1. “The Quantified Self: From Idiosyncratic Hobby to an Emerging Growth Industry” Invited Lecture Science & Technology Discovery Series Technology Alliance Seattle, WA October 10, 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 http://lsmarr.calit2.net 1

2. Abstract Starting a decade ago I began to increasingly quantify the changes of my body over time. Like most people I started with tracking my weight, then added diet and exercise apps and gadgets. But five years ago I began to go deeper - tracking over 100 biomarkers in my blood and stool. Eventually, I added in sequencing my human genome and my gut microbiome. All of this transition to Big Data became possible because of continuing technological exponentials. While my "hobby" seemed quirky to many in the past, an emerging growth industry, based on these practices, is developing with the goal of sustaining wellness, while fundamentally disrupting the current "sick care" industry. Simultaneously, research is accelerating in the same field, as exemplified by Lee Hood's 100 Person Wellness Project, headquartered in Seattle's Institute for System Biology. As one of the Pioneer 100, I will review some of the project's insights for personalized action to improve and sustain your health.

3. Calit2 Has Had a Vision of “the Digital Transformation of Health” for a Decade 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. By Measuring the State of My Body and “Tuning” It Using Nutrition and Exercise, I Became Healthier 2000 Age 41 2010 Age 61 1999 1989 Age 51 1999 My Decade Long Journey to Being a Quantified Self: I Arrived in La Jolla in 2000 After 20 Years in the Midwest I Reversed My Body’s Decline By Quantifying and Altering Nutrition, Exercise, Sleep, and Stress http://lsmarr.calit2.net/repository/LS_reading_recommendations_FiRe_2011.pdf

5. My Quantifying Experiments Became Public in Seattle in 2010

6. 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

7. Wireless Monitoring Helped Drive My Exercise Goals Since Starting November 3, 2011 Total Distance Tracked 3,223 miles = San Diego to Bangor, ME Total Vertical Distance Climbed 107,000 ft. = 3.7 Mt. Everest Using Polar Chest Strap During Elliptical Workouts My Resting Heartrate Fell from 70 to 40!

8. The Self-Monitoring Business Has Reached Market Takeoff MyFitnessPal –40 Million Users –Aug 2013 Raised $18M Series A, Led by Kleiner Perkins Fitbit –Has Raised ~$70M BodyMedia Was Bought by Jawbone –For ~$100M Zeo Sleep Monitor –Closed Down in 2013 More Mergers Likely as the Shakeout Continues

9. In 2013 QS Went Mainstream

10. Source: Samir Damani, MD Revolution 2014 is the Year of the Sensor Integrated Dashboard Combined with Coaching My RevUp! Age Has Decreased to 60 My Physical Age is 66

11. Deep Learning Will Provide Personalized Assistants to Coach Us to Wellness Where Medicine Coaching is Now Where Wellness Coaching is Going

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

13. From One to One Billion Data Points Defining Me: Big Data Coming to the Electronic Medical Record (EMR) Billion: My Full DNA, MRI/CT Images Million: My DNA SNPs, Zeo, FitBit Hundred: My Blood Variables One: My Weight Weight Blood Variables SNPs Human & Microbial Genome Today’s EMR Tomorrow’s EMR

14. Visualizing 5-10 Year Time Series of 150 Blood & Stool Variables Led Me to Discover a Chronic Disease Calit2 64 megapixel VROOM

15. Early Adopting MDs Are Creating Partnerships with Their Quantified Patients “The 100 participants will be guided on this 9-month journey by a coach and when necessary, be referred to their own health care practitioners.” The data sets that will be evaluated include: –Self-Tracking Devices –Medical History, Traits, Lifestyle –Blood, Urine, Saliva –Gut Microbiome –Whole Genome Sequencing There are 8760 Hours in a Year One of These Hours You Are With a Doctor… The Other 8759 Hours Are Up to You! https://pioneer100.systemsbiology.net/ Will Grow to 1000, then 10,000

16. I Titrate My Supplements by Measuring The Amounts Inside of My Red Blood Cells Increase Cu Decrease Mg Maintain Dose Test Results from Genova Diagnostics, Via Lee Hood’s Pioneer 100 Program

17. Healthcare Must Include a Vast Amount of Microbial Information That is Not in Today’s Medicine Inclusion of the Microbiome Will Radically Change Medicine 99% of Your DNA Genes Are in Microbe Cells Not Human Cells Your Body Has 10 Times As Many Microbe Cells As Human Cells

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

19. Using Supercomputing Allows Comparison of the Relative Abundance of 200 Gut Microbe Species Calit2 VROOM-FuturePatient Expedition Comparing 3 LS Time Snapshots (Left) with Healthy, Crohn’s, UC (Right Top to Bottom)

20. Using Microbiome Profiles to Survey 155 Subjects for Unhealthy Candidates

21. Comparison Across the Pioneer 100 Gut Microbiomes Allows For Early Detection of Deviation From Health Only 6 With Bacteriodetes <20% A Few With High % Proteobacteria or Verrucomicrobia

22. Inexpensive Consumer 16S Time Series of Microbiome Allows Similar Analysis Through Ubiome Data source: LS (Yellow Lines Stool Samples); Sequencing and Analysis Ubiome

23. 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?

24. Everything I Discussed Can Be Done by Startups - Outside of the Traditional Medical Complex Blood Variable Time SeriesStool Variable Time Series MicrobiomeTime SeriesHuman Genetic Variations

25. World’s Youngest Female Billionaire Aims to Disrupt the Medical Testing Industry

26. A Looming Disruption In Healthcare Systems From Personalized Medicine Citizens Create Vast Datasets Outside of EMRs Post-“Watson” Personalized Coaches Doctors Must Partner with Super-Informed Patients Increased Use of Supplements and Medical Foods From Treating Sickness to Maintaining Wellness

27. 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 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