UC Berkeley — Research on Drought-Tolerant Rice (Brian Staskawicz)

A rice farm in rural India. This grant supports research seeking to increase the drought tolerance of Indian rice. (Photo by Ramnath Bhat)

Grant Investigators: Chris Somerville and Heather Youngs

This page was reviewed but not written by the grant investigators. UC Berkeley staff also reviewed this page prior to publication.

The Open Philanthropy Project recommended a grant of $200,000 over three years to UC Berkeley to support Professor Brian Staskawicz’s work on CRISPR modifications to increase drought tolerance in Indian rice. It’s our understanding that sporadic drought has caused Indian rice yields to become erratic, which has negative impacts on the livelihood of about 100 million small farmers. The proposed experiments, which will be funded in part by a match from the Innovative Genomics Institute, will exploit recent advances in genome editing.

This discretionary grant follows our December 2016 support of a plant pathology workshop at UC Berkeley and falls within our interest in funding scientific research.

UC Berkeley — Plant Pathology Workshop (Brian Staskawicz)

Published: March 2017

The Open Philanthropy Project recommended a grant of $63,000 to the Innovative Genomics Institute at UC Berkeley to support a two-day workshop on plant pathology with a small group of experts organized by Professor Brian Staskawicz. The workshop was intended to identify and discuss specific research topics in plant pathology related to increasing crop disease tolerance and/or resistance that might merit philanthropic support, with the goal of improving the welfare of small farmers in the developing world.

Impossible Foods — R&D Investment

The Impossible Burger. (Photo courtesy of Impossible Foods)

Published: March 2017

Impossible Foods staff reviewed this page prior to publication.

The Open Philanthropy Project has invested in Impossible Foods (IF) to accelerate the development of plant-based meats.

 

Limited disclosure

IF asked us not to disclose a number of important pieces of information related to this investment because IF is a for-profit, privately held startup company with a significant portfolio of intellectual property. Therefore, we have not gone into as much detail as we otherwise would.

In particular, we agreed with IF not to publicly disclose the terms of the investment, which products we have seen or tasted at IF’s headquarters, or any information about specific scientific and technical challenges that IF’s team is working to overcome.

Background

The Open Philanthropy Project invested in IF as part of our work on farm animal welfare.

IF is a Silicon Valley-based technology startup that develops meat directly from plants. IF launched its first product, the Impossible Burger, in July 2016. The Impossible Burger is now on the menu of eleven restaurants across the U.S. IF is constructing a factory in California that, when fully ramped up in the second half of 2017, will increase supply of the Impossible Burger to restaurants throughout the United States.

While in the near term IF remains focused on the successful commercialization of the Impossible Burger as its flagship product, IF’s longer-term plans include development and commercialization of additional plant-based products to compete with all the foods that today are produced using animals in all major regions globally.

Since its founding in 2011, IF’s team of scientists has done advance research and development (R&D) on different products including ground and whole-cut beef, pork, chicken, fish, and dairy and cheese products. With our new investment, we hope to accelerate the development and commercialization of a second wave of plant-based foods, enabling IF to expand from the Impossible Burger to additional product categories.

Case for investment

In rough outline, we arrived at a decision to make this investment as follows:

  1. Farm animal welfare is one of our focus areas. We specifically wanted to invest in people who are working on plant-based alternatives to chicken, eggs and fish because very large numbers of animals are negatively affected by current practices related to producing these foods.
  2. We have chosen not to prioritize investment in R&D for cultured meat, especially for whole-cut meat (i.e. not ground meat) because we believe technical tractability is currently low (particularly with respect to getting costs acceptably low).
  3. We were interested in someone using a bioengineering-based approach, analogous to what IF has done with the Impossible Burger, to develop plant-based alternatives to chicken, eggs, and fish. We were particularly interested in IF’s approach based on:
    1. our Scientific Advisor Chris Somerville’s opinion that Pat Brown (IF’s Founder and CEO) is an outstanding scientist;
    2. a belief that technical barriers to a viable, low-cost product in this area are much smaller than technical barriers to developing whole-cut cultured meat;
    3. a belief that more science-heavy/bioengineering-oriented approaches were more likely to yield a transformative product than other attempts to develop plant-based alternatives;
    4. a taste test of the Impossible Burger, which we believe is a promising product.
  4. We were aware of the Impossible Burger and IF’s investments from venture capital firms, Google Ventures, Bill Gates and others. We decided to ask IF if it would be interested in working on whole-cut chicken in particular, or whether it could help us find someone else to work on chicken.
  5. IF told us that it could apply an investment to accelerate its work on the development of specific food categories. IF presented us with several scenarios in which the IF teams would work on one or more food categories.
  6. After a review of IF’s long-term product plan, interviews with key scientists and executives, and reviews with our financial advisors, we opted for an investment with the intention of accelerating the development of multiple food categories.
  7. We agreed informally with IF’s senior executives that IF would use Open Philanthropy’s investment to accelerate commercialization of multiple food categories.

    Plans for follow-up

    We hope that our investment will accelerate the development and commercialization of key products by a few years. We plan to meet with IF every 6 to 12 months over the next two years to check on IF’s progress.

    Key questions for follow-up include:

    • Is IF’s work toward the development of new categories of plant-based meat proceeding according to schedule?
    • How much scientific effort is directed toward each new food category? Is that in line with plans?
    • How much progress has been made on technical challenges or other potential roadblocks to commercialization?
    • Did IF’s cost of production per pound of ground beef decrease as anticipated?

Animal Product Alternatives

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

DOCUMENT SOURCE
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Amyris company history Source (archive)
Angel.co company profile, Hampton Creek Source (archive)
Angel.co company profile, Muufri Source (archive)
Apligraf website, How is it Made Source (archive)
Apligraf Medicare Product and Related Procedure Payment, 2015 Source (archive)
Apligraf website, What is Apligraf Source (archive)
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BBC 2011, Grow your own meat 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)
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CBInsights company profile, Modern Meadow Source (archive)
CNN 2009, Lab meat Source (archive)
Crunchbase company profile, Hampton Creek Source (archive)
Crunchbase company profile, Impossible Foods Source (archive)
Crunchbase company profile, Impossible Foods Investors Source (archive)
Crunchbase company profile, Modern Meadow Source (archive)
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)
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Exmoor In Vitro Meat Consortium Preliminary Economics Study, March 2008 Source (archive)
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Wired 2014, Forget GMOs. The Future of Food Is Data—Mountains of It Source (archive)

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