Genomics and SocietyToday’s AnswersTomorrow’s Questions25-26 October 2007
www.genomicsnetwork.ac.uk
Cellular Biological Systems:
Structure Meets Emergence
Alexander Powell, Egenis, University of Exeter
www.genomicsnetwork.ac.uk
Overview
I. From molecules to systems
- molecules & mechanisms
- systems perspectives & emergence
- synthetic biology
II. Disciplinary identity and discipline names
- case study: bioinformatics
- a mirror of nature?
www.genomicsnetwork.ac.uk
Where I’m coming from
My principal interest: scientific explanation (in molecular / cellular biology,
and more generally)
This is about the relationship between the mind and the world
- what’s the connection between our capacities to know and the way
the world is?
- central topic: causation
It connects with debates about disciplines and their relations
www.genomicsnetwork.ac.uk
From molecules to systems / standard picture
One view of the past 50 years:
Molecular Biology Systems Biology
Positivist philosophy
of science
Anti-reductionist
philosophy of science
REDUCTIONISM EMERGENTISM
www.genomicsnetwork.ac.uk
From molecules to systems / molecular biology
A common view about molecular biology (MB):
- MB was/is reductionist
- reductionism is bad
- MB has failed
BUT
What is meant by reductionism? (Various possibilities)
Surely MB has delivered an outstandingly rich base of knowledge?
www.genomicsnetwork.ac.uk
From molecules to systems / molecular biology
Think instead about the nature of MB’s many explanatory successes
What they show is that sometimes the fundamental biological processes
that play out in the cell (or at higher levels) can be accounted for in
terms of the details of molecular structure
www.genomicsnetwork.ac.uk
From molecules to systems / mechanisms
Structures are illuminating because they give insight into the mechanisms
associated with the performance of particular functions
Molecular mechanisms are analogous to macroscopic mechanical devices:
- they involve relatively stable, constrained configurations of ‘parts’
- there are far fewer degrees of freedom than in the same amount of
gaseous matter
- this means we can mentally simulate their operation (causal tracking)
www.genomicsnetwork.ac.uk
From molecules to systems / fluidity & interactions
But alas cells are in important respects unlike mechanical devices: fluidity
is intrinsic to their working
Cellular causal fluxes are underpinned by the specificity of molecular
interactions, in place of the more-or-less fixed spatial relationships
between the parts in solid-state mechanisms
This is a very different mode of operation, one that allows for much greater
complexity
- processes can become co-adapted and intertwined
- functions need not map neatly to discrete, localized, stable structures
www.genomicsnetwork.ac.uk
From molecules to systems / causal complexity
Signalling examples show how causal influences often fail to respect level
boundaries (and can act in a highly non-linear fashion)
Causes can work top-down as well as bottom-up
This means we can’t necessarily just look inwards at the properties of
entities to account for their behaviour: often must take into account their
context and interactions
In addition, it is clear that – notwithstanding the explicability of the
molecular mechanisms of gene expression and protein synthesis – the
coupling between genotype and phenotype is far from straightforward
www.genomicsnetwork.ac.uk
From molecules to systems / systems approaches
Such worries motivate doubts that knowledge of individual molecules and
sequences alone can fully account for biological phenomena
- apparently confirmed by e.g. slow progress in developing
understanding (and therapies) based on narrowly molecular
approaches
Systems biology (SB): we need to treat systems as systems
• A response to:
– large quantities of genomic and other ‘omic data
– availability of computing resources, algorithms, infrastructure, standards
• Able to draw on long-standing and recent scientific research streams
www.genomicsnetwork.ac.uk
From molecules to systems / emergence
SB came into being in a scientific climate sympathetic to the concept of
emergence (formerly seen as metaphysically excessive)
- interactions between system components can give rise to properties
not attributable to (identifiable with) the components in isolation
- think of the way musical effects often arise from the simultaneous
performance of independent parts by different instruments
So, structures can be explanatory, but not comprehensively so;
and emergence looks like a significant influence that we need to
take into account
www.genomicsnetwork.ac.uk
From molecules to systems / structure vs. emergence
Problem: how to do this
SB currently emphasizes interactions by representing cellular processes in
terms of gene circuits and reaction networks. Where has the structure
gone?
We want to know not just what reactions occur, when, and how fast, but
how the structures that result become organized and how that
constrains / directs cellular events
Key issue: at what point does molecular structural knowledge become
inadequate for explaining cellular phenomena? When must we get to
grips with emergence?
www.genomicsnetwork.ac.uk
From molecules to systems / synthetic biology
This could be where synthetic biology plays a crucial role
- just how much must be removed in order to create chassis that won’t
interfere with added components?
- how easy is it to create components that are portable across contexts
without loss of functionality?
Synthetic biology is interesting in disciplinary respects too:
- historical continuities with genetic, protein and metabolic engineering;
dependence on DNA synthesis; ambivalent relationship with systems
biology
- distinct schools with different aims, assumptions, methods
Synthetic biology: three schools
www.genomicsnetwork.ac.uk
(From O’Malley et al., forthcoming in BioEssays)
www.genomicsnetwork.ac.uk
Disciplinary identity and discipline names(Second part of talk!)
Synthetic biology shows how discipline names can give coherence to quite
disparate groups
- names are elastic
- they can contain and mask complex interactions and evolving
practices
- but at a certain point the capacity of names to stabilize particular
disciplinary configurations is stretched to breaking point
(see Powell et al., forthcoming in HPLS)
Bioinformatics makes an interesting case study concerning the
relationship between names and practices
www.genomicsnetwork.ac.uk
Disciplinary identity and discipline names
1988:
www.genomicsnetwork.ac.uk
Disciplinary identity and discipline names
www.genomicsnetwork.ac.uk
Disciplinary identity and discipline names
NB
www.genomicsnetwork.ac.uk
Disciplinary identity and discipline names
1996 - No mention here either:
www.genomicsnetwork.ac.uk
Disciplinary identity and discipline names
1997 – How about here?
www.genomicsnetwork.ac.uk
Disciplinary identity and discipline names
Tentative!
www.genomicsnetwork.ac.uk
Disciplinary identity and discipline names
- cf. Lesk (1988) “Computational molecular biology has become a mature
field of science”
www.genomicsnetwork.ac.uk
www.genomicsnetwork.ac.uk
Disciplinary identity and discipline names
cf. 1999
www.genomicsnetwork.ac.uk
Disciplinary identity and discipline names
Meanwhile in 1998…
www.genomicsnetwork.ac.uk
Disciplinary identity and discipline names
cf. 1997
www.genomicsnetwork.ac.uk
Disciplinary identity and discipline names
1998 – Reticent and self-conscious despite the title!
www.genomicsnetwork.ac.uk
Disciplinary identity and discipline names
2000 – consolidation in view?
www.genomicsnetwork.ac.uk
Disciplinary identity and discipline names
downplaying
previous
work?
www.genomicsnetwork.ac.uk
Disciplinary identity and discipline names
Wow – sounds like systems biology!
www.genomicsnetwork.ac.uk
Disciplinary identity and discipline names
2001
Doesn’t seem very clear-cut
www.genomicsnetwork.ac.uk
Disciplinary identity and discipline names
2005 – big ambitions?
www.genomicsnetwork.ac.uk
Conclusions / 1
Findings?
• The relationship between names and practices is pretty loose
• New names can hide significant continuities
• Discipline names increasingly fail to map neatly onto significant
research structures and patterns of interaction
• Perhaps the process of disciplinization is changing
– broad monolithic disciplines giving way to patchwork assemblies of practice
(Rheinberger)
– increasing disciplinary granularity and fluidity
• Important factor: increasing dependence on techniques (e.g.
algorithms) applicable in diverse areas
– leads to epistemic modularity and mobility of expertise (cf. stabilizing effect
of single-purpose physical expt’l equipment)
www.genomicsnetwork.ac.uk
Conclusions / 2
Parallels between biological disciplines and the systems they study:
• Involve complex, dynamic, interacting structures and entities
• Susceptible to specific influences that generate non-linear effects
(signalling and gene expression in cells ↔ personal contacts, chance
events in disciplinary settings)
• Striking ontological dubiousness of dynamic, high-turnover or emergent
structures
(To what extent can disciplines be said to exist? – to the extent that
their names pick out groupings that can figure usefully in our thinking)
www.genomicsnetwork.ac.uk
Conclusions / 3
Implications for regulators, policy makers?
• Simple conceptions of disciplinary identities and interests are likely to
be simplistic
• The lability of disciplinary structures, and the complex patterns of inter-
connection within and between them, may give rise to unexpected
patterns of sensitivity to external influences
• So interventions need to be well-informed, in terms of both level of
detail and breadth of view
• Need to look beyond names to see what people are doing
• Data markup standards can help here (another overlap: XML in
publishing and in science, e.g. SBML)
www.genomicsnetwork.ac.uk
Acknowledgements
Jane Calvert, Jonathan Davies, John Dupré, Staffan Műller-Wille,
Maureen O’Malley
& Egenis colleagues
The University of Exeter for £inancial assistance