co-cultures of explants with crude cell mixtures, maintenance of explants in media containing fetal bovine serum substitutes, and harvested explants which resembled fresh fish filets.” @Benjaminson, Gilchriest, and Lorenz 2002@.

    141. “There are eight people on earth who have already eaten lab-grown flesh, and artist and tissue scientist Oron Catts at the University of Western Australia is one of those few. As part of the Tissue Culture and Art Project’s Disembodied Cuisine, he was part of the team that grew some frog meat on a slide, fried it up and ate it as a part of a ‘feast’ to send their project into the uneasy relationship of meat and science. Following earlier successes in 2001 at growing lamb in a lab, Catts and his team grew coin-sized frog steak in 2003 at a cost of roughly $650 a gram, just millimetres thick. They fried the thumbnails of frogmeat in garlic and honey with a dash of Calvados, a recipe which they named ‘a la Davis’ in honour of a fellow bio-artist Joe Davis whose frog muscle powered ornithopter failed to launch on ethical grounds, a process as cruel as marinating dead amphibian in honey and eating it. The Lilliputian amphibian steaks were served with a selection of herbs, also lab-grown from plant tissue culture. Eight people sat down to this micro-degustation. The results were a success, at least in terms of replicating an uneasy relationship. ‘Four people spat it out. I was very pleased.’” @Lees 2008, The taste of test tube meat@.

    142. “The lab closure mostly affects Mironov’s other research focus: trying to grow meat in the lab — a goal that some scientists think could help to feed the world’s growing population with less strain on the environment (see ‘A taste of things to come?’). Mironov, like others in the same field, has had trouble getting funding for that work — he had a $25,000 grant years ago from the animal-rights organization People for the Ethical Treatment of Animals (PETA), which is interested in the prospect of producing meat without killing livestock. He has worked with turkey cells in his lab, has come up with a novel idea for how to exercise lab-grown muscle and says he has designed a better bioreactor, although the details are not public.

    ‘My health is under threat. My research is blocked. They say I am unstable. It has become surrealistic.’

    PETA recently gave postdoc Nicholas Genovese a 3-year grant to work on lab-grown meat, and he started working in Mironov’s lab in December as a visiting scholar.” @Nature News 2011, Meat-growing researcher suspended@.

    143. “Professor Mark Post first got involved in a Dutch government-funded programme investigating ‘in vitro meat’ in 2008, when he was a professor of tissue engineering at the Eindhoven University of Technology. The programme had been initiated by Willem van Eelen, an 86-year-old entrepreneur who held a long-time fascination for the possibility of culturing meat. When the director of the programme fell ill, about mid-way through the programme, Post took over supervision of the PhD students. Motivated by the potentially high societal impact, he continued research even after the funding had ended in 2010. Renewed funding by a private partner enabled the realisation of a project to create a processed meat product using muscle cells from a cow.” @Maastricht University, Mark Post bio@.

    144. “The fundamental problem is that myosatellite cells will only divide dozens of times, probably because their telomeres — the protective ends of the chromosomes — wear down with age. There are ways of boosting their proliferation. One is to add a gene for the repair enzyme telomerase. Another, being investigated by the start-up company Mokshagundam Biotechnologies in Palo Alto, California, involves inserting a tumour-growth-promoting gene. … At Mokshagundam Biotechnologies, the goal is to make a spam-like mix of different muscle and other cell types that provide the ‘umami’ taste that characterizes meat. Scientists will also have to find a way of adding nutrients such as iron (which comes from blood) and vitamin B12 (which comes from gut bacteria).” @Nature News 2010, Food: A taste of things to come?@.

    145. “Nonetheless, a group of six recent graduates from Singularity University’s graduate studies program—a 10 week program in Silicon Valley that asks participants to develop technologies that can impact 1 billion people in a decade—are entering the fray with a company that focuses on one specific (but vital) in-vitro meat challenge: developing better cell scaffolding, which is necessary to create 3-D meat.” @Fastcoexist 2013, Lifestock: The Newest Player In The Growing Lab-Made-Meat Industry@.

    146. The last update on their Facebook page’s timeline is from September 2013, and the timeline was previously active. @Lifestock Facebook Page@.

    147. “It seems fitting to first discuss the world’s first ever In-Vitro Meat Symposium which was held at the Norwegian Food Research Institute in Norway in April 2008. The purpose of this symposium was to identify and discuss the key scientific challenges that need to be solved for cultured meat to become a viable commercial product; to bring together a network of scientists working towards the same goal and organise their various efforts; and to facilitate the funding of the necessary research and activities.

    The Symposium was hosted by the In Vitro Meat Consortium and the Norwegian University of Life Sciences, and was attended by New Harvest’s founder Jason Matheny, FutureFood’s project leader Kurt Schmidinger, and over 50 other leading scientists and representatives from NGOs wanting to see the development of cell cultured meat.” @New Harvest 2014, World’s First In Vitro Meat Symposium@.

    148.“The workshop in Sweden engaged an interdisciplinary group of 25 scientists who all have special interest in cultured meat. Some of them have specialties in tissue engineering, stem cells and food technology. Others are environmental scientists, ethicists, social scientists and economists. All of these areas have been discussed during the workshop. The result is encouraging regarding the possibility to actually be able to supply consumers with cultivated meat in the future, and the scientists have not found any crucial arguments against cultured meat.” @Science Daily 2011, Growing meat in the lab@.

    149. “Ionat Zurr from Symbiotica will deliver an oral presentation titled “Framing in-vitro meat as art” as part of the ‘Tissue Engineered Nutrition’ panel in the 3rd TERMIS World Congress 2012.” @Pavillon 35, In vitro meat as art.

    150. “On May 29th, I had the great pleasure of attending the very first Edible Bioeconomy event in San Francisco, hosted jointly by New Harvest and Indie Bio. The event was a way for people who are involved and interested in the emerging economy that is being built around sustainable animal products (including but not limited to leather, eggs, dairy products, and eventually meat) to have the chance to taste and hear firsthand about some of what has been developed thus far, while engaging in discussions about how to tackle practical challenges like what language can be used to describe these kinds of products, how to overcome the misinformation and confusion felt by the general public on how science relates to food, and other topics.” @New Harvest 2015, Edible Bioeconomy Event–Recap@.

    151. “The First International Symposium on Cultured Meat in association with Maastricht University, New Harvest and Brightlands Maastricht Health Campus will be held:

    October 18-20th, 2015
    Maastricht, the Netherlands

    We strive to create an inspiring but also critical atmosphere discussing Tissue engineering for Food, in particular Cultured Meat.” @First International Symposium on Cultured Meat, 2015@.

    152.“Between 1990 and 2002, the worldwide cumulative capital investment in the tissue engineering industry was over $4.5B (Lysaght 2005), with more than 90% from the private sector.” @USG 2007, Advancing Tissue Science and Engineering@.

    153. “There are four main manufacturing approaches to TERM therapy: (a) manufacturing allogeneic (universal donor) TERM therapies, (b) manufacturing autologous (patient-specific) TERM products, (c) manufacturing decellularized scaffolds for TERM therapies, and (d) bioprinting for TERM therapies.” @Hunsberger et al. 2015, Manufacturing Road Map for Tissue Engineering and Regenerative Medicine Technologies@.

    154. “The Regenerative Medicine Foundation Annual Conference held on May 6 and 7, 2014, had a vision of assisting with translating tissue engineering and regenerative medicine (TERM)-based technologies closer to the clinic. This vision was achieved by assembling leaders in the field to cover critical areas. Some of these critical areas included regulatory pathways for regenerative medicine therapies, strategic partnerships, coordination of resources, developing standards for the field, government support, priorities for industry, biobanking, and new technologies. The final day of this conference featured focused sessions on manufacturing, during which expert speakers were invited from industry, government, and academia. The speakers identified and accessed roadblocks plaguing the field where improvements in advanced manufacturing offered many solutions. The manufacturing sessions included (a) product development toward commercialization in regenerative medicine, (b) process challenges to scale up manufacturing in regenerative medicine, and (c) infrastructure needs for manufacturing in regenerative medicine.” @Hunsberger et al. 2015, Manufacturing Road Map for Tissue Engineering and Regenerative Medicine Technologies@.

    155. “The increasing use of mammalian cell lines, including versatile and uniquely capable stem cells, in upstream bioprocessing has imposed specific demands on cell cultures: namely, better-defined media. The rising stakes and production levels of companies active in biopharmaceuticals have dictated improved reproducibility or consistency in product; mitigation of the risk of contamination; and the use of culture product more amenable to downstream processing or purification.

    Media can be organized into three broad types:

    • Chemically defined media not only lack animal-origin components, they also exclude components that lack known chemical structure. Chemically defined media do not contain proteins, hydrolysates, or other components of unknown composition.
    • Animal-free media contain no components of animal origin, but are not necessarily chemically defined. For example, animal-free media may contain bacterial or yeast hydrolysates or plant extracts.
    • Serum-free media are prepared without the use of animal serum, but they may not be entirely free of serum-derived products. Serum-free media may contain undefined animal-derived products such as serum albumin (purified from blood), hydrolysates, growth factors, hormones, carrier proteins, and attachment factors.

    The biopharmaceutical industry’s shift away from animal-derived culture products is expected to continue, particularly given the ascension of mammalian cell lines in biopharmaceutical production. Serum-free media is the more complex composition designed for universal use in culturing mammalian cell lines. Animal-free and chemically defined media formulations are less complex and more defined, but are limited to the cultivation of specific cell types.” @Genetic Engineering & Biotechnology News 2015, Biopharma Demand Is Driving the Cell Culture Market@.

    156. “Cultured meat is likely to be a very expensive product. An analogy is the cost to manufacture a six-pack of beer. The actual beer is the cheapest component. The price is significantly increased by the cost of the bottles, packaging, distribution, manufacturing and overhead costs. The same holds true for tissue engineering. The necessary infrastructure is much more expensive than the cells themselves. More significant costs include:

    • Employing the necessary skilled technicians, quality, regulatory and manufacturing staff
    • Maintaining sterile environments and lab spaces, especially cleanrooms, which use expensive fans and filters to maintain very low levels of air contamination
    • Sterile disposable plastic ware
    • Necessary supplements and cell media”

    @GiveWell’s non-verbatim summary of a conversation with a scientist with 18 years experience in the tissue engineering industry, April 23, 2015@.

    157. For example the Apligraf bundle price is over $1400 for 25 square cm of the wound dressing product, whereas ground beef is only a few dollars per pound. “2015 Apligraf Medicare Product and Related Procedure Payment: Leg. First 24 square cm: Hospital Payment $1,406.87 (includes Q4101, 15271 and 15272) and Physician Payment $87.00.” @Apligraf Medicare Product and Related Procedure Payment, 2015@.

    158. Based on a scientific advisor’s prior knowledge of the tissue engineering industry.

    159. This is an impression we have based on general background knowledge, and we believe it to be generally accepted wisdom. For an example of someone expressing a similar perspective, see the quote below:

    “It is unlikely the venture capitalists will make any big investments in cultured meat in the near future. Venture capitalists generally want 3-5X returns on their investments in three to five years. Making cultured meat profitable still depends on 3 major manufacturing hurdles and a big shift in consumer mindsets. A typical venture capitalist won’t be interested in taking on those risks.” @GiveWell’s non-verbatim summary of a conversation with a scientist with 18 years experience in the tissue engineering industry, April 23, 2015@.

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