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Selectively, but not exclusively

Plenary Talk, “Selectively, but not exclusively: understanding structural diversity and functional plasticity in complex systems”, Woolcock Research Symposium, Woolcock Institute of Medical Research, 20 Aug 2015.
by

Paul Mason

on 24 February 2016

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Transcript of Selectively, but not exclusively

Heterogeneous construction of disease
Alzheimer’s disease
Degeneracy
Tuberculosis
Statisticians say mean things
towards a complex systems model
Selectively, but not exclusively
From simple to complex models
multiple pathways
to
flexible endpoints
Tuberculosis
The biomedical narrative of tuberculosis orients people towards a monocausal bacteriological understanding of TB.
Discovery of
Mycobacterium tuberculosis
in 1882.
A vaccine became available in the 1920s.
Antibiotics to treat TB disease were discovered in the 1940s and 1950s
Towards a multifactorial model
Latent tuberculosis infection
Paul H. Mason
Pidoux wanted to enter nonspecific social and environmental variables into the etiological equation of tuberculosis.
Hermann Pidoux (1802-1882)
Robert Koch
(1843-1910)
Huntington's disease
Parkinson's disease
schizophrenia
asthma
sleep apnoea
Chronic Obstructive Pulmonary Disorder
corticobasal degeneration
dystonia
autism
attention-deficit/hyperactivity disorder
neuropathic pain
In the brain sciences...
The most accepted definition for neurodegenerative conditions enumerated a group of diseases united only by the gradually progressive disintegration of part (or systems) of the nervous system.
In the brain sciences...
'degeneration' is a term used only for neurological conditions where a scientific explanation is absent.

Most current neurology textbooks do not include degeneration as a nosological term

The largest book on Neurodegenerative diseases does not define these illnesses

‘degeneration’ has a very loose, imprecise meaning, and mostly refers to conditions we know little about and vague gradual disintegration. When brain scientists uncover the mechanics of a neuronal disease, the term ‘degenerative’ is forgotten and a more specific title is given.
“Degeneracy is the ability of different structures to yield the same output.”

Gerald Maurice Edelman, BioEssays, 2004
degeneracy is a more explanatory concept
Degenerate structure-function mapping is crucial for understanding the nature of brain networks.
Degeneracy
Brain sciences
Genetics
Epigenetics
Immunology
Pulmonary science
Economics
Sports science
Anatomy
Cognitive neuroscience
Molecular physiology
Cancer Research
Language evolution studies
Anthropology
Population dynamics
Cellular physiology
normal
Statistic
Gottfried Achenwall 1719-1772
- a term of statecraft first coined in 1749 to refer to systematic methods of summarising, in words, a nation's strength, in terms of its natural, economic, military, and human resources.
- the word entered the English language in 1791 and became used in the branch of mathematics concerned with proability and causal inference in the early 20th Century
L'homme moyen
Adolphe Quetelet 1796-1874
Using a mathematical methods from astronomy, Quetelet erroneously argued that the distribution of a population's characteristics served as a guide to its ideal value, one obscured by the imperfect variation of individuals.
once denoted a flag raised on a pole as a rallying point, but the "standhard" has become a metaphor for the values that a group hold up and aspire to and against which a person is measured
Standard
Battle Standar
statistic
In the 1840s, a carpentry term for upright and perpendicular, the “norm”, became the root for a constellation of words to refer to the common type or standard.
Norm
blindspots and biases
external donors
foreign aid
research bodies
targeted to TB
control of projects
Targeted Aid
Investment
For-Profit
Health Industry
Medical Staff
Insufficient TB treatment efforts
Insufficient TB screening efforts
Economic Conditions
Resistance to being diagnosed with TB
Resistance to diagnose TB
Education
Identify and examine any processes through which TB might be stigmatised
Stigma against TB
Home
Bars and enclosed public spaces
Workplace
Hospital
Sites of TB transmission
Experience of illness
Social constructions of ability, identity and stigma
Experiences shaped by medical technologies and corporate interests
What were the social forces that predisposesd certain individuals to be exposed to TB?
Broad consequences of diagnosis?
Illness as practice not as problem?
Examine social interaction to understand how people understand and experience illness.
Examine how people interact with and within the healthcare system.
What was the individual’s response?
What was the social response?
People with
Active TB
National investment in Health infrastructure.
Health investment priorities.
Neglect of non-TB related health issues
Neglect of TB health issues
Shortage of Medical Professionals.
Competition for Medical Professionals.
Competition between TB clinics and other places of healthcare.
Exposure risks?
Spread of TB
e.g. Pharmaceutical companies
Control of TB
Successful detection and treatment
Screening
Method
Successful
Detection
Unsuccessful
Detection
Hospitals &
Clinics
National Policy
Multidrug resistance
Common genes controlled by multiple regulators e.g.
MMPL operons (cell membrane transporters),
Lipases and esterases (lipid metabolism),
PPE proteins (unknown function).
multiple different copies of similar proteins e.g.
annotated succinate dehydrogenases (allows respiration under different conditions)
nicotinamide dinucleotide dehydrogenase (an otherwise useful drug target because no mammalian homologues)
Further reading
Mason, P.H., Degeling, C., Denholm, J. (In Press) Sociocultural Dimensions of Tuberculosis: An overview of key concepts, International Journal of Tuberculosis and Lung Disease.
Mason, P.H., Roy, A., Spillane, J., Singh, P. (2015) Social, historical and cultural dimensions of tuberculosis, Journal of Biosocial Science.
Mason, P.H. (2015) Degeneracy: Demystifying and destigmatising a core concept in systems biology,
Complexity, 20(3), 12-21.
Mason, P.H., Domínguez, J.F., Winter, B., Grignolio, A. (2015) Hidden in Plain View: Degeneracy in complex systems, BioSystems, 128, 1-8.
Mason, P.H. (2010) Degeneracy at multiple levels of complexity, Biological Theory: Integrating
Development, Evolution and Cognition, 5(3), 277-288.
Maleszka, R., Mason, P.H., and Barron, A.B. (2014) Epigenomics and the concept of degeneracy in biological systems, Briefings in Functional Genomics, 13 (3), 191-202. doi: 10.1093/bfgp/elt050
Park, H., & Friston, K. (2013) Structural and Functional Brain Networks: From Connections to Cognition. Science, 342, 579.
degeneration is passé
Degeneracy is an unfortunate term.
e.g. Johnson, A., 1898. Concerning a form of degeneracy. I. The condition and increase of the feeble-minded. Am. J. Sociol. 4326–4334.
People with tuberculosis were once described as degenerate.
degeneracy & pluripotentiality
bow tie
standard deviation
Karl Pearson introduced the term "standard deviation", which, together with Quetelet's work, oriented the scientific measurement of populations towards singular values.
Karl Pearson
1857-1937
Full transcript