road-mapping biologyweb.mit.edu/amarbles/www/docs/marblestone_revven_lecture2.pdf · 1) understand...
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Road-mapping BiologyHow the organization of biological knowledge impacts revolution strategy
Adam MarblestoneRevolutionary Ventures 2015
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Agenda
• What is a scientific roadmap?
• Structural inefficiencies in biology:
• Why does biology need roadmaps?
• Why are there so many hidden gems?
• Examples of roadmaps, and of hidden gems
• Improved software for mapping science
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• Roadmap: A map of constraints, on the way towards a goal, and of potential workarounds for those constraints
• Engineered Serendipity: Biology breakthroughs depend on serendipity. We can make serendipity more likely by systematically surveying for hidden gems.
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Why does biology need roadmaps?
Why are there so many hidden gems?
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knowledgetechniquesdisciplines
genetic circuits
micro-fluidics
meta-genomics
directed evolution
proteomics
DNA nanotechnology
genome engineeringpathway analysis
“Science” does not have a plan for solving biotech grand challenges
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A “sociological big bang”: does not scale well with problem complexity
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Discipline
Discipline
Apprenticeship
Serendipity
Inventions
New disciplines
Apprenticeship
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The elephant in the room: to make bio-technological quantum leapswe must change how biology is done
revolutionsby chance
revolutionsby design
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DNA barcoding
thin sectioning
super-resolution fluorescentin-situ sequencing
virusdesign
maps of entire domains tech architectures / strategies
fusionproteins
antibodies
Two conspicuously missing elementsin modern biology
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Well-known “systems engineering” methods in the sciences of simplicity...
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How to extend to the sciences of complexity?
innovation “algorithm” & “business model” in bio is ripe for change...
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How to create a bio-‐methods revolu4on(only par*ally joking)
1) Understand landscape of constraints (physics, design robustness)2) Find a conceptual assumption-violating workaround3) Find a hidden gem (e.g., in nature) that implements this concept
#3 can be done via:
a) searching existing knowledge and transplanting to new domainb) screening libraries of elements from nature (mining evolution)
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Mullis 1985Kleppe, Khorana 1971 (“important but ignored”)
Thermo-stablepolymerases
Research on archae-bacteria
Custom DNA primers
Phosphoramidite chemistry
Need toamplify DNA
Molecular cloning
Large-scale effortsto synthesize genetic constructs
Discovery ofrestrictionenzymes
Temperature controlAutomation
Polymerase ChainReaction (PCR)
Vast accelerationof biomedical research
Understanding DNAhybridization
genome project (1990-2001)
2nd-generation sequencing (2004-)
PCR: a gem “hiding in plain sight”
Goal: make lots of copies of an arbitrary DNA sequence
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Konrad Kording 2013; Alivasatos et al 2012
# n
euro
ns s
imul
tane
ousl
y re
cord
ed
Goal: record every “spike” from every neuron in a mammalian brain
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nobody has written down a design that clearly solves the problem does not violate any laws of physics does not severely damage the brain
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ATCG
A) Electrical B) Optical
C) Magnetic Resonance D) Molecular
B
< 2C temperature change: < 50 mW steady-state power dissipation
< 1% tissue volume displacement
Marblestone et al, Front. Comp. Neurosci (2013): with >17 co-authors
Landscape of constraints on brain activity mapping
http://arxiv.org/abs/1306.5709
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many electrodes are needed
embedded electronics are too power-hungry, at present
use IR or ultrasound, not RF, for data-transmission
light scattering can potentially be overcome in several ways
multi-photon optics is too dissipative
requires many parallel scanned beams
MRI needs new contrast mechanisms
ultrasound is potentially powerful
molecular recording is possible but hard
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Need for a conceptual work-around
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=010100101010101001010101010101010010101101110010110101010111010011
=
w/ Kording, Zamft, Church, Boyden et al
Assumption-violating concept:what if each cell could record its own activity?
$9M NIH grant to pursue this
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Molecular implementation of the concept:a molecular recording device in each neuron
Figure by Reza KalhorYuste and Church, Scientific American, 2014
Encode information via control of DNA polymerase copying error rate
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with Gary Marcus (NYU + Allen Institute) and Tom Dean (Google)
Mapping out the space of theories about the brain
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Can software tools accelerate the uptake of cross-disciplinary knowledge, helping us find the hidden gems?
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Word2Vec model trained on 150k PubMed abstracts
Automatically learning the “meanings” of science words
statistical model was only fed raw text, and knows nothing about neuroscience (or anything), yet it “discovers” neurotransmitters
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Word2Vec model trained on 150k PubMed abstracts
neurotransmission!
parts of neurons!
electrical interfacing!
non-invasive?
psychological?
molecular?
Automatically learning the “meanings” of science words
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Identifying the sub-fields/sub-topics:unsupervised document classification model
connexin is a gap-junction proteingaba is an inhibitory neurotransmitter
the dopamine system lives in the substantia nigra region of the striatum
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Identifying the sub-fields/sub-topics:community-detection on the citation graph
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Identifying the sub-fields/sub-topics:community-detection on the citation graph
The first large-scale publicly available citation graph
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Towards human-computer synergy for accelerated science
With Juan Batiz-Benet, Richard Littauer, Ed Boyden
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Towards human-computer synergy for accelerated science
With Juan Batiz-Benet, Richard Littauer, Ed Boyden