1. “The Digital Transformation of Healthcare”
Guest Lecture
Pharmacy Informatics 2014
University of California San Diego
June 2, 2014
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

2. The Vision of Digitally Enabled Genomic Medicine is an Emerging Reality
July/August 2011
February 2012

3. Systems Biology & Systems Medicine Consumer-Driven Social Networks
The Emergence of P4 Medicine -- Predictive, Preventive, Personalized, Participatory
Systems Biology & Systems Medicine
Consumer-Driven Social Networks P4
MEDICINE
Digital Revolution
Big Data
Converging Megatrends Driving the Transformation of Healthcare for Patients
Source: Lee Hood, ISB

4. 100 Pioneer Wellness Project: Started March 2014 –I Am One of The 100
Source: Lee Hood, ISB

5. How Did I Get Started? I Arrived in La Jolla in 2000 and Decided to Move Against the Obesity Epidemic
By Measuring the State of My Body and “Tuning” It Using Nutrition and Exercise, I Became Healthier
Age 41
Age 51
1999
2010
Age 61
1999
2000
1989
I Reversed My Body’s Decline By Quantifying and Altering Nutrition and Exercise

6. Wireless Monitoring Helps Drive Exercise Goals

7. Quantifying My Sleep Pattern Using a Zeo - Increased My Average to 8 Hours/Night
Stroke risk increased by sleeping less than six hours a night
-M. Ruiter, Sleep 2012
REM is Normally 20% of Sleep
Mine is Between 45-65% of Sleep
An Infant Typically Has 50% REM

8. MyFitnessPal- Calories Ingested
I Used a Variety of Emerging Personal Sensors To Quantify My Body & Drive Behavioral Change
Withings/iPhone-
Blood Pressure
MyFitnessPal- Calories Ingested
FitBit - Daily Steps &
Calories Burned
Azumio-Heart Rate
Zeo-Sleep
Withings WiFi Scale - Daily Weight

9. From Measuring Macro-Variables to Measuring Your Internal Variables

10. Visualizing Time Series of 150 LS Blood and Stool Variables, Each Over 5-10 Years
Calit2 64 megapixel VROOM

11. Episodic Peaks in Inflammation Followed by Spontaneous Drops
Only One of My Blood Measurements Was Far Out of Range--Indicating Chronic Inflammation
27x Upper Limit
Episodic Peaks in Inflammation Followed by Spontaneous Drops
Normal Range
<1 mg/L
Normal
Complex Reactive Protein (CRP) is a Blood Biomarker for Detecting Presence of Inflammation

12. But by Using Stool Analysis Time Series, I Discovered I Had Oscillating Immune Variables Far Above Normal
124x Upper Limit
Typical
Lactoferrin
Value for
Active
IBD
Normal Range
<7.3 µg/mL
Lactoferrin is a Protein Shed from Neutrophils -
An Immune System Antibacterial that Sequesters Iron

13. Colonoscopy Images Show Inflamed Pseudopolyps in 6 inches of Sigmoid Colon
Jan 2012
Dec 2010

14. I Obtained the MRI Slices From UCSD Medical Services
Confirming the IBD (Crohn’s) Hypothesis: Finding the “Smoking Gun” with MRI Imaging
Liver
I Obtained the MRI Slices From UCSD Medical Services
and Converted to Interactive 3D Working With Calit2 Staff & DeskVOX Software
Transverse Colon
Small Intestine
Descending Colon
Sigmoid Colon
Threading Iliac Arteries
Major Kink
Diseased Sigmoid Colon
MRI Jan 2012
Cross Section

15. 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
So I Set Out to Quantify All Three!
Paul B. Eckburg & David A. Relman
Clin Infect Dis. 44: (2007) 

16. This Has Enabled Sequencing of Both Human and Microbial Genomes
The Cost of Sequencing a Megabase of DNA Has Fallen Over 10,000x in the Last Ten Years!
This Has Enabled Sequencing of
Both Human and Microbial Genomes

17. I Wondered if Crohn’s is an Autoimmune Disease, Did I Have a Personal Genomic Polymorphism?
From
Polymorphism in Interleukin-23 Receptor Gene — 80% Higher Risk of Pro-inflammatory Immune Response
ATG16L1
IRGM
NOD2
SNPs Associated with CD
I am Now an Advisor
on the
23andme IBD Project

18. Imagine Crowdsourcing 23andme SNPs For Even a Small Portion of Crohnology!

19. Crowd-Sourcing the Effectiveness of Pharmaceutical Medications for Crohn’s Disease

20. Treating the Human Superorganism: Your Body Has Ten Microbes for Every Human Cell!
Nature Reviews Microbiology
v.9, p. 279 (2011)

21. To Map Out the Dynamics of My Microbiome Ecology I Partnered with the J. Craig Venter Institute
JCVI Did Metagenomic Sequencing on Seven of My Stool Samples Over 1.5 Years
Sequencing on Illumina HiSeq 2000
Generated 200 Million 100bp Reads
JCVI Lab Manager, Genomic Medicine
Manolito Torralba
IRB PI Karen Nelson
President JCVI
Illumina HiSeq 2000 at JCVI
Manolito Torralba, JCVI
Karen Nelson, JCVI

22. We Downloaded Additional Gut Microbiomes from NIH HMP For Comparative Analysis
From Sequences to Bacterial Species Relative Abundance
Required 25 CPU-Years at San Diego Supercomputer Center
“Healthy” Individuals
IBD Patients
250 Subjects
1 Point in Time
2 Ulcerative Colitis Patients,
6 Points in Time
Larry Smarr
6 Points in Time
5 Ileal Crohn’s Patients, 3 Points in Time
Total of 27 Billion Reads
Or 2.7 Trillion Bases
Source: Jerry Sheehan, Calit2
Weizhong Li, Sitao Wu, CRBS, UCSD

23. We Found Major Shifts in Microbial Ecology Between Healthy and Two Forms of IBD
On the IBD Spectrum
Explosion of
Proteobacteria
Collapse of
Bacteroidetes

24. Tracking How 1 Month Antibiotic, 2 Months Prednisone Therapy Alters the Gut Microbial Ecology
Reduced 45x
Reduced 90x
Therapy Greatly Reduced Two Phyla,
But Massive Reduction in Bacteroidetes
And Large % Proteobacteria Remain
Small Changes With No Therapy
How Does One Get Back
to a “Healthy” Gut Microbiome?

25. Time Points of Metagenomic Therapy: 1 Month Antibiotics
Comparing Changes in Gut Microbiome Ecology with Oscillations of the Innate and Adaptive Immune System
LS Data from Yourfuturehealth.com Stool Tests
Time Points of Metagenomic
Sequencing
of LS Stool Samples
Innate Immune System
Normal
Therapy: 1 Month Antibiotics
+2 Month Prednisone
Adaptive Immune System
Normal

26. Time Series Reveals Autoimmune Dynamics of Gut Microbiome by Phyla
Therapy
Six Metagenomic Time Samples Over 16 Months

27. Toward Microbiome Disease Diagnosis
UC 100x Healthy
CD 100x Healthy

28. Inexpensive 16S Time Series of Microbiome Now Possible Through Ubiome
Data source: LS (Yellow Lines Stool Samples);
Sequencing and Analysis Ubiome

29. 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.”

30. Evidence for the Efficacy of Probiotics is IBD is Mixed - More Clinical Research Needed
“...there is virtually no evidence of probiotic efficacy in Crohn’s disease.”

31. Problem of Alternative Stable States In Ecological System Dynamics
From the Single “Bad” Microbe Medical Target to the Microbiome Ecology Paradigm
Sci Transl Med 4, 137rv5 (2012);
Science 336, 1255 (2012)
Problem of Alternative Stable States
In Ecological System Dynamics

32. Microbiome Transfer May Be a Radical New Treatment for IBD
Procedures
Starting With
Natural Microbiome
Next Steps:
Create
Synthetic Microbiomes
Tuned to the Patient
See
Microbiome 1:3 (2013)
Dr. Alexander Khoruts, NY Times
Not FDA Approved Yet;
Increasing Number of Doctors Performing Procedure;
Clinical Trials Under Way;
Encouraging Results…

33. Next Decade Will See New Microbiome “Gardening Tools”
August 7, 2012
Journal of Nanotechnology (2012)

34. The Disruption of Consumer Health Data Gathering Is Growing Rapidly
Blood Variable Time Series
Stool Variable Time Series
Human Genetic Variations
MicrobiomeTime Series

35. Thanks to Our Great Team!
UCSD Metagenomics Team
Weizhong Li
Sitao Wu
Future Patient Team
Jerry Sheehan
Tom DeFanti
Kevin Patrick
Jurgen Schulze
Andrew Prudhomme
Philip Weber
Fred Raab
Joe Keefe
Ernesto Ramirez
JCVI Team
Karen Nelson
Shibu Yooseph
Manolito Torralba
SDSC Team
Michael Norman
Mahidhar Tatineni
Robert Sinkovits
UCSD Health Sciences Team
William J. Sandborn
Elisabeth Evans
John Chang
Brigid Boland
David Brenner