How Scientific Wellness will

Drive the Future of Health

Nathan Price, PhDInstitute for Systems Biology

Seattle, WA

Hyper Wellbeing

November 13, 2016

@ISBNathanPrice

Disclosures

• Dr. Price is a Co-Founder of Arivale, which

partially funded and may license discoveries

resulting from the Hundred Person Wellness

Project (to be described).

• Dr. Price serves on Scientific Advisory Board of

Habit, a new personalized nutrition company

Founders

Clayton Lewis, CEO and Co-founder

Maveron, MarketLeader, Harborview Medical Center, Capitol

Hill

Lee Hood, MD, PhD, Co-founder, SAB Chair

ISB, Amgen, National Academies, Presidential Medal

Nathan Price, PhD, Co-founder, Board of Directors

ISB, University of Illinois, Urbana-Champaign, UCSD, UW

86% of Healthcare Costs Treat Chronic Disease

Determinants of Health in U.S.

60%

30%

10%

Genetics

Behavior & environment

Health Care

Steven Schroeder et al. New England J Medicine, 2007

U.S. Healthcare Spending

$3.8 Trillion (2014)

Wellness Industry

Scientific Wellness → A New Industry

U.S. Healthcare Spending

$3.8 Trillion (2014)

Wellness Industry

Scientific Wellness→ ↔

Conceptual Themes of P4 Medicine

Disease DemystifiedWellness Quantified

P4 MedicinePredictive

Preventive

Personalized

Participatory

Scientific Wellness Industry Disease Industry

Proposing the 100K Wellness Project

Nature,

News

piece,

(2014)

Hood and Price, Science Translational Medicine (2014)

Hood and Price,

Clinical Omics,

(2014)

Scientific Wellness: Two Integrated Directions

Arivale• A consumer facing

scientific wellness

company

• 5,000 individuals in the

first 18 months

• Transform how biotech

industry operates

ISB-Providence

• Dense, dynamic, personal data clouds

• Research to validate wellness metrics

• Research for better assays

• Optimize wellness

• Study wellness to disease transitions

• Study disease [progression, response

to therapy and transition to wellness

PIONEER 100 PROJECTPrincipal Investigators: Lee Hood and Nathan Price

The 100K Wellness Project was initiated in 2014 with the generation of dynamic data clouds for 108 individuals. These data provided spectacular insights into what it is to be well and the nature of wellness to disease transitions (and vice versa).

• 108 participants

• Age range: 20s to 88+

• 9-month study launched March 2014

• IRB approved

• Evaluation / insights for next phase

• Whole genome sequence

• Detailed blood, urine, saliva measurements 3x

• Gut microbiome 3x

• Continual self-tracking and lifestyle monitoring

• Data integration & correlations

• Monthly coaching sessions on actionable data

• Discovery research

• Events and education

Assays / Measurements—108 Pioneers

Database

of actionable

possibilities that

will grow over

time

GENOME

Whole Genome

Sequencing.

SNPs Millions

LABS

Detailed lab tests 3x(blood, urine, saliva)Clinical chem. 150

Metabolites 700Proteins 400

SELF-

TRACKING

Continual

self-tracking

& lifestyle

monitoring

MICROBIOME

Gut Microbiome

3x

Creating dense and dynamic personal data clouds

Wellness coaching for participants

Sandi Kaplan, MS, RD Craig Keebler, MD

Wellness Coach Study Physician

Clinical Labs Discovery: Improvements in blood health with behavioral coaching

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

Cardiovascular Diabetes Inflammation Nutrition

% c

han

ge in

ou

t-o

f-ra

nge

me

asu

rem

en

ts

Baseline 3 months 6 months

Improved by 33%Improved by 6% Improved by 12% Improved by 21%

Clinical Labs Discovery: Significant pre-diabetes improvements

Seven participants with pre-diabetes were completely normalized in six months

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

HbA1c(Glycated hemoglobin)

Fasting glucose HOMA(Insulin resistance)

Insulin

% c

han

ge in

ou

t-o

f-ra

nge

me

asu

rem

en

ts

Baseline 3 months 6 months

Improved by 19%Improved by 38% Improved by 55% Improved by 56%

A wellness to disease transition—genetics

plus environment—an actionable

possibility

• Blood + Genetics illuminated the effects of increasing copies of the Hemochromatosis variant

• Left untreated, this disorder could lead to cartilage damage, liver cancer, diabetes, and heart disease: Easily treated by regular blood donations to reduce the iron stores

• One participant ALREADY had cartilage damage from his undiagnosed disease

• Subsequent family genetic testing detected other family members at risk

0.0

50.0

100.0

150.0

200.0

250.0

Zero copies of rarevariant

(86 individuals)

One copy of rarevariant

(12 individuals)

Two copies of rarevariant

(2 individuals)

Ferr

itin

leve

ls

Baseline 3 months

Genetics and Clinical Labs: HemochromatosisDetected risk of a deadly disease in two participants

Deriving Insights from Data: New Frontiers

A

B C

Identifying inter-related molecular modules

• Cholesterol is positively associated with alpha-tocopherol (Vitamin E)

• Cholesterol is negatively associated with endogenous thyroxine

• A beneficial side effect of the drug thryroxine(Synthroid) is lowering LDL cholesterol

Total cholesterol

community

The largest molecular community: related

to cardiometabolic health

We can determine your genetic risk for at least 60 diseases.

Estimated risk for the disease or trait relative to a population

GWAS variants have been determined for about 60

diseases and traits

Variant

rs6827

Variant

rs8572

Variant

rs68883 Variant

rs0994

Variant

rs9769

Variant

rs14445

Var

iant

Variant

rs111393

Variant

rs6837

Variant

rs5837

Variant

rs68279

Variant

rs59583

Variant

rs1352

Variant

rs6827

Variant

rs68883

Variant

rs9769

Variant

rs14445

Variant

rs5837

Detrimental VariantBeneficial Variant

0

20

40

60

80

100

120

140

Cumulative Risk

Below average

Distribution from 2000 GenomesADHD COPD Myopia

Alzheimer's disease Crohn's disease Obesity

Anorexia Esophageal cancer Osteoarthritis

Asthma Gout Osteoporosis

Atrial fibrillation Grave's disease Ovarian cancer

Breast cancer Hematocrit Pancreatic cancer

Bipolar disorder Hypertension Parkinson's disease

Blood pressure Hypothyroidism Primary biliary cirrhosis

Bone mineral density Inflammatory bowel disease Prostate cancer

Inflammation Iron levels Psoriasis

Calcium Lung Cancer Rheumatoid arthritis

Cardiovascular disease Lupus Schizophrenia

Celiac disease Macular degeneration Stroke

Cholesterol levels Magnesium levels Type 1 Diabetes

Chronic kidney disease Metabolic syndrome Type 2 Diabetes

Colorectal cancer Migraine Ulcerative colitis

Coronary heart disease Multiple sclerosis Urate levels

Nutrient measurements correlated with genetic predisposition for IBD

cystine

(plasma)

glutathione

(cytosol)

Sido, B., Hack, V., Hochlehnert, A., Lipps, H., Herfarth, C., and Dröge, W. (1998). Impairment of intestinal glutathione synthesis in patients with inflammatory bowel disease. Gut 42, 485–492.

Ulcerative colitis activity

Pilot Study Correlation Network

cysteine

(cytosol)

-2

0

2

4

6

-4

pla

sm

a c

ystin

e

-4 -2 0 2 4

Inflammatory bowel disease genetic

score

N = 107

rho = -

0.44

p =

2.3e-6

q = 0.03

Dense, Dynamic Personal Data Clouds

These personalized data clouds are the foundation of what Precision Medicine should be.

Enabling Individuals to take Responsibility for

their Own Wellness (and Disease)

Individuals taking responsibility for their own health

will dramatically reduce the cost of healthcare

Project Leadership

• Leroy Hood, MD, PhD

• Nathan Price, PhD

• Sean Bell, Business Director

Data Analytics

• Nathan Price, PhD – Analytics Lead

Gustavo Glusman, PhD, Genomics

• Andrew Magis, PhD, Multi-omics

• John Earls, Data integration

Project Management

• Kristin Brogaard, PhD Project Manager

• Sara Mecca, Project Assistant

• Mary Brunkow, PhD, Project Coordinator

Medical Advisory Board

• Robert Green, MD

• Jane Guiltinan, ND

• Michael Raff, MD

• Sarah Speck, MD

Communications

• Gretchen Sorenson, Consultant

• Hsiao-Ching Chou, Commun. Director

Participant Engagement

• Jennifer Lovejoy, PhD, VP Clinical Affairs

• Sandi Kaplan, Wellness Coach

• Craig Keebler, MD, Study Physician

ISB Hundred Person Wellness Project: TeamSpecial thanks to our funders: Robert Wood Johnson Foundation and M.J. Murdock Charitable Trust

@ISBNathanPrice