Bio-cryptoeconomy: Smart Contract Blockchain-based Bio-Nano Repair DACs

11th Annual Workshop on Geoethical NanotechnologyJuly 20, 2016, TerasemSlides: http://slideshare.net/LaBlogga

Melanie SwanPhilosophy & Economic Theory

New School for Social Research, [email protected]

Bio-cryptoeconomyPhilosophy of Biological Cell Repair informs

Geoethical NanotechnologyPart of a Series on Cryptophilosophy

July 20, 2016Cell 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, 2016Cell Repair

Agenda Introduction Biological cell repair Philosophy of biological

cell repair Top 9 nanotechnology

cell repair advances Conclusion

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Thesis

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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


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

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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

6Source: Wowk, B. Cell Repair Technology. 1988. http://www.alcor.org/Library/html/cellrepairmachines.html


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

7Source: Extended from http://www.geoethics.org/#!geoethics/c1m3f


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

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Earth 4.5 bn years old

100 years

Unknown





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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)

10Source: Krafts. Tissue Repair. Organogenesis 6:4, 225-233, 2010.


Cardiac Cell Repair process Accelerate natural healing following myocardial injury

11Source: 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


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

2. Inflammation (2-3 hours later) Attack any pathogens; vasodilation

3. Proliferation (2-3 days later) Load raw materials; dropped at construction

site); collagen protein in skin tissue to replace fibroblasts

4. Remodeling (days, weeks months later) Cell type differentiation (organize raw

materials); collagen rearranged & redeposited

12Source: Krafts. Tissue Repair. Organogenesis 6:4, 225-233, 2010.


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

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Futuristic Thinker image credit: https://in.pinterest.com/pin/32791903508619820/





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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

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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

16Source: http://pespmc1.vub.ac.be/systheor.html


Complexity Systems that are non-linear,

dynamic, emergent, open, unknowable at the outset, interdependent, self-organizing

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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.


Posthuman and Transhuman perspectives

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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


Big Data: Complexity and Machine Learning

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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


Complexity and Big Data Analytics

20Source: 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


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)

21Source: Barad, K. (2003). Posthumanist Performativity


`

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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


Abundance Philosophy of Economics

23Sources: Swan, M. "Automation Economy: An Abundance Philosophy of Economics" In Emerging Technology and Unemployment. Palgrave Macmillan. Forthcoming.

A

B

C


Economics as an Organizational Paradigm

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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.


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)

25Source: 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..


Bio-nanoeconomy and Bio-cryptoeconomyMedical 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

26Sources: 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


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

27Sources: 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


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

28Source: Klee “Fire and Death;” Kant, I. Critique of the Power of Judgment. 1790.


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

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1. Blood clot dissolution2. Microneedle array delivery3. Hydrogel cellular delivery4. Positional nanoassembly robot5. Nanotechnology-guided neural

regeneration6. DNA Nanobots in first human trial 7. Graphene electrode-neuron interface8. Nanobots cargo delivery in mouse 9. Aged skin gene expression

rejuvenation with broadband laser

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Neocortical Neurogenesis in Mammalslafayette.edu

Top 9 Nanotechnology Cell Repair Advances

Microfluidic array


Cell Repair Nanotechnology Killer AppBlood 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)

32Sources: 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


Cell Repair Nanotechnology Killer AppBlood 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)

33Sources: 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


Cell Repair Nanotechnology Killer AppMicroneedle Array Diagnostic/Delivery

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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


Microchanneled hydrogel

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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


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


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

37Sources: 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


Cell Repair Nanotechnology Killer App DNA Nanobots in First Human Trial

38Sources: 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


Cell Repair Nanotechnology Killer AppGraphene 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


Cell Repair Nanotechnology Killer AppNanobots 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/nn507097khttp://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


Cell Repair Nanotechnology Killer AppRejuvenation 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

41Sources: 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


Thesis

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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 NanotechnologyJuly 20, 2016, TerasemSlides: http://slideshare.net/LaBlogga

Melanie SwanPhilosophy & Economic Theory

New School for Social Research, [email protected]

Bio-cryptoeconomyPhilosophy of Biological Cell Repair informs

Geoethical NanotechnologyPart of a Series on Cryptophilosophy

Thank you! Questions?

Bio-cryptoeconomy: Smart Contract Blockchain-based Bio-Nano Repair DACs

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