Transcript Markets 2.0

DIYgenomics
Open-source preventive medicine and
scaling citizen science genomics
July 28, 2011, OSCON, Portland OR
Slides: http://slideshare.net/LaBlogga
Melanie Swan
Founder
DIYgenomics
415-505-4426
@DIYgenomics
www.DIYgenomics.org
[email protected]
About Melanie Swan





Founder DIYgenomics, hedge fund manager,
futurist, entrepreneur
Current projects: MelanieSwan.com
Work experience: Fidelity, JP Morgan, Arthur
Andersen, iPass, RHK/Ovum
Education: MBA Finance, Wharton; BA
French/Economics, Georgetown Univ
Sample publications




Swan, M. Multigenic Condition Risk Assessment in Direct-to-Consumer
Genomic Services. Genet. Med. 2010, May;12(5):279-88.
Swan, M. Translational antiaging research. Rejuvenation Res. 2010,
Feb;13(1):115-7.
Swan, M. Engineering Life into Technology: the Application of
Complexity Theory to a Potential Phase Transition of Intelligence.
Symmetry 2010, 2, 150:183.
Swan, M. Emerging patient-driven health care models: an examination
of health social networks, consumer personalized medicine and
quantified self-tracking. Int. J. Environ. Res. Public Health 2009, 2, 492525.
July 28, 2011
DIYgenomics.org
Source: http://melanieswan.com/publications.htm
1
Biology is an information technology
011011000110111110111011001100101 – I love you
011011000110111110111010001100101 – I hate you
Image credit: http://www.nanoporetech.com/sequences
Image credit: http://pubs.acs.org/cen/_img/87/i50/8750cover2_law.gif Dec. 14, 2009
July 28, 2011
DIYgenomics.org
2
Biology is the information technology
Organ regeneration (urethra)
Algal biofuel
Image credit: Anthony Atala lab
Image credit: http://www.rexresearch.com
Artificial cell booted to life Whole organ decellularization and DNA nanotechnology latch
recellularization (heart)
box for drug delivery
Image credit: J. Craig Venter Institute
Image credit: Thomas Matthiesen
July 28, 2011
DIYgenomics.org
Image credit: Aarhus University
3
Agenda
Citizen science progress to date
Scaling citizen science
Grand vision next steps
July 28, 2011
DIYgenomics.org
Image credit: http://www.gettyimages.com
4
Citizen science definition

Investigation without professional training
Traditional science
research
DIYbio
Citizen
science: 200+
organizations1
July 28, 2011
DIYgenomics.org
1http://scienceforcitizens.net/finder
5
Politics of personalized genomics

Genetic Information Nondiscrimination Act (GINA) 2008
 Our world is not Gattaca
 Genomic test regulation expected
 Genomic rights
 Petitions




Petition for Access to Genetic Information
http://www.thepetitionsite.com/1/mydna
Petition for Health Data Rights
http://www.healthdatarights.org
Health as a currency
Health as a human right
July 28, 2011
DIYgenomics.org
Image credit: http://www.sonypictures.com
6
Consumer genomics test landscape
Cost
$
Knome
$350,000
Genetic disorders,
Drug sensitivity,
Predisposition
DNA Direct $200-$3,500
Matrix Genomics $199-$799
Paternity
Genelex $200-$475
Identigene $149-$399
Pregnancy Screening
Counsyl $349
Nutrigenomics
APO E Gene Diet $389
Inherent Health $99
Matchmaking
ScientificMatch $1,995
GenePartner $10-$99
Single/few condition
1Lower
Knome
Pathway*
Navigenics*
$19,500
$99,500
40 conditions
Genomics
EdgeBio
71 conditions
$6,000 Illumina $68,500
23andme
deCODEme
$48,000
49 conditions
201 conditions
$39,500
$10,0001
$2,500
$299
$2,000
$985
$99
*Must be physician-ordered
Public studies
Coriell
Scripps (Navigenics)
Harvard Med. Sch.
Pers. Genome Proj.
15 conditions
28 conditions
Conditions undisclosed
Multiple condition
cost with family group or medical condition
July 28, 2011
DIYgenomics.org
$999
$1,000
Exome
Whole genome
Service Breadth
7
Genomics comparison scorecard

Which service to buy?
Consumer
genomic service
#
Conditions
Cost
Report
Data
access
Visible
research
quality1
Updates
deCODEme
49
$2,000
23andme
201
$99
40
$999



+



+
Navigenics
Pathway Genomics
71
$299
+



Coriell
15
public
study
PGP (Personal
Genome Project)
n/a
public
study
July 28, 2011
DIYgenomics.org
1Conditions,
genes, variants, underlying research references, and methodology white paper(s)
available on public website
8
Consumer genomics: interpretation variance
July 28, 2011
DIYgenomics.org
Source: www.DIYgenomics.org and Swan, M. Multigenic Condition Risk Assessment in Direct-to-Consumer
Genomic Services. Genet. Med. 2010, May;12(5):279-88. Private data upload: Marat Nepomnyashy
9
Open-source mobile apps (5,000+ downloads)



Health condition, drug
response, athletic
performance
23andMe data upload
Android
TTT
TTT
TCC
“genomics”

iPhone
“genomics”
July 28, 2011
DIYgenomics.org
Android development: Michael Kolb, Lawrence S. Wong, Laura Klemme, Melanie Swan
iPhone development: Ted Odet, Greg Smith, Laura Klemme, Melanie Swan
10
Citizen science health landscape
Health social
networks
July 28, 2011
DIYgenomics.org
Health
collaboration
communities
Source: Extended from Swan, M. Emerging patient-driven health care models: an examination of health social networks, consumer
personalized medicine and quantified self-tracking. Int. J. Environ. Res. Public Health 2009, 2, 492-525.
11
Lifecycle of a health condition
Pre-clinical (80%)
Preventive medicine
Self-tracking
Wellness profiling
Health community collaboration
Applied healthspan engineering
Clinical (20%)
Traditional medicine
Disease treatment
Medical expertise
Emergency
Exceptions
Goal: decrease in clinical conditions over time
# conditions
becoming
clinical
Time
July 28, 2011
DIYgenomics.org
12
Genome hacking philosophy

Goal: preventive medicine
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
Realize preventive medicine by establishing baseline markers of
wellness and pre-clinical interventions
Generalized hypothesis

One or more polymorphisms may result in out-of-bounds
baseline levels of phenotypic markers. These levels may be
improved through personalized intervention.
Genotype
July 28, 2011
DIYgenomics.org
+ Phenotype + Intervention =
Source: http://diygenomics.pbworks.com/MTHFR
Outcome
13
Vitamin B deficiency / MTHFR mutation


Do common mutations in the MTHFR gene prevent
vitamin B from working correctly?
Test whether 2 variations in the MTHFR gene keep
vitamin B9 (folic acid) from being metabolized into its
active form (folate)


rs1801133/C677T
rs1801131/A1298C

Without this form of vitamin B, homocysteine may
accumulate (risk of cardiovascular disease, etc.)
 50% or more of the population may have some form of
MTHFR polymorphism
July 28, 2011
DIYgenomics.org
Source: http://diygenomics.pbworks.com/MTHFR
14
Homocysteine metabolism pathway
July 28, 2011
DIYgenomics.org
Source: Swan, M., Hathaway, K., Hogg, C., McCauley, R., Vollrath, A. Citizen science genomics as a model
for crowdsourced preventive medicine research. J Participat Med. 2010 Dec 23; 2:e20.
15
Vitamin B / MTHFR study protocol


Investigate genotype-phenotype linkage and apply
interventions to improve phenotypic outcomes
Protocol confirmed with two separate experts in the field
1. Genotype
2. Phenotype
MTHFR gene SNPs:
Blood tests:
rs1801133 (A/G)
B-12 and
1.
B-complex
rs1801131 (A/G)
Homocysteine
2.
L-methylfolate
3.
B-complex + Lmethylfolate
July 28, 2011
DIYgenomics.org
Source: http://diygenomics.pbworks.com/MTHFR
3. Intervention
(2 week periods)
16
Vitamin B / MTHFR pilot study results

Drug store vitamin (Centrum) reduced homocysteine
levels for 6/7 participants
DIYgenomics MTHFR Vitamin B deficiency study1
1. Genotype profiles
2. Homocysteine levels
Homocysteine umol/l
Baseline Centrum
1Results
are not statistically significant and are intended as
a pilot demonstration of citizen science genomic studies
July 28, 2011
DIYgenomics.org
LMF
Centrum
+ LMF
Baseline
Blood Test #
LMF = L-methylfolate
Source: Swan, M., Hathaway, K., Hogg, C., McCauley, R., Vollrath, A. Citizen science genomics as a model
for crowdsourced preventive medicine research. J Participat Med. 2010 Dec 23; 2:e20.
17
Personal health collaboration studies
More information: www.DIYgenomics.org
www.DIYgenomics.org/DIYgenomics_poster.ppt
July 28, 2011
DIYgenomics.org
18
Agenda
Citizen science progress to date
Scaling citizen science
Grand vision next steps
July 28, 2011
DIYgenomics.org
Image credit: http://www.gettyimages.com
19
Scaling citizen science

Engaging participants and building trust
 Innovating the Institutional Review Board
 Accessing blood tests 2.0
 Developing a philosophy of epistemology of citizen
science
Image credit: http://slobodkina.com
July 28, 2011
DIYgenomics.org
20
Engaging personal health collaborators

Participation must be fun and easy
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Relevant value proposition to
target market

Crowdsourcing the value chain:
data, questions, financing, analysis

Nomenclature framing:
enhancement, optimization
July 28, 2011
DIYgenomics.org
Image credit: http://www.superstock.com
21
Athletic performance
Category
Genes
Image credit: http://www.istockphoto.com
V
%
S
Endurance, power, and energy
Endurance
ACE, ACTN3, ADRB2/ ADRB3, BDKRB2, COL5A1, GNB3
7
50
22
Power
ACE, ACTN3, AGT
3
50
8
Energy
HIF1A, PPARGC1A
3
25
9
Musculature, and heart and lung capacity
Muscle fatigue and repair
HNF4A, NAT2 and IL-1B
5
40
4
Strength
HFE, HIF1A, IGF1, MSTN GDF8
5
17
15
Heart and lung capacity
CREB1, KIF5B, NOS3, NPY and ADRB1, APOE, NRF1
9
36
11
Metabolism, recovery, and other
Metabolism
AMPD1, APOA1, PPARA, PPARD
5
50
9
Recovery
CKMM/CKM, IL6
2
50
5
Ligament and tendon strength
Ligament strength
COL1A1, COL5A1, CILP
3
50
4
Tendon strength
COL1A1, COL5A1, GDF5, MMP3
7
63
5
V = number of variants; % = ratio of favorable polymorphisms to total alleles for a sample individual; S = number of studies
July 28, 2011
DIYgenomics.org
Source: Swan, M. Applied genomics: personalized interpretation of athletic performance GWAS. Jan 2011.
22
Study design template: MTHFR example
Cyanocobalamin
Image credit: http://wikimedia.org
July 28, 2011
DIYgenomics.org
Source: http://diygenomics.pbworks.com
http://diygenomics.pbworks.com/w/file/36469280/DIYgenomics+study+design+template+blank.doc
23
DIYgenomics study ecosystem – CRO 2.0
Funders
Sponsors
Study
advisors*
Study manager
Oversight
Graduate
student
partner*
Study operation
platform
(Genomera)
Participants
July 28, 2011
DIYgenomics.org
* Domain expert
24
Innovating the research model
Traditional Research Model
Citizen Science Research Model
Institutional
Review Board
(IRB)
Citizen ethicists
FAQs
Grant
funding
Institutional PI
(principal
investigator)
Journal
publication
Patient
advocacy
groups
Research
foundations
Citizen scientists
Investigators =
Participants
Self
publishing
Social VC
Research subjects
July 28, 2011
DIYgenomics.org
Crowdsourcing
25
Health hackers need Blood Tests 2.0

Low-cost home-administered self-read finger-stick
blood, urine, saliva tests:

Traditional blood tests (Homocysteine, Vitamin B-12,
Folate, Vitamin D, Creatinine, eGFR, Cortisol,
Calcium, Iron, Aldosterone)
 Hormones (Estrogen, Progesterone, Testosterone,
Estradiol)
 Immune system: CD4, CD8/CD28 ratio, IL-1, IL-6
 Chemical / heavy metal burden: mercury, cadmium,
lead, tin
July 28, 2011
DIYgenomics.org
26
Towards an epistemology of citizen science

Provide a structure and context for self-derived health
knowledge
 Q1: Are new kinds of knowledge are being formed
through group collaborations such as wikipedia and
health social networks?
 Q2: Are there differences in the types of knowledge
generated by traditional medicine, selfexperimentation, and health collaboration
communities?
July 28, 2011
DIYgenomics.org
27
Image credit: http://inkingrey.com
Ontological shift
Image credit: http://efx3.com
Old thinking:
My health is the responsibility of my physician
New thinking:
My health is my responsibility
… and I have the tools to make it fun and easy
July 28, 2011
DIYgenomics.org
28
Agenda
Citizen science progress to date
Scaling citizen science
Grand vision next steps
July 28, 2011
DIYgenomics.org
Image credit: http://www.gettyimages.com
29
Preventive wellness

Personal uses of the personal genome







Ancestry
Carrier status
Disease risk profiling
Drug response
Athletic performance capability
Product response
Wellness profiling



Cancer
Immune system
Aging
July 28, 2011
DIYgenomics.org
30
Predictive wellness profiling: cancer
Image credit: http://utmb.edu

Proto-oncogene/tumor suppressor gene polymorphisms
Gene
RSID
1
TP53
TP53
2
MDM2
1
MDM4
1
HAUSP
Alleles
Poss
Unf
Fav
23andMe alleles
Poss Fav
Ex
p-value
OR
Case
Ctrl
Citation
rs1042522
rs1860746
CG
GT
C
T
G
G
CG
n/a
G
n/a
CG
n/a
0.77
0.04
1.23
1.47
685
6,127
778
5,197
Joshi 2010
Liu 2009
rs2279744
GT
G
T
GT
T
GT
0.91
1.27
685
778
Joshi 2010
rs1380576
CG
G
C
n/a
n/a
n/a
0.95
1.03
4,073
n/a
Sun 2010
rs1529916
AG
G
A
n/a
n/a
n/a
0.07
1.05
4,073
n/a
Sun 2010
PTEN
1
rs701848
CT
C
T
CT
T
CT
0.00
0.12
53
107
Hosgood 2010
PTEN
1
rs1903858
AG
G
A
AG
A
AA
0.01
0.13
53
107
Hosgood 2010
2
938C>A
AC
A
C
n/a
n/a
n/a
0.05
n/a
40
40
Fingas 2010
2
rs5443
CT
T
C
CT
C
CC
0.05
n/a
40
40
Fingas 2010
MYC
rs6983267
GT
G
MYC
rs1050477
AC
A
MYC
rs7014346
AG
A
1
2
Tumor Suppressor, Proto-oncogene
T
C
G
GT
GT
AG
T
G
G
TT
GG
GG
0.00
0.00
0.00
1.21
1.17
1.19
930
7,480
14,500
960
7,779
13,294
Tomlinson 2007
Zanke 2007
Tenesa 2008
BCL2
GNB3
2
TP53: cell cycle arrest, PTEN: cell cycle progression modulator,
MYC: cell cycle regulator
July 28, 2011
DIYgenomics.org
Source: DIYgenomics
31
Lung cancer risk and drug response

Risk and drug response for specific cancers
July 28, 2011
DIYgenomics.org
Image credit: http://www.xianet.net
Source: Swan, M. Review of cancer risk prediction in direct-to-consumer genomic services. (poster) Canary
Foundation Early Detection Symposium, May 25-27, 2010, Stanford University, Stanford CA.
32
Wellness profiling: immune system

Immune system genomic wellness profiling
 Immune response: T-cell activation
Image credit: http://www.iayork.com

Gene
CTLA4
CTLA4
CTLA4
CD226
CD86
IL3
IL3
IL3
CTLA4, CD226, CD86, IL3
RSID
rs231775
rs5742909
rs733618
rs763361
rs1129055
rs181781
rs2073506
rs40401
Poss
A/G
C/T
C/T
C/T
A/G
A/G
A/G
C/T
Alleles
Unf Fav
A
G
C
T
C
T
T
C
G
A
A
G
A
G
T
C
23andMe alleles
Poss Fav
Ex
AA
AG
G
CC
CT
T
TT
CT
T
CC
CT
C
GG
AG
A
GG
AG
G
CC
CT
C
CC
CT
C
p-value
0.007
0.098
0.041
0.000
0.006
0.041
0.009
0.014
OR
0.642
0.67
4.62
1.22
0.51
0.55
0.32
2.18
Case
172
172
269
1,990
269
60
60
60
Ctrl
145
145
395
1,642
395
270
270
270
Citation
Duan 2010
Duan 2010
DallaCosta 2010
Dieudé 2010
DallaCosta 2010
Lee 2010
Lee 2010
Lee 2010
CTLA4: T-cell inhibition; IL3: growth-promoting cytokine
July 28, 2011
DIYgenomics.org
Source: DIYgenomics
33
Aging: TA-65, telomere length & TERC mutation


Herbal supplement TA-65 (astragalus root) taken by
1000 people worldwide. Telomere and immune
system benefits in humans published Mar 2011.1
TERC (RNA gene that extends telomeres) SNPs:

rs10511887, rs12696304, rs16847897, rs2293607, rs610160
July 28, 2011
DIYgenomics.org
1Source:
Harley CB, et al. A natural product telomerase activator as part of a health maintenance program. Rejuvenation Res. 2011
Feb;14(1):45-56.
34
Aging: applied healthspan engineering
Representative Rational Healthspan Interventions
Target=process
Intervention
1 Blood pressure
Multiple; exercise, dietary, sodium restriction, see RAS (below)
2 Heart rate
Exercise, vagal nerve stimulation
3 Dyslipidemia
Fish oil; flaxseed oil, olive oil niacin, statins
4 Renin–angiotensin system (RAS)
Exercise, dietary, sodium restriction, ACE inhibitors, ARBs, renin inhibitors
5 Medial elastocalcinosis
Vitamin K2
6 Glucose homeostasis
Exercise, metformin, dietary-caloric restriction
7 mTOR pathway
Resveratrol, rapamycin, dietary-caloric restriction
8 Inflammation
Aspirin, NF-kB inhibitors (e.g., EGCG, quercetin, etc.)
9 Autophagy
Verapamil, trephalose, others
10 Extracellular matrix cross-link
Alagebrium, ALT-711
11 Chemopreventive
Aspirin, bioflavonoids
Legend: ACE, angiotensin converting enzyme; ARBs, angiotensin receptor blockers; EGCG, epigallocatechin 3-gallate; mTOR, mammalian
target of rapamycin.
July 28, 2011
DIYgenomics.org
Source: Larrick JW, Mendelsohn A. Applied Healthspan engineering. Rejuvenation Res. 2010 Apr-Jun;13(2-3):265-80, Table 2.
35
Circles of preventive medicine
1. Automated digital
health monitoring
Individual
2. Preventive Care
Health Social Networks
Citizen Science Studies
Health Advisors
3. Traditional health care
system and physicians
July 28, 2011
DIYgenomics.org
Source: Extended from Swan, M. Emerging patient-driven health care models: an examination of health social networks, consumer
personalized medicine and quantified self-tracking. Int. J. Environ. Res. Public Health 2009, 2, 492-525.
36
Health self-management
July 28, 2011
DIYgenomics.org
Source: Extended from Swan, M. Emerging patient-driven health care models: an examination of health social networks, consumer
personalized medicine and quantified self-tracking. Int. J. Environ. Res. Public Health 2009, 2, 492-525, Figure 1.
37
Collaborators:
Crowd-sourced clinical trials
Personal genome apps
Lorenzo Albanello
Janet Chang
Thank you!
Cindy Chen
Jon Dekay
Louis Nahum
John Furber
Marat Nepomnyashy
Eri Gentry
Ted Odet
Kristina Hathaway
Roland Parnaso
Takashi Kido
William Reinhardt
Laura Klemme
Greg Smith
Lucymarie Mantese
Aaron Vollrath
Raymond McCauley
Lawrence S. Wong
Creative Commons 3.0 license
Slides: http://slideshare.net/LaBlogga
Melanie Swan
Founder
DIYgenomics
415-505-4426
@DIYgenomics
www.DIYgenomics.org
[email protected]