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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 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



Ontology computer science l.jpg
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 l.jpg
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 l.jpg

From

chromosome

to disease

http://org.buffalo.edu


Slide8 l.jpg

  • genomics

  • transcriptomics

  • proteomics

  • reactomics

  • metabonomics

  • phenomics

  • behavioromics

  • connectomics

  • toxicopharmacogenomics

  • bibliomics

  • … legacy of Human Genome Project

http://org.buffalo.edu



Slide10 l.jpg

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


Obo foundry project l.jpg
OBO Foundry Project biomedicine?

  • 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 l.jpg
When a gene is identified biomedicine?

  • 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 l.jpg

where in the cell ? biomedicine?

what kind of

molecular function?

what kind of

biological process ?

http://org.buffalo.edu


Go s three ontologies l.jpg
GO’s three ontologies biomedicine?

molecular functions

biological processes

cellular components

http://org.buffalo.edu


Three granularities l.jpg
Three granularities: biomedicine?

  • Cellular (for components)

  • Molecular (for functions)

  • Organ + organism (for processes)

http://org.buffalo.edu



The granularity gulf l.jpg
The Granularity Gulf biomedicine?

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

  • many (all?) clinical phenomena cross granularities

http://org.buffalo.edu


Go s three ontologies22 l.jpg
GO’s three ontologies biomedicine?

biological process

molecular function

cellular component

http://org.buffalo.edu


Go s three ontologies23 l.jpg
GO’s three ontologies biomedicine?

cellular

process

organism-level

biological process

molecular function

cellular component

http://org.buffalo.edu


Slide24 l.jpg

Normalization of Granular Levels biomedicine?

molecular function

organism-level

biological process

cellular

process

molecule

cellular component

organism

http://org.buffalo.edu


Need to separate function from activity l.jpg
need to separate function from activity biomedicine?

http://org.buffalo.edu


Slide26 l.jpg

organism-level biomedicine?

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 l.jpg
types of process biomedicine?

  • 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 l.jpg

organism-level biomedicine?

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 l.jpg

organism-level biomedicine?

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 l.jpg

  • What does “function” mean? biomedicine?

  • 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 l.jpg
Problem of aging and death biomedicine?

  • are their parts of the organism involved in bringing about aging processes?

  • is this their function?

http://org.buffalo.edu


Problem of reproductive organs l.jpg
Problem of reproductive organs biomedicine?

  • 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 l.jpg
Problem of reproductive organs biomedicine?

  • 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 biomedicine?

  • 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 l.jpg
Functions are organized in a modular hierarchy biomedicine?

  • 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 l.jpg

What do the kidneys do? biomedicine?

The function of the kidney is to purify blood

http://org.buffalo.edu


Slide37 l.jpg

How does a kidney work? biomedicine?

The nephron is the cardinal functional unit of the kidney

http://org.buffalo.edu


Slide38 l.jpg

Nephron Functions biomedicine?

10 functional segments

15 different cell types

http://org.buffalo.edu


Challenge l.jpg
Challenge biomedicine?

  • 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 l.jpg
Function is what gives rise to biomedicine?normal activity

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

http://org.buffalo.edu


Functions l.jpg

This is a screwdriver biomedicine?

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 l.jpg
Functions and Prototypes biomedicine?

  • 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 l.jpg
Prototypes biomedicine?

functioning

http://org.buffalo.edu


Slide44 l.jpg

poor functioning biomedicine?

http://org.buffalo.edu


Slide45 l.jpg

malfunctioning biomedicine?

http://org.buffalo.edu


Slide46 l.jpg

not functioning at all biomedicine?

http://org.buffalo.edu


What clinical medicine is for l.jpg
What clinical medicine is for biomedicine?

  • 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 l.jpg
What is health biomedicine?

  • 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 biomedicine?

  • 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 l.jpg
The GO is a canonical representation biomedicine?

  • “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 biomedicine?

  • “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 l.jpg

organism-level biomedicine?

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 l.jpg
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 l.jpg
FMA representation

  • 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 l.jpg
A solution representation

  • 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 l.jpg
Model organisms representation

  • 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 l.jpg
Canonical lifeplan = the physiological counterpart of canonical anatomy

http://org.buffalo.edu


The canonical life plan l.jpg
the canonical life (plan) canonical anatomy

birth infancy teenagerdom early adulthood maturity late adulthood death

http://org.buffalo.edu


Slide60 l.jpg

  • What does “function” mean? canonical anatomy

  • 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 l.jpg
Improved version canonical anatomy

  • 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 l.jpg
This canonical life plan might include canonical anatomy

  • 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 anatomy

  • 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 primarily Gestalt includes:

  • spontaneity

  • society

  • culture

  • technology

birth infancy teenagerdom early adulthood maturity late adulthood death

http://org.buffalo.edu


Canonical life gestalten l.jpg
canonical life primarily 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 l.jpg
What would the life of a wild type human being involve? primarily

  • 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 l.jpg
Just as there are 2 x primarily 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 l.jpg
Is talk of ‘life plan’ descriptive or prescriptive primarily

  • 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 l.jpg
What is primarily life?

http://org.buffalo.edu


What is a canonical environment l.jpg
What is a canonical environment? primarily

  • What is a canonical family?

http://org.buffalo.edu


What does every human canonical life involve l.jpg
What does every human canonical life involve primarily

  • 9 months of development

  • later acquisition of consciousness, language ...

  • cycles of waking, sleeping

  • death

http://org.buffalo.edu


Different perspectives on the canonical life l.jpg
Different perspectives on the canonical life primarily

  • 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