1. BFO and Disease Barry Smith 8/19.2012

2. A Chart representing how John’s temperature changes 2

3. 3

4. John’s temperature, the temperature he has throughout his entire life, cycles through different determinate temperatures from one time to the next John’s temperature is a physiology variable which, in thus changing, exerts an influence on other physiology variables through time 4

5. BFO: The Very Top continuant independent continuant dependent continuant quality occurrent temperature 5

6. Blinding Flash of the Obvious independent continuant dependent continuant quality temperature types instances organism John John’s temperature 6

7. Blinding Flash of the Obvious independent continuant dependent continuant quality temperature types instances organism John John’s temperature 7

8. Blinding Flash of the Obvious temperature types instances organism John John’s temperature. 8 inheres_in

9. temperature types instances John’s temperature 9 37ºC37.1ºC37.5ºC37.2ºC37.3ºC37.4ºC instantiates at t 1 instantiates at t 2 instantiates at t 3 instantiates at t 4 instantiates at t 5 instantiates at t 6

10. human types instances John 10 embryofetusadultneonateinfantchild instantiates at t 1 instantiates at t 2 instantiates at t 3 instantiates at t 4 instantiates at t 5 instantiates at t 6

11. Temperature subtypes Development-stage subtypes are threshold divisions (hence we do not have sharp boundaries, and we have a certain degree of choice, e.g. in how many subtypes to distinguish, though not in their ordering) 11

12. independent continuant dependent continuant quality temperature types instances organism John John’s temperature 12

13. independent continuant dependent continuant quality temperature organism John John’s temperature occurrent process course of temperature changes John’s temperature history 13

14. independent continuant dependent continuant quality temperature organism John John’s temperature occurrent process temperature process profile John’s temperature history

15. independent continuant dependent continuant quality temperature organism John John’s temperature occurrent process life of an organism John’s life 15

16. BFO: The Very Top continuantoccurrent independent continuant dependent continuant qualitydisposition 16

17. Disposition - of a glass vase, to shatter if dropped - of a human, to eat - of a banana, to ripen - of John, to lose hair 17

18. Disposition if it ceases to exist, then its bearer and/or its immediate surrounding environment is physically changed its realization occurs when its bearer is in some special physical circumstances its realization is what it is in virtue of the bearer’s physical make-up 18

19. :. Function - of liver: to store glycogen - of birth canal: to enable transport - of eye: to see - of mitochondrion: to produce ATP functions are dispositions which are designed or selected for 19

20. independent continuant dependent continuant function to see eye John’s eye function of John’s eye: to see occurrent process process of seeing John seeing 20

21. OGMS Ontology for General Medical Science http://code.google.com/p/ogms 21

22. 22 Physical Disorder

23. :. Physical Disorder – independent continuant fiat object part A causally linked combination of physical components of the extended organism that is clinically abnormal. 23

24. Clinically abnormal –(1) not part of the life plan for an organism of the relevant type (unlike aging or pregnancy), –(2) causally linked to an elevated risk either of pain or other feelings of illness, or of death or dysfunction, and –(3) such that the elevated risk exceeds a certain threshold level.* *Compare: baldness 24

25. Realizable dependent continuants Role: nurse role, pathogen role, food role Disposition: fragility, virulence, susceptibility, genetic disposition to disease X Function: to pump (of the heart), to unlock (of the key) 25

26. Role (Externally-Grounded Realizable Entity) role =def. a realizable entity which exists because the bearer is in some special physical, social, or institutional set of circumstances in which the bearer does not have to be, and is not such that, if it ceases to exist, then the physical make-up of the bearer is thereby changed. 26

27. Disposition (Internally-Grounded Realizable Entity) disposition =def. a realizable entity which if it ceases to exist, then its bearer is physically changed, and whose realization occurs when this bearer is in some special physical circumstances, in virtue of the bearer’s physical make-up 27

28. Function (A Disposition Designed or Selected For) function =def. a disposition that exists in virtue of the bearer’s physical make-up,, and this physical make-up is something the bearer possesses because it came into being, either through evolution (in the case of natural biological entities) or through intentional design (in the case of artifacts), in order to realize processes of a certain kind. 28

29. 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. HL7, most standard terminologies, confuse 2. and 4 29

30. 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 30

31. 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 31

32. Disposition Internally-Grounded Realizable Entity A disposition is a realizable entity which is such that, if it ceases to exist, then its bearer is physically changed, whose realization occurs, in virtue of the bearer’s physical make-up, when this bearer is in some special physical circumstances 32

33. Disorder 1.person – independent continuant objects fiat object part object aggregate 33

34. Disorder A fiat object part of an organism which serves as the bearer of a disposition of a certain sort This fiat object may have no determinate boundaries (compare: Downtown Santa Barbara) 34

35. Where does Mount Everest begin and end? Cf. Barry Smith and David M. Mark, “Do Mountains Exist?”, Environment and Planning B, 30, 2003. 35

36. Big Picture (with thanks to Richard Scheuermann) 36

37. A disease is a disposition rooted in a physical disorder in the organism and realized in pathological processes. etiological process produces disorder bears disposition realized_in pathological process produces abnormal bodily features recognized_as signs & symptomsinterpretive process produces diagnosis used_in 37

38. Elucidation of Primitive Terms ‘bodily feature’ - an abbreviation for a physical component, a bodily quality, or a bodily process. disposition - an attribute describing the propensity to initiate certain specific sorts of processes when certain conditions are satisfied. clinically abnormal - some bodily feature that (1) is not part of the life plan for an organism of the relevant type (unlike 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 38

39. Definitions - Foundational Terms Disorder =def. – A causally linked combination of physical components that is clinically abnormal. Pathological Process =def. – A bodily process that is a manifestation of a disorder and 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. 39

40. Dispositions and Predispositions All diseases are dispositions; not all dispositions are diseases. A predisposition is a disposition. Predisposition to Disease of Type X =def. – A disposition in an organism that constitutes an increased risk of the organism’s subsequently developing the disease X. HNPCC is caused by a disorder (mutation) in a DNA mismatch repair gene that disposes to the acquisition of additional mutations from defective DNA repair processes, and thus is a predisposition to the development of colon cancer. 40

41. Definitions - Clinical Evaluation Terms Sign =def. – A bodily feature of a patient that is observed in a physical examination and is deemed by the clinician to be of clinical significance. (Objectively observable features) Symptom =def. – A experienced bodily feature of a patient that is observed by and observable only by the patient and is of the type that can be hypothesized by a patient to be a realization of a disease. (A restricted family of phenomena including pain, nausea, anger, drowsiness, which are of their nature experienced in the first person) Symptoms are subjective. But this does not mean that there is no objective fact of the matter whether a given symptom exists 41

42. Cirrhosis - environmental exposure Etiological process - phenobarbitol- induced hepatic cell death produces Disorder - necrotic liver bears Disposition (disease) - cirrhosis realized_in Pathological process - abnormal tissue repair with cell proliferation and fibrosis that exceed a certain threshold; hypoxia-induced cell death produces Abnormal bodily features recognized_as Symptoms - fatigue, anorexia Signs - jaundice, splenomegaly Symptoms & Signs used_in Interpretive process produces Hypothesis - rule out cirrhosis suggests Laboratory tests produces Test results - elevated liver enzymes in serum used_in Interpretive process produces Result - diagnosis that patient X has a disorder that bears the disease cirrhosis 42

43. Influenza - infectious Etiological process - infection of airway epithelial cells with influenza virus produces Disorder - viable cells with influenza virus bears Disposition (disease) - flu realized_in Pathological process - acute inflammation produces Abnormal bodily features recognized_as Symptoms - weakness, dizziness Signs - fever Symptoms & Signs used_in Interpretive process produces Hypothesis - rule out influenza suggests Laboratory tests produces Test results - elevated serum antibody titers used_in Interpretive process produces Result - diagnosis that patient X has a disorder that bears the disease flu But the disorder also induces normal physiological processes (immune response) that can results in the elimination of the disorder (transient disease course). 43

44. Huntington’s Disease - genetic Etiological process - inheritance of >39 CAG repeats in the HTT gene produces Disorder - chromosome 4 with abnormal mHTT bears Disposition (disease) - Huntington’s disease realized_in Pathological process - accumulation of mHTT protein fragments, abnormal transcription regulation, neuronal cell death in striatum produces Abnormal bodily features recognized_as Symptoms - anxiety, depression Signs - difficulties in speaking and swallowing Symptoms & Signs used_in Interpretive process produces Hypothesis - rule out Huntington’s suggests Laboratory tests produces Test results - molecular detection of the HTT gene with >39CAG repeats used_in Interpretive process produces Result - diagnosis that patient X has a disorder that bears the disease Huntington’s disease 44

45. 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) 45

46. 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 Death 46

47. Definition: Etiology Etiological Process =def. – A process in an organism that leads to a subsequent disorder. Example: toxic chemical exposure resulting in a mutation in the genomic DNA of a cell; infection of a human with a pathogenic virus; inheritance of two defective copies of a metabolic gene The etiological process creates the physical basis of that disposition to pathological processes which is the disease. 47

48. Definitions - Diagnosis Clinical Picture =def. – A representation of a clinical phenotype that is inferred from the combination of laboratory, image and clinical findings about a given patient. Diagnosis =def. – A conclusion of an interpretive process that has as input a clinical picture of a given patient and as output an assertion to the effect that the patient has a disease of such and such a type. 48

49. Definitions - Qualities Manifestation of a Disease =def. – A bodily feature of a patient that is (a) a deviation from clinical normality that exists in virtue of the realization of a disease and (b) is observable. Observability includes observable through elicitation of response or through the use of special instruments. Preclinical Manifestation of a Disease =def. – A manifestation of a disease that exists prior to its becoming detectable in a clinical history taking or physical examination. Clinical Manifestation of a Disease =def. – A manifestation of a disease that is detectable in a clinical history taking or physical examination. Phenotype =def. – A (combination of) bodily feature(s) of an organism determined by the interaction of its genetic make-up and environment. Clinical Phenotype =def. – A clinically abnormal phenotype. 49