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Denmark DigBio part 1

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Raymond McCauley

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Transcript of Denmark DigBio part 1

Singularity
University

for your attention
raymond@raymondmccauley.net
DNA Structure
Biology now falls under Moore's Law
Raymond McCauley
biochemistry
biophysics
electrical engineering
computer science
bioinformatics
nanotechnology
genetic engineering
DNA sequencing
personalized health
DISCLAIMER
These are my opinions and are not intended to reflect the views of any group or organization with which I may be affiliated.
DNA Sequencing Economics
Cost
Exponential Biosciences
systems
biology
DNA Sequencing Tech 5X ~ 10X

Computer Tech
1.5X ~ 2X
past:
Biotech Chair: Singularity U
Co-Founder: Playtpus Project
Co-Founder & Chief Architect: BioCurious
Principal: Exponential Biosciences

Current Research Areas:
Personal Genomics
Low Cost Access to Biotech Tools
Genetic Engineering
Cancer Sequencing
Companies to Watch
Illumina
Complete Genomics
Ion Torrent / Life Technologies
Oxford Nanopore
Genia
DNAnexus
Invitae
NuMedii
Personalis
Station X *
Strand LS
SV Bio
Genentech
Genomic Health
Counsyl
Vecoy Nanomedicines
Verinata **
Second Genome
Next Gen Sequencing
Next Next Gen Sequencing
Informatics
Diagnostics/Treatment
Watson, Crick & Franklin
& a Garage Near You...
Writing DNA
Genetic Engineering
=
Software Development
Innovation Lessons
from being in
an exponential business
Find an exponential trend,
then hitchhike
A prototype beats a plan
Product Development Process (PDP)
typical product:
18 month development cycle,
9 month market life

make new & rev old products
core team leaders involved from start
phase-gated milestones
manage technical and business risk
New Developments
Nothing fades faster than last year's technology
2008
$500K
Today
$1
Closing Thoughts
In the future,
if it is made out of
atoms,

you will make it with
biology.
What does your industry
make or use?
DNA Origami
Genetic Engineering
Industrial
Human
Food
PGD
mitochondrial therapy
germ line therapy
Biology as Technology
"Redneck Genetic Engineering"

bone marrow replacement
HIV cure
Nic Volker cure
Gene doping
"
The GM debate is over...
We no longer need to discuss whether or not it is safe — over a decade and a half with three trillion GM meals eaten, there has never been a single substantiated case of harm.
You are more likely to get hit by an asteroid than to get hurt by GM food.”
- Mark Lynas, GMO crop burning environmental activist
"...There is no more risk
in GMO food than conventionally
farmed food."
- Anne Glover,
European Commission’s
Chief Scientific Advisor
Digital Agriculture
versus
Digital Agriculture
Okanagan Specialty Fruits
Aqua Bounty
Arcadia BioSciences
Species Conservation
Scientist seeks
"adventurous
human woman"
to have
Neanderthal baby
:(
:)
Singularity
University
or need to unmake?
What's Next
People
Teams
Interdisciplinary
Innovation Lessons
from being in
an exponential business
Find an exponential trend,
then hitchhike
A prototype beats a plan
Product Development Process (PDP)
typical product:
18 month development cycle,
9 month market life

make new & rev old products
core team leaders involved from start
phase-gated milestones
manage technical and business risk
Nothing fades faster than last year's technology
2008
$500K
Today
$1
People
Teams
Interdisciplinary
=
DNA sequencing
and synthesis prices
continue to plummet
Synthetic
Biology
*
Hype Cycle
but...
Metagenomics
Meta
Raymond McCauley
@raymondmccauley
+1-650-776-4561
Thank you
Peter DiLaura
Second Genome
New Yorker article
DNA has 521 year half-life
GMO
Anxiously watching
IP
Hopefully watching
Crowdfunding
Democratization
Democratization
of
Biotechnology
How fast can you get to
"Hello World"
with 2 guys & a laptop in a garage?
A hackerspace for biotech

First and largest biohacker lab in the world

Committed to making biotech
accessible, affordable, and open to everyone

Located in Sunnyvale, California

501c3 all-volunteer community lab, supported by monthly memberships and classes
Let's do that for biotech
iGEM 2004
international
Genetically
Engineered
Machines
competition
iGEM World Jamboree 2010
Who wants to be a
Genetic Engineer?
We teach
classes...
bioprinter project
We build things..
OpenPCR
$599 DNA Copy Machine
We mentor the
next generation
of scientists
and technologists
We support inventors
and entrepreneurs
We take safety
and security
seriously
In the last year,
31 startup companies
have done work
and recruited partners
at BioCurious
We build
community
BioCurious/FBI
Joint Conference on
Biohacking
June 12-16, 2012
http://openpcr.org/
Garage Labs
When we talk about garage labs
in Silicon Valley, we aren't kidding...
Helixis Real Time PCR
Industry: $30,000
Helixis: $13,900
How does
$599
sound?
The Biotech
Revolution
is Here!
If you've got:
Who wants to build something?
Dremelfuge
Centrifuge
=
$57
>$500
on Shapeways
used, on eBay
Research Tools
Better, Cheaper, Faster
US$750000,
a PhD in molecular biology,
and a fully equipped lab
Edge
Indicators
What do
we do?
iGEM Inaugural Competition, 2004
More tools in more hands
=
More Breakthroughs
Watching in
rearview mirror
Regulatory
Covers
Disease risk, carrier status,
genealogy, random stuff

What do
you
want to know?
Some of your info also applies to
family...

Privacy:
to share or not to share?
Do you want to be found by long-lost relatives?
Health insurance
protected by law

(GINA)
Life insurance, long-term disability is
not
Human
Prenatal Genetic Dx
Mitochondrial therapy
Germ line therapy
"Redneck Genetic Engineering"

bone marrow replacement
HIV cure
Nic Volker cure
Gene doping
How long until
genetic engineering
for
humans
?
How long until
genetic engineering
for
adults
?
New Engineering School at Stanford
Bioengineering
Big Deal?
What was the
last new school
at Stanford
?
Hint: established
1965
Answer: Department of
Computer Science
Graduates built
Silicon Valley

& triggered the
computer revolution
We are
everywhere
...
currently tracking
23 community labs
200+ individual labs
on 6 continents
Algae Chassis Project
DNA
Origami
a new kind of
Pharma Deal
Collgard Biopharmaceuticals
licensed compound halofuginone (
HT-100
)
to
Halo Therapeutics
for
$1M
Duchenne
Muscular Dystrophy
(DMD)
Meet the Halo board of directors...
The Seckler
Family
the Wicka
Family
DIY Drug Development
Orphan Drug status in US
Thumbs up from EU's Treat-NMD
Clinical trials start 2013
“We are ready to be the ones who get to make the decision of go or no go on this one." - Thomas Wicka
You let
kids go hands-on
with blowtorches?!?
Why, yes!
Yes we do!
5 year old Harlan
makes Calcium burn
red
.
DNA Synthesis
is now as easy as typing
Do you
believe?
$300M
Synthetic
Biology
*
Hype Cycle
Scaling Problems
Cells are
not

computers
Materials & Self-Assembly
arcane biological property

important
to manufacturers
materials, surface science, coatings
displays, self-cleaning, self repairing
Block
Co-Polymers
FF v. FFPE
Applications
If you get cancer,
remember
Fresh
Frozen
Formalin Fixed Parrafin Embedded
good preview
of things to come
Biomimetics / Packaging
yogurt = finger food
WikiFood, WikiPearl
Dave Edwards, Harvard bioengineer
Nutrigenomics
3D bioprinting / synthetic biology
tissue engineering / cultured meat / food
environmental impact
food security
Retail / Vertical Farming
3D printed
pipetter
+ straw
+ spring from PEZ dispenser
DNA Sequencing Economics
Cost
Time
Yovivo! Yogurt
gene-hacked yogurt + resveratrol
food as a hackable nutraceutical platform
from Radiant Genomics
ApE = A Plasmid Editor
Hacking DNA
latest
Looking for innovation in biotech?
Look in a garage near you...
Modern Meadow
Sample6
Evolva
Food & Synthetic Biology
Sample6
Modern Meadows *
Evolva
Small
Medium
Large
biologic drugs
research tools
biotech supply
cosmetics, flavors
materials
environment
biofuels
plastics
industrial synthesis
Vanillin
$300M
Genentech
rDNA human insulin
made in E. Coli
1978
Itakura, Riggs, Goeddel, and Crea, at City of Hope Medical Research Center
Raymond McCauley
Digital Biology:
Life Is the New Black
Artist: Ákos Maróy
biodisplay.tyrell.hu
Bio.Display
Medicines
for 30+ years
scale
scale
Food
"
The GM debate is over...
We no longer need to discuss whether or not it is safe — over a decade and a half with three trillion GM meals eaten, there has never been a single substantiated case of harm.
You are more likely to get hit by an asteroid than to get hurt by GM food.”
- Mark Lynas, GMO crop burning environmental activist
"...There is no more risk
in GMO food than conventionally
farmed food."
- Anne Glover,
European Commission’s
Chief Scientific Advisor
versus
GMOs
Digital Agriculture
(Genetically Modified Organisms)
Future
of genetic engineering
raymond@raymondmccauley.net
@raymondmccauley
Timothy Ray Brown
HIV diagnosed 1995
AML diagnosed 2006
CCR5Δ32 stem cell transplant
HIV-free since 2009
Blood, March 10, 2011, vol. 117, no. 10, 2791-2799
Photo: Peter Rigaud, for Stern, 2010
GMOs

3.0
Genetically
Modified
Organisms
better yield
better nutrition
better digestion
drought tolerance
saline soli tolerance
fungus resistance
virus resisitance
2020 - the global population consumes
120 more million tons of meat
220 more million tons of milk
290 more million tons of cereals
2030 - 8 billion people
2050 - 9 billion people
2050 - 2 X milk and meat demand
more food
more feed
less water
less land
less greenhouse gases
inhibit and modify

pollen
= hypoallergenic crops
modify lignin and
fructan biosynthesis
= lower methane
_
New Genetic Engineering Prototypes
=
The Sugarbelt Bioeconomy
What areas of the world will
drive a green bioeconomy?
x
x
Land prices,
Political stability
Water access
Sunlight access
Argentina
Brazil
Uruguay
=
The Sugar Economy
What areas of the world will
drive a green bioeconomy?
x
x
Land prices,
Political stability
Water access
Sunlight access
Argentina
Brazil
Uruguay
=
Synthetic Biology Explained
James Hudson/Bridge 8
Video
6 min 27 sec (partial)
for now
ZFPs
TALENs
CRISPR
$10000
$5000
$1000
Better, Cheaper, Faster
Genetic Engineering Tools
*
The
small
"Wet" Nanotechnology
Diversity of molecular machines
Mother Nature has no patent lawyer
Future tech is a wet/dry hybrid
Biotechnology =
"CRISPRs, young man!"
scale
future
is
industrial microbiology
"Mary had a little microbe"?
gene prospecting
Drag and Drop
Genetic Engineering
TALENs
Transcription
Activator
Like
Effector
Nucleases
TALENs have modified genes in:
yeast
fruitfly
roundworm
cricket
zebrafish
frog
rat
pig
cow
thale cress
rice
silkworm
human somatic cells
pluripotent stem cells
Nature Reviews Molecular Cell Biology 14, 49-55 (January 2013)
http://www.brc.a-star.edu.sg/index.php?sectionID=12
hijacked from plant bacteria that genetically engineer their host plants
discovered by Bogdanove & Moscou, Iowa State University, in 2009
make double stranded breaks to knock-out and knock-in genes
Clustered
Regularly
Interspaced
Short
Palindromic
Repeats
hijacked prokaryotic immune system mechanism
discovered by Horvath & Barrangou, DuPont/Danisco, in 2010
immunize industrial bacteria
gene silencing in stem cells
CRISPRs
MSTN
LRP5
APP
CCR5
PCSK9
FUT2
Lean muscles
Extra-strong bones
Alzheimer’s-resistant
HIV-resistant
Lower coronary risk
Stomach flu resistant
Genes to Knock Out
adapted from George Church, private communication
Behavioral and Mental Traits
MAOA gene & aggression
last to implement
poorly understood
Therapeutics,
then
Enhancement
Gene Expression
"gene doping"
EPO, red blood cell production
Myostatin, muscle growth inhibition
VEGF, blood vessel production
IGF-1, targeted muscle mass increase
Qualified
Speculation
RNA-Guided Human Genome Engineering via Cas9
Prashant Mali, Luhan Yang, Kevin M. Esvelt, John Aach, Marc Guell, James E. DiCarlo, Julie E. Norville, and George M. Church
Science 15 February 2013

Multiplex Genome Engineering Using CRISPR/Cas Systems
Le Cong, F. Ann Ran, David Cox, Shuailiang Lin, Robert Barretto, Naomi Habib, Patrick D. Hsu, Xuebing Wu, Wenyan Jiang, Luciano A. Marraffini, and Feng Zhang
Science 15 February 2013
Academically (for reference)...
Commerically...
$43 million Series A , Nov 2013
Flagship Ventures
Polaris Partners
Third Rock Ventures
Partners Innovation Fund
TALENs
CRISPRs
The
future
is
coming
fast
Your chance to try it...
Consumer access to research tool
"Recreational genomics"
Disease risk, carrier status, genealogy
Human Genome Project
2001, 13 years
~$2.7B

Celera Genome Project
2001, ~3 years
$70M+

454 James Watson Genome
2007, ~2 months
$1M

Illumina Yoruban Trio
2008, 6 weeks
$100K

Illumina Consumer Sequencing
May 2009, 2 weeks
$48K

Illumina Consumer Sequencing
June 2010, 1 week
$9500 = $19500

Illumina Consumer Sequencing
June 2011, 1 week
$5000

Personal Genome Project (Various)
Jan 2012, 3-7 days
$2000

Illumina HiSeq X Configuration
Jan 2014, <3 days
<$1000
DNA Sequencing
Reading DNA
2020
2016
2014
2020
=
=
=
=
Source: National Human Genome Research Institute, Exponential Biosciences
in 2008,
Illumina HiSeq
200+ gigabases of DNA
2 human genomes
in 5 days
less than $10,000 each
Complete Genomics
Illumina
Life Technologies/Ion Torrent
Pacific Biosciences
and
Genia
GnuBio
NABsys
Oxford Nanopore
Genomics'
Greatest Hits
Pharmacogenomics
Cancer
Rare Disease
Treating a patient for
a particular
lung cancer

becomes

Treating a patient for
cancer of the PI3K pathway
Drugs
1578 approved drugs
240 with genetic information
Just 21 shown in 23andMe
sources:
http://www.drugbank.ca/stats
http://www.pharmgkb.org/
http://www.23andme.com/
Drug:
Clopidogrel (Plavix)
Reduces blood clots. Treats heart attack and stroke

Genotypes:
rs4244285 = AG
rs4986893 = GG
rs28399504 = AA
rs41291556 = TT
rs12248560 = CC

Haplotype:
CYP2C19 *1/*2

Phenotype:
Reduced clopidogrel efficacy
(higher dosage needed).

Patient:
Me!
CYP450
Cytochrome P450s
ADME/Tox
Absorption
Distribution
Metabolism
Excretion
TOXicology
Longevity
People who never got:
cancer
cardiovascular disease
neurological conditions
Nicholas Volker's story
"One In A Billion:
A boy's life, a medical mystery"
Milwaukee Wisconsin Journal Sentinel,
by Mark Johnson and Kathleen Gallagher
Nic Volker
Pharmacogenomics
Cancer
Rare Disease
Longevity
First Human
Saved by
DNA Sequencing
Q: Secret to live a long time?
Every Disease
is a
Rare Disease...
Stephen Kingsmore &
Center for Pediatric Genomic Medicine
prepare samples
sequence DNA
digital analysis
4.5 hrs
25.5 hrs
20.0 hrs
~ $10 000 per case
"very helpful" in 7 out of 9 cases so far
marginal cost,
market segmentation
& value-added services
1 human genome + interpretation
=
$5000

4 human genomes, raw data
=
$6000

1 human exome
=
$1000

1 human "gene scan"
=
$99
Batten Disease Finding Ends a Diagnostic Odyssey for California Family
Bio-IT World January 24, 2013
Dylan
Jacob
Dietrich Stephan at
Hanahan & Weinberg

Hallmarks of Cancer:
The Next Generation

Cell, March 2011
Acromegaly
ostreolin
peptide somatostatin analog
Genentech deal for $545M
Underdiagnosed
Difficult to diagnose
Presents in adults
Genetic cause!
aryl hydrocarbon receptor interacting protein (AIP)
chief cause? of pituary tumors
Companion
Diagnostic?
as part of full genome scan
version 3:
Illumina Custom OmniExpress+ BeadChip
Assays about 1,200,000 SNPs
DNA Scan
DNA Sequence
most interesting/best known
1.2 million bases
0.04%
almost all
3.2 billion bases
100%
DNA Microarrays
Tools
What can you do about
being at risk for
an
unpreventable
disease?!?
It turns out, lots of things:

prevention - vitamins, avoid UV
testing - Amsler grid
new opthamologist
investigate clinical trials
support research
don't put off that trip to the Louvre...
Try it...
So What?
Personal Example
When I first found out about
my AMD risk
it was
"
untreatable
" & "
incurable
"
but
Genentech

now has 2 treatments available
footnote
*
Rare Disease
is the
Long Tail
of human health...
Coming Soon!
epigenomics
regulomics
environomics
metagenomics
your name here + omics
from a research lab near you!
metagenomics
Peter DiLaura, CEO
Practical Advice
Use antibiotics wisely
Eat like ancestors
Get a dog
metagenomics
population census
for your bacteria
=
Crowd-Sourced
Metagenomics
If it's so great,
why doesn't my doctor have it?
sequencing =
easy
interpretation =
hard
2001
=
+
2013
=
2007
=

Covers
Disease risk, carrier status, genealogy

What do
you
want to know?
Some of your info also applies to
family...

Privacy:
to share or not to share?
Do you want to be found by long-lost relatives?
In US,
Health insurance
protected by law

(GINA)
Life insurance, long-term disability is
not
Eye Problems
Genetic
Nearsightedness
Farsightedness
Color blindness
Retinitis pigmentosa
Genetic + Environmental
Glaucoma
AMD
Amblyopia / “lazy eye”
Strabismus
More genetic discoveries all the time...
March 2013: 24 new genes associated with
refractive error / nearsightedness
Virginie Verhoven, Erasmus Med Center, Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia
FFPE
FF
Formalin Fixed
Paraffin Embedded
Fresh
Frozen
versus
This could save your life...
from Eric Topol, MD
Next Generation Sequencing
Next
STATION
Foundation Medicine
FoundationOne Test Video
2 min 18 sec
Clinical Genetics
Cancer Genetics
Software for
A: Pick good parents!
New Research!
Chimeras & Neurons
Dec 2013 - Meditation, COX2,
& Anti-inflammation
Retrotransposons
& Self-Modifying Code in Your Brain
Kaliman, P., Álvarez-López, M. J., Cosín-Tomás, M., Rosenkranz, M. A., Lutz, A., & Davidson, R. J. (2014). Rapid changes in histone deacetylases and inflammatory gene expression in expert meditators. Psychoneuroendocrinology, 40, 96–107.
Chan WFN, Gurnot C, Montine TJ, Sonnen JA, Guthrie KA, et al. (2012) Male Microchimerism in the Human Female Brain. PLoS ONE 7(9): e45592. doi:10.1371/journal.pone.0045592
63% fetal microchimerism
in female brain
genes: tumor suppression & neuron dev
regions: learning and memory
Nature 479(7374):534-7.
Somatic retrotransposition alters the genetic landscape of the human brain.
Baillie JK, Barnett MW, Upton KR, Gerhardt DJ, Richmond TA, De Sapio F, Brennan PM, Rizzu P, Smith S, Fell M, Talbot RT, Gustincich S, Freeman TC, Mattick JS, Hume DA, Heutink P, Carninci P, Jeddeloh JA, Faulkner GJ.
14 Jan 2014
HiSeqX 10
$10M
20 000 genomes/year
$1000/genome, all in
NextSeq 500
$250K
1-10 genomes/day
Now
Good place to pause
& take a breath...
Control of
cell differentiation
& growth
Action Items
Embrace genetic info for preventive health
Encourage gene scans in corporate wellness programs
Insurance changes forever
in the biotech 21st century
Absolute
Privacy , Data
Escrow
Expose your kids (& yourself) to biotechnology
Raymond McCauley
+1-650-776-4561
Build a
biohacker
space
Get a Book
The Stuff of Life
by Mark Schultz
Illustrated by
Zander Cannon
& Kevin Cannon
good preview
of things to come
Try it
Best Conference
Future of Genomic Medicine
Dr. Eric Topol, Scripps Health
March 6&7 2014
Clinicians - Keep Learning
hyperorganic, hyperlocal
pesticide & herbicide free
Fiesta Hypermart, Houston, Texas, 1991
10,000+ sq ft hydroponic produce dept
Houston's biggest tourist attraction
Backed by NASA CELSS research group
6 months
700 000 meals sold
$2+M revenues
biodegradable & delicious
protein-based packaging
Bob's, Brazil
just the beginning...
Making Leather and Meat Better
Courtesy Ruby Gadelrab, Invitae
Quantified Self / Big Data / Deep Marketing
Courtesy Eli Mohammed, Walkmore
data driven loyalty platform
activity data -> marketing predictions
users sync apps and redeem rewards
+engagement, +revenues, -costs
GTE, Coca Cola, Vancity, Connex
Functional Foods
Artificiality
Next
Big
Thing
perception of
appeal of
React to
Disruptive
Innovation
Be in front of
Concern
How we try to help
example: Okanagan Fruit Specialties
Not multinational, but family startup
Not implanted, but adjusted
Not labeled, but branded
Drag & Drop Tools
DNA Synthesis
Lab Automation
Systems Biology
TALENs & CRISPRs
Renaissance in
Genetic Engineering
Industry Materials Energy Agriculture Medicine Research
Basic Research
Always Pays Off
Mitacs Accelerate's research internship program
NRC’s Industrial Research Assistance Program
CRA's Scientific Research and Experimental Development Tax Incentive
Gov't & Industry Cooperation in Canada
Drag & Drop Tools
DNA Synthesis
Lab Automation
Systems Biology
TALENs & CRISPRs
Renaissance in
Genetic Engineering
Industry Materials Energy Agriculture Medicine Research
Basic Research
Always Pays Off
Mitacs Accelerate's research internship program
NRC’s Industrial Research Assistance Program
CRA's Scientific Research and Experimental Development Tax Incentive
Gov't & Industry Cooperation in Canada
Raymond McCauley
Biotechnology
raymond@raymondmccauley.net
@raymondmccauley
4 270 500 000 X
Improvement in
throughput
since 2001
Cancer
Diagnosis and Treatment
Foundation Medicine
FoundationOne Test Video
2 min 18 sec
Cancer
Diagnosis and Treatment
Cancer
Drugs
Microbiome
de-extinction
the future looks like
a brewery...
control of gene expression
and natural growth processes
biofuels
precise control
complex assembly
Industrial Biology
digital
agriculture
synthetic
biology
How does it work?
What do you get?
Get-around-the-FDA hack
Raw Data
Demo:
Anyone want to share?
Other applications
NIPT = Non-invasive Prenatal Test
Replaces Amniocentesis
Tests for chromosomal disorders
Fetal DNA in blood: Data Problem
Disclosure
Crowd-Sourced
Metagenomics
Ready for prime time?
No prescriptive advice
Be a guinea pig - for Science!
Good self test / crossover study
Cell Spot
Microarrays
Growth
+ siRNA =
Test
Cancer Therapy CSMA
The cancer therapy is a database
tested on your printed tissue
Personalized testing of... everything
Biggest Drug Problem?
compliance
+
personalization
Rohan Coelho, Rexanto
packaging
&
sensors
Peter DiLaura, CEO
Practical Advice
Use antibiotics wisely
Eat like ancestors
Get a dog
No more
Colonoscopies
Mammographies
?
Circulating Tumor Cells (CTCs)
Full transcript