“The Deeply Quantified Self:A Case Study”

Future Technology Keynote

Minimally Invasive Surgery Week 2015

Society of Laparoendoscopic Surgeons

New York City, NY

September 5, 2015

Dr. Larry Smarr

Director, California Institute for Telecommunications and Information Technology

Harry E. Gruber Professor,

Dept. of Computer Science and Engineering

Jacobs School of Engineering, UCSD

http://lsmarr.calit2.net1

By Measuring the State of My Body and “Tuning” ItUsing Nutrition and Exercise, I Became Healthier

2000

Age 41

2010

Age 61

1999

1989

Age 51

1999

I Arrived in La Jolla in 2000 After 20 Years in the Midwestand Decided to Move Against the Obesity Trend

I Reversed My Body’s Decline By Quantifying and Altering Nutrition and Exercise

http://lsmarr.calit2.net/repository/LS_reading_recommendations_FiRe_2011.pdf

Calit2 Has Been Had a Vision of “the Digital Transformation of Health” for 15 Years

• Next Step—Putting You On-Line!– Wireless Internet Transmission– Key Metabolic and Physical Variables– Model -- Dozens of Processors and 60 Sensors /

Actuators Inside of our Cars

• Post-Genomic Individualized Medicine– Combine

–Genetic Code –Body Data Flow

– Use Powerful AI Data Mining Techniques

www.bodymedia.com

The Content of This Slide from 2001 Larry Smarr Calit2 Talk on Digitally Enabled Genomic Medicine

I Used a Variety of Emerging Personal SensorsTo Quantify My Body & Drive Behavioral Change

Withings/iPhone-Blood Pressure

Zeo-Sleep

Azumio-Heart Rate

MyFitnessPal-Calories Ingested

FitBit -Daily Steps &

Calories Burned

Withings WiFi Scale -Daily Weight

Wireless Monitoring Produced Time Series That Helped Me Improve My Health

Since Starting November 3, 2011Total Distance Tracked 3,223 miles = San Diego to Bangor, ME

Total Vertical Distance Climbed 107,000 ft. = 3.7 Mt. Everest

Using Polar Chest StrapDuring Elliptical WorkoutsMy Resting Heartrate

Fell from 70 to 40!

Quantifying My Sleep Pattern Using Zeo -Surprisingly About Half My Sleep is REM!

REM is Normally 20% of SleepMine is Between 45-65% of Sleep

An Infant Typically Has 50% REM

From Measuring Macro-Variables to Measuring Your Internal Variables

www.technologyreview.com/biomedicine/39636

Quantifying Your Inner Self:A Case Study

An N=1 Case Study of Using Quantified SelfTo Discover and Track an Autoimmune Disease

I Have Turned My Body into a Genomic and Biomarker Observatory

One Blood DrawFor MeCalit2 64 Megapixel VROOM

Only One of My Blood Measurements Was Far Out of Range--Indicating Chronic Inflammation

Normal Range <1 mg/L

27x Upper Limit

Complex Reactive Protein (CRP) is a Blood Biomarker for Detecting Presence of Inflammation

Episodic Peaks in Inflammation Followed by Spontaneous Drops

Adding Stool Tests RevealedOscillatory Behavior in an Immune Variable Which is Antibacterial

Normal Range<7.3 µg/mL

124x Upper Limit for Healthy

Lactoferrin is a Protein Shed from Neutrophils -An Antibacterial that Sequesters Iron

TypicalLactoferrin Value for Active Inflammatory

Bowel Disease (IBD)

Colonoscopy Images Show PersistentInflamed Pseudopolyps in 6 inches of Sigmoid Colon

Dec 2010 Jan 2012

“Inflammatory polyp versus inflamed fold in the distal sigmoid colon and apthous ulcers in the rectum, consistent with active Crohn’s colitis.”

William J. Sandborn, MD UCSD Jan 3, 2012

Descending Colon

Sigmoid ColonThreading Iliac Arteries

Major Kink

Confirming the Colonic Crohn’s Hypothesis:Finding the “Smoking Gun” with MRI Imaging

I Obtained the MRI Slices From UCSD Medical Services

and Converted to Interactive 3D Working With

Calit2 Staff & DeskVOX Software

Transverse ColonLiver

Small Intestine

Diseased Sigmoid ColonCross Section

MRI Jan 2012

MRE Reveals Inflammation in 6 Inches of Sigmoid ColonThickness 15cm – 5x Normal Thickness

“Long segment wall thickening in the proximal and mid portions of the sigmoid colon,

extending over a segment of approximately 16 cm, with suggestion of intramural sinus tracts.

Edema in the sigmoid mesentery and engorgement of the regional vasa recta.”

– Cynthia Santillan, MD Radiologist MRI reportJan 2012

Clinical MRI Slice Program

DeskVOX 3D Image3D vs. 2D VisualizationOf DICOM file of LS MRI

Wall Thickness 5x Normal

Why Did I Have an Autoimmune Disease like IBD?

Despite decades of research, the etiology of Crohn's disease

remains unknown. Its pathogenesis may involve a complex interplay between

host genetics, immune dysfunction,

and microbial or environmental factors.--The Role of Microbes in Crohn's Disease

Paul B. Eckburg & David A. RelmanClin Infect Dis. 44:256-262 (2007) 

I Have Been Quantifying All Three

The Cost of Sequencing a Human GenomeHas Fallen Nearly 10,000x in the Last Ten Years

This Has Enabled Sequencing of Both Human and Microbial Genomes

Person A

Person B

Single Nucleotide Polymorphisms (SNPs) Make Up About 90% of All Human Genetic Variation

www.23andme.com Tracks One Million SNPs

SNPs Occur Every 100 to 300 Bases

Along Human DNA

I Found I Had One of the Earliest Known SNPsAssociated with Crohn’s Disease

From www.23andme.com

SNPs Associated with CD

Interleukin-23 Receptor Gene— 80% Higher Risk of Pro-inflammatoryImmune Response

NOD2

IRGM

ATG16L1

23andme is Seeking 10,000 Volunteers

with IBD to Determine SNP Distributionto Stratify Disease Spectrum

To Understand the Interaction of Genetics with Disease StatesWe Must Consider the Human Microbiome and Not Just the Human Genome

Your Microbiome is Your “Near-Body” Environment

and its CellsContain 300x

as Many DNA GenesAs Your Human Cells

Your Body Has 10 Times As Many Microbe Cells As Human Cells

June 8, 2012 June 14, 2012

Interest in the Human MicrobiomeHas Moved Quickly From Frontier Science to Public Awareness

August 18, 2012June, 2012

When We Think About Biological DiversityWe Typically Think of the Wide Range of Animals

But All These Animals Are in One SubPhylum Vertebrataof the Chordata Phylum

All images from Wikimedia Commons. Photos are public domain or by Trisha Shears & Richard Bartz

Think of These Phyla of Animals When You Consider the Biodiversity of Microbes Inside You

All images from WikiMedia Commons. Photos are public domain or by Dan Hershman, Michael Linnenbach, Manuae, B_cool

PhylumAnnelida

PhylumEchinodermata

PhylumCnidaria

PhylumMollusca

Phylum Arthropoda

PhylumChordata

The Genetic Distance Between MicrobesVastly Exceeds That Among All Animals and Plants

You Are

Here

Source: Carl Woese, et al

Tree of Life Derived from 16S rRNA Sequences

To Map Out the Dynamics of Autoimmune Microbiome Ecology Couples Next Generation Genome Sequencers to Big Data Supercomputers

Illumina HiSeq 2000 at JCVI

SDSC Gordon Data Supercomputer

Example: Inflammatory Bowel Disease (IBD)

We used 25 CPU-yearsto compute

comparative gut microbiomesstarting from

7 trillion DNA bases of my samples,

255 healthy, and 20 IBD controls

We Found Major State Shifts in Microbial Ecology PhylaBetween Healthy and Three Forms of IBD

Most Common Microbial

Phyla

Average HE

Average Ulcerative Colitis

Average LSColonic Crohn’s Disease

Average Ileal Crohn’s Disease

Collapse of BacteroidetesExplosion of Actinobacteria

Explosion of Proteobacteria

Hybrid of UC and CDHigh Level of Archaea

This Year We Will Extend My Stool Time SeriesCollaborating with the UCSD Knight Lab

Larry’s 40 Stool Samples Over 3.5 Years to Rob’s lab on April 30, 2015

We Must Move From Combating Single Microbe Diseases to Developing the Human/Microbiome System Approach to Public Health

Bach (2002) N Engl J Med, Vol. 347, 911-920

2014For Public Health It is Still About Microbes,But from Single Species to Entire Ecologies

The United States Population’s Human Gut MicrobiomeHas Diverged a Great Deal from Hunter-Gatherers

“The microbiome of uncontacted Amerindians,” J. C. Clemente, et al. Science Advances 1, e1500183 (2015).

[Amerindians in Venezuela/Columbia]

[Africa]

HumanMicrobiomeProject

Missing Microbes

The Coupled Neural, Immune, and Microbiome SystemsProvide a Model Explaining How Nutrition Can Alter Neurodevelopment

From War to Gardening:New Therapeutical Tools for Managing the Microbiome

“I would like to lose the language of warfare,” said Julie Segre, a senior investigator at

the National Human Genome Research Institute. ”It does a disservice to all the bacteria

that have co-evolved with us and are maintaining the health of our bodies.”

Reports Are Being Published on The Birth of the Human Microbiome Market

www.insightpharmareports.com/human-microbiome-report

October 2014

Fecal Microbiome TransferIs a Rapidly Growing New Treatment for IBD

Dr. Bill Sandborn, Chief UCSD GI

Dr. Brigid Boland, UCSD GI

Where I Believe We are Headed: Predictive, Personalized, Preventive, & Participatory Medicine

www.newsweek.com/2009/06/26/a-doctor-s-vision-of-the-future-of-medicine.html

Will Grow to 1000, Then 10,000,Then 100,000

Genetic Sequencing of the DNA of Humans and Their MicrobesIs a Huge Growth Area and the Future Foundation of Medicine

Source: @EricTopolTwitter 9/27/2014

From One to a Billion Data Points Defining Me:The Exponential Rise in Body Data in Just One Decade

Billion: My Full DNA,MRI/CT Images

Million: My DNA SNPs,Zeo, FitBit

Hundred: My Blood VariablesOne: My WeightWeight

BloodVariables

SNPs

Microbial Genome

Improving Body

Discovering Disease

Thanks to Our Great Team!

UCSD Metagenomics TeamWeizhong LiSitao Wu

Calit2@UCSD Future Patient TeamJerry SheehanTom DeFantiKevin PatrickJurgen SchulzeAndrew PrudhommePhilip WeberFred RaabJoe KeefeErnesto Ramirez

AyasdiDevi RamananPek Lum

JCVI TeamKaren NelsonShibu YoosephManolito Torralba

SDSC TeamMichael NormanMahidhar Tatineni Robert Sinkovits

UCSD Health Sciences TeamRob KnightWilliam J. SandbornElisabeth EvansJohn ChangBrigid BolandDavid Brenner

Dell/R SystemsBrian KucicJohn Thompson