My N=1 Experience

        Pioneer Session: "N=1: Pioneers of Self-Tracking“
Panel at the Genomes, Environment, and Traits Conference
                 Harvard Medical School
                     Cambridge, MA
                      April 25, 2012
                         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
              Follow me at http://lsmarr.calit2.net
I am the Digitally-Enabled “Patient of the Future”:
   Measuring the State of Your Body and “Tuning” It


                            1999                           2010
                             2000



Age                                                                 Age
51                                                                  61




      I Arrived in La Jolla in 2000 After 20 Years in the Midwest
                  and Discovered I was Pre-Diabetic.

                  I Reversed My Body’s Decline By
                    Altering Nutrition and Exercise
From Measuring Macro-Variables
to Measuring Your Internal Variables




   www.technologyreview.com/biomedicine/39636
My Quarterly Blood Tests In Addition to Lipids:
         Only One Was Far Beyond Normal Limits
•   Electrolytes                          •   Liver
     – Sodium, Potassium, Calcium,             – GGTP, SGOT, SGPT, LDH, Total
       Magnesium, Phosphorus, Boron,             Direct Bilirubin,
       Chlorine, CO2                             Alkaline Phosphatase
•   Micronutrients                        •   Thyroid
     – Arsenic, Chromium, Cobalt,              – T3 Uptake, T4, Free Thyroxine
       Copper, Iron, Manganese,                  Index, FT4, 2nd Gen TSH
       Molybdenum, Selenium, Zinc         •   Blood Cells
•   Blood Sugar Cycle                          – Complete Blood Cell Count
     – Glucose, Insulin, A1C Hemoglobin        – Red Blood Cell Subtypes
•   Cardio Risk                                – White Blood Cell Subtypes
     – Complex Reactive Protein           •   Cancer Screen
     – Homocysteine                            – CEA, Total PSA, % Free PSA
•   Kidneys                                    – CA-19-9
     – Bun, Creatinine, Uric Acid         •   Vitamins & Antioxidant Screen
•   Protein                                    – Vit D, E; Selenium, ALA, coQ10,
     – Total Protein, Albumin, Globulin          Glutathione, Total Antioxidant Fn.


                  I Track Over 100 Blood Variables Over Time
Natural Anti-Inflammation Can Be Much Larger Effect
  Than Antibiotic-Induced Inflammation Remission

                                                                27x
          Much of the Inflammation Drop
                Is Spontaneous


                           15x


                                 Antibiotics


                                                  Antibiotics
                      Normal Range CRP < 1




      Demonstrates Value of Fine-Grained Time Series
Frequent Stool Analysis Reveals Lactoferrin Spike
      to Active Crohn’s Disease (CD) Level
                                                           Colonoscopy
                                               Typical      May 2011
  Normal Lactoferrin Level < 7               Lactoferrin
                                              Value for
                                               Active
                                               Crohn’s




       Colonoscopy
        May 2006                                                   Colonoscopy
                                                                    Jan 2012

                                        Colonoscopy
                                       December 2010




                     Colonoscopy and Biopsies
                      Support CD Diagnosis
Confirming the Crohn’s Hypothesis:
  Finding the “Smoking Gun” with MRI Imaging
Liver                                    I Obtained the MRI Slices
           Transverse Colon
                                       From UCSD Medical Services
                                      and Converted to Interactive 3D
                                                Working With
  Small Intestine                     Calit2 Staff & DeskVOX Software
                                                                     Descending Colon




             Diseased Sigmoid Colon




                                                                          Major Kink
                                              Sigmoid Colon
                                          Threading Iliac Arteries
LS Sigmoid Colon Cross Sections
                     Showing Inflamed Wall
  Jan 2012 MRI Enterography report: “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.

 Ulcerative
  Colitis is
Restricted to
the Mucosa,
    while
  Crohn's
  Disease                                                                   Note
 Affects the                                                             Thickness
   Whole                                                                  of Wall -
Bowel Wall                                                                Normal
                                                                          is 3mm
                                                                           (like a
                                                                          Balloon)


                Source: L Smarr Using Calit2’s Jurgen Schultz Software
I Wondered if Crohn’s is an Autoimmune Disease,
  Did I Have a Personal Genomic Polymorphism?
            From www.23andme.com              Polymorphism in
                                       Interleukin-23 Receptor Gene
                                            — 80% Higher Risk
            ATG16L1
                                             of Pro-inflammatory
                                             Immune Response
                  IRGM




     NOD2        SNPs Associated with CD
Crohn’s Disease Patients Have Number of Firmicute
      Gut Microbe Species Reduced by Over 2/3!
                       Healthy Gut Microbes



Actinobacteria

    7              Bacteroidetes              Proteobacteria   Firmicutes

                        33                        5                43



                         IBD Gut Microbes


Actinobacteria

    7              Bacteroidetes              Proteobacteria   Firmicutes

                        33                        5                13

          The Missing Firmicutes Inhibit Pro-Inflammation

                    Manichanh, et al, Gut 2006;55:205–211
Microbial Metagenomics
Can Diagnose Disease States
From www.23andme.com
                               Mutation in Interleukin-23
                              Receptor Gene—80% Higher
                                Risk of Pro-inflammatory
                                   Immune Response


                                          IBD Patients Harbored,
                                               on Average,
                                                25% Fewer
    SNPs Associated with CD
                                              Microbial Genes
                                            than the Individuals
                                          Not Suffering from IBD.




                       2009
First Stage of Metagenomic Sequencing of
My Gut Microbiome at J. Craig Venter Institute


                                              I Received
                                       a Disk Drive Last Week
                                       With 35 GB FASTQ Files

                                          Weizhong Li, UCSD
                                            NGS Pipeline:
                                            230M Reads
                                          Only 0.2% Human

                                       Next: 10-100,000 cpu-hrs


 Gel Image of Extract from Smarr Sample-Next is Library Construction
      Manny Torralba, Project Lead - Human Genomic Medicine
                        J Craig Venter Institute
                           January 25, 2012

My N=1 Experience

  • 1.
    My N=1 Experience Pioneer Session: "N=1: Pioneers of Self-Tracking“ Panel at the Genomes, Environment, and Traits Conference Harvard Medical School Cambridge, MA April 25, 2012 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 Follow me at http://lsmarr.calit2.net
  • 2.
    I am theDigitally-Enabled “Patient of the Future”: Measuring the State of Your Body and “Tuning” It 1999 2010 2000 Age Age 51 61 I Arrived in La Jolla in 2000 After 20 Years in the Midwest and Discovered I was Pre-Diabetic. I Reversed My Body’s Decline By Altering Nutrition and Exercise
  • 3.
    From Measuring Macro-Variables toMeasuring Your Internal Variables www.technologyreview.com/biomedicine/39636
  • 4.
    My Quarterly BloodTests In Addition to Lipids: Only One Was Far Beyond Normal Limits • Electrolytes • Liver – Sodium, Potassium, Calcium, – GGTP, SGOT, SGPT, LDH, Total Magnesium, Phosphorus, Boron, Direct Bilirubin, Chlorine, CO2 Alkaline Phosphatase • Micronutrients • Thyroid – Arsenic, Chromium, Cobalt, – T3 Uptake, T4, Free Thyroxine Copper, Iron, Manganese, Index, FT4, 2nd Gen TSH Molybdenum, Selenium, Zinc • Blood Cells • Blood Sugar Cycle – Complete Blood Cell Count – Glucose, Insulin, A1C Hemoglobin – Red Blood Cell Subtypes • Cardio Risk – White Blood Cell Subtypes – Complex Reactive Protein • Cancer Screen – Homocysteine – CEA, Total PSA, % Free PSA • Kidneys – CA-19-9 – Bun, Creatinine, Uric Acid • Vitamins & Antioxidant Screen • Protein – Vit D, E; Selenium, ALA, coQ10, – Total Protein, Albumin, Globulin Glutathione, Total Antioxidant Fn. I Track Over 100 Blood Variables Over Time
  • 5.
    Natural Anti-Inflammation CanBe Much Larger Effect Than Antibiotic-Induced Inflammation Remission 27x Much of the Inflammation Drop Is Spontaneous 15x Antibiotics Antibiotics Normal Range CRP < 1 Demonstrates Value of Fine-Grained Time Series
  • 6.
    Frequent Stool AnalysisReveals Lactoferrin Spike to Active Crohn’s Disease (CD) Level Colonoscopy Typical May 2011 Normal Lactoferrin Level < 7 Lactoferrin Value for Active Crohn’s Colonoscopy May 2006 Colonoscopy Jan 2012 Colonoscopy December 2010 Colonoscopy and Biopsies Support CD Diagnosis
  • 7.
    Confirming the Crohn’sHypothesis: Finding the “Smoking Gun” with MRI Imaging Liver I Obtained the MRI Slices Transverse Colon From UCSD Medical Services and Converted to Interactive 3D Working With Small Intestine Calit2 Staff & DeskVOX Software Descending Colon Diseased Sigmoid Colon Major Kink Sigmoid Colon Threading Iliac Arteries
  • 8.
    LS Sigmoid ColonCross Sections Showing Inflamed Wall Jan 2012 MRI Enterography report: “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. Ulcerative Colitis is Restricted to the Mucosa, while Crohn's Disease Note Affects the Thickness Whole of Wall - Bowel Wall Normal is 3mm (like a Balloon) Source: L Smarr Using Calit2’s Jurgen Schultz Software
  • 9.
    I Wondered ifCrohn’s is an Autoimmune Disease, Did I Have a Personal Genomic Polymorphism? From www.23andme.com Polymorphism in Interleukin-23 Receptor Gene — 80% Higher Risk ATG16L1 of Pro-inflammatory Immune Response IRGM NOD2 SNPs Associated with CD
  • 10.
    Crohn’s Disease PatientsHave Number of Firmicute Gut Microbe Species Reduced by Over 2/3! Healthy Gut Microbes Actinobacteria 7 Bacteroidetes Proteobacteria Firmicutes 33 5 43 IBD Gut Microbes Actinobacteria 7 Bacteroidetes Proteobacteria Firmicutes 33 5 13 The Missing Firmicutes Inhibit Pro-Inflammation Manichanh, et al, Gut 2006;55:205–211
  • 11.
    Microbial Metagenomics Can DiagnoseDisease States From www.23andme.com Mutation in Interleukin-23 Receptor Gene—80% Higher Risk of Pro-inflammatory Immune Response IBD Patients Harbored, on Average, 25% Fewer SNPs Associated with CD Microbial Genes than the Individuals Not Suffering from IBD. 2009
  • 12.
    First Stage ofMetagenomic Sequencing of My Gut Microbiome at J. Craig Venter Institute I Received a Disk Drive Last Week With 35 GB FASTQ Files Weizhong Li, UCSD NGS Pipeline: 230M Reads Only 0.2% Human Next: 10-100,000 cpu-hrs Gel Image of Extract from Smarr Sample-Next is Library Construction Manny Torralba, Project Lead - Human Genomic Medicine J Craig Venter Institute January 25, 2012