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Shojinmeat Project : Open-Source Cell-Ag Initiative

2021.03

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“Shojinmeat Project” - Who we are

“Democratization of cellular agriculture”

Nonprofit non-corporate non-university citizen science community of DIY bio/fab enthusiasts, students, researcher, artists, writers etc. for cellular agriculture

Open source cellular agriculture” by DIY bio

Public communication by art and education

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Ongoing projects

Creative Cells Kyoto, @CleanmeatKyoto

・DIY bio & cell culture experiments

・Workshops and micro-conferences

・Advocacy for cellular agriculture

・Media and social communication

・Art, design and creativity project

・Career advice in cellular agriculture

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Means of food production

Hunting

Farming

Domestication

Fermentation

Synthesis

Cell culture

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“Meat”

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From where?

Meat is ~x40 more resource intensive

Lamb:~x50, Beef:~x40, Pork:~x20, Poultry:~x7

“Meat”←animals←feed, water, land

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Deforestation

Public health hazard

Water shortage

“Meat”←animals←feed, water, land

Hoekstra, Mekonnen, PNAS 2012

http://www.pnas.org/content/109/9/3232

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Food vs. Feed vs. Fuel

Agri-

cultural resources

Food

Feed

Fuel

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Anticipated alternative proteins

*As demand for protein grows, existing meat cannot sustainably serve for all.

Meat

Soy etc.

Dairy

Meat

Dairy

Soy etc.

New alternative protein

Plant-based

Tofu

Algae

Insects

Biosynthetic

Cell-based

New protein source

“Meat & dairy produced in new ways”

Plant-based meat & dairy equivalent

Now

Future

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Cellular Agriculture

Agricultural products by cell culture

Medicine technology, Agriculture application

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Cell-cultured meat (cell-cultivated meat)

Muscle cells

Bioreactor

Culture medium

Processing

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Energy conversion efficiency

< 0.1%

Prospectively,

Microalgae: 4~11%?

“Artificial leaf”: 10%+?

https://aiche.onlinelibrary.wiley.com/doi/abs/10.1002/btpr.2941 Y.Okamoto et al. Biotech. Prog. 2019

~4%

~35%

50~90%

Unregulated

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Cell-ag: living things as engineering materials

Ores to metal

Petroleum to plastics

Live cells to tissues

Cyborg parts?

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Research track record 1

1997

Goldfish meat

@NASA

Appearance in sci-fi - Concept known since 19th century

2004

New Harvest founded

Jason Matheny contacts NASA staff

2005

Netherlands funds €2M

2007

In vitro meat consortium

funding discontinued

funds

2000

Works by

Oron Catts

@Harvard

Lead by Willem van Eelen (deceased)

Patent filed in 1997

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Research track record 2

2012

Sergey Brin from Google contacts former member of In vitro meat consortium

2013

Demonstration by Prof. Post

2014

Shojinmeat Project

2015

Memphis Meats

2015

“Cellular agriculture” - term coined

2013

New Harvest invests in cell-ag startups

(Clara Foods, Perfect Day)

2016

SuperMeat

2017

Finless Foods

€280k burger

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Ongoing cellular agriculture projects

Wild Type

Fish without catch

IntegriCulture

Foie gras without ducks

Shiok Meats

Shrimp without pond or catch

The products are not “imitations” - they are (or try to be) molecularly the same!

Perfect Day

Milk without cows

Clara Foods

Egg white without chicken

Ginkgo Bioworks

Vanilla, scent, various ingredients

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The positive impact

Science & Technology

・Technological hurdles?

・Medical applications?

Politics & Economics

・Shift in food market?

・Industry landscape?

Arts and Culture

・Religious views?

・Social norms to change?

Hanna Tuomisto 2011

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The technical problem

$325,000

Cell-based burger, 200g

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Technological milestones

1. Inexpensive media

2. Scaling & automation

CapEx &

Staffing

Culture medium

$200k+/kg

Conventional method

$2

Conventional meat

price & quality parity?

3. Added value and consumer acceptance

Technological goals

  1. Food grade culture medium
  2. Scaled culture plant design
  3. Tissue engineering for flavor and texture

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Gospodarowicz D and Moran JS, 1976, Annu Rev Biochem Eagle H, 1959, Science

Culture medium

Expensive for what’s actually in (as they are made by the bio-pharma grade)

Expensive and insecure supply, and serum risks infectious diseases - viruses, “mad cow” etc.

Made by fermentation of recombinants, but regulatory approval and extraction are expensive.

Basal medium

Foetal bovine serum

Signal compounds

Sugar, Amino acids, Vitamins, Minerals

$20/L

Albumin, Buffer, Insulin, Transferin

$900/L

Growth factors

Survival factors

$450/mg

Bottlenecks in culture medium

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Standard DMEM(FBS10%) 500ml

DMEM 450ml $10

Serum(FBS) 50ml $45

Non essential amino acid $1.30

LIF  10 U/ml $2.00 etc・・・

Medium for 1~2g of cells: $58.30~

$5000+ for 100g

Cost of culture media for “easy” cells

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Myoblast culture by Essential 8® defined serum

An analysis of culture medium costs and production volumes for cell-based meat, Liz Specht, Good Food Institute (2018)

https://www.gfi.org/files/sci-tech/clean-meat-production-volume-and-medium-cost.pdf

Basal medium

DMEM components

The E8 medium based on TeSR medium does not contain albumin and other animal-based materials, and its composition is publicly known. Its price is around $380/L.

Serum

ITS, AA2P

Signal compounds

FGF2, TGFβ

$1.60

Bulk-purchase price

$5.44

$181.36

AA2P:Vitamin C derivative

ITS:Insulin, transferin, Na2Se

500ml culture medium

100g of cells

$188.40

$15,000~

Myoblast requires FGF2 and TGFβ peptides to culture. Besides peptides, some fatty acids and cholesterols also act as signaling compounds.

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Hepatocyte (liver cells) and iPSC’s, 100g

Basal medium

Serum

Signal compounds

Hepatocyte

iPSC(medical)

DMEM 450ml $10

FBS 50ml $45

Additional amino acids $1.30

HGF 20µg ~$700

EGF 10µg ~$6.40

~$760

~$90,000

~$3000

$300,000+?

Specialised medium,

~$1000/L

Often not required

Multiple GF’s i.e. “bFGF” consumed for each steps

500ml culture medium

100g of cells

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Cost of goods analysis

Basal medium

Serum

&

Signal compounds

Material[2]

Price

Purpose

Why expensive

Possible actions

NaCl

$56

Medium

Used a lot

Recycle medium

Glucose

$50

Cell mass

Used a lot

Less expensive procurement channel

Amino acids

$395

Cell mass

Used a lot

Less expensive procurement channel

HEPES

$3933

Medium

High unit price

Use an alternative, recycle medium

AA2P

$10,035

Medium

High unit price

Use an alternative, recycle medium

Cost of goods analysis of E8 medium per 20,000L(3.5t of meat) - bulk procurement assumed[1]

Insulin

$131,920

Serum

High unit price

Use an alternative

Transferin

$85,600

Serum

High unit price

Use an alternative

FGF2

$4,010,000

GF

Extreme price

Use an alternative

TGFβ

$3,236,000

GF

Extreme price

Use an alternative

[2] NaCl, HEPES and AA2P remains in medium while glucose and amino acids are consumed or converted into cell mass.

[3] Serum and signal compounds are expensive, but can not be recycled as they are consumed.

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Strategy A:Driving down the cost

Efficiency

Stability

Unit price

Alternative

Actions taken

References

Expert interview on less expensive growth factors in Good Food Institute’s grant program:

Dr. Peter Stogios, Senior Research Associate, University of Toronto, Canada (2019):

https://www.gfi.org/dr-peter-stogios-growth-factor-research

GFI competitive grant program

https://www.gfi.org/2019-competitive-research-grant-program

Use alternatives such as fatty acids and egg yolk components

Design the growth factor molecules to increase the efficiency and reduce the required quantity

Use of larger bioreactors to grow recombinants, use of plant-based GF’s, cheaper extraction method etc.

Design the growth factor to give higher structural and thermal stability to withstand less expensive extraction methods

Serum & Signal compounds

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Cost of goods (ingredients) analysis

Medium Meat

$41/L $100/lb

$15/L $36.6/lb

$4.7/L $11.5/lb

$3.7/L $9.0/lb

$0.77/L $2.2/lb

Scenario A~E

A: All GF’s down to 1/10 in cost

B: FGF2 & TGFβ at insulin price

C: A&B

D: All GF’s at $4/g

E: Basal medium at $0.23/L

“Strategy A” assumed

Analysis by the Good Food Institute (2019)

https://www.gfi.org/files/sci-tech/clean-meat-production-volume-and-medium-cost.pdf

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Cocultured hepatocyte produces serum and signal compounds without a need for their external addition.

PCT/JP2016/067599 JP Pat.6111510

Integriculture Inc. / Dr. Ikko 2016

Strategy B : Large-scale coculture

Feeder bioreactor system by IntegriCulture (Japan)

Quadruple co-culture by Aleph Farms (Israel)

Basal medium

Serum &

Signal compounds

4 cell species mutually stimulate cell proliferation, i.e. fat cells enhances muscle cell proliferation.

Basal medium

Serum &

Signal compounds

Myoblast

Hepatocyte

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Demonstration of coculture

Significant hepatocyte growth without added growth factors (HGF)

Control (0%)

10% conditioned medium

25% conditioned medium

50% conditioned medium

Count of cells of all sizes,

relative to the control group

mouse placental cells

dishes with Day-12 foetal liver cells in FBS 10% medium

7 Days

Transfer culture medium

Dr. Ikko 2016

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Cell-based chicken liver demonstration

cell-based chicken liver paste

Grow cells

Fat-load cells

Assemble cells

Dr. Ikko 2016

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Low-cost Liver cell culture

Figure by Integriculture Inc.

DMEM  450ml  $10

Non essential amino acid  $13.0

FBS 50ml $45

HGF 40ng/ml $700 (20µg)

EGF 20ng/ml $6.40(10µg)

$760~

Liver cell aggregate on collagen scaffold- HGF/EGF obtained from cocultured cells

DMEM  450ml  $10

50ml $1.70

~$12

yeast extract, an FBS alternative

Yeast extract

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“Food grade DMEM”

Culture medium, as inexpensive as bottled beverages?

DMEM  450ml  $10

50ml $1.70

~$12

”DMEM” 450ml  $0.09

50ml $0.01

$0.10

Sugar

Amino acids

Vitamins

Minerals

Basal

medium

=

Yeast extract

Yeast extract

Use of yeast extract marketed as food, not laboratory reagent

or its equivalent

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“Food grade” demo - Sports drink culture media

90% DAKARA

80%

70%

60%

0%

(DMEM only)

50%

Days

Cell divisions

Proliferation of mouse L6 in DMEM/GreenDakara 10% FBS

#pH and osmolality of Dakara adjusted by NaHCO3(s) and 2M NaOH

Fluid name osmolality pH

DMEM(-, hi glu) 345 7.4

Pocari 338 3.4

Aquarius 291 3.37

Amino-Value 4000 289 3.63

AminoVital Gold 186 3.33

Vitamin Water 302 3.3

Green DAKARA 322 3.28

Amiiru Water 249 3.4

Mamoru Chikara 546 3.58

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DIY-DMEM (home made medium)

Glucose, amino acids, vitamin B’s, salts

Mix and filter to prepare

Chicken foetus heart cells primary culture

Protein supplement

Vitamin pills

Glucose

Salts

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Basal medium turning commodity product

Individual ingredients

Digested yeast residue?

Algae? Artificial photosynthesis?

Bulk purchase may partly reduce costs

Mixture of 20 amino acids, along with undigested dipeptides and tripeptides - impurities are acceptable as long as cells can be cultured, even with lower efficiency - the cheapest

”Minimum grade medium”?

Digest

Production at a Mega-ton scale

Alage

Artificial leaves

Power

Hydrogen bacteria

Electrolysis

Minimum grade medium

2020

Bridging methods

Basal medium as a commodity

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Mainstream demand for cell-based meat requires large supply of inexpensive amino acids. Novel raw materials and production process (the incumbent is fermentation) must be developed.

Rice

720Mt

Wheat, Barley

830Mt

Corn

880Mt

Cassava, Tubers 630Mt

Soy

260Mt

Sugar beet Canes, 2.1Bt

Oil Palms

Starch※1

40Mt

Sugar

170Mt

Meats 300Mt

(Beef 60Mt, Pork 110Mt, Poultry 80Mt※3)

Bioethanol※2

100BL

Amino acids※4

6Mt

Oil

40Mt

Food

(Carbs)

Cell-based meat

Plant-based protein sources

Process residue

Food

(Fats)

Food

(Carbs)

Figures are as of 2011, Geographic Annals 2014 (Ninomiya Books) ※1https://www.alic.go.jp/joho-d/joho08_000573.html   ※2 Monthly Report, MAFF Japan March 2015, http://www.maff.go.jp/j/zyukyu/jki/j_rep/monthly/201503/201503.html  ※3 USDA「World Markets and Trade」   ※4 Ajinomoto Co. Ltd.

Food

(Protein)

Food

(Protein)

Source: Mr. Akito Chinen

2nd Cell-Ag Conf. in Japan

Sources of amino acids for cell-based meat

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“Matter cycle” of cell-based meat

Convert to culture media

Large-scale cell culture

Waste fluid treatment

Algal production

Algae

sewage

Fertilizer

Culture medium

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“Is it tasty?” - Tissue engineering to add value

Sausage/burger

Proven ※although expensive

Low cost large scale cell culture

Sheet meat / “bacon”

Cell scaffold

Muscle/fat coculture

Steak / tissue

Tissue morphogenesis

Vascularization

Meat texture

Regenerative medicine

Where we are

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Tissue engineering, regenerative medicine and cellular agriculture

Cell culture�(human)

Cell culture

(animals)

Distribution

Distribution

Regenerative medicine

Cellular agriculture

Med.

Ag.

Procu-rement

Culture medium

Cell-ag and Regen. Medicine share the same technology.

Main differences are in purity, traceability and regulations

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Toolbox for cell-based meat

Scaled cheap cell culture

“Molded meat”

Cell paste

Living tissue

Cells are in order

Functions as a living tissue

Cell differentiation

Vascularization

Cell positioning by 3D bioprinting

Cellular scaffolds

in any order

Cell proliferation

Aleph Farms, 2021

Maastricht Uni, 2013

Acquisition of

differentiated cells

Ref: E.A. Specht, D.A. Welch, E.M.R.Clayton et al., https://www.sciencedirect.com/science/article/pii/S1369703X1830024X

It may be sufficient as long as it is edible, regardless of its viability as a living tissue

Viability as a living tissue

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3D culture by cellular scaffolds

Cellular scaffold has large surface area, which improves the efficiency of cell culture.

Sponge collagen scaffolds

Liver cells on scaffolds

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Other functions of cellular scaffolds

Edible scaffolds i.e. collagen, chitosan, chitin, arginate, cellu- lose, polysaccharides

Simulate fibre and meat texture

Moulds shape in mm or bigger scales

Aleph Farms (2019)

J.R. Gershlak et al., Biomaterials vol.125, pp13-22(2017) https://www.sciencedirect.com/science/article/pii/S0142961217300856?via%3Dihub

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3D bioprinting & plant hybrids

3D Bioprinting

Plant-based meat and cellular scaffolds

Cell-based fat and meat

・Simulates texture without constructing as viable live tissue

・Scaling is a WIP

3D printed plant-based meat startups, 2020~

(NovaMeat, Redefine Meat etc.)

adding cultured cells as “inks” for their products

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Building “meat” : Method 2

”In Vitro Engineering of Vascularized Tissue Surrogates” https://www.nature.com/articles/srep01316

Culture medium and starter cells

Procurement

Cell growth, vascularization

Tissue growth

※Further down the development timeline

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Tissue engineering to and beyond thick steak

Cells on scaffold

around 2020

Cell aggregate

2013

Cultured tissue

2026?

Designer meat?

2030?

Burger, sausage

Bacon, meat chips

Thick steak

Is this even ”meat”!?

Algae-myoblast co-culture

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Scaling as it is...

How cultured burger was made in 2013

⇒$260,000

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Conventional “scaled” cell culture

Needs much more scale

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The process needs a fundamental re-design

Labs, Hospitals

Brewery, Petrochemical complex

Culturing of cells has been optimised for laboratory scale

⇒€250k per burger

Culturing of cells becomes industrial scale

⇒Production at $2/kg

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Dr. Marianne Ellis, 2017

Implementation of scaled production methods

⇒”Chemical engineering”, “Plant Engineering”

Integration and systemization

“Cell culture processes suitable for scaling”

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How is temperature controlled?

Mixing method?

Pipeline diameter & flow rate?

Sterilization method & frequency?

How are filters cleaned?

Plant engineering - what exactly?

Speculative fish meat culture plant

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Production strategy and estimated cost

A:”Batch”

B:”Fed batch”

C:”Perfusion”

A:Produce (culture) cells for ~40 days, harvest once full

B:Produce by feeding the batch until waste metabolites build up

C:Produce while feeding and recycling the culture medium

←Estimated medium cost of cell- based meat based on method C-

$1.37/kg (GFI 2019)

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Comprehensive cost and footprint assessment

・Resource requirement from ‘cradle to the grave’

Life cycle assessment (LCA)

https://rationalwiki.org/wiki/File:LCA.PNG

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LCA uncertainties

Current quantitative LCA estimates depend on unestablished production processes and uncertainties may exceed 50%. LCA is expected to be a key point of discussion in international standardization of production processes.

2014 estimate included steam sterilization of bioreactors.

Hanna Tuomisto 2011

Hanna Tuomisto 2014

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Animal co-products and “secondary LCA”

Co-product alternatives

By synthetic materials and products[1]

Gelatin production by cell-ag[2]

Source of energy

Without decarbonization of the power source, GHG reduction may be limited.[3]

How is land freed from animal agriculture be used? (Secondary LCA)

The environmental footprint taking into account the alternative land use[4]

[1]https://www.atkearney.com/retail/article/?/a/how-will-cultured-meat-and-meat-alternatives-disrupt-the-agricultural-and-food-industry (AT Kearney)

[2] https://geltor.com/ Geltor Inc. markets cellular agriculture gelatin

[3] https://www.frontiersin.org/articles/10.3389/fsufs.2019.00005/full

Footprint of cultured meat if coal power remains for the next 1000 years

[4]https://drive.google.com/drive/u/0/folders/0B1yPiUX43toZY2sxUUtVRjlZTDA Tuomisto et al. 2017, Int’l Sym. Cultured Meat, (unpublished)

Other products include manure, gelatin etc.

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The positive impact

Science & Technology

・Technological hurdles?

・Medical applications?

Politics & Economics

・Shift in food market?

・Industry landscape?

Arts and Culture

・Religious views?

・Social norms to change?

Hanna Tuomisto 2011

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“Protein problem” in different stages

Is there enough protein?

Is it a secure source?

Is it sustain-able?

Many rely on imports while

overfishing continues

( Economic and Social Research Institute, Dublin, Ireland, 2010 https://www.esri.ie/pubs/WP340.pdf)

“Public expenses due to meat is set to reach $1.6T by 2050”

Farm Animal Investment Risk and Return Initiative

Poor conturies

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“Impending food crisis”?

”Boiling frog"

・Food prices rise incrementally over decades

・Lower living standards, more frequent civil unrest

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How cellular agriculture is a solution

1

2

Reduce protein consumption.

Change the way we eat.

Find sustainable protein source.

Preserve culinary culture.

Meat supply chain

Externalities

“Wicked problem” of climate change, poverty and local ecological losses

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Global protein market outlook

Population growth and emerging economies:

$2T market cap. by 2030?

Global meat demand 1980-2030

Rabobank (2011)

Lamb Poultry Pork Beef

Demand, 10 million tons

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By Olivia Fox Cabane, http://newprotein.org

※Also describes investors (VC’s, corporates)  

IP info: https://www.culturedabundance.com/about

Startups list: https://futurefoodshow.com/list-of-cultured-meat-companies/

Japan $50B

Seafood $250B

Global meat

$1.9T

Global beef

$0.7T

Market size along the value chain of meat (in billion $)

Source: AT Kearney

Cellular agriculture startups and market size

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Product launches

“Brewed milk”, ice cream

Collagen for cosmetics

2019

2020

Chicken nuggets

Chicken

2021

2022

Product Launch dates?(MosaMeat https://www.mosameat.com/faq

“We are aiming for a first market introduction in the next few years. It is very difficult to commit to a particular timeframe because there are still some scientific unknowns and factors outside our control (such as the regulatory process). The first introduction will likely be small-scale. Several years beyond that, we aim to be widely available in restaurants and supermarkets.”

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Cell-ag market predictions (By A.T.Kearney)

・⅓ becomes meat alternatives by 2030.

・Plant-based meat in 2035 reaches maturity.

・CAGR 40% is expected for cell-based meat.

・The shift will also affect surrounding sectors i.e. retail and distribution.

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The road ahead in protein transformation

Improving technology reduces the amount of capital for market entry. Individuals enter and technology democratizes.

Hype crash and cycle

Reaches price parity with animal meat

Conversion by regions and product categories

Vertical integration with large plants

2020~

2030~

Animal meat

Cell-based meat

Price

Time

Foie gras

Beef

Chicken

Importer

Half-producer

Producer

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“Adjacent industries”

Entry from nearby fields

Beverage companies

Food companies

Medical supply manufacturer

Plant engine- ering firms

Effect to nearby fields

Functional & pharmaceutical foods

Food branding

Biomanufacturing

Regen. medicine

Indoor farms

Cell-based meat industry mind map

Good Food Institute (2016)

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Non-profits

USA

Israel

USA

Japan

USA

・Plant-based and cell-based meat advocacy group founded by New Crop Capital that promotes cell-ag from the industry side.

・GFI has branches in global locations to act on governments.

・Headquartered in Washington DC

https://www.gfi.org/

・Funded by crowdfunding

・Promotes open-source DIY cellular agriculture

・Spun off IntegriCulture Inc. and CAIC

http://shojinmeat.com

Founded by university students, aims to connect academia and industry

https://www.cellag.org/

・Originally animal welfare centered group

・Spun off SuperMeat and FM Technologies

https://www.futuremeat.org/

etc.

・Donor-funded 501(c)(3) that coined the term “cellular agriculture” in 2015

・Supports its academic research and one of the key advisors to FDA

https://www.new-harvest.org

Spin-off

Cell-Ag Inst. of the Commons

Academic and policy advisory and public communication

※Still in preparation on 2020.01

https://cellagri.org

Lobbying

etc.

Grants

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Notable conferences

Alternative protein and cell-ag sessions are also common in ”Food Tech” events, i.e. Smart Kitchen Summit (Seattle) and Agri-Food Innovation Week (Singapore)

~Sept. in San Francisco by GFI, More industry oriented, on both plant-based and cell-based meat

https://goodfoodconference.com

~Oct. in Maastricht, Netherlands,

An academic conference

https://www.culturedmeatconference.com/

~July in Boston by New Harvest, Academics and biohackers

https://www.new-harvest.org/new_harvest_2019

~Nov. in San Francisco, cell-ag specialized industry event

https://2020.cmsymp.com/

~Feb. in San Francisco, Industry meeting by Hanson Wade(UK)

https://industrializingcellbasedmeats.com

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Academic researches

Supports New Harvest

Japan Science and Technology Agency “JST-Mirai” program (government grant), ~$20M for FY2018-2023

https://www.jst.go.jp/mirai/jp/uploads/application-guideline-h30-en.pdf

While startups raise large amounts, Dolgin points out on a Nature article the relative lack of basic research in cell-ag https://www.nature.com/articles/d41586-019-00373-w

EU(2020):€2.7M grant to Meat4All consortium as a part of Horizon2020

US(2020):$3.5M 5year grant from NSF to a team at UC Davis

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Government & regulatory moves (mid-2020)

Joint regulation by USDA and FDA was announced in 2019/03.

https://www.fda.gov/news-events/press-announcements/usda-and-fda-announce-formal-agreement-regulate-cell-cultured-food-products-cell-lines-livestock-and

Product-by-product approvals are expected and the FDA requests early consultations

(EU)2015/2283 sets cell-ag products as novel food and applications are handled by the European Commission & EFSA.

https://eur-lex.europa.eu/legal-content/en/TXT/?uri=CELEX%3A32015R2283

A high-rank official in People's Political Consultative Conference mentions cell-ag as a national priority, but no substantial moves to date. Shifts in government priorities may change the pace overnight.

The pre-existing rules tacitly approves cellular agriculture products.

Ongoing rulemaking conversations (Foodtech Study Group) initiated by the Ministry of Agriculture, Forestry & Fishery in 2020

The novel food regulations in each state tacitly covers cell-ag products.

No substantial actions are taken beyond requirement for proof of safety as written in the pre-existing rules

The Good Food Institute is lobbying governments to set regulations for cell-based meat

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Cellular agriculture as a strategic priority

10% self-sufficiency

The territory is heavily urban and food is mostly imported.

Risk of “water war”

Military tension over critical agricultural resources

The government sets “Singapore Food Story” to raise the food self-sufficiency (10%->30%) and establishes Singapore Food Agency to regulate food tech products.

A government-backed food tech incubator, public interest in meat alternatives and active startup scenes gave rise to multiple startup efforts. In 2020, Prime Minister tastes a sample after the government finds strategic importance in the technology.

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Inclusive rulemaking on cellular agriculture (Japan)

Foodtech Study Group 2020.04~

Inherits cell-ag working group

Japan Assoc. for Cell-Ag

2019.07~

・Comprehensive discussions to assist food tech industry growth

・More than 300 participants from various sectors including traditional industry -

Interim report: https://www.maff.go.jp/j/press/kanbo/kihyo01/200731.html

Other working groups i.e. insects

Policy advice

2021.04?

Food companies

Farmers

Cell-ag startups

Academics

Policy makers

General public

Additional Potential stakeholders

Ideally, No one left behind in “cell-ag revolution”

Cell licensing by farmers?

Collaborations between startups and big food?

How do we reflect consumer voices to product R&D?

etc...

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Nomenclature

Cultivated meat

(used to claim “clean meat”)

https://www.gfi.org/how-we-talk-about-meat-grown-without-animals

cultured meat, also acknowledges “cell-based meat”)

Officially “cell-cultured meat”, but also acknowledges the industry nomenclature of cell-based meat

純粋培養肉(純肉)、(細胞)培養肉

・How do general consumers perceive?

・Is it a neutral name?

・Does it comply with food labeling law?

Good Food Institute(2017)

(Japanese)

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Regulations and cellular agriculture products

A food product must be manufactured from food and (approved) food additives under proper process control. A “food” must have history of consumption (⇔ “Novel food”). There is a list for (FDA, in case of USA) approved food additives.

cell-based meat

Growth factors

Could have a GRAS status

Requires safety tests and approval if used.

Sugar

Amino acids

Vitamins

Minerals etc.

(Food & additives)

Basal media

Basal media

Process control:

HACCP& GMP

Could use sports drink

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Where are the risks?

BSE prions?

Cells mix-ups?

Viral contamination?

Is it GMO?

Are growth factors safe?

What’s in the medium?

Bacterial contamination?

Cancerous cells?

Safety of cell metabolites?

Will it be labelled?

Unexpected health risk from “too clean meat”?

Is meat healthy?

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Points of considerations & solutions?

Use of primary cells or cell line cells?

Viral DNA can be monitored real-time in near future?

Can be avoided by cell acquisition from prion-free parts?

Use of cell sorter may separate by each cell types

Existing food regulations can evaluate the food safety of growth factors?

Use of methods that does not require external addition of growth factors?

Use of known medium? Prompt reporting of any changes made to medium? https://www.sigmaaldrich.com/life-science/cell-culture/learning-center/media-formulations/dme.html

Would require contamination detection mechanism for quality assurance

“Substantial equivalence” - how do the amount of abnormal or cancerous cells compare to existing meat?

How should it be labeled? “Beef(cell-based)” ?

Long-term safety - how do cell-based meat differ from conventional?

Is meat consumption healthy - regardless of traditional or cell-based?

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Who will regulate meat? (And what is “meat”?)

USCA and other unions petition against “meat” label for plant and cell-based claiming that such labels deceive consumers

Cell-ag startups set up a “trade union” AMPS Innovation for lobbying purpose

https://ampsinnovation.org/

Influence from animal rights movements

Differences in the tones of social communication

Lobby for plant-based and cell-based meats

Legal action claiming that such law is Unconstitutional

Lobbying over food labels to distinguish traditional meat

Active disclosures and lobbying to establish safety of cell-ag products

etc.

Publicity from each positions

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Safety and labelling standards - WIP

USDA

USDA/FDA[1] agreement (2019)

FDA

FDA

USDA

Labelling

[1]While most food is under the jurisdiction of FDA, “meat and poultry” are under USDA.

Regulations on cell-based poultry (SG, 2020)

・Used to approve food based on the regulatory status of the product in the country of origin, before SFA (estab.2018)

・SFA is working to define “Novel Food”, and cell-ag products under “novel food” are required premarket approvals.

https://www.sfa.gov.sg/docs/default-source/legislation/sale-of-food-act/first-public-consultation-on-proposed-regulatory-framework-for-novel-foo.pdf

・Evaluates seed cell traceability, genomic stability and residual growth factors for cellular agriculture products

https://www.sfa.gov.sg/docs/default-source/food-import-and-export/Requirements-on-safety-assessment-of-novel-foods_23-Nov-2020.pdf

・Requires to label the product being “cell-cultured”

Labelling

USDA/FDA positions(2020)

・Aims to ensure food safety while fostering industry innovation

・Process-based regulations than prescriptive requirements, possibly except for the levels of residual growth factors.

・Urges industry players to start early pre-market consultation, noting that the technology is still nascent.

Cell extraction

Cell culture

Tissue harvest

Consumer products

Cell source

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The positive impact

Science & Technology

・Technological hurdles?

・Medical applications?

Politics & Economics

・Shift in food market?

・Industry landscape?

Arts and Culture

・Religious views?

・Social norms to change?

Hanna Tuomisto 2011

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Socio-cultural implications

Would vegetarians eat?

Is it Halal?

Goes with Buddhist “nonviolence”?

Animal welfare?

Consumer acceptance?

At the end, is it tasty?

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Regional differences in agenda

  1. Animals, religion

B. Food security

C. Food safety

D. Env. footprint

EU/US: A~D > C > B

E.Asia: B~C > D > A

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Western vegetarianism

・Vegetarians

・Pescetarians

・Vegans are the most common

3~10% of the population

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Practical ethics: “Utilitarianism”

“Decision should be made to maximize utility”

Utility = happiness x number of sentient beings

“Only 1 death is better than 5”...?

May be so in very short term, but...

If “killing for public good” becomes the norm, no one is there to stop dictators

→ Is the utility maximized, in the long run?

Utilitarian decision making is strongly dependent on subject and timeline

“Runaway trolley problem”

As it is, 5 will die. If you switch, only 1 will. Will you do it?

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Animal welfare as deductions from utilitarianism

◆Animals are capable of feeling happiness and thus sentient.

◆All sentient beings count.

◆”Species” as defined by biology is irrelevant in ethical decisions.

⇒From a utilitarian point-of-view,

“making sentient beings suffer is unethical”

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Acknowledges health and environment, but mainly animal welfare and ethical

“Animal welfare” based on utilitarianism

Reason for being a vegetarian

Vegetarian Society

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East Asian vegetarianism

”Religion”←Not utilitarianism or other ethics

Ethical value of clean meat described by utilitarianism don’t directly translate into East Asian religious (i.e. Buddhist) importance.

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“Shojin ryori” Buddhist cuisine

Cuisine for for zen practitioners

Common name for “Buddhist cuisine”

All aspects must serve the purpose of zen.

-NO FOOD WASTE

-Use local produce to avoid food waste

-No cruelty (avoid fish and meat)

-Avoid ingredients that stimulate desires i.e. onions

-All donated food (incl. meat) must be consumed

-Cooking is also a part of zen practice

※contested

Known as “zhai cai” (齋菜) in Chinese

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Would “murderless meat” help Zen?

”Would cell-based meat serve the purpose of Zen?”

・Overcoming personal desires is a major theme in zen

・”Desire” includes meat apetite

・”Fake meat” is a compromise, but compromise is permissible

・Cell-based meat fits in the same category as tofu - meat imitations.

Cell-based meat being “murderless” does not make it Zen - there are multiple more important criteria.

“Shojin” means “devotion to the righteous path”

Shojinmeat Project will stay committed to the path that obsoletes unsustainable meat

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Meat in historical Japan

Before 7th century:

Eating meat was common. People just had to eat whatever was in hand.

675c. Imperial decree of “No Killing (of animals)”

To direct labour force to rice production and put a stop to local animal-sacrifice rituals & reinforce imperial authority

※Newly arrived Buddhism was used as justification

Meat avoidance continues till 19th c. and commoners only started eating meat around 1900 c.

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・Totals half billion? Region-specific

・More common among upper castes

・Some upper caste members fund cultured meat research

・Hinduism doesn’t explicitly forbid meat but adherents choose to avoid meat.

Mr. Modi (Indian PM as of 2017) is a vegetarian.

Vegetarianism in India

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Is it Halal?

“The halal cultured meat can be obtained if the stem cell is extracted from a (Halal) slaughtered animal, and no blood or serum is used in the process.”

J Relig Health. 2018 Dec;57(6):2193-2206.

https://link.springer.com/article/10.1007%2Fs10943-017-0403-3

“As long as the cells used are not from pigs, dogs or other animals banned under the halal laws, the meat would be vegetative and "similar to yogurt and fermented pickles."

Abdul Qahir Qamar, The International Islamic Fiqh Academy, Jeddha, Saudi Arabia

https://gulfnews.com/going-out/restaurants/is-shmeat-the-answer-in-vitro-meat-could-be-the-future-of-food-1.1176127

“Work in progress, and being settled”

Halal authentication by JAKIM (backed by the Malaysian government) is widely acknowledged.

“It is Halal” may become the single decisive purchase reason in Islamic sphere.

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Potential future shift in ethical landscape

Then what if on 2040, meat alternatives rise to 30% market share and ever more people stop consuming conventional meat?

・Uncontrollable ”hate campaign” against traditional farmers?

・Trade ban of conventional meat due to animal cruelty?

Why are animal experimentation, Japanese whaling and Chinese cat/ dog consumption is problematised far more than factory farming?

⇒Because they are “remote things” for the protesters.

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Ethical issues due to technological immaturity

(Transient) issues upon R&D:

・FBS production is not cruelty-free

“Unavoidable” issue:

・Extraction of cells

Likely to be solved in the future

May pose an issue during R&D

Can bovine foetus feel pain?

It may still inflict some pain.

Will animals still be chained?

Genetic selection of animals for the sake of “tasty” - is it eugenics?

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Changing perceptions of “meat”?

Gen. 1

chooses cell-based meat due to animal welfare and footprint. Some start choosing by price and taste.

Gen. 2

consumes cheap cell based meat on daily basis and feel repulsive against conventional meat.

Livestocks are for food, pets are not, wild animals may be hunted for food

30yrs

Gen. 3?

feel uneasy on protein food nomenclatures or appearances that reminds of specific living things.

30yrs

Animals are for pets or labor. Slaughter is barbaric.

“Meat appearance reminds me of pain, wound and death”

Sentiments similar to cell-based human meat today?

“It is just not a food for all, regardless of how it’s made!”

More protein food brands without animal associations i.e. “Quorn”?

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Ethical issues of “captive carnivore”

Wild animals exist outside human control and no ethical questions are raised against humans.

However, captive carnivores as pets and zoo animals are under human control → ethical questions

?? Is it ethical to let carnivores to prey on others??

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Future court case: “Patent or Life (of animals)”

・Can rich countries with cell-based meat production technology blame (poor) emerging countries for animal abuse?

・Court cases over “economic incentives (patent) vs. animal suffering”

Case study: Generic HIV drug lawsuit:

An Indian pharmaceutical company allegedly infringed retroviral drug patent to manufacture generic HIV drugs, because the original drugs by Western pharmaceutical companies were too expensive for people in poor African countries.

After high-profile court-martials, the Indian company won the case on humanitarian basis.

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Consumer acceptance

Chris Bryant (2017)

3rd Intl’ Conf. for Cultured Meat

Large variations exist between different marketing research attempts and speculations, mainly due to the lack of actual clean meat products on market.

←Factors consumers weigh

Consumer acceptance research result→

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What would a corporate monopoly do?

Technological details were concealed as “trade secret”, drawing widespread accusation and allegations of “technology for corporate profit than social good”

Science may have proved the safety of GMO, but failed to convince the public to feel safe.

Cell-cultured meat: Lessons from GMO adoption and resistance

(Review paper)

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Cellular agriculture ecosystem

Advocacy, Academic research with universities

DIY bio, speculative art projects, “avant-garde” advocacy

Sponsor

Research and project grants

Commercialization,

Production technology development

Individual biohackers in communities such as

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Shojinmeat Project as citizen science

Citizen Science

Non-Profit

Advocacy, Academic research with universities

DIY bio, speculative art projects, “avant-garde” advocacy

Sponsor

Research and project grants

Spin-off Startup

Commercialization,

Production technology development

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Cellular agriculture with initiatives on citizens

How to make ⇒ Open

How to scale ⇒ Proprietary

Number in demand

Degree of personalization

Product dev.

Citizen Science domain

Business domain

and other businesses to come

Transparency

in technology

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Citizens are the decision makers

Academia hints the way

Citizens act and set the direction

Businesses scale and deliver

Wilsdon, James and Willis, Rebecca, why public engagement needs to move upstream (2004), Demos, London.

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“Growing meat at home”

=DIY bio methodology=

Konjac cell scaffold

Cells from fertilized eggs

Egg white as antimycotic

Egg yolk as FBS

⇒DIY cell culture in kitchen

High schooler on DIY cultured meat experiment, TV news

Airtight box

CO2 source

humidity source

dish

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Development of DIY bio equipments

DIY incubator

Temperature can be set to ~40℃ by reducing the AC input voltage of a towel warmer from ~100V to 30V.

The blueprint of DIY incubator is on GitHub. Both are at ~$100.

https://github.com/sotakan/RPi-Incubator

Household fan centrifuge (~100G at ~1000rpm)

Egg white antimycotic and DIY clean bench

(@earthlyworld

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Development of DIY cell culture protocols

Materials and methods are uploaded on blogs, video sharing sites, GitHub etc. for other participants to confirm reproducibility.

Creative Cells Kyoto reproduces sports drink culture medium experiment

https://cleanmeat-kyoto.hatenablog.com/

Ms. Sugisaki - consultant by the day, biohacker at home (aired on TV)

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Demonstration video online

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Development of home and school cell culture kit

Pre-survey to high school teachers

School cell culture kit should be

at <$300

DIY cell culture hardwares and protocols deployed in a class

Less than $100 for a class of 20

-At what budget?

-Cell culture in school classes?

(9 respondents)

<$300

<$500

<$1000

<$3000

<$5000

Yes

No

Yes, as an extra-

curricular activity

Yes, if there is time

Depends on budget

@thesow41

(towel warmer)

(DIY protocols)

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DIY cell culture and future

Other cell types?

Coculture system, better DIY serum?

Cell scaffold, DIY tissue engineering

….etc.

What’s next?

DIY cell culture experiments

Materials and methods on blogs and online videos

Cell culture kit

Results are shared, other participants also reproduce results

Cell culture protocols

Cell passage protocols, cell library

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Why stop at meat? DIY tissue engineering?

Tastier than meat

DIY kidney!

DIY differentiation & morphogenesis to make heart

Is this even “meat”!?

“Green meat” algae- meat composite food

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5282507/

・Bioreactors improve over time, enabling cell, tissue & organ culture

・DIY tissue engineering is ubiquitous, innovative prototypes everywhere

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Local farmers design their own meat brands

・Local farmers, butchers and chefs can develop their own cell-based meat recipe.

・Brand ownership opportunity opens up for local farmers.

・Hobbyists come up with unique meat recipe.

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Fewer cows

Bioreactors in the backyard

Many cows

Cows are the product

Cell or meat is the product

Traditional farmscape

Cell-ag farmscape

The Cell-Ag Farmscape

Fewer cows mean less cleaning, feeding, waste treatment

More facility management and cell culture protocol dev., as in brewery

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Business models of meat in cell-ag era

Fabless farmers

Contract farmer

Lend cows

Meat brewery

Sends cells

Sells meat

Fabless farmer

Farmers

Cell licensing

Cell bank

Sends cells

Food companies

Sells meat

Shared recipe

Recipe website

Warehouse

People

cell culture protocols

Domestic culture vat

Down-�load

Farmers

Stores cells

Sends cells

Cell-Ag Firms

People

Cell-ag firm

“New farmer”

People

Sells meat

Food companies

Meat brewery

Sells

cells

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Celebrity Star Cow branded beef

The cell source Star Cow is alive

Scan the QR code printed on package

Watch the Star Cow

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Myoblast grown at 200t scale

Looks like a beer factory?

Future: Meat brewery

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Steak brewery

Single use culture bags⇒

Steak grows inside⇒

Ready to ship⇒

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Seafood by cellular agriculture

Cell culture at room temperature

Small ponds as cell source

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Culture media produced by microalgae

Short food miles

Farm high-rise

Cell-ag towers

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Farmscape, A.D.2203

Vertical farms

Vast land reverted to nature

Artificial photosynthesis

Cellular agriculture manu- facturing industry complex

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Martian food production facility

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Orbital Zero-G Farm

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Creative support for artists

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Miyo-san

”Myosin”

age.20・164cm

Chemical engineering student intern at Mars Huygens Crater cellular agriculture facility.

Aco-chan

”Actin”

age.13・149cm

Helps elder sister Miyo in her extracurricular activity at Mars Colonists Middle School.

Miyo & Aco

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Miyo-san (Chibi)

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Aco-chan (Chibi)

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Visual novel source files

Source files

https://drive.google.com/drive/u/0/folders/0B0ShPzNziL05THlwU2IwTTNueHM

(Feel free to produce alternative scenarios, derivative works, add characters, etc. under CC-BY-NC license.)

“Miyo-san” and “Aco-chan” whole body and face PNG images and sci-fi themed background images available for manga and VN’s.

Miyo

Aco

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Perhaps, someday in the future on Mars….

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Zine's (DIY cell culture manuals)

Distributed at Comic Market, COMITIA, TechBookFest, etc. Also available from MelonBooks

Sold out

Online materials (slideshare)

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Members participate in their respective expertise (experiments, gatherings, art projects etc.) - no defined “membership”

#Food Security

#Food Miles

#Regulations

#Cooking

#Culture & thoughts

#History

#Food safety

#Life ethics

#Animal welfare

#Regenerative medicine

#Tissue engineering

#Bioreactor

#Culture medium

#Commercialization

#LCA

#R&D

#Soc.&Econ.

#Global collab.

#Space

#Art

Shojinmeat Project “Distributed Clusters”

All welcome:

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Some past questions (part 1)

Q: I would like to participate

A: There is no formal definition of membership. Please Tweet to us or join slack channel.

Q: I’m not a biologist but would like to join�A: All disciplines welcome - multiple journalism, art & other non-sci/tech projects are ongoing

Q: Where are carbon and nitrogen sourced?�A: Culture medium contains sugar and amino acids. Amino acid is sourced from yeast which feed on sugar. In future, artificial photosynthesis and nitrogen fixation may take this role.

Q: Is fungal farming cellular agriculture?

A: Depends on if cell culture procedure is involved in the process. Cultivation of entire fungal body would be conventional farming.

Q: Is cell-based meat GMO?

A: Gene editigin is not required for cell culture. In future, “designer meat” such as “allergen-free meat” may require gene editing.

Q: Is it tasty?

A: It’s pasty (for now). In future, advanced tissue engineering may enable complete reconstruction of meat taste and texture and even go beyond.

Q: How quickly would “meat” grow?

A: Cells multiply every 1½~2 days. 1E5 cells grow to visible size in 20~30 days. Flow process in factories may enable continuous production.

Q: What will happen to farm animals?

A: They don’t disappear as starter cells would still be required, but their number may decline.

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Some past questions (part 2)

Q: Could meat be cocultured with probiotics?

A: Unknown. It depends on their growth rates and mutual effect of cell metabolites.

Q: Why would people eat cell-based meat? 

A: Initially, vegans and environmentally-conscious would consume, but at the end, taste, price and convenience would decide.

Q: My kids should try DIY cell culture

A: Hardware and methods are open for public. Please contact us for details.

Q: Desktop clean bench may help?

A: Egg white can suppress mould growth, but a clean bench always help.

Q: What will happen to farmers?

A: Farmers may gain an opportunity to build a brand around his/her cow cell and meat culture recipe, but it depends on what business model cellular agriculture companies take in the future.

Q: Is cell-based meat Halal/Kosher?

A: It may potentially become Halal/Kosher under certain conditions, according to a publication: https://www.ncbi.nlm.nih.gov/pubmed/28456853

Q: Is it vegan?

A: Depends on technological maturity. Our DIY procedure uses egg white as antimycotic and therefore not vegan. In future, it depends on the exact procedure of cell acquisition.

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References for common facts

More than 80% of arable land, or 20% of Earth’s land surface is used for meat production. It is also responsible for 18% of total greenhouse gas emissions.

“Reducing food’s environmental impacts through producers and consumers” Poore, Nemecek, Science 2018 http://science.sciencemag.org/content/360/6392/987

More than 80% of arable land is used for meat in some ways.

FAO www.fao.org/animal-production/en/

20~30% of all freshwater is used for farm animals

“The water footprint of humanity”, Hoekstra, Mekonnen, PNAS 2012, http://www.pnas.org/content/109/9/3232

Energy and protein feed-to-food conversion efficiency is 3% and 4% respectively.

“Energy and protein feed-to-food conversion efficiencies in the US and potential food security gains from dietary changes”, Shepon, Eschel et al, IOP Science 2016

http://iopscience.iop.org/article/10.1088/1748-9326/11/10/105002/meta

1kg of beef requires 25kg of feed and 15000L of freshwater

Hoekstra, Mekonnen, UNESCO IHE 2010 “The green, blue and grey water footprint of farm animals and animal products” http://waterfootprint.org/media/downloads/Report-48-WaterFootprint-AnimalProducts-Vol1.pdf

90% of soybean and 40% of crops are consumed as feed

How to feed the world 2050 High-level expert forum, Rome 12-13 Oct.2009

http://www.fao.org/fileadmin/templates/wsfs/docs/Issues_papers/HLEF2050_Global_Agriculture.pdf

World’s feed can support 3.5B people if consumed as food.

1kg of beef requires 12~24kg of feed.

“Redefining agricultural yields: from tonnes to people nourished per hectare”, Cassidy, West e tal, IOP Science, Environmental Research Letters, 2013, http://iopscience.iop.org/article/10.1088/1748-9326/8/3/034015/meta

1kg of poultry requires 2~4kg of feed

Meat or wheat for the next millennium? Alternative futures for world cereal and meat consumption

https://pdfs.semanticscholar.org/ae0c/a5b5556e57a2c4cf904b218d0edbac2c32d9.pdf

80% of antibiotics are used in farm animals.

“The antibiotic resistance crisis: part 1: causes and threats.”, Ventola, NCBI 2015, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378521/

Organic farming requires larger land area per unit yield.

“Is organic really better for the environment than conventional agriculture?”, Ritchie, OWID 2017, https://ourworldindata.org/is-organic-agriculture-better-for-the-environment

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Contacts for businesses

“Shojinmeat Project” is a citizen science community.

Please contact IntegriCulture Inc. for industry & business collaboration.

Please contact CAIC for market information & industry consultation.

And welcome to the Shojinmeat Project to passionate individuals!

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Get involved in cellular agriculture!

DIY Bio, Make. , public communication

Wednesdays19:30

FabCafeTokyo 2F

https://fabcafe.com/tokyo/access/

@shojinmeat

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Acknowledgements

All Shojinmeat Project participants!

Patrons at Campfire Crowdfunding