This document discusses medicine as a knowledge processing discipline and how understanding this can help improve patient care and outcomes. It presents examples of how analyzing large amounts of medical data can help find uncommon patterns that lead to new diagnoses, treatments, and insights. The author advocates for liberating medical data, understanding data more deeply, finding the uncommon in common cases, and engaging patients as partners. The goal is to systematize serendipity and personalized medicine by treating medicine as an information science.

1. What If Medicine Understood
Itself as a Knowledge Processing
Discipline
Isaac Kohane, MD, PhD
January 2019

3. 3
Worsening dystonia
(not walking, not speaking)
L-Dopa
Folinic Acid
5-hydroytryptophan
GTP cyclohydrolase I deficiency
Walking, talking!
Undiagnosed Disease Network

6. Trying to make rare more common.

8. 8

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2
4
6
8
10
12
14
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CusumofHospitalizationsduetoMyocardialInfarction
Rofecoxib introduced Rofecoxib withdrawn
Brownstein, PLoS One, 2007

10. Netflix

11. How are we going to get there?
•Find the uncommon in the common.
•Understand our data.
•Liberate our data.
•Understand medicine’s core as a knowledge-
processing discipline.
•Accept patients as our partners in care AND
science.

12. How do we systematize serendipity?

13. MemberID BirthYear Gender RelationshipToEmployee
00000018889576628825 2002 F C

14. Phenocopy of
the UDN patient

15. A common diagnosis becomes undiagnosed
• 3 years and 10 months old with bloody stool.
• Underwent endoscopy in November 2005 at 4 years old which showed a pancolitis.
• He was started on sulfasalazine; maintained on fish oil and sulfasalazine until age 13 ½ at which
point he flared. That was in July 2015.
• He’s been in a flare since. Unsuccessful wean from prednisone, vancomycin effect transient
• Started on 6MP in March 2016 with no effect over 3 months despite therapeutic levels.
• Started on infliximab 5mg/kg 7/6/2016 with no effect.
• Aug 20th tried a course of Rifaximin with initial, temporally related, transient improvement.
• Has tried multiple forms of PR meds with no effect, including cortisone enemas, cortifoam,
canasa suppos. .
• In September 2016, stool turned bloody and frequency was hourly, hospitalized for tacrolimus
• which improved symptoms but did not produce a remission.
• Vedolizumab was added in October with no appreciable effect.

16. Boundary between diseased and
healthy patients
Can we identify an existing drug that
will move these patients towards the
healthy region?
IBD Expression Profiles:
Whole Blood

17. Tissue: Blood
Drug: Azathioprine

18. Best ranked compound for our patient
• Indirubin
• Chemical compound
most often produced
as a byproduct of
bacterial metabolism
• Constituent of indigo
naturalis (also known
as qing dai),

19. How are we going to get there?
•Find the uncommon in the common.
•Understand our data.
•Liberate our data.
•Understand medicine’s core as a knowledge-
processing discipline.
•Accept patients as our partners in care AND
science.

20. Thousands with
unproductive expensive
course

21. Avoiding cost and
pain.

22. Survival 3 Years After a WBC Test
(White, Male, 50-69 Years; Using Last WBC Between 7/28/05 and 7/27/06)

23. Predicting Survival from Ordering a Lab Test
Higher Mortality RateHigher Survival Rate

24. How are we going to get there?
•Find the uncommon in the common.
•Understand our data.
•Liberate our data.
•Understand medicine’s core as a knowledge-
processing discipline.
•Accept patients as our partners in care AND
science.

25. SMART Vision
• Write codes onc for use in many clinical
platforms
• Eliminate barriers for clinical IT developers
to
• Create clinically specific medical UX
• Integrate medical knowledge faster
• Respond promptly to market needs and wants
• Increase ROI in EMR/clinical systems
• Stimulate supply to address demand
25

26. 26
Result: SMART Cardiac Risk App
Original design by Dave McCandless/Creative Commons
Inspired by critique and makeover
of heart disease test found in
Wired (issue 18.12)
BEFORE
AFTER

28. http://www.decaturcountyhospital.org
Dignity Health (Arizona, California, and Nevada)
https://www.dignityhealth.org
Duke Health (North Carolina)
http://dukehealth.org
Eisenhower Health (California)
https://www.eisenhowerhealth.org
Family Foot and Ankle Clinic, P.A. (Minnesota)
https://www.familyfootmn.com
Family Footcare Specialist (New Jersey)
https://familyfootcarespecialist.com
Fisher-Titus Health (Ohio)
https://www.fishertitus.org
Fitzgibbon Hospital (Missouri)
https://www.fitzgibbon.org
Foot and Ankle Specialist (Arizona)
Fort Healthcare (Wisconsin)
https://www.forthealthcare.com
Franciscan Missionaries of Our Lady Health System (Louisiana)
https://fmolhs.org
Geisinger (Pennsylvania)
http://geisinger.org
Genesis Healthcare System (Ohio)
https://www.genesishcs.org
Grace Cottage Hospital (Vermont)
https://gracecottage.org
Greater Hudson Valley Health System (New York)
https://www.ormc.org/about-us/ghvhs
Greenville Health System (South Carolina)
https://www.ghs.org
Group Health Cooperative of South Central Wisconsin (Wisconsin)
https://ghcscw.com
Adult Internal Medicine (North Carolina)
http://www.adultinternalmedicine.net
Adventist Health System (Colorado, Florida, Georgia, Illinois,
Texas, and others)
https://www.adventisthealthsystem.com
AtlantiCare (New Jersey)
http://atlanticare.org
Austin Regional Clinic (Texas)
https://www.austinregionalclinic.com
Dan Bangart, DPM (Arizona)
https://peoriafootandanklespecialists.com
Baptist Health (Kentucky, Indiana, and Illinois)
https://www.baptisthealth.com/pages/home.aspx
BayCare (Florida)
https://baycare.org
Better Me Healthcare (Florida)
http://www.bettermehealthcare.com
Black River Memorial Hospital (Wisconsin)
https://www.brmh.net
Bon Secours Health System (Kentucky, Maryland, South
Carolina, Virginia, and Florida)
https://bonsecours.com
Boone County Health Center (Nebraska)
https://boonecohealth.org
Dr. Albert Boyd, MD (Texas)
https://www.alboydmd.com
Brain Vitals (California)
Buffalo Medical Group (New York)
https://www.buffalomedicalgroup.com
Carroll County Memorial Hospital (Missouri)
http://www.carrollcountyhospital.org
Carson Valley Medical Center (Nevada)
https://cvmchospital.org
Cedars-Sinai (California)
https://www.cedars-sinai.org
Center for Manual Medicine (Kansas)
http://www.ctrmm.com
Central Valley Medical Center (Utah)
https://www.centralvalleymedicalcenter.com
Centura Health (Colorado and Kansas)
https://www.centura.org
Cerner Healthe Clinic (Kansas, Missouri)
https://healtheatcerner.com
Chase County Community Hospital (Nebraska)
https://www.chasecountyhospital.com
Christiana Care Health System (Delaware, Pennsylvania,
Maryland, and New Jersey)
https://christianacare.org
Circle Health (Massachusetts)
http://www.circle-health.org
Cleveland Clinic (Ohio, Nevada, and Florida)
https://my.clevelandclinic.org
Cogdell Memorial Hospital (Texas)
https://cogdellhospital.com
Cone Health (North Carolina)
https://www.conehealth.com
Confluence Health (Washington)
https://www.confluencehealth.org
Coquille Valley Hospital (Oregon)
http://www.cvhospital.org
CoxHealth (Missouri)
https://www.coxhealth.com
David J. MacGregor MD (California)
http://450derm.com
Deaconess Health System (Indiana)
https://www.deaconess.com
http://www.decaturcountyhospital.org
Dignity Health (Arizona, California, and Nevada)
https://www.dignityhealth.org
Duke Health (North Carolina)
http://dukehealth.org
Eisenhower Health (California)
https://www.eisenhowerhealth.org
Family Foot and Ankle Clinic, P.A. (Minnesota)
https://www.familyfootmn.com
Family Footcare Specialist (New Jersey)
https://familyfootcarespecialist.com
Fisher-Titus Health (Ohio)
https://www.fishertitus.org
Fitzgibbon Hospital (Missouri)
https://www.fitzgibbon.org
Foot and Ankle Specialist (Arizona)
Fort Healthcare (Wisconsin)
https://www.forthealthcare.com
Franciscan Missionaries of Our Lady Health System
(Louisiana)
https://fmolhs.org
Geisinger (Pennsylvania)
http://geisinger.org
Genesis Healthcare System (Ohio)
https://www.genesishcs.org
Grace Cottage Hospital (Vermont)
https://gracecottage.org
Greater Hudson Valley Health System (New York)
https://www.ormc.org/about-us/ghvhs
Greenville Health System (South Carolina)
https://www.ghs.org
A-G
From
https://support.apple.com/en-us/HT208647
371 hospitals as of
10/19/2019

29. How are we going to get there?
•Find the uncommon in the common.
•Understand our data.
•Liberate our data.
•Understand medicine’s core as a knowledge-
processing discipline.
•Accept patients as our partners in care AND
science.

30. The young doctors-to be-KNOW that medicine is
an information processing discipline

32. How are we going to get there?
•Find the uncommon in the common.
•Understand our data.
•Liberate our data.
•Understand medicine’s core as a knowledge-
processing discipline.
•Accept patients as our partners in care AND
science.

33. Network for Enigmatic Exceptional
Responders
Eric Perakslis, MS, PhD
JnJ/FDA/DBMI/Takeda/Datavant
Isaac Kohane, MD, PhD
Harvard Medical School

34. PPM System Architecture

35. NEER Outline
Individual registers and
provides brief
description of why they
are considered an
exceptional responder
to cancer treatment;
reviewed and approved
by PI.
Participant
completes online
questionnaire
about health and
family history.
Participant gives
access to medical
and clinical trial
records.
Participant provides
blood sample and
microbiome sample.
+
Immunoassay
Participant
wears a Fitbit to
track activity,
heart rate, sleep,
etc.
Participant
provides access to
publicly-available
social media data.

36. PPM: NEER Eligibility
• Eligibility Criteria
• 18 years of age or older
• Living in the United States
• Demonstrated exceptional response to cancer therapies
• Not currently pregnant or detained (vulnerable population)

37. Big start
to a
people
powered
study:
Join Us!

38. Thank you