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SALT 2015 05 McCauley DigBio v2

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Raymond McCauley

on 17 September 2015

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Transcript of SALT 2015 05 McCauley DigBio v2

TALENs
Reading
DNA
+1-650-776-4561
for your attention
raymond@raymondmccauley.net
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.
Exponential Biosciences
systems
biology
past:
Biotech Chair: Singularity U
Co-Founder: Playtpus Project
Co-Founder & Chief Architect: BioCurious
Principal: Exponential Biosciences

Current Research Areas:
Personal Genomics
Therapeutic Genetic Engineering
Low Cost Access to Biotech Tools
Cancer Dx and Treatment
Singularity
University
Raymond McCauley
@raymondmccauley
Thank you
Applications
good preview
of things to come
Biomimetics / Packaging
yogurt = finger food
WikiFood, WikiPearl
Dave Edwards, Harvard bioengineer
Nutrigenomics
Retail / Vertical Farming
Raymond McCauley
Digital Biology:
raymond@singularityu.org
+1-650-776-4561
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...
Courtesy Ruby Gadelrab, Invitae
Functional Foods
Conflicts
Medicine
Agriculture
Energy & Manufacturing
Biotechnology =
1/3 of Global Economy
& Financial Interests
Anthrocyte
Deloitte
Exogen
Genomera
GLG
Illumina
Intellimed
Platypus Project
QIAGEN
Singularity University
Verinata
WellPoint
Marked with throughout presentation.
*
Caterpillar
Disruption
is never
Expected
Personalized Foods &
Food for Thought...
Food
example: Okanagan Fruit Specialties
Not multinational, but family startup
Not implanted, but adjusted
Not labeled, but branded
What is Food?
Cocoa
$2.1B
Chocolate
$131.7B
by 2019...
shifting production
global warming, disease
genetic engineering
shifting consumption
Asian markets
production innovation
health benefits
source:
Cocoa & Chocolate Market - Global Trends & Forecasts to 2019.
Entire presentation copyright 2014 by Raymond McCauley
Disruption
Mother (Nature)
Biotech
or
is the
of all
2020
=
+
2001
=
ApE = A Plasmid Editor
Rise of the
Biotech
Garage
Inventor
bioprinter project
OpenPCR
$599 DNA Copy Machine
+
Industrial
Biology
Biohacking
Cow-Free
Milk & Cheese
Genetic
Engineering
Software Development
=
The
small
future
is
industrial microbiology
yeast = tiny factories
like microbreweries
gene prospecting
supply chain disruption
Microbiomes
Bacterial Reservoir
Eat ammonia
Eliminate smell
Crowd out
tinea pedis
Keep feet healthy
Peter DiLaura, CEO
Practical Advice
Use antibiotics wisely
Eat like ancestors
Get a dog
Citizen Science
& Crowd-Sourced
Metagenomics
Drag & Drop Tools
DNA Synthesis
Lab Automation
Industrial Biology
Systems Biology
TALENs & CRISPRs
Renaissance in
Digital Biology
Industry Materials Energy Agriculture Medicine Research
Microbiomes
Wearables/
Implantables
Microbiome Roles
Digest food
Synthesize nutrients
Protect against disease
Mood, sleep, eating behavior
Partnership with Mayo Clinic, as of Oct 2014
inflammatory bowel diseases
metabolic disorders
colorectal cancer

Secret Clinical Trials, revealed Feb 2015
1. Avoid excess sugary foods
2. Good quality sleep
3. Meditation and relaxation
4. Eat fiber
5. Eat natural probiotic foods
6. Consider probiotic supplements
The Gut Microbiome,
Anxiety and Depression:
6 Steps to Take
by Peter Bongiorno, ND, LAc
November 8, 2014
Jessica
Richman,
CEO
microbiome hacking
& DIY fecal transplants
Phage
Therapy
Use viruses to kill bacteria
Specifically targeted
Alternative to wide spectrum antibiotics
Developed in Russia, new Western interest
Image credit: Bacteriophages and Biotechnology
http://www.pharmainfo.net/luckypharmacist/bacteriophages
Athletic Sensors
Medical Sensors
200+ sensors
Car
Phone
You
12+ sensors
0 sensors
Edge
Scanadu
importance
of
hearing
to be a
cyborg
http://rockhealth.com/tag/wearables/
now
next
wearables
implantables
We are
all
cyborgs
vaccination
biotechnological
artifact
xNTi kit
RFID chipset
2x12mm cylindrical USP grade lead-free Schott 8625 biocompatible glass casing
Pre-loaded injection assembly
Use with 13.56MHz RFID systems & NFC

$99 from
dangerousthings.com
to show
implants are
easy
very intimate...
Shaping the oral microbiota
through intimate kissing
Remco Kort, Martien Caspers, Astrid van de Graaf, Wim van Egmond, Bart Keijser and Guus Roeselers
...we investigated the effects of intimate kissing on the oral microbiota of 21 couples by self-administered questionnaires about their past kissing behavior and by the evaluation of tongue and salivary microbiota samples in a controlled kissing experiment...
"
"
brings up many questions...
Expose yourself
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
Plague, Inc
Download an app
to biotechnology
Biohacking & You
Cold Spring Harbor Labs Press
Childrens Books
igem.org
international
Genetically
Engineered
Machines
competition
RFID
Hackers:
Learn by
Doing
2015
=
Implant Procedure
Nov 2014, SU Summit Amsterdam
2m 34s
App: NFC TagInfo
Read chip, unlock phone, open websites
Open (some) hotel doors
What can I do?
Access (a few) credit card machines
and
biosensing
and
command & control
are
coming soon
but mainly, I get a lot of funny looks
One More Thing...
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
2012
$1
People
Teams
Interdisciplinary
Disruption
is never
Expected
Salim Ismail
Add a specialty
Be half of a team
Assemble a varied team
Find translators
Develop internal people
Innovation Lessons
Triple Major?
Design Your Own Major?
A hackerspace for biotech

First 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
BioCurious/FBI
Joint Conference on
Biohacking
June 12-16, 2012
Ask
Questions
Marty Blazer
Short pulsed antibiotics
Permanently alters body composition.
= how we dose kids
= obesity
23andMe and Apple
enter drug research business
"crowd-sourced clinical trials"
Apple ResearchKit
- Asthma
- Parkinson's Disease
- Breast Cancer
- Diabetes
- Cardiovascular
Enrolled 7400+ people in 24 hours.
Previous largest study was 1700.
Makes vaccines using mRNA from diseases
"Vaccinated with information"
Gates Foundation invests $57M
"Cellular scissors chop up HIV virus"
Salk Institute
Nature Communications "Use of the CRISPR/​Cas9 system as an intracellular defense against HIV-1 infection in human cells", Liao et al
How long until
genetic engineering
for
humans
?
ZFPs
TALENs
CRISPR/Cas9
$10000
$5000
$1000
Better, Cheaper, Faster
Genetic Engineering Tools
*
The
future
is
coming
fast
2010: discovered
2011: microbes
2012: plants, animals
2013: human cells, company
2014: patent fight
Drag and Drop
Genetic Engineering
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
PCSK9
SLC30A8
Lean muscles
Extra-strong bones
Alzheimer’s-resistant/immune
HIV-resistant/immune
Lower coronary risk
Stomach flu resistant
Heart disease
Type 2 Diabetes
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
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
CRISPR/Cas9
is a toolkit for
Genes
and regulatory regions
Knock-out
Knock-in
Repair
Edit
cheap
highly targeted
improvable
bluebird bio
Editas Medicine
GenSight
Lysogene
Spark
uniQure BV
Voyager Therapeutics
and others
Genetic Engineering
Therapeutics
Companies
they work,
everywhere
Genome Editing with CRISPR-Cas9
Animation created by:
McGovern Institute for
Brain Research at MIT,
Feng Zhang, Sputnik Animation
Human
Infertility
Prenatal Genetic Dx
Mitochondrial Therapy
Germ-Line Therapy
Enhancement
- Disease Risk
+ Intelligence
+ Longevity
NOW
NEXT
genetic
engineering
sports
music
+
23andMe and Apple
enter drug research business
"crowd-sourced clinical trials"
Apple ResearchKit
- Asthma
- Parkinson's Disease
- Breast Cancer
- Diabetes
- Cardiovascular
Enrolled 7400+ people in 24 hours.
Previous largest study was 1700.
lots of sensors
play music = command & control
running = biosensing
very intimate - next to eardrum
Why did I do it?
2020
=
small
The
future
is
The future is
cheap
Industrial
Biology
The future is
coming
fast
Human
genetic
engineering
The future is
bringing
Big
Things
The
future
is
Inside
Us
Microbial
Nation
The future is
All Around Us
Please remember this...
CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes
Puping Liang, et al, Guangdong Province Key Laboratory of Reproductive Medicine
Announced 22 April 2015
Attempted Beta-Thalassemia therapy
Used nonviable embryos
Found it hard to do - off target & chimerism
Too controversial for most journals
Francis Collins on funding
Announced First Human Embryos Edited by CRIPSR
Biology now falls under Moore's Law
DNA Sequencing Economics
Cost
DNA Sequencing Tech
5X ~ 10X

Computer Tech
1.5X ~ 2X
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
2020
2016
2020
=
=
=
Source: National Human Genome Research Institute, Exponential Biosciences
Genomics' Greatest Hits
Pharmacogenomics
Cancer
Rare Disease
Longevity
People who never got:
cancer
cardiovascular disease
neurological conditions
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...
marginal cost,
market segmentation
& value-added services
1 human genome + interpretation
=
$3900

5 human genomes, raw data, in bulk
=
$3000

1 fast delivery human genome
= $5000

1 human exome
=
$500

1 point-of-care bacterial identification
= $200+

1 human "gene scan" / 23andMe
=
$99 - $250
Hanahan & Weinberg

Hallmarks of Cancer:
The Next Generation

Cell, March 2011
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
untreatable
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...
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
FFPE
Formalin Fixed
Paraffin Embedded
Next Generation Sequencing
Next
STATION
Foundation Medicine
FoundationOne Test Video
2 min 18 sec
Clinical Genetics
Cancer Genetics
Software for
A: Pick good parents!
14 Jan 2014
HiSeqX 10
$10M
20 000 genomes/year
$1000/genome, all in
NextSeq 500
$250K
1-10 genomes/day
Now
Reactive
Near Future
Medicine
Cancer
Diagnosis and Treatment
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
Has replaced Amniocentesis
Tests for chromosomal disorders
Finding Fetal DNA in blood: Data Problem
Biggest Drug Problem?
compliance
+
personalization
Rohan Coelho, Rexanto
packaging
&
sensors
NASDAQ: ILMN
Market Cap: 27.26 B
P/E: 66.42
dominates market
virtual monopoly
large cash reserves
purchase/license new dev

*
=
Predictive
The End of
Mammograms
Colonoscopies
&
?
circa 2018-2020
*
2015
=
"What kind of infection?"
DNA Sequencing
Reading DNA
Genetic Engineering
Writing DNA
Hacking DNA
Democratization
Access to Tools
Bacterial Identification
"Another Cost Center"
"More Gadgets"
Skepticism
Pharmacogenomics
More Accurate - Less Risk - Fraction of the Cost
Risk Factors
1+
Preventive Visits Per Year
2
2+
3-4
0
1
"Patient Stratification for Preventive Care in Dentistry", Giannobile WV, Braun TM, Caplis AK, Doucette-Stamm L, Duff GW, Kornman KS.
Journal of Dental Research.
2013.
(diabetes, smoking, genetics)
Periodontitis genetic test
Looks at IL-1 gene variations
How many yearly cleanings?
Stacks the deck... / double-edged
Test Types
Throat swab culture
DNA probe
RADT - Optical Immunoassay
RADT - Enzyme Immunoassay
Rapid qPCR
Time

48 hours
2 hours
<1 hour
<1 hour
<1 hour
Special Equip
-
$$
$$$
-
$
Dental Genetics
blood sugar
blood chemistry
temperature, blood pressure, ECG
transplant rejection
heat attack, stroke early warning
untreatable
incurable
You can't buy ENIAC for a penny

But you
can
buy:
Decent Laptop, $800
An 100 hours of cloud computing, $130
Graphics workstation, $11000
Moore's Law
Decent Laptop, $800
An 100 hours of cloud computing, $130
Graphics workstation, $11000
BETTER
circa 2010
circa 2015
Today:
$200
qPCR
with
20 minute prep and run time
Scandu Scout Promo Trailer
1 min 37 sec
Stealth companies that contacted me
Reading, Writing & Hacking DNA
Full transcript