Philosophy of Biological Cell Repair informs Geoethical Nanotechnology: Cellular repair is an age-old function in biology. This talk examines the cellular process of repair in philosophical terms. Biologically, wound-healing is the primary form of cellular repair, drawing on numerous cell types and the extracellular matrix to perform a variety of operations during the phases of inflammation, proliferation, and maturation. Philosophically, these functions can be discussed from a systems theory perspective, through the concepts pairs of parts-whole, autonomy-dependency, self-other, sickness-wellness, and scarcity-abundance. Understanding cellular repair at the theory level could facilitate the development of nanotechnology solutions that augment biological processes in ways that are congruently geoethical with nature’s ethos.
1. 11th Annual Workshop on Geoethical
Nanotechnology
July 20, 2016, Terasem
Slides: http://slideshare.net/LaBlogga
Melanie Swan
Philosophy & Economic Theory
New School for Social Research, NY
melanie@BlockchainStudies.org
Bio-cryptoeconomy
Philosophy of Biological Cell Repair informs
Geoethical Nanotechnology
Part of a Series on Cryptophilosophy
2. July 20, 2016
Cell Repair 2
About Melanie Swan
New School, Singularity University, IEET
Affiliate Scholar, EDGE Contributor
Founder DIYgenomics, Institute for
Blockchain Studies, GroupPurchase
Education: MBA Finance, Wharton; BA
French/Economics, Georgetown Univ
Professional: Fidelity, JP Morgan, iPass,
RHK/Ovum, Arthur Andersen
Sample publications:
Source: http://melanieswan.com/publications.htm
Kido T, Kawashima M, Nishino S, Swan M, Kamatani N, Butte AJ. Systematic Evaluation of Personal
Genome Services for Japanese Individuals. Nature: Journal of Human Genetics 2013, 58, 734-741.
Swan, M. The Quantified Self: Fundamental Disruption in Big Data Science and Biological Discovery.
Big Data June 2013, 1(2): 85-99.
Swan, M. Sensor Mania! The Internet of Things, Wearable Computing, Objective Metrics, and the
Quantified Self 2.0. J Sens Actuator Netw 2012, 1(3), 217-253.
Swan, M. Health 2050: The Realization of Personalized Medicine through Crowdsourcing, the
Quantified Self, and the Participatory Biocitizen. J Pers Med 2012, 2(3), 93-118.
Swan, M. Steady advance of stem cell therapies. Rejuvenation Res 2011, Dec;14(6):699-704.
Swan, M. Multigenic Condition Risk Assessment in Direct-to-Consumer Genomic Services. Genet Med 2010,
May;12(5):279-88.
3. July 20, 2016
Cell Repair
Agenda
Introduction
Biological cell repair
Philosophy of biological
cell repair
Top 9 nanotechnology
cell repair advances
Conclusion
3
4. July 20, 2016
Cell Repair
Thesis
4
Understanding biological cell repair at the
philosophical level might help in developing
nanotechnology solutions that facilitate and
augment biological processes congruently and
geoethically with nature
5. July 20, 2016
Cell Repair
Introduction
Cellular repair is an age-old
function in biology
Natural cells already perform
many complex acts of
molecular synthesis,
manipulation, repair, and
replacement as part of their
normal function
Philosophically, these
functions reflect a systems
theory perspective
5
6. July 20, 2016
Cell Repair
Frame: augment natural healing processes
Nanotechnology-enabled cell repair examples
Apply synthetic growth factors and morphogens to
induce tissue regeneration
Introduce novel genetic programs for to reverse
cellular and tissue injuries for which natural healing
mechanisms do not exist
Example applications
Short-term: Control and reverse ischemic and
freezing injuries (presently irreversible)
Long-term: Atom-by-atom cellular and tissue repair
6
Source: Wowk, B. Cell Repair Technology. 1988. http://www.alcor.org/Library/html/cellrepairmachines.html
7. July 20, 2016
Cell Repair
Geoethics
Emerging field of geoethical behavior
Definition: research, reflection, and implementation of
values and actions which support practices where
human activities interact with the geosphere
7
Source: Extended from http://www.geoethics.org/#!geoethics/c1m3f
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Cell Repair
Temporal Asymmetries
Planetary time
Geological time (Scottish geologist
James Hutton, 1726-1797)
Geo-philosophies of time
Human time
Life-span, generation-span
Historical events (moon landing)
Nanotechnology Lifecycles
Unknowable
Lingering effects
8
Earth 4.5 bn years old
100 years
Unknown
9. July 20, 2016
Cell Repair
Agenda
Introduction
Biological cell repair
Philosophy of biological
cell repair
Top 9 nanotechnology
cell repair advances
Conclusion
9
10. July 20, 2016
Cell Repair
Human body cell types by Function
1. Conductive (nerve, muscle)
2. Connective (bone, blood)
3. Glandular (secretive)
4. Storage (adipose, liver)
5. Supportive (glial)
6. Specialized (stem,
rod/cone, sperm/egg)
10
Source: Krafts. Tissue Repair. Organogenesis 6:4, 225-233, 2010.
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Cell Repair
Cardiac Cell Repair process
Accelerate natural healing following myocardial injury
11
Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2755807
Replacement
Tissue transplant
Rejuvenation or restoration
Activation of resident cardiac stem cells
or other stem cells via paracrine or
autocrine mechanisms
Modulation of apoptosis, inflammation,
angiogenesis, or metabolism
Regeneration
Progenitor or stem cell engraftment
forming differentiated myocytes
Myocardial regeneration therapy
12. July 20, 2016
Cell Repair
Biologically, wound-healing is the primary form of cellular repair
Normal wound-healing (skin) cell repair
1. Hemostasis (immediate)
Lock-down, blood loss, compromised barrier,
vasoconstriction, fibrin protein cross-links at
top of skin; border secured, bleeding stopped
1. Inflammation (2-3 hours later)
Attack any pathogens; vasodilation
1. Proliferation (2-3 days later)
Load raw materials; dropped at construction
site); collagen protein in skin tissue to replace
fibroblasts
1. Remodeling (days, weeks months later)
Cell type differentiation (organize raw
materials); collagen rearranged & redeposited
12
Source: Krafts. Tissue Repair. Organogenesis 6:4, 225-233, 2010.
13. July 20, 2016
Cell Repair
Philosophical Lens of Cell Repair
Properties of biological cell repair
Highly processual
Globally systemic
Specialized functions
Many participants (cells, factors)
Communication and coordination
Sequentiality as coordination
mechanism
Signaling as communication mechanism
Presuppositions, dependencies
On-demand availability
13
Futuristic Thinker image credit:
https://in.pinterest.com/pin/32791903508619820/
14. July 20, 2016
Cell Repair
Agenda
Introduction
Biological cell repair
Philosophy of biological
cell repair
Top 9 nanotechnology
cell repair advances
Conclusion
14
15. July 20, 2016
Cell Repair
Philosophical Lens of Cell Repair
Under the umbrella of Systems Theory…
1. Complexity…
2. Process Philosophy…
3. Relational Ontology…
4. Posthuman-Transhuman…
5. Assemblage…
6. Economics…
7. Aesthetics…
…as a theoretical model for biological
organization
15
16. July 20, 2016
Cell Repair
Systems Theory
Interdisciplinary study of the abstract organization of
complex phenomena,
independent of their substance, type, or spatial-temporal scale of
existence,
investigating and describing principles common to all complex
entities or systems of behavior
16
Source: http://pespmc1.vub.ac.be/systheor.html
17. July 20, 2016
Cell Repair
Complexity
Systems that are non-
linear, dynamic,
emergent, open,
unknowable at the
outset, interdependent,
self-organizing
17
Sources: Morin, Edgar. (2007). "Restricted complexity, general complexity." Trans. C. Gershenson. In Worldviews, Science
and Us: Philosophy and Complexity, ed. C. Gershenson, D. Aerts, and B. Edmonds, 5–29. World Scientific, Singapore.
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Cell Repair
Posthuman and Transhuman perspectives
18
Always-already technological: making tools out of tools
Notion that superintelligent AI would take over the world
is an outdated master-slave hierarchical paradigm
Mode of organization-association: affinity communities
Multispecies (post)humanisms: geo-aware, animal,
human, machine, brain-computer interfacing
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Cell Repair
Big Data: Complexity and Machine Learning
19
1. Science and
Biology becomes a
math problem
2. Simple Machine
Learning algorithms
running over large
data corpora
3. Deep-learning algorithms: real-time
image & video processing, lip-reading
transcription, emotion-recognition
Sources: http://arxiv.org/abs/1112.6209, http://karpathy.github.io
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Cell Repair
Complexity and Big Data Analytics
20
Source: https://medium.com/@akelleh/if-correlation-doesnt-imply-causation-then-what-does-c74f20d26438#.mrmot5t7t
Contemporary era: Algorithmic reality, big data,
machine learning analytics
Similar goals in causal analysis frameworks
Whether structural equation modeling, causal
graphical models, potential outcomes…
...mindset shift from Causality to Predictability
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Cell Repair
Relational Processes
The relations between entities, and the
effects produced by interactions are
more relevant than the underlying
substance, morphology, or classification
Relational Ontology (Barad): replace
agential realist conceptions of causality
Process Philosophy (Alfred North
Whitehead): substance is temporary
patterns produced by processes
Assemblages (Deleuze and Guattari)
Fusion of horizons (Gadamer)
21
Source: Barad, K. (2003). Posthumanist Performativity
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Cell Repair
`
22
BaselineFixed-Pie model:
Maximum possibility is pre-determined, the
recouping of a pre-specified baseline ideal
Philosophy of Immanence
Sources: Swan, M. (2015). A New Kind of Economic Philosophy: Network Economies of Abundance.
http://ieet.org/index.php/IEET/more/swan20150914
Scarcity
Abundance
Expanding-Pie model:
Open-ended possibility trajectories up and out
from baseline into new territory
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Cell Repair
Abundance Philosophy of Economics
23
Sources: Swan, M. "Automation Economy: An Abundance Philosophy of Economics" In Emerging Technology and
Unemployment. Palgrave Macmillan. Forthcoming.
A
B
C
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Cell Repair
Economics as an Organizational Paradigm
24
New economic principles (since scarcity no longer valid)
Social goods: autonomy, choice, recognition, contribution
Digital goods: zero marginal cost, infinitely copiable
Commons goods: Wikipedia, open-source software, Creative
Commons licensing
New modes of economic life
Decentralization, technological unemployment, bio-cryptoeconomy
Sources: Swan, M. "Automation Economy: An Abundance Philosophy of Economics" In Emerging Technology and
Unemployment. Palgrave Macmillan. Forthcoming.
25. July 20, 2016
Cell Repair
A General Biological Economy
Modeled on Bataille’s General Economy
Biological and information economies
are systems based on consumption and
expenditure rather than accumulation
and scarcity (Bataille)
The principle of living matter requires
that the chemical operations of life,
which demand an expenditure of
energy, be gainful, and productive of
surpluses (Styhre)
25
Source: Bataille, G. 1927-1939; 1991, p 9. The Accursed Share: an Essay on General Economy. Styhre, A. Information and
Communication Technology and the Excess(es) of Information: An Intro to Bataille’s General Economy. Ephemera 2(1): 28-42..
26. July 20, 2016
Cell Repair
Bio-nanoeconomy and Bio-cryptoeconomy
Medical nanorobotic DACs to coordinate cell repair
Bio-economics, bio-cryptoeconomics, for
secure automation and coordination of
medical nanorobotics for geoethical cell
repair in human cells
Secure crypto-transaction tracking
Automated coordination
Medical nanorobotics as coming-onboard
repair platform for the human body
Activity coordinated, tracked, monitored
High number of agents and “transactions”
Automation is obvious
Crypto-tracking DAC coordinates medical
nanorobotic cell repair
26
Sources: Swan, M. Blockchain Thinking: The Brain as a DAC (Decentralized Autonomous Corporation). Technology and Society
Magazine, IEEE 2015; 34(4): 41-52. http://www.slideshare.net/lablogga/brain-as-a-dac-swan
27. July 20, 2016
Cell Repair
Digital Cryptocitizen:
Bio-Nano Repair DACs
In-cell repair DACs monitoring individual cell
health and facilitating augmentation
Bio-DACs manage physical health and mental
performance as a demurrage (action-inciting)
health currency
Sensibility of the Digital Crypto-biocitizen
Design personal bio-economic systems
Service on-board cellular repair DAC nano-robots
‘Quantified-self plus’: greater stance of self-authority
taking, self-care, self-maintenance
Longevity DAC bots connect to brain-computer
interfaces to record memories and augment social
goods quality-of-life experiences
27
Sources: Swan, M. Blockchain Thinking: The Brain as a DAC (Decentralized Autonomous Corporation). Technology and Society
Magazine, IEEE 2015; 34(4): 41-52. http://www.slideshare.net/lablogga/brain-as-a-dac-swan
28. July 20, 2016
Cell Repair
Aesthetics as an organizational paradigm
Form and content
Integrated structure and function
Symmetry, well-formedness,
integrity, functionality
Aesthetic judgment (Kant)
Directive judgment: recognizing
that this new particular example is
one in a certain class of
universality
Reflective judgment: an encounter
with a new concept; a new
particular that also belongs to a
new universal, which prompts our
noticing, reflection, and naming
28
Source: Klee “Fire and Death;” Kant, I. Critique of the Power of Judgment. 1790.
29. July 20, 2016
Cell Repair
Systems Theory Philosophical Principles of
Nanotechnology Design for Cell Repair
Complexity
Non-linear, emergent, open, interdependent, self-
organizing systems; predictability over causality
Posthuman-Transhuman
Multispecies geo-awareness
Relational Ontology
Relational fabric between entities
Economics
Coordination models relational exchange;
abundance over scarcity
Aesthetics
Integrated form and function in design
29
30. July 20, 2016
Cell Repair
Agenda
Introduction
Biological cell repair
Philosophy of biological
cell repair
Top 9 nanotechnology
cell repair advances
Conclusion
30
31. July 20, 2016
Cell Repair
1. Blood clot dissolution
2. Microneedle array delivery
3. Hydrogel cellular delivery
4. Positional nanoassembly robot
5. Nanotechnology-guided neural
regeneration
6. DNA Nanobots in first human trial
7. Graphene electrode-neuron interface
8. Nanobots cargo delivery in mouse
9. Aged skin gene expression
rejuvenation with broadband laser
31
Neocortical Neurogenesis in Mammals
lafayette.edu
Top 9 Nanotechnology Cell Repair Advances
Microfluidic array
32. July 20, 2016
Cell Repair
Cell Repair Nanotechnology Killer App
Blood Clot Dissolution
Problem: dissolve life-threatening blood clots in stroke
Novel nanotherapeutic for clearing obstructed blood
vessels: biodegradable nanoparticle aggregate coated
with tissue plasminogen activator (tPA) (clot-busting drug)
32
Sources: Marosfoi, et al (2015) Shear-Activated Nanoparticle Aggregates Combined With Temporary Endovascular
Bypass to Treat Large Vessel Occlusion
Donald Ingber, Wyss Institute and Ajay Wakhloo, U Mass
33. July 20, 2016
Cell Repair
Cell Repair Nanotechnology Killer App
Blood Clot Dissolution
Novel approach for complete
vascular blockages where there is no
blood flow (the usual case for stroke)
The nanotherapeutic reacts to fluid
shear force, releasing tPA-coated
nanoparticles in narrowed regions
where vessels are occluded, binding
to the blood clot and dissolving it
Application: less-invasive alternative
to existing method (stent-retriever
thrombectomy procedure)
33
Sources: Marosfoi, et al (2015) Shear-Activated Nanoparticle Aggregates Combined With Temporary Endovascular
Bypass to Treat Large Vessel Occlusion
Donald Ingber, Wyss Institute and Ajay Wakhloo, U Mass
34. July 20, 2016
Cell Repair
Cell Repair Nanotechnology Killer App
Microneedle Array Diagnostic/Delivery
34
Problem: less-invasive diagnostic/delivery
Implantable microneedle array mimics
normal arachnoid granulations surrounding
the brain and spinal cord
Microfabricated arachnoid granulations
punctured through dura mater membrane
in the brain to provide a conduit for
cerebrospinal fluid flow (porcine tests)
Application: hydrocephalus treatment
Communicating Hydrocephalus caused by
deficient arachnoid granulation valves that
poorly regulate cerebrospinal fluid flow
Sources: Oh et al, A novel microneedle array for the treatment of hydrocephalus, 2015.
Jonghyun Oh, Chonbuk National University, Korea and Tim Medina, Drexel University
35. July 20, 2016
Cell Repair
Microchanneled hydrogel
35
Cell Repair Nanotechnology Killer App
Hydrogel Cellular Delivery
Sources: Kim et al, Artificially Engineered Protein Hydrogels Adapted from the Nucleoporin Nsp1 for Selective Biomolecular Transport, 2015.;
https://www.cce.caltech.edu/content/chemical-engineering-seminar-126, Lee et al, A bio-inspired, microchanneled hydrogel, 2015.
Problem: selective permeability of the
hydrogel-coated lipid bilayer
Artificially-engineered protein hydrogels
Nucleosporin-like polypeptide hydrogels mimic
nucleosporin to access the nucleus
Tunable mechanical and transport properties
Microchanneled hydrogel scaffolding ability
to control spatial organization of
biomolecules in a 3D matrix
Application: selective biomolecular
transport, transport protein cargo,
molecular separation
Katharina Ribbeck, Biological Engineering, MIT
36. July 20, 2016
Cell Repair 36
Cell Repair Nanotechnology Killer App
Molecular Robot for Positional Nanoassembly
Sources: Kaszemm et al, Pick-up, transport and release of a molecular cargo using a small-molecule robotic arm, 2016.
http://www.nature.com/nchem/journal/v8/n2/pdf/nchem.2410.pdf.
Problem: small-molecule transport and
assembly
Artificial robotic arm transports molecular
cargo by inducing conformational and
configurational changes
Results: 79–85% of 3-
mercaptopropanehydrazide molecules
transported between platform sites
without cargo dissociation
Application: reposition single molecules;
atom-length scale positioning
David Leigh, University of Manchester, http://www.catenane.net
37. July 20, 2016
Cell Repair
Cell Repair Nanotechnology Killer App
Nanotechnology-guided Neural Regeneration
Problem: directed neural stem cell
differentiation into neurons and
oligodendrocytes
Nanoparticle-based system to deliver
nanomolecules to the microenvironment to
modulate cell surface chemistry
Surface properties influence changes in cell
adhesion, shape, and spreading
Nanoscaffolds enhance gene delivery,
facilitate axonal alignment
Application: regenerate damaged nerve
tissue
37
Sources: Shah et al, Nanotechnology-Based Approaches for Guiding Neural Regeneration, 2016,
http://www.slideshare.net/ajaygeorge91/bci-ppt
Shreyas Shah, Rutgers and Physiological Communications, Bell Labs
38. July 20, 2016
Cell Repair
Cell Repair Nanotechnology Killer App
DNA Nanobots in First Human Trial
38
Sources: Amir et al, Folding and Characterization of a Bio-responsive Robot from DNA Origami, 2015. Hachmon et al, A Non-
Newtonian Fluid Robot, 2016. http://nextbigfuture.com/2015/05/pfizer-partnering-with-ido-bachelet-on.html
Problem: Targeted cancer treatment less
destructive than chemo and radiation
DNA Nanobots: single strand DNA folded
into clamshell shaped box
Clamshell contains existing cancer drugs
Protective box has two states
Closed during targeted transport
Open to disgorge cancer drug to expose
cancerous cells
Application: targeted drug delivery
Ido Bachelet, Bar-Ilan University and Pfizer
39. July 20, 2016
Cell Repair 39
Cell Repair Nanotechnology Killer App
Graphene Electrode-Neuron Interface
Sources: Fabbro et al, Graphene-Based Interfaces Do Not Alter Target Nerve Cells, 2016. http://www.gizmag.com/graphene-electrode-
brain-disorders/41591/
Problem: Effective implantable electrode
materials to interface with human neurons
Created direct graphene-to-neuron
interface where neurons retained
signaling properties (rat brain culture)
Improvement over currently implanted
electrodes (tungsten and silicon) which
have scar tissue and high disconnection
rate per stiff materials; pure graphene is
flexible, non-toxic
Application: restore lost sensory function
Laura Ballerini, University of Trieste; Andrea Ferrari, Cambridge University
40. July 20, 2016
Cell Repair 40
Cell Repair Nanotechnology Killer App
Nanobots Cargo Delivery in Live Mouse
Problem: Wider range of targeted
in vivo delivery methods
Nanobot micromotors delivered
first medical payload in living
creature (mouse stomach tissue)
Sources: Gao, Artificial Micromotors in the Mouse's Stomach, 2015. http://pubs.acs.org/doi/ipdf/10.1021/nn507097k
http://www.gizmag.com/nanobot-micromotors-deliver-nanoparticles-living-creature/35700/?li_source=LI&li_medium=default-widget
Joseph Wang, Nanoengineering, UCSD
Zinc-coated synthetic micromotors used stomach
acid-driven propulsion to install themselves in the
stomach wall
Micromotor bodies dissolved in gastric acid,
releasing cargo, leaving nothing toxic behind
Application: Autonomous delivery and release of
therapeutic payloads in vivo, cell manipulation
41. July 20, 2016
Cell Repair
Cell Repair Nanotechnology Killer App
Rejuvenation of aged skin gene expression
Problem: Rejuvenation of aged skin
Rejuvenation of gene expression pattern of
aged human skin by broadband light
treatment; 1293 of 2265 coding and
noncoding RNAs rejuvenated to youthful
expression levels
Improvement in fine and course wrinkles,
abnormal pigmentation, longevity
Application: restore gene expression
pattern of photoaged and intrinsically aged
human skin to resemble young skin
41
Sources: Bitter PH Jr et al. Rejuvenation of gene expression pattern of aged human skin by broadband light treatment:
a pilot study. J Invest Dermatol. 2013 Feb;133(2):394-402. http://www.ncbi.nlm.nih.gov/pubmed/22931923
Patrick H. Bitter Jr., Stanford University
42. July 20, 2016
Cell Repair
Thesis
42
Understanding biological cell repair at the
philosophical level might help in developing
nanotechnology solutions that facilitate and
augment biological processes congruently and
geoethically with nature
43. 11th Annual Workshop on Geoethical
Nanotechnology
July 20, 2016, Terasem
Slides: http://slideshare.net/LaBlogga
Melanie Swan
Philosophy & Economic Theory
New School for Social Research, NY
melanie@BlockchainStudies.org
Bio-cryptoeconomy
Philosophy of Biological Cell Repair informs
Geoethical Nanotechnology
Part of a Series on Cryptophilosophy
Thank you! Questions?