The document discusses different approaches to conceptualizing health, disease, and biological kinds across multiple levels of granularity. It notes that traditional biology data conceptualized entities based on observable instances, while new biology data represents entities at the molecular level through genetic sequences. It argues that linking different kinds of phenomena represented at various levels requires annotation with terms from controlled vocabularies like ontologies. Ontologies provide a structured framework for integrating data across databases and supporting logical reasoning by standardizing references to biological entities, processes, and functions.

1. Disease, and Other Clinical
Natural Kinds
Barry Smith
Gradualist Approaches to Health and Disease
Berlin, March 23, 2012
1

2. Natural Kind
Synonyms: universal, type
= entities of the sorts which are referred to by
general terms of natural science
Instances, particulars, individuals
= entities of the sorts which can be observed
in experiments of natural science
2/

3. Old biology data
3/

4. New biology data
MKVSDRRKFEKANFDEFESALNNKNDLVHCPSITLFESIPTEVRSF
YEDEKSGLIKVVKFRTGAMDRKRSFEKVVISVMVGKNVKKFLTFV
EDEPDFQGGPISKYLIPKKINLMVYTLFQVHTLKFNRKDYDTLSLF
YLNRGYYNELSFRVLERCHEIASARPNDSSTMRTFTDFVSGAPIV
RSLQKSTIRKYGYNLAPYMFLLLHVDELSIFSAYQASLPGEKKVDT
ERLKRDLCPRKPIEIKYFSQICNDMMNKKDRLGDILHIILRACALNF
GAGPRGGAGDEEDRSITNEEPIIPSVDEHGLKVCKLRSPNTPRRL
RKTLDAVKALLVSSCACTARDLDIFDDNNGVAMWKWIKILYHEVA
QETTLKDSYRITLVPSSDGISLLAFAGPQRNVYVDDTTRRIQLYTD
YNKNGSSEPRLKTLDGLTSDYVFYFVTVLRQMQICALGNSYDAFN
HDPWMDVVGFEDPNQVTNRDISRIVLYSYMFLNTAKGCLVEYAT
FRQYMRELPKNAPQKLNFREMRQGLIALGRHCVGSRFETDLYES
ATSELMANHSVQTGRNIYGVDFSLTSVSGTTATLLQERASERWIQ
WLGLESDYHCSFSSTRNAEDVDISRIVLYSYMFLNTAKGCLVEYA
4
TFRQYMRELPKNAPQKLNFREMRQGLIALGRHCVGSRFETDLYE

5. How to do biology across the genome?
MKVSDRRKFEKANFDEFESALNNKNDLVHCPSITLFESIPTEVRSFYEDEKSGLIKVVKFRTGAMDRKRSFEKVVIS
VMVGKNVKKFLTFVEDEPDFQGGPISKYLIPKKINLMVYTLFQVHTLKFNRKDYDTLSLFYLNRGYYNELSFRVLER
CHEIASARPNDSSTMRTFTDFVSGAPIVRSLQKSTIRKYGYNLAPYMFLLLHVDELSIFSAYQASLPGEKKVDTERL
KRDLCPRKPIEIKYFSQICNDMMNKKDRLGDILHIILRACALNFGAGPRGGAGDEEDRSITNEEPIIPSVDEHGLKVC
KLRSPNTPRRLRKTLDAVKALLVSSCACTARDLDIFDDNNGVAMWKWIKILYHEVAQETTLKDSYRITLVPSSDGIS
LLAFAGPQRNVYVDDTTRRIQLYTDYNKNGSSEPRLKTLDGLTSDYVFYFVTVLRQMQICALGNSYDAFNHDPWM
DVVGFEDPNQVTNRDISRIVLYSYMFLNTAKGCLVEYATFRQYMRELPKNAPQKLNFREMRQGLIALGRHCVGSR
FETDLYESATSELMANHSVQTGRNIYGVDFSLTSVSGTTATLLQERASERWIQWLGLESDYHCSFSSTRNAEDVM
KVSDRRKFEKANFDEFESALNNKNDLVHCPSITLFESIPTEVRSFYEDEKSGLIKVVKFRTGAMDRKRSFEKVVISV
MVGKNVKKFLTFVEDEPDFQGGPISKYLIPKKINLMVYTLFQVHTLKFNRKDYDTLSLFYLNRGYYNELSFRVLERC
HEIASARPNDSSTMRTFTDFVSGAPIVRSLQKSTIRKYGYNLAPYMFLLLHVDELSIFSAYQASLPGEKKVDTERLK
RDLCPRKPIEIKYFSQICNDMMNKKDRLGDILHIILRACALNFGAGPRGGAGDEEDRSITNEEPIIPSVDEHGLKVCK
LRSPNTPRRLRKTLDAVKALLVSSCACTARDLDIFDDNNGVAMWKWIKILYHEVAQETTLKDSYRITLVPSSDGISL
LAFAGPQRNVYVDDTTRRIQLYTDYNKNGSSEPRLKTLDGLTSDYVFYFVTVLRQMQICALGNSYDAFNHDPWM
DVVGFEDPNQVTNRDISRIVLYSYMFLNTAKGCLVEYATFRQYMRELPKNAPQKLNFREMRQGLIALGRHCVGSR
FETDLYESATSELMANHSVQTGRNIYGVDFSLTSVSGTTATLLQERASERWIQWLGLESDYHCSFSSTRNAEDVM
KVSDRRKFEKANFDEFESALNNKNDLVHCPSITLFESIPTEVRSFYEDEKSGLIKVVKFRTGAMDRKRSFEKVVISV
MVGKNVKKFLTFVEDEPDFQGGPISKYLIPKKINLMVYTLFQVHTLKFNRKDYDTLSLFYLNRGYYNELSFRVLERC
HEIASARPNDSSTMRTFTDFVSGAPIVRSLQKSTIRKYGYNLAPYMFLLLHVDELSIFSAYQASLPGEKKVDTERLK
RDLCPRKPIEIKYFSQICNDMMNKKDRLGDILHIILRACALNFGAGPRGGAGDEEDRSITNEEPIIPSVDEHGLKVCK
LRSPNTPRRLRKTLDAVKALLVSSCACTARDLDIFDDNNGVAMWKWIKILYHEVAQETTLKDSYRITLVPSSDGISL
LAFAGPQRNVYVDDTTRRIQLYTDYNKNGSSEPRLKTLDGLTSDYVFYFVTVLRQMQICALGNSYDAFNHDPWM
DVVGFEDPNQVTNRDISRIVLYSYMFLNTAKGCLVEYATFRQYMRELPKNAPQKLNFREMRQGLIALGRHCVGSR
FETDLYESATSELMANHSVQTGRNIYGVDFSLTSVSGTTATLLQERASERWIQWLGLESDYHCSFSSTRNAEDVM
KVSDRRKFEKANFDEFESALNNKNDLVHCPSITLFESIPTEVRSFYEDEKSGLIKVVKFRTGAMDRKRSFEKVVISV5
MVGKNVKKFLTFVEDEPDFQGGPISKYLIPKKINLMVYTLFQVHTLKFNRKDYDTLSLFYLNRGYYNELSFRVLERC

6. how to link the kinds of
phenomena represented here
6/

7. or here
7

8. or here
8

9. MKVSDRRKFEKANFDEFESALNNKNDLVHCPSITLFESIPTEVRSFYEDEKSGLIKVVKFRTGAMDRK
to this?
RSFEKVVISVMVGKNVKKFLTFVEDEPDFQGGPIPSKYLIPKKINLMVYTLFQVHTLKFNRKDYDTLSLF
YLNRGYYNELSFRVLERCHEIASARPNDSSTMRTFTDFVSGAPIVRSLQKSTIRKYGYNLAPYMFLLLH
VDELSIFSAYQASLPGEKKVDTERLKRDLCPRKPIEIKYFSQICNDMMNKKDRLGDILHIILRACALNFG
AGPRGGAGDEEDRSITNEEPIIPSVDEHGLKVCKLRSPNTPRRLRKTLDAVKALLVSSCACTARDLDIF
DDNNGVAMWKWIKILYHEVAQETTLKDSYRITLVPSSDGISLLAFAGPQRNVYVDDTTRRIQLYTDYN
KNGSSEPRLKTLDGLTSDYVFYFVTVLRQMQICALGNSYDAFNHDPWMDVVGFEDPNQVTNRDISRI
VLYSYMFLNTAKGCLVEYATFRQYMRELPKNAPQKLNFREMRQGLIALGRHCVGSRFETDLYESATS
ELMANHSVQTGRNIYGVDSFSLTSVSGTTATLLQERASERWIQWLGLESDYHCSFSSTRNAEDVVAG
EAASSNHHQKISRVTRKRPREPKSTNDILVAGQKLFGSSFEFRDLHQLRLCYEIYMADTPSVAVQAPP
GYGKTELFHLPLIALASKGDVEYVSFLFVPYTVLLANCMIRLGRRGCLNVAPVRNFIEEGYDGVTDLYV
GIYDDLASTNFTDRIAAWENIVECTFRTNNVKLGYLIVDEFHNFETEVYRQSQFGGITNLDFDAFEKAIF
LSGTAPEAVADAALQRIGLTGLAKKSMDINELKRSEDLSRGLSSYPTRMFNLIKEKSEVPLGHVHKIRK
KVESQPEEALKLLLALFESEPESKAIVVASTTNEVEELACSWRKYFRVVWIHGKLGAAEKVSRTKEFV
TDGSMQVLIGTKLVTEGIDIKQLMMVIMLDNRLNIIELIQGVGRLRDGGLCYLLSRKNSWAARNRKGEL
PPKEGCITEQVREFYGLESKKGKKGQHVGCCGSRTDLSADTVELIERMDRLAEKQATASMSIVALPS
SFQESNSSDRYRKYCSSDEDSNTCIHGSANASTNASTNAITTASTNVRTNATTNASTNATTNASTNAS
TNATTNASTNATTNSSTNATTTASTNVRTSATTTASINVRTSATTTESTNSSTNATTTESTNSSTNATT
TESTNSNTSATTTASINVRTSATTTESTNSSTSATTTASINVRTSATTTKSINSSTNATTTESTNSNTNA
TTTESTNSSTNATTTESTNSSTNATTTESTNSNTSAATTESTNSNTSATTTESTNASAKEDANKDGNA
EDNRFHPVTDINKESYKRKGSQMVLLERKKLKAQFPNTSENMNVLQFLGFRSDEIKHLFLYGIDIYFCP
EGVFTQYGLCKGCQKMFELCVCWAGQKVSYRRIAWEALAVERMLRNDEEYKEYLEDIEPYHGDPVG
YLKYFSVKRREIYSQIQRNYAWYLAITRRRETISVLDSTRGKQGSQVFRMSGRQIKELYFKVWSNLRE
SKTEVLQYFLNWDEKKCQEEWEAKDDTVVVEALEKGGVFQRLRSMTSAGLQGPQYVKLQFSRHHR
QLRSRYELSLGMHLRDQIALGVTPSKVPHWTAFLSMLIGLFYNKTFRQKLEYLLEQISEVWLLPHWLD
LANVEVLAADDTRVPLYMLMVAVHKELDSDDVPDGRFDILLCRDSSREVGELIGLFYNKTFRQKLEYL 9
LEQISEVWLLPHWLDLANVEVLAADDTRVPLYMLMVAVHKELDSDDVPDGRFDILLCRDSSREVGELI

10. or this?
10

11. answer: through annotation of data with terms
from a controlled vocabulary or ‘ontology’
sphingolipid transporter activity
Holliday junction helicase complex
11

12. this allows integration of databases
MouseEcotope GlyProt
Holliday junction
helicase complex
DiabetInGene
GluChem
13

13. and supports logical reasoning over data
15

14. ‘Ontology’ in PubMed
16/24

15. GO, in particular, is tremendously successful
17

16. $100 million invested in literature and
data curation using GO
over 11 million annotations relating gene
products described in the UniProt,
Ensembl and other databases to GO
terms
experimental results reported in 52,000
scientific journal articles manually
annoted by expert biologists using GO
18

17. Benefits of the GO
1. rooted in basic experimental biology
2. links people to data and to literature
3. links data to data
• across species (human, mouse, yeast, fly ...)
• across granularities (molecule, cell, organ,
organism, population)
1. links medicine to biological science
2. promotes cumulation of scientific
knowledge in algorithmically tractable form
19

18. National Center for Biomedical Ontology
(NIH Roadmap Center)
− Stanford Biomedical Informatics Research
− The Mayo Clinic
− University at Buffalo Department of
Philosophy
http://bioportal.bioontology.org
24

19. 25

20. 26

21. GO supports only three types of annotation
what cellular component?
what molecular function?
what biological process?
no diseases in GO 27

22. 28

23. CONTINUANT OCCURRENT
RELATION
TO TIME
INDEPENDENT DEPENDENT
GRANULARITY
Anatomical
Organism Organ
ORGAN AND Entity
(NCBI Function
ORGANISM (FMA,
Taxonomy) (FMP, CPRO) Phenotypic Biological
CARO) Quality Process
(PaTO) (GO)
CELL AND Cellular Cellular
Cell
CELLULAR Component Function
(CL)
COMPONENT (FMA, GO) (GO)
Molecule
Molecular Function Molecular Process
MOLECULE (ChEBI, SO,
(GO) (GO)
RnaO, PrO)
OBO Foundry (first version, 2006)
Yellow = Gene Ontology 29

24. http://obofoundry.org
30

25. Current OBO Foundry Ontologies
• Biological process (GO)
• Cellular component (GO)
• Chemical entities of biological interest
• Molecular function (GO)
• Phenotypic quality
• PRotein Ontology (PRO)
• Xenopus Anatomy and Development
• Zebrafish Anatomy and Development
31

26. Foundry ontologies under review
Cell Ontology (CL)
Foundational Model of Anatomy (FMA)
Infectious Disease Ontology (IDO)
Staph. aureus Ontology (IDO Sa)
Malaria Ontology (IDO MAL)
Influenza Ontology (IDO Flu)
HIV Ontology (IDO HIV)
Ontology for Biomedical Investigations (OBI)
Ontology for General Medical Sciences (OGMS)
Plant Ontology (PO) 32

27. Ontologies under construction
Allergy Ontology
Environment Ontology (EnvO)
Immunology Ontology (IDO)
Mental Functioning Ontology (MFO)
Emotion Ontology (MFO-EM)
Pain Ontology
Mental Disease Ontology (MDO)
Neurological Disease Ontology (ND)
Vaccine Ontology (VO)
33

28. Foundational Model of Anatomy Ontology
FMA has 83281 types and 3 million relations
representing canonical adult human anatomy
= the anatomy generated by the coordinated
expression of the organism’s own structural
genes.
32 teeth one nose
two arms two nostrils
two legs two kidneys, …
Canonical ≠ statistically normal
34

29. Anatomical
Anatomical Space
Structure
Organ Cavity Organ
Organ Organ Part
Subdivision Cavity
Serous Sac Serous Sac Organ Organ
Cavity Cavity
Serous Sac Component Subdivision
Tissue
Subdivision
is_a
Pleural Sac
Pleural Sac Pleura(Wall
Pleural Pleura(Wall
Pleural of Sac)
of Sac)
Cavity
of
Cavity
Parietal
Parietal
Pleura
t_
Pleura Visceral
Visceral
Interlobar Pleura
Pleura
Interlobar
r
recess
recess Mediastinal
pa
Mediastinal
Pleura
Pleura Mesothelium
Mesothelium
of Pleura
of Pleura
35
dational Model of Anatomy (FMA)

30. An ontology
is a controlled structured vocabulary
that includes a backbone taxonomy
(nodes connected by the is_a [subtype]
relation)
together with further logically defined
relations such as part_of, regulated_by
36

31. Basic Formal Ontology (BFO)
A simple top-level ontology to support
information integration in scientific
research
Serves as starting point for OBO
Foundry ontologies
Domain ontologies built by downward
population
38

32. Continuant Occurrent
Basic Formal Ontology
Life
Independent Dependent
http://www.ifomis.org/bfo/
Continuant Continuant
Organism Temperature
39

33. Example: The Cell Ontology

34. Continuant
Independent Dependent TYPES
Continuant Continuant
Realizable
Non-realizable
Dependent
Dependent
Continuant
Continuant
(function, role,
..... .....
(quality)
disposition)
INSTANCE

35. depends_on
Continuant
TYPES
example:
Independent Dependent temperature depends
Continuant Continuant
on bearer
thing quality
.... ..... INSTANCE

36. Dependent
Continuant
Realizable Dependent
Quality Continuant
Disposition Function Role
of banana, of heart, of employee,
to ripen to pump blood to work for pay
46

37. process of realization depends_on
realizable
Continuant Occurrent
Realizable
Independent
Dependent
Continuant
Continuant Process of
bearer realization
.... ..... .......
disposition
47

38. Four distinct classificatory tasks
1. of people (patients, carriers, …)
2. of diseases (cases, instances, problems, …)
3. of courses of disease (symptoms, treatments…)
4. of representations (records, observations, data,
diagnoses…)
ICD confuses 1. & 2.
Most standard terminologies confuse 2. and 4
51

39. Four distinct BFO categories
1. person (patient, carrier, …)
– independent continuant
2. disease (case, instance, problem, …)
– specifically dependent continuant
3. course of disease (symptom, treatment…)
– occurrent
4. representation (record, datum, diagnosis…)
– generically dependent continuant
52

40. Four distinct BFO categories
1. people (patients, carriers, …)
– independent continuants
2. disease (case, instance, problem, condition …)
– disposition
3. course of disease (symptom, episode, outbreak …)
– realization of dispositions
4. representations (records, data, diagnoses…)
– generically dependent continuants
53

41. Big Picture (Ontology for General Medical Science)
55

42. Elucidation of Primitive Terms
 ‘extended organism’ = the organism and all
the material entities located within it
 ‘bodily feature’ = either a physical part of the
extended organism, a bodily quality, or a
bodily process.
56

43. Elucidation of Primitive Terms
 clinically abnormal - some bodily feature that
 (1) is not part of the life plan for an organism of the
relevant type (unlike loss of milk teeth, aging or
pregnancy),
 (2) is causally linked to an elevated risk either of
pain or other feelings of illness, or of death or
dysfunction, and
 (3) is such that the elevated risk exceeds a certain
threshold level.*
*Compare: baldness
57

44. Disorder
A material entity (fiat object part) which is
clinically abnormal and part of an extended
organism
Compare:
Downtown Santa Barbara
Mount Everest
Peter Hucklenbroich’s pate
58

45. Definitions - Foundational Terms
 Pathological Process =def. – A bodily process that is
clinically abnormal.
 Disease =def. – A disposition (i) to undergo
pathological processes that (ii) exists in an organism
because of one or more disorders in that organism.
60

46. http://code.google.com/p/ogms/ 61

47. Big Picture (Ontology for General Medical Science)
62

48. http://code.google.com/p/ogms/ 63

49. Disease Course
=Def. The sum of processes through which a
given disease instance is realized.
65

50. independent dependent
occurrent
continuant continuant
TYPES
disposition process
organism
disease course of
disease
INSTANCE
course of
John John’s
John’s disease
disease

51. coronary heart
in nature, no sharp disease
boundaries here
CHD in phase CHD in phase
CHD in phase of
of early lesions of surface unstable stable
asymptomatic
and small disruption of angina angina
(‘silent’) infarction
fibrous plaques plaque
instantiates instantiates instantiates instantiates instantiates
at t1 at t2 at t3 at t4 at t5
John’s coronary heart disease
67

52. human
in nature, no sharp
boundaries here
embryo fetus neonate infant child adult
instantiates instantiates instantiates instantiates instantiates instantiates
at t1 at t2 at t3 at t4 at t5 at t6
John
68

53. A disease is a disposition
produces bears realized_in
etiological process disorder disposition pathological process
produces
diagnosis interpretive process signs & symptoms abnormal bodily features
produces used_in recognized_as
71

54. Cirrhosis - environmental exposure
 Etiological process - phenobarbitol-  Symptoms & Signs
induced hepatic cell death  used_in
 produces  Interpretive process
 produces
 Disorder - necrotic liver
 bears
 Hypothesis - rule out cirrhosis
 suggests
 Disposition (disease) - cirrhosis
 realized_in
 Laboratory tests
 produces
 Pathological process - abnormal tissue  Test results - elevated liver enzymes
repair with cell proliferation and in serum
fibrosis that exceed a certain  used_in
threshold; hypoxia-induced cell death
 Interpretive process
 produces
 produces
 Abnormal bodily features  Result - diagnosis that patient X has a
 recognized_as disorder that bears the disease
 Symptoms - fatigue, anorexia cirrhosis
 Signs - jaundice, splenomegaly 72

55. Influenza - infectious
 Etiological process - infection of  Symptoms & Signs
airway epithelial cells with influenza  used_in
virus  Interpretive process
 produces  produces
 Disorder - viable cells with influenza  Hypothesis - rule out influenza
virus  suggests
 bears  Laboratory tests
 produces
 Disposition (disease) - flu
 realized_in  Test results - elevated serum antibody titers
 used_in
 Pathological process - acute
inflammation
 Interpretive process
 produces
 produces
 Result - diagnosis that patient X has a
 Abnormal bodily features
disorder that bears the disease flu
 recognized_as
 Symptoms - weakness, dizziness
 Signs - fever 73

56. Huntington’s Disease - genetic
 Etiological process - inheritance of
>39 CAG repeats in the HTT gene  Symptoms & Signs
 produces  used_in
 Disorder - chromosome 4 with  Interpretive process
abnormal mHTT  produces
 bears  Hypothesis - rule out Huntington’s
 Disposition (disease) - Huntington’s  suggests
disease  Laboratory tests
 realized_in
 produces
 Pathological process - accumulation of  Test results - molecular detection of
mHTT protein fragments, abnormal the HTT gene with >39CAG repeats
transcription regulation, neuronal cell  used_in
death in striatum
 produces
 Interpretive process
 produces
 Abnormal bodily features
 recognized_as
 Result - diagnosis that patient X has a
disorder that bears the disease
 Symptoms - anxiety, depression Huntington’s disease
 Signs - difficulties in speaking and
swallowing 74

57. Dispositions and Predispositions
Some dispositions are predispositions to
other dispositions.
75

58. HNPCC - genetic pre-disposition
 Etiological process - inheritance of a mutant mismatch repair gene
 produces
 Disorder - chromosome 3 with abnormal hMLH1
 bears
 Disposition (disease) - Lynch syndrome
 realized_in
 Pathological process - abnormal repair of DNA mismatches
 produces
 Disorder - mutations in proto-oncogenes and tumor suppressor genes with
microsatellite repeats (e.g. TGF-beta R2)
 bears
 Disposition (disease) - non-polyposis colon cancer
 realized in
 Symptoms (including pain)
76

59. Arterial Aneurysm
Disposition – atherosclerosis
realized in
Pathological process – fatty material collects within the walls of arteries
produces
Disorder – artery with weakened wall
bears
Disposition – of artery to become distended
realized_in
Pathological process – process of distending
produces
Disorder – arterial aneurysm
bears
Disposition – of artery to rupture
realized in
Pathological process – (catastrophic event) of rupturing
produces
Disorder – ruptured artery, arterial system with dangerously low blood pressure
bears
Disposition – circulatory failure
realized in
Pathological process – exsanguination, failure of homeostasis
produces 77
Death

60. Systemic arterial hypertension
 Etiological process – abnormal  Symptoms & Signs
reabsorption of NaCl by the kidney  used_in
 produces  Interpretive process
 produces
 Disorder – abnormally large scattered
molecular aggregate of salt in the  Hypothesis - rule out hypertension
blood  suggests
 bears  Laboratory tests
 produces
 Disposition (disease) - hypertension
 realized_in  Test results -
 used_in
 Pathological process – exertion of
abnormal pressure against arterial wall
 Interpretive process
 produces
 produces
 Result - diagnosis that patient X has a
 Abnormal bodily features
disorder that bears the disease hypertension
 recognized_as
 Symptoms -
 Signs – elevated blood pressure 82

61. Type 2 Diabetes Mellitus
 Etiological process –  Symptoms & Signs
 produces  used_in
 Disorder – abnormal pancreatic beta
 Interpretive process
 produces
cells and abnormal muscle/fat cells
 bears
 Hypothesis - rule out diabetes mellitus
 suggests
 Disposition (disease) – diabetes
mellitus
 Laboratory tests – fasting serum blood
glucose, oral glucose challenge test, and/or
 realized_in
blood hemoglobin A1c
 Pathological processes – diminished  produces
insulin production , diminished  Test results -
muscle/fat uptake of glucose  used_in
 produces
 Interpretive process
 Abnormal bodily features  produces
 recognized_as  Result - diagnosis that patient X has a
 Symptoms – polydipsia, polyuria, disorder that bears the disease type 2
polyphagia, blurred vision diabetes mellitus
 Signs – elevated blood glucose and 83
hemoglobin A1c

62. Type 1 hypersensitivity to penicillin
 Etiological process – sensitizing of mast  Symptoms & Signs
cells and basophils during exposure to  used_in
penicillin-class substance  Interpretive process
 produces  produces
 Disorder – mast cells and basophils with  Hypothesis -
epitope-specific IgE bound to Fc epsilon  suggests
receptor I  Laboratory tests –
 bears  produces
 Disposition (disease) – type I  Test results – occasionally, skin testing
hypersensitivity  used_in
 realized_in  Interpretive process
 produces
 Pathological process – type I
hypersensitivity reaction  Result - diagnosis that patient X has a
 produces disorder that bears the disease type 1
hypersensitivity to penicillin
 Abnormal bodily features
 recognized_as
 Symptoms – pruritis, shortness of breath 84
 Signs – rash, urticaria, anaphylaxis

63. Early Onset Alzheimer’s Disease
Disorder – mutations in APP, PSEN1 and PSEN2
bears
Disposition – impaired APP processing
realized in
Pathological process – accumulation of intra- and extracellular protein in the
brain
produces
Disorder – amyloid plaque and neurofibrillary tangles
bears
Disposition – of neurons to die
realized in
Pathological process – neuronal loss
produces
Disorder – cognitive brain regions damaged and reduced in size
bears
Disposition (disease) – Alzheimer’s dementia
realized in
Symptoms – episodic memory loss and other cognitive domain impairment
85

64. Arterial Aneurysm
• Disposition – atherosclerosis
– realized in
• Pathological process – fatty material collects within the walls of arteries
– produces
• Disorder – artery with weakened wall
– bears
• Disposition – of artery to become distended
– realized_in
• Pathological process – process of distending
– produces
• Disorder – arterial aneurysm
– bears
• Disposition – of artery to rupture
– realized in
• Pathological process – (catastrophic event) of rupturing
– produces
• Disorder – ruptured artery, arterial system with dangerously low blood pressure
– bears
• Disposition – circulatory failure
– realized in
• Pathological process – exsanguination, failure of homeostasis
– produces 86
• Death

65. Hemorrhagic stroke
• Disorder – cerebral arterial aneurysm
– bears
• Disposition – of weakened artery to rupture
– realized in
• Pathological process – rupturing of weakened blood vessel
– produces
• Disorder – Intraparenchymal cerebral hemorrhage
– bears
• Disposition (disease) – to increased intra-cranial pressure
– realized in
• Pathological process – increasing intra-cranial pressure, compression of brain
structures
– produces
• Disorder – Cerebral ischemia, Cerebral neuronal death
– bears
• Disposition (disease) – stroke
– realized in
• Symptoms – weakness/paralysis, loss of sensation, etc
87

66. Advantages of the Disposition Theory
Only something like the disposition
theory enables us to explain why a
fracture is not a disease
PETER HUCKLENBROICH
−Radius fracture loco classico “ is a disease”
88

67. PETER HUCKLENBROICH
A disease entity is a set of possible alternative
courses
x has disease entity D ≡
(x has course D1) or (x has course D2) or … or (x
has course Dn)
Only something like the disposition theory can
allow us to determine what does and what does
not belong to this list.
89

68. Think of all the different temporal extents of
the disease courses association with any
given disease
• for those who die in an accident 5 seconds
after catching the disease
• for those who have no treatment
• for those who have truly excellent treatment
• …
90

69. Think of all the different combination cases:
of diseases with other diseases
of diseases with complications
of diseases at different stages of life
of diseases with different environments
in igloos
in Ost-Thüringen
in sub-Saharan Africa
in space-ships
…
91

70. Think of all the different types of patient:
smoker
non-smoker
banana-leaf-smoker
Am-Sonntag-bei-Mutti-Esser
Aspirin-vor-dem-Schlafen-Gehen-Nehmer
Auf-dem-Schiessplatz-Ohrstöpsel-Träger
Auf-Weihnachtsmarkt-Lebkuchenherz-Käufer
Auto-in-Waschstrasse-Abschliesser
92

71. 93

72. human
in nature, no sharp
boundaries here
embryo fetus neonate infant child adult
instantiates instantiates instantiates instantiates instantiates instantiates
at t1 at t2 at t3 at t4 at t5 at t6
John
94

73. portion of Phrase
water
transitions
portion of portion of portion of
ice liquid water gas
instantiates instantiates instantiates
at t1 at t2 at t3
this portion of H20
95

74. temperature
in nature, no sharp
boundaries here
37ºC 37.1ºC 37.2ºC 37.3ºC 37.4ºC 37.5ºC
instantiates instantiates instantiates instantiates instantiates instantiates
at t1 at t2 at t3 at t4 at t5 at t6
John’s temperature
96