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SYNTHETIC BIOLOGY AND
             DATA-DRIVEN SYNTHETIC
                  D
             BIOLOGY FOR PERSONALIZED
             MEDICINE AND CLEAN
             ENERGY
                   Russell Hanson
                   OSCON D t J l 25 27 2011
                            Data July 25-27,
                   Portland, OR



Russell Hanson
Dec 27, 2004       TheCureIsNow.org
Outline
 What is synthetic biology?
            y            gy
 How does synthetic biology relate to genomic
  science/personalized medicine
 Open source tools in science and
  bioengineering/synbio
 Bio-Computer aided design (AutoCAD, etc.)
 Mesoscopic Physics
           p    y
 Diff Eqs and parameter optimizations


                                  OSCON Data  Portland, OR
Outline, cont.

 IP Issues in personalized medicine
 Pink Army and co-op, open-source biopharma
 Non-profit clinical research organizations
  Non profit
  (CROs)
 Disease-management companies, broken
  Disease management
  business model
 Big Data in electronic medical records,
  personal genomics, biostatistics, hospitals,
  community health centers

                                 OSCON Data  Portland, OR
OSCON Data: This may not be a talk
about a social web app and the
                     pp
database technologies used for that
app, but truly, what would a social web,
 pp,         y,                         ,
etc. app be without the life or biology
on that social graph
               g p



                             OSCON Data  Portland, OR
What is life?
                      What is artificial life?
 And, incidentally, what is consciousness?
   Igor Aleksander (1995)                    Bernard Baars (1988)
    Brain as state machine                   Definition and context setting
    Inner neuron partitioning                Adaptation and learning
    Conscious and unconscious states         Editing
    Perceptual learning and memory           Flagging and debugging
    Prediction                               Recruiting and control
    Self-Awareness                           Decision-making (executive function)
    Representation and meaning               Analogy forming-function
    Learning utterances                      Metacognitive and self monitoring
                                                                  self-monitoring
    Learning language                       function
    Will                                     Autoprogramming and self-maintenance
    Instinct                                function
    Emotion                                  Definitional and context-setting
                                                                context setting
                                             function
                                                                        OSCON Data  Portland, OR
from When The Turing Test Is Not Enough, by George Dvorsky
We are open source
     Life is open source
We should have excellent tools
to manage our source (code)



                     OSCON Data  Portland, OR
OpenWetWare.org




             OSCON Data  Portland, OR
BioBricks Foundation




                  OSCON Data  Portland, OR
iGEM




       OSCON Data  Portland OR
NextGen sequencing




               OSCON Data  Portland, OR
SNP Chips




Affymetrix 500K probe chip ~$450USD   OSCON Data  Portland, OR
Single nucleotide polymorphism
(SNP) and gene expression arrays
CCopy number profile
            b       fil
 Gene expression/over expression levels in
  a tissue
 Major copy proportion
      j    py p p
 Machine learning on SNPs, SVM, Bayesian
  networks, Markov chains
 Biomarker identification, verification, and
  development.
  development Biomarker for autism lack
                                 autism, lack
  of empathy                     OSCON Data  Portland, OR
Where are we?
 How much do we know about cellular
  processes, regulation, oncogenes,
                  l ti
  protein-protein interactions, microbiome
  interactions?
  i t    ti    ?
 How much do we know about brain
  structure-function relationships, gene
  activation in neurons, memory,
  eletrophysiology, neuronal cognition,
  brainmaps from C. elegans, to Mus
  musculus, to Homo sapiens?
                              OSCON Data  Portland, OR
How to Access the Human Genome (and other
                          seque ced genomes)
                          sequenced ge o es)
 ftp://ftp.ncbi.nih.gov




                                hs_phs0.fna.gz   Survey sequence (appr
                                hs_phs1.fna.gz   Unordered contigs (ea
                                hs_phs2.fna.gz   Ordered contigs (each
                                hs_phs3.fna.gz   Finished sequence




                                             21C3  Berlin
The second wave of synthetic
    biology: from modules to systems
                             systems




The second wave of synthetic biology: from
                      y            gy
modules to systems, Purnick PEM, Weiss R,
Nature Reviews Molecular Cell Biology, Vol 10   OSCON Data  Portland, OR
Iss 6 P410-422 Jun 2009
Using increasing abstraction, performance
    characteristics, datasheets -- like
         integrated circuits (ICs)




                                OSCON Data  Portland, OR
Graphical layout, design and
            programming, CellDesigner
             programming
tutorial at: http://celldesigner.org/~funa/CellDesignerTutorial2007.pdf
Graphical layout, design and
programming, CellDesigner 2
 programming
Nanobots to treat NK leukemia cells
DNA scaffolds and
cell-surface receptors

Software, etc. for DNA
origami, scaffold design




                           OSCON Data  Portland OR
23andMe, NextGen sequencing and
      SynBio get together
 23andMe version 3 uses
  Illumina
  HumanOmniExpress
  BeadChip SNP chips
  ($250/sample)
 Genome Wide Association
  Studies

 --> At $250/sample,
  genomic personalization is
  very realizable              OSCON DATA  Portland, OR
More new CAD/BioCAD software tools
 Matter compiler
 Thingiverse, cheap 3d printers, laser
      g       ,      p    p     ,
  cutters, Shapeways, personal fab
  technology, makerbot, etc.
           gy,          ,
 AutoDesk, EugeneCAD,
ClothoCAD
 RepRap  exponentially
scalable matter compiler
/
/extruding 3D p
         g      printer
                                   OSCON Data  Portland, OR
 Movie at:
         p //                       /
      http://www.molecularmovies.com/movi
      es/berry_apoptosis.html




Apoptosis Maya Animation by Drew Berry   OSCON Data  Portland, OR
Biological simulators
                   simulators
 NAMD  and other molecular dynamics, etc.
 Mixed Quantum Mechanics/Molecular
  Mechanics (QM/MM/)
              (QM/MM/ )
 Biological pathway/chemical reaction
  simulators/optimizers
 Many projects on gene network analysis,
  stochastic simulation, etc.
      h i i l i


                              OSCON Data  Portland, OR
Design of bio/chemical devices from
(1) first principles and functional
    fi t i i l         df    ti   l
abstractions and (2) from data

    Data




Bio/chem/phys first principles
and functional abstractions
                                 OSCON DATA  Portland, OR
How and where these data are
   used,
   used or made usable
 Randomized clinical trials
 Biomarker development, genomic tests
  in CLIA certified labs
 Licensing to other companies for
  marketing and development




                            OSCON Data  Portland, OR
Tools that are used to analyze
these data
 R (!), BioConductor
 Biostatistics, Matlab
 Python
 Chi-square tests,
permutation tests, Monte Carlo resampling
 Parametric statistics, nonparametric
  statistics, generative statistics
 Statistical learning theory, online learning
                       theory
                                   OSCON Data  Portland, OR
Approval of processes for
    cellular therapies/treatments
  FDA approval for process, not f
                lf             t for
   drug/biologic/device
progress on the development of a new experimental MCL treatment called
immunotherapy, in which a patients own immune cells are collected from the
bloodstream before ASCT, treated in the laboratory to have antitumor activity,
and reintroduced into the body after ASCT. The goal of this immunotherapy is
to reduce the likelihood of relapse after transplantation. A major challenge of
immunotherapy is getting the transferred immune cells to persist in the body
after the transfer. In preclinical studies, Dr. Jensen and his colleagues found
 ft th t       f I         li i l t di D J               d hi    ll       f   d
that using a certain subset of immune cells called central memory T-cells in-
creased the likelihood that the transferred T-cells will persist.

Report from the Lymphoma Research Foundation, Spring 2010, Volume 8,
Number 1                                           OSCON Data  Portland, OR
Pink Army  a
                           biopharma co-op
                           bi h
 You own your own cells, therapies based off your
  own cells should be yours in the co-op.
 If a biopharma company cures your disease, they
  lose a customer, who is cured.
              2 weeks and
              $1000 in lab resources




                                       OSCON Data  Portland OR
Cancer 5-year survival rates, US




                                                      OSCON Data  Portland, OR

Division of Cancer Control and Population Sciences, 2008
Non-profit clinical research
    organizations ( (CROs)
                          )
 Randomized trials
 A melanoma trial with 1,000 patients
                        1 000
  costs $60M in CRO expenses
 A 10,000 patient chronic obstructive
    10 000
  pulmonary disease (COPD) costs $240-
  $250M in CRO expenses


                            OSCON Data  Portland, OR
More medical foci of SynBio
                        y
 Oncolytic viruses
       y
 RNAi for HER2 in breast cancer (also an
  iGEM team project)
 Designed, logic, and programmed
 Not comp tational devices b t use logic
      computational de ices but se
  and/or procedures



                              OSCON Data  Portland OR
Using data to engineer therapies
     or cures for genetic diseases
IF (   RNA   AND   RNA   AND   RNA   AND   RNA     AND      RNA        )

THEN
   RELEASE PROTEIN INITIATING APOPTOSIS IN THE TUMOR CELL




                                            OSCON Data  Portland OR
More biological nanobots
 T t h d l robots, made from biological or organic
  Tetrahedral b t       d f      bi l i l        i
  substrate: 12Tet Tetrahedral Rover Robot
  http://www.youtube.com/watch?v txZMLS7YD6Q
  http://www.youtube.com/watch?v=txZMLS7YD6Q




                                       OSCON Data  Portland, OR
More biological nanobots, 2
DNA O i
    Origami
          i




                      OSCON Data  Portland, OR
Energy, biofules
Energy biofules, and bioreactors
   The oil multinational, despised by green activists for its support of
                           ,    p       yg                 f        pp    f
scientists skeptical of climate change, plans to invest $600 million (贈370
million) in a joint venture with Mr Venters company, Synthetic Genomics. The
thinking is that algae is a more efficient source of fuel than conventional
biofuels, such as ethanol made from corn or sugar cane and biodiesel made
from wheat or palm oil. Algae can be processed into fuels similar to petrol
and diesel  and it consumes carbon dioxide as it grows.
   According to Exxon, the yield of biofuel from algae is 2,000 gallons per
   A      di      E        h i ld f bi f l f          l      i 2 000 ll
acre, more than three times that of biodiesel from palm oil and eight times the
ethanol yield from corn. It is also believed to have the edge over other
biofuels because of its suitability for use as a jet fuel. The real challenge to
                                                     fuel The
creating a viable, next-generation biofuel is the ability to produce it in large
volumes, Mr Venter said.
via http://www.timesonline.co.uk/tol/news/environment/article6710846.ece

                                                           OSCON Data  Portland OR
Biological light sources
E.glowli: a bioluminescent future




                            U Cambridge, iGEM 2010 team




                                     OSCON Data  Portland, OR
Biological memory   CUHK, iGEM 2010 team




                       OSCON Data  Portland OR
OSCON Data  Portland, OR
Microbiome Engineering
 Use the microbiome to produce therapies
  for existing diseases in controlled,
  continuous ways: insulin for diabetics,
  interleukin 10 for Crohns disease, etc.
 Highly competitive environment: microbe
  needs orthogonal edge to survive
               g       g




                                OSCON Data  Portland, OR
And so forth and biology

 PolySilicon and biology
 SynBio in chemicals industry  cleaning
                                  cleaning,
  refinement, scalability, sensors, etc.




                               OSCON Data  Portland, OR
Conclusions
 Wide ranging implications to existing problems in
  health, engineering, energy, manufacture
 P ti l l for human healthcare, genomic research
  Particularly f h       h lth               i       h
  on diseases, data-aided design and testing
 New manufacture processes for new biologically-
                                        biologically
  designed constructs




http://www.linkedin.com/in/russellhanson
http://twitter.com/russell_hanson
http://www.russellhanson.com/
http://www russellhanson com/
                                            OSCON Data  Portland OR

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Synthetic Biology and Data-Driven Synthetic Biology for Personalized Medicine and Clean Energy at O\'Reilly\'s OSCON Data in Portland, OR

  • 1. SYNTHETIC BIOLOGY AND DATA-DRIVEN SYNTHETIC D BIOLOGY FOR PERSONALIZED MEDICINE AND CLEAN ENERGY Russell Hanson OSCON D t J l 25 27 2011 Data July 25-27, Portland, OR Russell Hanson Dec 27, 2004 TheCureIsNow.org
  • 2. Outline What is synthetic biology? y gy How does synthetic biology relate to genomic science/personalized medicine Open source tools in science and bioengineering/synbio Bio-Computer aided design (AutoCAD, etc.) Mesoscopic Physics p y Diff Eqs and parameter optimizations OSCON Data Portland, OR
  • 3. Outline, cont. IP Issues in personalized medicine Pink Army and co-op, open-source biopharma Non-profit clinical research organizations Non profit (CROs) Disease-management companies, broken Disease management business model Big Data in electronic medical records, personal genomics, biostatistics, hospitals, community health centers OSCON Data Portland, OR
  • 4. OSCON Data: This may not be a talk about a social web app and the pp database technologies used for that app, but truly, what would a social web, pp, y, , etc. app be without the life or biology on that social graph g p OSCON Data Portland, OR
  • 5. What is life? What is artificial life? And, incidentally, what is consciousness? Igor Aleksander (1995) Bernard Baars (1988) Brain as state machine Definition and context setting Inner neuron partitioning Adaptation and learning Conscious and unconscious states Editing Perceptual learning and memory Flagging and debugging Prediction Recruiting and control Self-Awareness Decision-making (executive function) Representation and meaning Analogy forming-function Learning utterances Metacognitive and self monitoring self-monitoring Learning language function Will Autoprogramming and self-maintenance Instinct function Emotion Definitional and context-setting context setting function OSCON Data Portland, OR from When The Turing Test Is Not Enough, by George Dvorsky
  • 6. We are open source Life is open source We should have excellent tools to manage our source (code) OSCON Data Portland, OR
  • 7. OpenWetWare.org OSCON Data Portland, OR
  • 8. BioBricks Foundation OSCON Data Portland, OR
  • 9. iGEM OSCON Data Portland OR
  • 10. NextGen sequencing OSCON Data Portland, OR
  • 11. SNP Chips Affymetrix 500K probe chip ~$450USD OSCON Data Portland, OR
  • 12. Single nucleotide polymorphism (SNP) and gene expression arrays CCopy number profile b fil Gene expression/over expression levels in a tissue Major copy proportion j py p p Machine learning on SNPs, SVM, Bayesian networks, Markov chains Biomarker identification, verification, and development. development Biomarker for autism lack autism, lack of empathy OSCON Data Portland, OR
  • 13. Where are we? How much do we know about cellular processes, regulation, oncogenes, l ti protein-protein interactions, microbiome interactions? i t ti ? How much do we know about brain structure-function relationships, gene activation in neurons, memory, eletrophysiology, neuronal cognition, brainmaps from C. elegans, to Mus musculus, to Homo sapiens? OSCON Data Portland, OR
  • 14. How to Access the Human Genome (and other seque ced genomes) sequenced ge o es) ftp://ftp.ncbi.nih.gov hs_phs0.fna.gz Survey sequence (appr hs_phs1.fna.gz Unordered contigs (ea hs_phs2.fna.gz Ordered contigs (each hs_phs3.fna.gz Finished sequence 21C3 Berlin
  • 15. The second wave of synthetic biology: from modules to systems systems The second wave of synthetic biology: from y gy modules to systems, Purnick PEM, Weiss R, Nature Reviews Molecular Cell Biology, Vol 10 OSCON Data Portland, OR Iss 6 P410-422 Jun 2009
  • 16. Using increasing abstraction, performance characteristics, datasheets -- like integrated circuits (ICs) OSCON Data Portland, OR
  • 17. Graphical layout, design and programming, CellDesigner programming tutorial at: http://celldesigner.org/~funa/CellDesignerTutorial2007.pdf
  • 18. Graphical layout, design and programming, CellDesigner 2 programming
  • 19. Nanobots to treat NK leukemia cells DNA scaffolds and cell-surface receptors Software, etc. for DNA origami, scaffold design OSCON Data Portland OR
  • 20. 23andMe, NextGen sequencing and SynBio get together 23andMe version 3 uses Illumina HumanOmniExpress BeadChip SNP chips ($250/sample) Genome Wide Association Studies --> At $250/sample, genomic personalization is very realizable OSCON DATA Portland, OR
  • 21. More new CAD/BioCAD software tools Matter compiler Thingiverse, cheap 3d printers, laser g , p p , cutters, Shapeways, personal fab technology, makerbot, etc. gy, , AutoDesk, EugeneCAD, ClothoCAD RepRap exponentially scalable matter compiler / /extruding 3D p g printer OSCON Data Portland, OR
  • 22. Movie at: p // / http://www.molecularmovies.com/movi es/berry_apoptosis.html Apoptosis Maya Animation by Drew Berry OSCON Data Portland, OR
  • 23. Biological simulators simulators NAMD and other molecular dynamics, etc. Mixed Quantum Mechanics/Molecular Mechanics (QM/MM/) (QM/MM/ ) Biological pathway/chemical reaction simulators/optimizers Many projects on gene network analysis, stochastic simulation, etc. h i i l i OSCON Data Portland, OR
  • 24. Design of bio/chemical devices from (1) first principles and functional fi t i i l df ti l abstractions and (2) from data Data Bio/chem/phys first principles and functional abstractions OSCON DATA Portland, OR
  • 25. How and where these data are used, used or made usable Randomized clinical trials Biomarker development, genomic tests in CLIA certified labs Licensing to other companies for marketing and development OSCON Data Portland, OR
  • 26. Tools that are used to analyze these data R (!), BioConductor Biostatistics, Matlab Python Chi-square tests, permutation tests, Monte Carlo resampling Parametric statistics, nonparametric statistics, generative statistics Statistical learning theory, online learning theory OSCON Data Portland, OR
  • 27. Approval of processes for cellular therapies/treatments FDA approval for process, not f lf t for drug/biologic/device progress on the development of a new experimental MCL treatment called immunotherapy, in which a patients own immune cells are collected from the bloodstream before ASCT, treated in the laboratory to have antitumor activity, and reintroduced into the body after ASCT. The goal of this immunotherapy is to reduce the likelihood of relapse after transplantation. A major challenge of immunotherapy is getting the transferred immune cells to persist in the body after the transfer. In preclinical studies, Dr. Jensen and his colleagues found ft th t f I li i l t di D J d hi ll f d that using a certain subset of immune cells called central memory T-cells in- creased the likelihood that the transferred T-cells will persist. Report from the Lymphoma Research Foundation, Spring 2010, Volume 8, Number 1 OSCON Data Portland, OR
  • 28. Pink Army a biopharma co-op bi h You own your own cells, therapies based off your own cells should be yours in the co-op. If a biopharma company cures your disease, they lose a customer, who is cured. 2 weeks and $1000 in lab resources OSCON Data Portland OR
  • 29. Cancer 5-year survival rates, US OSCON Data Portland, OR Division of Cancer Control and Population Sciences, 2008
  • 30. Non-profit clinical research organizations ( (CROs) ) Randomized trials A melanoma trial with 1,000 patients 1 000 costs $60M in CRO expenses A 10,000 patient chronic obstructive 10 000 pulmonary disease (COPD) costs $240- $250M in CRO expenses OSCON Data Portland, OR
  • 31. More medical foci of SynBio y Oncolytic viruses y RNAi for HER2 in breast cancer (also an iGEM team project) Designed, logic, and programmed Not comp tational devices b t use logic computational de ices but se and/or procedures OSCON Data Portland OR
  • 32. Using data to engineer therapies or cures for genetic diseases IF ( RNA AND RNA AND RNA AND RNA AND RNA ) THEN RELEASE PROTEIN INITIATING APOPTOSIS IN THE TUMOR CELL OSCON Data Portland OR
  • 33. More biological nanobots T t h d l robots, made from biological or organic Tetrahedral b t d f bi l i l i substrate: 12Tet Tetrahedral Rover Robot http://www.youtube.com/watch?v txZMLS7YD6Q http://www.youtube.com/watch?v=txZMLS7YD6Q OSCON Data Portland, OR
  • 34. More biological nanobots, 2 DNA O i Origami i OSCON Data Portland, OR
  • 35. Energy, biofules Energy biofules, and bioreactors The oil multinational, despised by green activists for its support of , p yg f pp f scientists skeptical of climate change, plans to invest $600 million (贈370 million) in a joint venture with Mr Venters company, Synthetic Genomics. The thinking is that algae is a more efficient source of fuel than conventional biofuels, such as ethanol made from corn or sugar cane and biodiesel made from wheat or palm oil. Algae can be processed into fuels similar to petrol and diesel and it consumes carbon dioxide as it grows. According to Exxon, the yield of biofuel from algae is 2,000 gallons per A di E h i ld f bi f l f l i 2 000 ll acre, more than three times that of biodiesel from palm oil and eight times the ethanol yield from corn. It is also believed to have the edge over other biofuels because of its suitability for use as a jet fuel. The real challenge to fuel The creating a viable, next-generation biofuel is the ability to produce it in large volumes, Mr Venter said. via http://www.timesonline.co.uk/tol/news/environment/article6710846.ece OSCON Data Portland OR
  • 36. Biological light sources E.glowli: a bioluminescent future U Cambridge, iGEM 2010 team OSCON Data Portland, OR
  • 37. Biological memory CUHK, iGEM 2010 team OSCON Data Portland OR
  • 38. OSCON Data Portland, OR
  • 39. Microbiome Engineering Use the microbiome to produce therapies for existing diseases in controlled, continuous ways: insulin for diabetics, interleukin 10 for Crohns disease, etc. Highly competitive environment: microbe needs orthogonal edge to survive g g OSCON Data Portland, OR
  • 40. And so forth and biology PolySilicon and biology SynBio in chemicals industry cleaning cleaning, refinement, scalability, sensors, etc. OSCON Data Portland, OR
  • 41. Conclusions Wide ranging implications to existing problems in health, engineering, energy, manufacture P ti l l for human healthcare, genomic research Particularly f h h lth i h on diseases, data-aided design and testing New manufacture processes for new biologically- biologically designed constructs http://www.linkedin.com/in/russellhanson http://twitter.com/russell_hanson http://www.russellhanson.com/ http://www russellhanson com/ OSCON Data Portland OR