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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

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The canonical life l.jpg

The Canonical Life

Barry Smith

http://ontology.buffalo.edu/smith

http://org.buffalo.edu


Ontology phil l.jpg

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 l.jpg

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


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http://org.buffalo.edu


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ontology (computer science)

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

http://org.buffalo.edu


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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


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From

chromosome

to disease

http://org.buffalo.edu


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  • genomics

  • transcriptomics

  • proteomics

  • reactomics

  • metabonomics

  • phenomics

  • behavioromics

  • connectomics

  • toxicopharmacogenomics

  • bibliomics

  • … legacy of Human Genome Project

http://org.buffalo.edu


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http://org.buffalo.edu


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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


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how create broad-coverage semantic annotation systems for biomedicine?

covering:

in vitro biological phenomena

model organisms

humans

http://org.buffalo.edu


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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


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http://org.buffalo.edu


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http://org.buffalo.edu


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http://org.buffalo.edu


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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


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where in the cell ?

what kind of

molecular function?

what kind of

biological process ?

http://org.buffalo.edu


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GO’s three ontologies

molecular functions

biological processes

cellular components

http://org.buffalo.edu


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Three granularities:

  • Cellular (for components)

  • Molecular (for functions)

  • Organ + organism (for processes)

http://org.buffalo.edu


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http://org.buffalo.edu


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The Granularity Gulf

  • most existing data-sources are of fixed, single granularity

  • many (all?) clinical phenomena cross granularities

http://org.buffalo.edu


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GO’s three ontologies

biological process

molecular function

cellular component

http://org.buffalo.edu


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GO’s three ontologies

cellular

process

organism-level

biological process

molecular function

cellular component

http://org.buffalo.edu


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Normalization of Granular Levels

molecular function

organism-level

biological process

cellular

process

molecule

cellular component

organism

http://org.buffalo.edu


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need to separate function from activity

http://org.buffalo.edu


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organism-level

biological process

cellular

process

molecular process

organism-level

biological function

cellular

function

molecular function

molecule

cellular component

organism

http://org.buffalo.edu


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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


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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


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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


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  • 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


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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


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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


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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 l.jpg

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


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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


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What do the kidneys do?

The function of the kidney is to purify blood

http://org.buffalo.edu


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How does a kidney work?

The nephron is the cardinal functional unit of the kidney

http://org.buffalo.edu


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Nephron Functions

10 functional segments

15 different cell types

http://org.buffalo.edu


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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


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Function is what gives rise to normal activity

  • But: that sperm function (to penetrate the ovum) is rare

http://org.buffalo.edu


Functions l.jpg

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


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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


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Prototypes

functioning

http://org.buffalo.edu


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poor functioning

http://org.buffalo.edu


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malfunctioning

http://org.buffalo.edu


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not functioning at all

http://org.buffalo.edu


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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


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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 l.jpg

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


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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 l.jpg

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


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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


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http://org.buffalo.edu


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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


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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


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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


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Model organisms

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

http://org.buffalo.edu


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Canonical lifeplan = the physiological counterpart of canonical anatomy

http://org.buffalo.edu


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the canonical life (plan)

birth infancy teenagerdom early adulthood maturity late adulthood death

http://org.buffalo.edu


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  • 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


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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


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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 l.jpg

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 l.jpg

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 l.jpg

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


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canonical life Gestalten

  • + variant life Gestalten (vegetarians, lesbians)

  • + pathological life Gestalten (serial murderers)

http://org.buffalo.edu


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What would the life of a wild type human being involve?

  • Reproduction ...

  • Aging ...

http://org.buffalo.edu


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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


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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


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What is life?

http://org.buffalo.edu


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What is a canonical environment?

  • What is a canonical family?

http://org.buffalo.edu


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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


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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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http://org.buffalo.edu


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