“The Deeply Quantified Self: A Case Study” Future Technology Keynote Minimally Invasive Surgery...
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Transcript of “The Deeply Quantified Self: A Case Study” Future Technology Keynote Minimally Invasive Surgery...
“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