What is synthetic biology? How quickly is it developing? How does it work? What do we need to know about the synthetic biology industry? What impact does this all have on biodiversity and farmers? What are GMO 1.0, GMO 2.0, GMO+? Presentation by Jim Thomas of ETC Group, during Redesigning the Tree of Life: Synthetic Biology and the Future of Food, 2-4 November 2017 in Toronto.

1. Untangling
“Synthetic
Biology”
An Introduction…

2. “Technology Watchdog”
(+corporate concentration + food + biodiversity etc)

3. Tracking
Emerging Technologies
And Corporate Concentration
…on behalf of
marginalised people.

5. 1What is
“Synthetic
Biology”?

6. Jim Wagner: I went back over my notes. I have five definitions
we were offered and not necessarily complementary ranging
from DNA construction to be the number one technology of the
21st Century, to having it defined as synthetic genomics that
must exist in digital code and processed in the genome and
activated in a living system, to others saying this is really just an
extension of genetic engineering, and, in fact, one person saying
there no clear distinction between synthetic biology and genetic
engineering. We had one definition offered saying it was making
biology easier to engineer.
Amy Gutman: You haven’t gotten them all!
(AUDIENCE LAUGHTER)
Well, I remember Dr. Prather told us if you had
five in the room, we’d get six definitions. So
lets see if we can get another one…

7. Drew Endy:Well, I refuse. [AUDIENCE LAUGHTER] And my
counsel to you would be don’t stress out about it too
much. I have seen, particularly in Europe, meeting after
meeting creating meeting after meeting with the primary
agenda item being to come to a definition.
Jim Wagner:Then I suggest we don’t discuss
it further…

8. Synthetic
Biology
What is
Syn Bio?
It’s broadly defined:
NEXT GENERATION GENETIC ENGINEERING
“Synthetic Biology is a further development and
new dimension of modern biotechnology that
combines science, technology and engineering to
facilitate and accelerate the understanding,
design, redesign, manufacture and/or
modification of genetic materials , living
organisms and biological systems”
- Operational definition adopted by the UN Convention on
Biological Diversity COP13, Cancun - December 2016.

10. “Genetic Engineering ain’t what it used to be”

11. GMO 1.0
Transgenics
Experimental
Artisanal

12. DNA as an instruction ‘code’

13. Changing the code back then…

14. Changing the code back then…
GMO’s 1.0 – two
techniques plus only a
handful of products.

15. Genome READING
2015 Study: 2,500 high-throughput instruments, located in nearly 1,000 sequencing centers in 55 countries
PLoS Biol. 2015 Jul; 13(7): Stephens et al “Big Data: Astronomical or Genomical?”
This is now…

16. Annual genomic data If 1 bp was a grain of sand… New industrial raw material
PLoS Biol. 2015 Jul; 13(7): Stephens et al “Big Data: Astronomical or Genomical?”
2015: 35 petabases of genome
sequencing (35 thousand trillion BP)
-32,000 microbial genomes, ~5,000
plant and animal genomes, and
~250,000 individual human genomes .
2025: 1 zetabase of genome sequencing
(1 thousand million trillion BP).
Encompass All 1.2 million described species
of plants and animals.
Estimated that there will be at least 2.5
million plant and animal genome
sequences
X 154

17. This is now… new industrial tools
GMO’s 2.0 – Wider
toolbox of techniques,

18. This is now… Clustered Regularly Interspersed Short Palindomic
Repeats (CRISPR),
Directed Evolution,
DNA-based genetic circuits,
DNA Synthesis and Assembly,
Epigenetic Modification,
Expanded Genetic Alphabets,
Genome Editing,
Genome-level Engineering,
Genome Shuffling,
Gibson Assembly,
Minimal Genomes,
Multiplex Automated Genome Engineering,
Oligonucleotide Directed Mutagenesis,
Protocell Construction,
Refactoring of Genomes,
RNA-Directed DNA Methylation (RDDM).
RNAi (RNA Interference)
Standard Modular DNA ‘parts’ or ‘Biobricks’
Synthetic Metabolic Pathway Engineering,
Synthetic Genomics,
Transcription-Activator-like Effector Nucleases (TALENs),
Xenobiology,
Zinc Finger Nucleases(ZFN),

19. Making biology ‘engineer-able’
Standardised,
predictable genetic
“parts”

20. Making nature more “engineerable”:

21. Synthesizing the parts of life

22. Genome WRITING
Commercial gene synthesis: 7- 17 cents per base Currently a billion base market – around a million genes.
Commercial Oligo Synthesis – 5 cents per base. Currently a 4.8 billion base market
Roughly equivalent to one human genome per year.
Source Rob Carlson synthesis.cc – March 2016

23. 7500bp
Polio genome =
Approx $500 to
synthesize??

24. Genome WRITING
Human genome currently $21
billion
¼ Gates (approx)
1/3 Zuckerberg
1/5 Bezos
1 week US military spending

25. Genome ‘editing’
CRISPR-CAS9, Zinc Fingers,
TALENS, Directed Mutagenesis

26. Genome EDITING Talens - Transcription activator-like effector nucleases
Rapid Trait Developent System (cibus)
ODM - OligoNucleotide Directed Mutagenesis
ZFN - Zinc finger Nucleases
CRISPR-Cas9 – Clustered Regularly Insterspersed Palindromic Repeats
and beyond CRISPR:
four new CRISPR associated proteins found by Feng Zhang of the Broad
Institute -similar proteins to CRISPR. Cas9One candidate, Cpf1, has a
number of benefits over its Cas9 counterpart
16s RNA - New Venter bacterial genome editing system for yeast,
ngAgo: DNA-guided genome editing using the Natronobacterium gregoryi
Argonaute
EXPECT MORE…..

27. ZYMERGEN
TRANSCRIPTIC
“Zymergen’s algorithms suggest making
1,000 or so changes to the
microbe’s genetic material .
Then the robots take over, injecting the
suggested DNA snippets into the
specimens, testing their properties,
collecting data and feeding that information
back into the data trove.”
“AI - POWERED BIOTECH”
Robotic Genome construction

29. “programming”
lifeforms
>
GTTCACTAGCCATTAGGTA

30. Synthetic Life:–
Digital, remixable, programmable

32. • Rapid market growth ($10.8 billon for
2016. $38.7 billion by 2020)
• Govt funding rapidly growing
(US: dominated by Defence/DARPA)
• Many deals with fortune 500 companies –
food, flavour, chemicals, cosmetics, fuels,
pharma, textiles.
• Rapid expansion in venture capital :
$900 million in first 9 months of 2016
• 192 – Number of Syn Bio firms (Wilson
Center 2013)
• 508 - Number of research entities (Wilson
Center 2013)
SYNTHETIC BIOLOGY INDUSTRY

33. THREE INDUSTRIAL WAVES:
1. Biosynthesis – fuel and chemicals, foods
, fragrances and cosmetics
2. New GMO - organisms for release –
Plants, Animals, Insects, Parasites etc
3. ‘Molecular computing’ - Using DNA/life
for data storage, computation and
communication.
SYNTHETIC BIOLOGY INDUSTRY

34. 1st Wave:
Biosynthesis
Aka. Making stuff
in vats of
engineered
organisms.
(fermentation)

35. Imagine a yeast or
bacteria cell as a
tiny “factory” eg
turning sugar into
alcohol

37. Cell becomes a
tiny programmed
“factory”
Apply the tools of
synthetic biology

38. Cell becomes a
tiny programmed
“factory”
Microbial Cell
“factory” is now
“reprogrammed”
to produce
compound of
interest

39. Microbial Cell
“factory” scaled
up in
fermentation
vat..

40. Biosynthesisze
d compound
can be brought
to market

41. FIRST WAVE:
FUELS AND CHEMICALS
SYNTHETIC BIOLOGY INDUSTRY

42. < High volume, low value
Low Volume, High Value >

43. Secondary Metabolites
Or
Natural Plant Products

45. Isoprenoids
=
class of
Up to 75,000
compounds.

46. Over 200,000
natural compounds

48. “There is potential for
biosynthetic routes to
completely replace any natural
sources”
-Kalib Kersh
Industry Analyst, Lux Research

49. “Through the Pathways Program, partners can, with a small initial
investment,
sponsor and secure a molecule
they are interested in having Amyris produce using the next-generation tools and
technologies being developed through the company’s recently announced technology investment
agreement with the Defense Advanced Research Projects Agency (DARPA). Amyris expects the
powerful combination of its existing core technology and bioengineering advancements enabled by its
project with DARPA will significantly reduce the time and cost of bringing new molecules to market
using industrial biotechnology. The Pathways Program allows partners to access these latest
developments and
explore bio-synthetic production opportunities
with minimal risk and commitment. ”

50. FOODS, FLAVOURS, FRAGRANCES
SYNTHETIC BIOLOGY INDUSTRY

51. Synthetic
Biology
Where is
Syn Bio?
Cosmetics, fragrances, soaps

52. Six of the top 10 companies have
entered R&D agreements with
synthetic biology firms or have their
own synthetic biology R&D activities.

53. Why is the F&F industry going all-in on Syn Bio replacements?
1. Reliability of supply:
- Vat-grown vs Farmer-grown – centralized.
- no weather related problems - not seasonally dependent.
- can switch feedstock between sugars (or methane)
- Can ferment entire supply at one go.
2. “Natural” claim – biosynthetically derived compounds are considered
products of fermentation. Considered “natural” under US and European law.
Massive growth of “natural flavours” market.
3. Price - Price is tied to sugar/feedstock and IP – can undercut botanical and
still get ‘natural’ premium.

54. Flavours and Fragrance (F&F) Market:
• 26.5 Billion dollar market in 2016
• Expected to grow to over $35 billion by 2019
• Includes essential oil exports valued at US$3.6 billion in 2012.
• The F&F industry currently sources 200 to 250 different botanical crops
grown on an estimated 250,000 hectares worldwide.
• Around 95% of these crops are grown by small-scale farmers and
agricultural workers, mostly in the global South.
• An estimated 20 million small-scale farmers and agricultural workers
depend on botanical crops sourced for natural flavors and fragrances. (low
estimate and does not include common flavors such as cocoa or coffee.)

56. “ The Forest is protected by the people to
help preserve their vanilla beans, because it
needs to grow in the shadow the forest
provides. If they can no longer grow vanilla
because it has lost its value, the forest in
most communities will be cleared”
– Tsara Samson – Sambava Vanilla grower

57. “Step aside, Cocoa Farm, Synthetic Biology is on its way!”
– Maxx Chatsko Synbiobeta
“We can dislocate the production of
that oil from a tropical climate to the
middle of Iowa in winter … It is truly
revolutionary that we can take what is
a normal crop cycle and compress that
into three days”
- Mark Brooks. Senior VP
Solazyme/TerraVia

60. Changing Feedstock – Sugar and
methane

61. SECOND WAVE:
CROPS, INSECTS, ANIMALS
GMO 2.0 INDUSTRY

62. Genome edited crops:
- CRISPR-CAS9
- Zinc Finger Nucleases
- TALENS
- Oligo-Directed Mutagenesis
Epigenetic Enginering
- RNAi (RNA Interference)
- RDDM (RNA Directed DNA Methylation)

63. Biotech Industry argues:
- Not GMO’s according to regulations (legal argument around wording) – the techniques
do not give rise to ‘a GMO’
- More ‘precise’/ less intervention (‘editing’)
- Do not use ‘foreign DNA’ therefore consumers will not be concerned.
- In some cases do not even involve modifying DNA.
NGO’s/critics argue:
- This is genetic engineering 2.0 – therefore should be regarded as GMO’s
- Genome editing has similar ‘off-target’ effects as 1st gen GMO’s – risks.
- Techniques are new and more powerful therefore GMO risk concerns are magnified.
- Creates entirely novel sequences.
- Wrong to claim that new edited sequences are ‘predictable’/well understood. Small
genome changes > big changes in organism.

66. “The firm has sold enough seed, branded as SU Canola, to cover
about 8,000 acres in North Dakota
It just happens to develop non-GMO plants which are tolerant to
sulfonylurea herbicides through gene editing, says James Radtke,
vice president for product development at Cibus.
The firm has a partnership with Cargill to market the product,
Radtke explained.
“People can get a contract to grow our canola, sell to Cargill and
get a premium because it’s non-GMO,” he added.
“We all understand GMO to be transgenic,” said Radtke. “And as
such, we’re not GMO.”
“It was a somewhat limited launch last year,” Sanders said.
“But we’ll have a presence this year in the (U.S.) marketplace.”

67. - The underlying technology is Oligonucluotide Directed
Mutagenesis (ODM) – Synthetic DNA sequences
- Cibus has been told by US EPA no need to regulate as a GMO
- Currently being evaluated in Canada as ‘novel trait’ plant
- Europe: differing opinions by States. 2 conflicting opinions by
different German Ministry’s about whether it is a GMO.
- EU legal opinion on whether new plant breeding techniques
are GMO’s is being delayed and delayed . EU Commission
expected to treat at least some new plant breeding techniques
- including ODM - as non-GMO.
- Non-GMO project considers Cibus Canola as a GMO.

68. “Gene editing could, for example, be used to knock
out the receptor that the fungus uses to invade cells,
without any need, in Kim’s view, to classify the
resulting banana as a GMO”

69. RNAi
(RNA Interference)
Spraying synthetic
RNA on crops to
interfere with DNA
functioning.
Big Ag very invested:
Monsanto, Syngenta
“non-GMO”

71. Nothing but pale yellow flies kept emerging. “We were stunned,”
says Bier, who is Gantz’s Ph.D. adviser. “It was like the sun rose in
the west rather than the east.”

72. Eradicating Mice on Islands
with Gene Drives
GBIRd –Genetic Biocontrol of Invasive Rodents
5 partners: Island Conservation, USDA, Texas A&M,
North Carolina State University, CSIRO .
- Mouse gene drive work at NC State,
- Co-ord: Island conservation.
- Aim to be Ready for Release/approval by 2020
- Galapagos? Falklands? Hawaii? Nantucket?

73. Eradicating Avian Malaria in
Hawaii with Gene Drives
Exterminating Culex quinquefasciatus
 Focus on Honeycreeper bird (note: resistance already)
 Was significant topic of discussion in World Congress for
Conservation – Hawaii Sept 2016
 3 step approach:
1. Sterile Male Mosquitos (irradiated)
2) RIDL – genetically engineered mosquitos
3) Gene Drive Mosquitos
> Release/experimentation on Hawaii involves interaction with
indigenous, farming and other communities.

74. Eradicating Human Malaria in
Africa with Gene Drives

76. “Given the obvious dangers
of irretrievably releasing
genocidal genes into the
natural world, and the
moral implications of taking
such action, we call for a
halt to all proposals for the
use of gene drive
technologies, but especially
in conservation”

77. Synthetic
Biology
more on
Syn Bio?
www.synbiowatch.org
www.etcgroup.org/issue
s/syntheticbiology
@etc_group
@synbiowatch @jimetc