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The Canonical Life. Barry Smith http://ontology.buffalo.edu/smith. Ontology ( Phil. ). = the science of the types of objects, qualities, proesses, events, funktions, environments, relations ... in all spheres of reality. Google hits (in millions) 12.10.06. ontology 24.0

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the canonical life

The Canonical Life

Barry Smith

http://ontology.buffalo.edu/smith

http://org.buffalo.edu

ontology phil
Ontology (Phil.)
  • = the science of the types of objects, qualities, proesses, events, funktions, environments, relations ... in all spheres of reality

http://org.buffalo.edu

google hits in millions 12 10 06
Google hits (in millions) 12.10.06
  • ontology 24.0
  • ontology + philosophy 4.6
  • ontology + information science 7.4
  • ontology + database 11.1

http://org.buffalo.edu

ontology computer science
ontology (computer science)
  • (roughly) the construction of standardized classification systems designed to make databases compatible with each other

http://org.buffalo.edu

national center for biomedical ontology
National Center for Biomedical Ontology
  • $18.8 mill. NIH Roadmap Center
  • Stanford Medical Informatics
  • University of San Francisco Medical Center
  • Berkeley Drosophila Genome Project
  • Cambridge University Department of Genetics
  • The Mayo Clinic
  • University at Buffalo Department of Philosophy

http://org.buffalo.edu

slide7

From

chromosome

to disease

http://org.buffalo.edu

slide8
genomics
  • transcriptomics
  • proteomics
  • reactomics
  • metabonomics
  • phenomics
  • behavioromics
  • connectomics
  • toxicopharmacogenomics
  • bibliomics
  • … legacy of Human Genome Project

http://org.buffalo.edu

slide10

we need to know

where in the body

we need to know

what kind of

disease process

we need semantic annotation of data

= we need ontologies

http://org.buffalo.edu

slide11

how create broad-coverage semantic annotation systems for biomedicine?

covering:

in vitro biological phenomena

model organisms

humans

http://org.buffalo.edu

obo foundry project
OBO Foundry Project
  • ontology developers in the life sciences have agreed in advance to accept a growing set of best practices in ontology development to ensure interoperability and additivity of annotations
  • http://obofoundry.org

http://org.buffalo.edu

when a gene is identified
When a gene is identified
  • three types of questions need to be addressed:
  • 1. Where is it located in the cell?
  • 2. What functions does it have on the molecular level?
  • 3. To what biological processes do these functions contribute?

http://org.buffalo.edu

slide17

where in the cell ?

what kind of

molecular function?

what kind of

biological process ?

http://org.buffalo.edu

go s three ontologies
GO’s three ontologies

molecular functions

biological processes

cellular components

http://org.buffalo.edu

three granularities
Three granularities:
  • Cellular (for components)
  • Molecular (for functions)
  • Organ + organism (for processes)

http://org.buffalo.edu

the granularity gulf
The Granularity Gulf
  • most existing data-sources are of fixed, single granularity
  • many (all?) clinical phenomena cross granularities

http://org.buffalo.edu

go s three ontologies22
GO’s three ontologies

biological process

molecular function

cellular component

http://org.buffalo.edu

go s three ontologies23
GO’s three ontologies

cellular

process

organism-level

biological process

molecular function

cellular component

http://org.buffalo.edu

slide24

Normalization of Granular Levels

molecular function

organism-level

biological process

cellular

process

molecule

cellular component

organism

http://org.buffalo.edu

slide26

organism-level

biological process

cellular

process

molecular process

organism-level

biological function

cellular

function

molecular function

molecule

cellular component

organism

http://org.buffalo.edu

types of process
types of process
  • stochastic processes (Brownian motion of blood cells)
  • accidents (heart penetrated by bullet)
  • functionings (heart pumping) (elite processes)
  • side-effects (heart beating)
  • malfunctionings ...

http://org.buffalo.edu

slide28

organism-level

biological process

cellular

process

molecular process

functioning

functioning

functioning

organism-level

biological function

cellular

function

molecular function

molecule

cellular component

organism

http://org.buffalo.edu

slide29

organism-level

process

cellular

process

molecular process

functionings

functionings

functionings

organism-level

biological function

cellular

function

molecular function

The new age of teleology

http://org.buffalo.edu

slide30
What does “function” mean?
  • an entity has a biological function if and only if it is part of an organism and has a disposition to act reliably in such a way as to contribute to the organism’s survival
  • the function is this disposition

http://org.buffalo.edu

problem of aging and death
Problem of aging and death
  • are their parts of the organism involved in bringing about aging processes?
  • is this their function?

http://org.buffalo.edu

problem of reproductive organs
Problem of reproductive organs
  • an entity has a biological function if and only if it is part of an organism and has a disposition to act reliably in such a way as to contribute to the organism’s survival

http://org.buffalo.edu

problem of reproductive organs33
Problem of reproductive organs
  • an entity has a biological function if and only if it is part of an organism and has a disposition to act reliably in such a way as to contribute to a group’s survival

http://org.buffalo.edu

problem of reproductive organs34
Problem of reproductive organs
  • an entity has a biological function if and only if it is part of an organism and has a disposition to act reliably in such a way as to contribute to genes’ survival

http://org.buffalo.edu

functions are organized in a modular hierarchy
Functions are organized in a modular hierarchy
  • The function of each functional part is: to contribute to the functioning of the whole
  • we need to understand ‘function’ in relation to the actual environing whole of the part in question

http://org.buffalo.edu

slide36

What do the kidneys do?

The function of the kidney is to purify blood

http://org.buffalo.edu

slide37

How does a kidney work?

The nephron is the cardinal functional unit of the kidney

http://org.buffalo.edu

slide38

Nephron Functions

10 functional segments

15 different cell types

http://org.buffalo.edu

challenge
Challenge
  • Can we provide an account of the functions of sexual organs within this framework
  • an entity has a biological function if and only if it is part of an organism and has a disposition to act reliably in such a way as to contribute to the organism’s survival

http://org.buffalo.edu

function is what gives rise to normal activity
Function is what gives rise to normal activity
  • But: that sperm function (to penetrate the ovum) is rare

http://org.buffalo.edu

functions
This is a screwdriver

This is a good screwdriver

This is a broken screwdriver

This is a heart

This is a healthy heart

This is an unhealthy heart

Functions

http://org.buffalo.edu

functions and prototypes
Functions and Prototypes
  • In its functioning, a heart creates a four-dimensional process shape. Good hearts create other process shapes than sick hearts do.

http://org.buffalo.edu

prototypes
Prototypes

functioning

http://org.buffalo.edu

slide44

poor functioning

http://org.buffalo.edu

slide45

malfunctioning

http://org.buffalo.edu

slide46

not functioning at all

http://org.buffalo.edu

what clinical medicine is for
What clinical medicine is for
  • to eliminate malfunctioning by fixing broken body parts
  • (or to prevent the appearance of malfunctioning by intervening e.g. at the molecular level)

http://org.buffalo.edu

what is health
What is health
  • Boorse: the state of an organism is theoretically healthy, i.e., free from disease, in so far as its mode of functioning conforms to the natural design of that kind of organism
  • = all its functional parts function in such a way as to promote survival and reproduction

http://org.buffalo.edu

the gene ontology
The Gene Ontology
  • is a canonical ontology – it represents only what is normal in the realm of (molecular) functioning
  • = what pertains to normal (‘wild type’) organisms (in all species)

http://org.buffalo.edu

the go is a canonical representation
The GO is a canonical representation
  • “The Gene Ontology is a computational representation of the ways in which gene products normally function in the biological realm”
  • Nucl. Acids Res. 2006: 34.

http://org.buffalo.edu

the go is a canonical representation51
The GO is a canonical representation
  • “The Gene Ontology is a computational representation of the ways in which gene products normally function in the biological realm”
  • Nucl. Acids Res. 2006: 34.

http://org.buffalo.edu

slide52

organism-level

process

cellular

process

molecular process

functionings

functionings

functionings

organism-level

biological function

cellular

function

molecular function

molecule

cellular component

organism

everything here is typical

http://org.buffalo.edu

the foundational model of anatomy is a canonical representation
The Foundational Model of Anatomy is a canonical representation
  • = a representation of types and relations between types deduced from the qualitative observations of the normal human body, which have been refined and sanctioned by successive generations of anatomists and presented in textbooks and atlases of structural anatomy.

http://org.buffalo.edu

slide55
FMA
  • recognizes also variant anatomical structures (e.g. coronary arteries or bronchopulmonary segments which deviate from the canonical anatomical pattern of organization)

http://org.buffalo.edu

a solution
A solution
  • Canonical anatomy = anatomy of the canonical human being in the canonical anatomical position (no amputation stumps, no effects of steroids, …)
  • For each type of organism there is a canonical Bauplan, but there is also a canonical life plan (canonical life Gestalt)

http://org.buffalo.edu

model organisms
Model organisms
  • you can buy a mouse with the prototypical mouse Bauplan according to a precise genetical specification

http://org.buffalo.edu

canonical lifeplan the physiological counterpart of canonical anatomy
Canonical lifeplan = the physiological counterpart of canonical anatomy

http://org.buffalo.edu

the canonical life plan
the canonical life (plan)

birth infancy teenagerdom early adulthood maturity late adulthood death

http://org.buffalo.edu

slide60
What does “function” mean?
  • an entity has a biological function if and only if it is part of an organism and has a disposition to act reliably in such a way as to contribute to the organism’s survival
  • the function is this disposition

http://org.buffalo.edu

improved version
Improved version
  • an entity has a biological function if and only if it is part of an organism and has a disposition to act reliably in such a way as to contribute to the organism’s realization of the canonical life planfor an organism of that type

http://org.buffalo.edu

this canonical life plan might include
This canonical life plan might include
  • canonical embryological development
  • canonical growth
  • canonical reproduction
  • canonical aging
  • canonical death

http://org.buffalo.edu

for all animals the canonical life gestalt includes
For all animals the canonical life Gestalt includes:
  • canonical embryological development
  • canonical growth
  • canonical reproduction
  • canonical aging
  • canonical death

http://org.buffalo.edu

for non human organisms the canonical life gestalt is primarily canonical physiology
For non-human organisms the canonical life Gestalt is primarily canonical physiology

http://org.buffalo.edu

for a human being the canonical life gestalt includes
For a human being the canonical life Gestalt includes:
  • spontaneity
  • society
  • culture
  • technology

birth infancy teenagerdom early adulthood maturity late adulthood death

http://org.buffalo.edu

canonical life gestalten
canonical life Gestalten
  • + variant life Gestalten (vegetarians, lesbians)
  • + pathological life Gestalten (serial murderers)

http://org.buffalo.edu

what would the life of a wild type human being involve
What would the life of a wild type human being involve?
  • Reproduction ...
  • Aging ...

http://org.buffalo.edu

just as there are 2 x n canonical baupl ne for human beings male and female at n successive stages
Just as there are 2 x n canonical Baupläne for human beings (male and female at n successive stages)
  • so there may be different canonical life plans for different types of human beings
  • if so, what are the different types?

http://org.buffalo.edu

is talk of life plan descriptive or prescriptive
Is talk of ‘life plan’ descriptive or prescriptive
  • If prescriptive we can use it as a benchmark e.g. to measure the success of different policies
  • Use it as a measure of flourishing
  • Relevance to debates about endangered species
  • Relevance to debates about ‘what is a life worth living?’

http://org.buffalo.edu

what is life
What is life?

http://org.buffalo.edu

what is a canonical environment
What is a canonical environment?
  • What is a canonical family?

http://org.buffalo.edu

what does every human canonical life involve
What does every human canonical life involve
  • 9 months of development
  • later acquisition of consciousness, language ...
  • cycles of waking, sleeping
  • death

http://org.buffalo.edu

different perspectives on the canonical life
Different perspectives on the canonical life
  • Aristotle: the golden mean
  • Catholic: no contraception, no sin
  • Evolutionary psychology: life in the African savannah
  • Roger Barker: behavior settings
  • Clinical medicine: goal to bring patient back in the direction of a canonical life
  • Cryonics view: ‘life’ is defined entirely conventionally
  • Transhumanism

http://org.buffalo.edu

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