The Canonical Life
Barry Smith
http://ontology.buffalo.edu/smith
1
http://org.buffalo.edu
Ontology (Phil.)
= the science of the types of objects,
qualities, proesses, events, funktions,
environments, relations ... in all spheres of
reality
2
http://org.buffalo.edu
Google hits (in millions) 12.10.06
ontology
24.0
ontology + philosophy
4.6
ontology + information science 7.4
ontology + database
11.1
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ontology (computer science)
(roughly) the construction of
standardized classification
systems designed to make
databases compatible with each
other
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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
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From
chromosome
to disease
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genomics
transcriptomics
proteomics
reactomics
metabonomics
phenomics
behavioromics
connectomics
toxicopharmacogenomics
bibliomics
… legacy of Human Genome Project
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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 d
= we need ontologies
http://org.buffalo.edu
10
how create broad-coverage semantic
annotation systems for biomedicine?
covering:
in vitro biological phenomena
model organisms
humans
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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
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http://org.buffalo.edu
Ontology
Scope
URL
Custodians
Cell Ontology
(CL)
cell types from prokaryotes
to mammals
obo.sourceforge.net/cgibin/detail.cgi?cell
Jonathan Bard, Michael
Ashburner, Oliver Hofman
Chemical Entities of Biological Interest (ChEBI)
molecular entities
ebi.ac.uk/chebi
Paula Dematos,
Rafael Alcantara
Common Anatomy Reference Ontology (CARO)
anatomical structures in
human and model organisms
(under development)
Melissa Haendel, Terry
Hayamizu, Cornelius Rosse,
David Sutherland,
Foundational Model of
Anatomy (FMA)
structure of the human body
fma.biostr.washington.
edu
JLV Mejino Jr.,
Cornelius Rosse
Functional Genomics
Investigation Ontology
(FuGO)
design, protocol, data
instrumentation, and analysis
fugo.sf.net
FuGO Working Group
Gene Ontology
(GO)
cellular components,
molecular functions,
biological processes
www.geneontology.org
Gene Ontology Consortium
Phenotypic Quality
Ontology
(PaTO)
qualities of anatomical
structures
obo.sourceforge.net/cgi
-bin/ detail.cgi?
attribute_and_value
Michael Ashburner, Suzanna
Lewis, Georgios Gkoutos
Protein Ontology
(PrO)
protein types and
modifications
(under development)
Protein Ontology Consortium
Relation Ontology (RO)
relations
obo.sf.net/relationship
Barry Smith, Chris Mungall
RNA Ontology
(RnaO)
three-dimensional RNA
structures
(under development)
RNA Ontology Consortium
Sequence Ontology
(SO)
properties and features of
song.sf.net
http://org.buffalo.edu
nucleic sequences
13
Karen Eilbeck
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http://org.buffalo.edu
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http://org.buffalo.edu
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?
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where in the cell ?
what kind of
molecular function?
what kind of
biological process ?
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GO’s three ontologies
biological
processes
molecular
functions
cellular
components
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Three granularities:
Cellular (for components)
Molecular (for functions)
Organ + organism (for processes)
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The Granularity Gulf
most existing data-sources are of
fixed, single granularity
many (all?) clinical phenomena
cross granularities
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GO’s three ontologies
biological
process
molecular
function
cellular
component
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GO’s three ontologies
molecular
function
cellular
process
organismlevel
biological
process
cellular
component
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Normalization of Granular Levels
molecular
function
molecule
cellular
process
cellular
component
organismlevel
biological
process
organism
24
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need to separate function from
activity
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molecular
process
cellular
process
organismlevel
biological
process
molecular
function
cellular
function
organismlevel
biological
function
molecule
cellular
component
organism
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http://org.buffalo.edu
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 ...
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http://org.buffalo.edu
molecular
process
cellular
process
organismlevel
biological
process
functioning
functioning
functioning
molecular
function
cellular
function
organismlevel
biological
function
molecule
cellular
component
organism
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molecular
process
cellular
process
organismlevel
process
functionings
functionings
functionings
molecular
function
cellular
function
organismlevel
biological
function
The new age of teleology
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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
30
http://org.buffalo.edu
Problem of aging and death
are their parts of the organism involved in
bringing about aging processes?
is this their function?
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http://org.buffalo.edu
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
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http://org.buffalo.edu
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
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http://org.buffalo.edu
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
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http://org.buffalo.edu
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
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What do the kidneys do?
The function of the kidney is to purify blood
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How doesThe
a kidney
work?
nephron
is the
cardinal functional unit
of the kidney
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http://org.buffalo.edu
Nephron Functions
10 functional segments
15 different cell types
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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
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http://org.buffalo.edu
Function is what gives rise to
normal activity
But: that sperm function (to penetrate the
ovum) is rare
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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
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Functions and Prototypes
In its functioning, a
heart creates a fourdimensional process
shape.
Good hearts create
other process
shapes than sick
hearts do.
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Prototypes
functioning
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poor
functioning
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malfunctioning
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not
functioning
at all
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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)
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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
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http://org.buffalo.edu
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)
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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.
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http://org.buffalo.edu
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.
58
http://org.buffalo.edu
molecular
process
cellular
process
organismlevel
process
functionings
functionings
functionings
molecular
function
molecule
cellular
function
organismlevel
biological
function
cellular
component
organism
everything here is typical
59
http://org.buffalo.edu
Ontology
Scope
URL
Custodians
Cell Ontology
(CL)
cell types from prokaryotes
to mammals
obo.sourceforge.net/cgibin/detail.cgi?cell
Jonathan Bard, Michael
Ashburner, Oliver Hofman
Chemical Entities of Biological Interest (ChEBI)
molecular entities
ebi.ac.uk/chebi
Paula Dematos,
Rafael Alcantara
Common Anatomy Reference Ontology (CARO)
anatomical structures in
human and model organisms
(under development)
Melissa Haendel, Terry
Hayamizu, Cornelius Rosse,
David Sutherland,
Foundational Model of
Anatomy (FMA)
structure of the human body
fma.biostr.washington.
edu
JLV Mejino Jr.,
Cornelius Rosse
Functional Genomics
Investigation Ontology
(FuGO)
design, protocol, data
instrumentation, and analysis
fugo.sf.net
FuGO Working Group
Gene Ontology
(GO)
cellular components,
molecular functions,
biological processes
www.geneontology.org
Gene Ontology Consortium
Phenotypic Quality
Ontology
(PaTO)
qualities of anatomical
structures
obo.sourceforge.net/cgi
-bin/ detail.cgi?
attribute_and_value
Michael Ashburner, Suzanna
Lewis, Georgios Gkoutos
Protein Ontology
(PrO)
protein types and
modifications
(under development)
Protein Ontology Consortium
Relation Ontology (RO)
relations
obo.sf.net/relationship
Barry Smith, Chris Mungall
RNA Ontology
(RnaO)
three-dimensional RNA
structures
(under development)
RNA Ontology Consortium
Sequence Ontology
(SO)
properties and features of
song.sf.net
http://org.buffalo.edu
nucleic sequences
60
Karen Eilbeck
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.
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http://org.buffalo.edu
FMA
recognizes also variant anatomical
structures (e.g. coronary arteries or
bronchopulmonary segments which
deviate from the canonical anatomical
pattern of organization)
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http://org.buffalo.edu
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)
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http://org.buffalo.edu
Model organisms
you can buy a mouse with the prototypical
mouse Bauplan according to a precise
genetical specification
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Canonical lifeplan = the
physiological counterpart of
canonical anatomy
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the canonical life (plan)
birth
infancy
teenagerdom
early adulthood maturity
late adulthood
death
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http://org.buffalo.edu
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
67
http://org.buffalo.edu
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 plan for an organism of
that type
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http://org.buffalo.edu
This canonical life plan might
include
canonical embryological development
canonical growth
canonical reproduction
canonical aging
canonical death
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For all animals the canonical life
Gestalt includes:
canonical embryological development
canonical growth
canonical reproduction
canonical aging
canonical death
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http://org.buffalo.edu
For non-human organisms the
canonical life Gestalt is primarily
canonical physiology
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For a human being the canonical
life Gestalt includes:
birth
infancy
teenagerdom
early adulthood maturity
late adulthood
death
• spontaneity
• society
• culture
• technology
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canonical life Gestalten
+ variant life Gestalten (vegetarians, lesbians)
+ pathological life Gestalten (serial murderers)
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What would the life of a wild type
human being involve?
Reproduction ...
Aging ...
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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?
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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?’
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What is life?
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What is a canonical environment?
What is a canonical family?
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As You Like It, II.vii.139-166
Jacques: All the world's a stage, And all the men and women merely players:
They have their exits and their entrances; And one man in his time plays
many parts, His acts being seven ages. At first the infant, Mewling and
puking in the nurse's arms. And then the whining school-boy, with his
satchel, And shining morning face, creeping like snail Unwillingly to school.
And then the lover Sighing like furnace, with a woeful ballad Made to his
mistress' eyebrow. Then a soldier, Full of strange oaths, and bearded like
the pard, Jealous in honour, sudden and quick in quarrel, Seeking the
bubble reputation Even in the cannon's mouth. And then the justice, In fair
round belly with good capon lin'd, With eyes severe, and beard of formal
cut, Full of wise saws and modern instances; And so he plays his part. The
sixth age shifts Into the lean and slipper'd pantaloon, With spectacles on
nose and pouch on side, His youthful hose well sav'd a world too wide For
his shrunk shank; and his big manly voice, Turning again toward childish
treble, pipes And whistles in his sound. Last scene of all, That ends this
strange eventful history, Is second childishness and mere oblivion, Sans
teeth, sans eyes, sans taste, sans everything.
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What does every human canonical
life involve
9 months of development
later acquisition of consciousness, language
...
cycles of waking, sleeping; eating and not
eating
...
death
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FirstGov Life Events Taxonomy
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Family
Work
Money
Adoption
Aging
Birth
Child care
Death
Disability
Divorce
Domestic Violence
Driving
Elder Care
Empty Nesting
Health
Illness
Kids
Marriage
Parenting
Retirement
Schooling
Teenagers
Travelling
Employment
Injury
Job Seeking
Re-employment
Small Business
Self-employment
Telecommuting
Unemployment
Volunteering
Workplace Violence
Bankruptcy
Budgeting
Charitable Contributions
College
Credit
Disasters
Home Improvement
Home Purchase
Home Selling
Insurance
Investing
IRS Audit
Lawsuits
Mortgage
Property
Renting
Saving
Taxes
Trusts
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Wills
http://org.buffalo.edu
Infancy has six states
quiet sleep and active sleep
quiet waking, and active waking
fussing and crying
and reflexes such as:
crying
sucking
suckling
grasping
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Toddler
Early Childhood
Childhood
Adolescence
Early Adulthood
Middle age
Old age
Death
GERONTOLOGY
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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
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The organizing principle of
complex living systems
Iberall, A. S. and McCulloch, W. S. The organizing principle of complex living systems.
Journal of Basic Engineering. 290-294. June 1969.
As a suitable engineering definition, we may provisionally define a life-like system as any
compact system containing an order and distribution of sustaining nonlinear limit
cycle oscillators, and a related system of algorithmic guide mechanisms, that is
capable of regulating its interior conditions for a considerable range of ambient
environmental conditions so as to permit its own satisfactory preservative operation;
that is capable of performing these preservative functions for a long period of time
commensurate with the “life” of its mechanical-physical-chemical elements; and that
is capable of recreating its own internal systems, or being recreated, out of materials
and equipment at hand in the ecological milieu.
An essential characteristic of a living system is its marginal instability. Its principal
dynamic properties are that it hungers, feeds, and can move or creep so that it can
continue to hunger, feed, and move or creep. At the right unfolding time, it couples
and reproduces so that the newly formed unit can hunger, feed and move about.
Both the external and internal environment constantly present the organism with an
impulsive (vicissitudinous) input against a background of the slowly searched,
changing milieu. As a result, the motor systems of the organism are plunged into
intermittent search modes to satisfy all of its hungers.
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Iberall and McCulloch 20 action modes:
Action Modes
% of time
Sleeps
30
Eats
5
Drinks
1
Voids
1
Sexes
3
Works
25
Rests (no motor activity, indifferent internal sensory flux)
3
Talks
5
Attends (indifferent motor activity, involved sensory activity)
4
Motor practices (runs, walks, plays, etc.)
4
Angers
1
Escapes (negligible motor and sensory input)
1
“Anxioius-es”
2
”Euphorics”
2
Laughs
1
Aggresses
1
Fears, fights, flights
1
Interpersonally attends (body, verbal or sensory contact)
8
Envies
1
Greeds
1
Total:
100% +/- 20% of time involvement
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