Understanding Cultures and Addressing Disparities in Society: Degrees of Health and Well-Being Public Lecture Series University of California, San Diego January 20, 2016

1. “Know Thyself: Quantifying Your Human Body
and Its One Hundred Trillion Microbes”
Understanding Cultures and Addressing Disparities in Society:
Degrees of Health and Well-Being Public Lecture Series
University of California, San Diego
January 20, 2016
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.net

2. “Know Thyself”
From the Temple of Apollo to the Quantified Self
From the Reichert-Haus in Ludwigshafen, Germany

3. Calit2 Has Been Had a Vision of
How to Digitally “Know Thyself” 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

4. 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
Blood
Variables
Human Genome
SNPs
Microbial Genome
Improving Body
Discovering Disease
“Be the change that you wish to see in the world”

5. I Used a Variety of Emerging Personal Sensors
To 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

6. Wireless Monitoring
Produced Time Series That Helped Me Improve My Health
Since Starting November 3, 2011
Total Distance Tracked 5495 miles = Round Trip San Diego to Bangor, ME
Total Vertical Distance Climbed 176,560 ft. = 6x Mt. Everest
My Resting Heartrate
Fell from 70 to 40!
Elliptical
Walking
Sunday January 17, 2016
137
42
I Increased
Walking,
Aerobic, and
Resistance
Training,
All of Which
Have Health
Benefits

7. From Measuring Macro-Variables
to Measuring Your Internal Variables
www.technologyreview.com/biomedicine/39636

8. I Decided to Track My Internal Biomarkers
Just As I Did My External Body
One Blood Draw
For MeCalit2 64 Megapixel VROOM

9. Only One of My Blood Measurements
Was Far Out of Range--Indicating Chronic Inflammation
Normal Range <1 mg/L
15x Upper Limit
Complex Reactive Protein (CRP) is a Blood Biomarker
for Detecting Presence of Inflammation

10. 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
15x Upper Limit

11. Adding Stool Tests Revealed
Dramatic Episodic Spikes in Immune Variables
Normal Range
<7.3 µg/mL
124x Upper Limit for Healthy
Lactoferrin is An Antibacterial that Sequesters Iron
Typical
Lactoferrin Value for
Active Inflammatory
Bowel Disease
(IBD)

12. Descending Colon
Sigmoid Colon
Threading Iliac Arteries
Major Kink
Confirming the IBD (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
Transverse Colon
Liver
Small Intestine
Diseased Sigmoid Colon
Cross Section
MRI Jan 2012
Severe Colon
Wall Swelling

13. Why Did I Have an Autoimmune Disease
like Crohn’s Disease?
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. Relman
Clin Infect Dis. 44:256-262 (2007)
I Have Been Quantifying All Three

14. Person A
Person B
Single Nucleotide Polymorphisms (SNPs) in the Human Genome
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

15. I Found I Had One of the Earliest Known SNPs
Associated with Crohn’s Disease
From www.23andme.com
SNPs Associated with CD
Polymorphism in
Interleukin-23 Receptor Gene
— 80% Higher Risk
of Pro-inflammatory
Immune Response
NOD2
IRGM
ATG16L1
23andme is Now Collecting
10,000 IBD Patient’s SNPs

16. I Reasoned That The Driver of My Gut Autoimmune Disease
Was a Disturbance in My Gut Microbiome Ecology
Inclusion of the “Dark Matter” of the Body
Will Radically Alter Medicine
99% of Your
DNA Genes
Are in Microbe Cells
Not Human Cells
Your Body Has 10 Times
As Many Microbe Cells As DNA-Bearing
Human Cells

17. June 8, 2012 June 14, 2012
Interest in the Human Microbiome
Has Moved Quickly From Frontier Science to Public Awareness
August 18, 2012June, 2012

18. 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-years
to compute
comparative gut microbiomes
starting from
7 trillion DNA bases
of my samples,
255 healthy,
and 20 IBD controls

19. When We Think About Biological Diversity
We Typically Think of the Wide Range of Animals
But All These Animals Are in One SubPhylum Vertebrata
of the Chordata Phylum
All images from Wikimedia Commons.
Photos are public domain or by Trisha Shears, Richard Bartz, & Matt Clancy

20. Think of These Phyla of Animals When
You Consider the Biodiversity of Microbes Inside You
Phylum
Annelida
Phylum
Echinodermata
Phylum
Cnidaria
Phylum
Mollusca
Phylum
Arthropoda
Phylum
Chordata
Phylum
Porifera
All images from WikiMedia Commons.
Photos are public domain or by Dan Hershman, Michael Linnenbach, Manuae, B_cool, Nick Hobgood

21. We Found Major State Shifts in Microbial Ecology Phyla
Between Healthy and Three Forms of IBD
Most
Common
Microbial
Phyla
Average HE
Average
Ulcerative Colitis
Average LS
Colonic Crohn’s Disease
Average
Ileal Crohn’s Disease

22. Just Genome Sequencing the Stool of 300 Patients
Sorted Out Their Health or Disease Type
Source: Thomas Hill, Ph.D.
Executive Director Analytics
Dell | Information Management Group, Dell Software
Healthy
Ulcerative Colitis
Colonic Crohn’s
Ileal Crohn’s

23. This Year We Sequencing and Computing My Stool Time Series
Collaborating with the UCSD Knight Lab
Larry’s 50 Stool Samples Over 3.5 Years
to Rob’s lab on April 30, 2015

24. My Gut Microbiome Ecology Varying Over 3.5 Years:
Sequencing by UCSD’s Knight Lab and Institute for Genomic Medicine
LS Analysis, January 2016
Next Step: Comparing Time Series of Microbiome,
Immune Biomarkers, & Symptoms to Guide Therapy

25. From N=1 to UC San Diego Undertaking
a Major Clinical Study of IBD Using These Techniques
Inflammatory Bowel Disease Biobank
For Healthy and Disease Patients
Drs. William J. Sandborn, John Chang, & Brigid Boland
UCSD School of Medicine, Division of Gastroenterology
Over 200 Enrolled
Announced November 7, 2014!
Knight and Smarr Have Been Awarded a CPU-Century of Supercomputer Time
To Analyze 50 IBD Patients, LS Time Series, and 300 Healthy People’s Microbiome

26. Center for
Microbiome
Innovation
Seminars
Faculty
Hiring
Education
UCSD Microbial Sciences Initiative
Instrument
Cores
Seed Grants
Fellowships
Chancellor Khosla Launched the UC San Diego
Microbiome and Microbial Sciences Initiative October 29, 2015

27. UC San Diego Microbiome and Microbial Sciences Initiative:
Leadership Team
Rob Knight
Pediatrics/CSE
Pieter Dorrestein
Pharmacy
Kit Pogliano
Biol Sci
Bernhard Palsson
BioE/Pediatrics
Bill Sandborn
Gastroenterology
Jeff Hasty
Biol Sci
Karsten Zengler
Pediatrics
Larry Smarr
Calit2 /CSE
Paul Jensen
SIO
Pavel Pevzner
CSE
Rachel Dutton
Biol Sci
Rommie Amaro
Chem & Biochem
Victor Nizet
Pediatrics/Pharmacy
Vineet Bafna
CSE

28. 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
2014
For Public Health It is Still About Microbes,
But from Single Species to Entire Ecologies

29. The United States Population’s Human Gut Microbiome
Has 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]
U.S. Human
Microbiome
Project
Missing Microbes

30. We Have Much to Learn from Indigenous Peoples
“Our work emphasizes the value of deep characterization
of microbiomes of people living ancestral life-styles,
particularly if practices in industrialized societies might eradicate
potentially beneficial microbes and their encoded functions.”
“The average Yanomami's microbiota had twice as many genes
as that of the average US person.”

31. The Coupled Neural, Immune, and Microbiome Systems
Provide a Model Explaining How Nutrition Can Alter Neurodevelopment

32. There is a Huge New Field of Products Coming
Which Enable You to “Garden” Your 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.”
Will Medical Foods Provide New Tools
for Altering Gut Microbiome?

33. Massive Research is Underway to Discover
A Wide Range of Methods for Gardening Your Microbiome
http://vitals.lifehacker.com/beyond-probiotics-can-you-hack-your-microbiome-1689720231

34. Manipulating Your Microbiome Can Work -- Fecal Microbiome Transfer
Is a Rapidly Growing New Treatment for Clostridia Difficile
Dr. Bill Sandborn,
Chief UCSD GI
Dr. Brigid Boland,
UCSD GI
C. diff is the nation’s
most common
hospital-acquired
infection,
affecting 500,000
and killing 30,000
Americans/year.
Fecal transplants
are 90% curative.
OpenBiome supplies
to over 500 hospitals
in all 50 states, so
far 10,000
transplants.
www.cidrap.umn.edu/news-perspective/2015/02/cdc-puts-c-difficile-burden-453000-cases-29000-deaths

35. Consumer Internal Self-Tracking Tools
Are Growing Rapidly
Blood Variable Time Series Stool Variable Time Series
Human Genetic Variations
Integrated Wellness
Human Microbiome

36. The Emergence of P4 Medicine --
Predictive, Preventive, Personalized, Participatory
Systems Biology &
Systems Medicine
Consumer-Driven
Social Networks
P4
MEDICINE
Digital Revolution
Big Data
How Will the Quantified Consumer
Be Integrated into Healthcare Systems?
Lee Hood, Director ISB

37. Genetic Sequencing of Humans and Their Microbes
Is a Huge Growth Area and the Future Foundation of Medicine
Source: @EricTopol
Twitter 9/27/2014

38. The Looming Disruption
In Integrated Healthcare Systems
• Citizens Create Vast Datasets Outside of Medical Records
• Doctors Must Partner with Super-Informed Patients
• From Pharmaceuticals to Medicinal Foods
• From Treating Sickness to Maintaining Wellness

39. Thanks to Our Great Team!
UCSD Metagenomics Team
Weizhong Li
Sitao Wu
Calit2@UCSD
Future Patient Team
Jerry Sheehan
Tom DeFanti
Kevin Patrick
Jurgen Schulze
Andrew Prudhomme
Philip Weber
Fred Raab
Joe Keefe
Ernesto Ramirez
Ayasdi
Devi Ramanan
Pek Lum
JCVI Team
Karen Nelson
Shibu Yooseph
Manolito Torralba
SDSC Team
Michael Norman
Mahidhar Tatineni
Robert Sinkovits
UCSD Health Sciences Team
Rob Knight
William J. Sandborn
Elisabeth Evans
John Chang
Brigid Boland
David Brenner
Dell/R Systems
Brian Kucic
John Thompson