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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
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.
July 20, 2016
Cell Repair
Agenda
 Introduction
 Biological cell repair
 Philosophy of biological
cell repair
 Top 9 nanotechnology
cell repair advances
 Conclusion
3
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
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
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
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
July 20, 2016
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
July 20, 2016
Cell Repair
Agenda
 Introduction
 Biological cell repair
 Philosophy of biological
cell repair
 Top 9 nanotechnology
cell repair advances
 Conclusion
9
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.
July 20, 2016
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
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.
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/
July 20, 2016
Cell Repair
Agenda
 Introduction
 Biological cell repair
 Philosophy of biological
cell repair
 Top 9 nanotechnology
cell repair advances
 Conclusion
14
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
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
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.
July 20, 2016
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
July 20, 2016
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
July 20, 2016
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
July 20, 2016
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
July 20, 2016
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
July 20, 2016
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
July 20, 2016
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.
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..
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
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
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.
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
July 20, 2016
Cell Repair
Agenda
 Introduction
 Biological cell repair
 Philosophy of biological
cell repair
 Top 9 nanotechnology
cell repair advances
 Conclusion
30
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
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
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
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
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
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
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
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
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
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
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
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
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
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Bio-cryptoeconomy: Smart Contract Blockchain-based Bio-Nano Repair DACs

  • 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
  • 8. July 20, 2016 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.
  • 11. July 20, 2016 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.
  • 18. July 20, 2016 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
  • 19. July 20, 2016 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
  • 20. July 20, 2016 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
  • 21. July 20, 2016 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
  • 22. July 20, 2016 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
  • 23. July 20, 2016 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
  • 24. July 20, 2016 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?