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Tissue-Level Intelligence �via Synthetic Living Constructs

Wesley Clawson

Levin Lab

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WCDO 2025

Burlington, VT

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Tissue-Level Intelligence �via Synthetic Living Constructs

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WCDO 2025

Burlington, VT

COMPUTATIONALLY DESIGNED

Wesley Clawson

Levin Lab

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Library of Intelligence Tests

Catalogue of “bio-rithms”

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wow so smart

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wow so smart

any biological system

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any biological system

self-centered world, Jakob von Uexküll

“constituted by a more or less broad series of elements [called] 'carriers of significance' or 'marks' which are the only things that interest the animal

Giorgio Agamben

The Open: Man and Animal

umwelt

“constituted by a more or less broad series of elements [called] 'carriers of significance' or 'marks' which are the only things that interest the animal system

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  • Biological systems have a remarkable ability to adapt, or learn, to a variety of change

  • Importantly, this learning can occur across a variety of scales and spaces

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Biological Learning

Figures adapted from Levin (2021), with permission

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  • Biological systems have a remarkable ability to adapt, or learn, to a variety of changes

  • Importantly, this learning can occur across a variety of scales and spaces

  • Intelligence is the degree of competency of navigating any space

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Intelligence

Figures adapted from Levin (2021), with permission

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Biological Intelligence

Figures adapted from Levin (2021), with permission

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Biological Intelligence

Behavior 2

Behavior 1

Marder, E., & Goaillard, J. M. (2006). Variability, compensation and homeostasis in neuron and network function. Nat Rev Neurosci, 7(7), 563-574.

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Pyloric Rhythm

Marder, E., & Goaillard, J. M. (2006). Variability, compensation and homeostasis in neuron and network function. Nat Rev Neurosci, 7(7), 563-574.

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Biological Computation

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Adapted from Krakauer et al, 2017

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Biological Computation

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Adapted from Krakauer et al, 2017

cognition

spiking

neurons

Neuro

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Biological Computation

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Adapted from Krakauer et al, 2017

cognition

spiking

neurons

Neuro

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Biological Computation

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Adapted from Krakauer et al, 2017

why

how

what

Every piece can scale!

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Biological Computation

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why

how

what

Every piece can scale!

  • Biological systems have a remarkable ability to adapt, or learn, to a variety of changes

  • Importantly, this learning can occur across a variety of scales and spaces

  • Intelligence is the degree of competency of navigating any space

  • Multiscale competency – each scale is agential, or pretty darn good at its problem set

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Biological Learning

Figures adapted from Levin (2021), with permission

Figure from P.H. Mason et al. (2015)

Some ‘Mechanisms’ of Problem Solving

why

how

what

  • Biological systems have a remarkable ability to adapt, or learn, to a variety of changes

  • Importantly, this learning can occur across a variety of scales and spaces

  • Intelligence is the degree of competency of navigating any space

  • Multiscale competency – each scale is agential, or pretty darn good at its problem set

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  • Fundamental principles of multicellular plasticity are obscured as biology is evolved and complex�
  • We propose teleonomic (goal-seeking, problem-solving) behavior in diverse problem spaces as a powerful invariant across possible beings regardless of composition or origin.

  • Analysis of living forms that have never existed before is necessary to reveal deep design principles of life as it can be.

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  • How trainable/persuadable is a given system?
    • Depends on system and scale
    • Guess and check

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Training Biology

Axis of Persuadability

Technological Approach to Mind Everywhere, Levin (2021)

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  • How trainable/persuadable is a given system?
    • Depends on system and scale
    • Guess and check

  • We’re starting from C
    • Train an artificial ‘why’
    • Observe the ‘what’ and ‘how’ during and after training

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Training Biology

Axis of Persuadability

why

how

what

Technological Approach to Mind Everywhere, Levin (2021)

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wow so smart

any biological system

“constituted by a more or less broad series of elements [called] 'carriers of significance' or 'marks' which are the only things that interest the animal system

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Embodiment

an environment that acts on an organism

a mind that at least partially processes this input

a body that can change the relationship to environment

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Virtual Embodiment

an environment that acts on an organism

a mind that at least partially processes this input

a body that can change the relationship to environment

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graphic by: Alexis Pietak

Experimental Paradigm

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  • 26400 electrodes
  • 2x4 mm2 recording area
  • low-noise readouts, 2.4µVrms

17.5 µm

This slide adapted with permission from Maxwell Bio

Measuring tissue activity

CMOS microelectrode array (MEA) allows for high-resolution recording of local field potential (LFP) and spiking activity

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Local Field Potentials

Microelectrode array (MEA) allows for high-resolution recording of local field potential (LFP) and spiking activity

Obien M. et al., Front. In Neurosc. (2015)

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Each square is an electrode

Each line is electrical activity

Each electrode is 18 μm

4 visible neurons in this area

  1. Blue
  2. Purple
  3. Orange
  4. Yellow

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This is day 7 of growth

  • You can see soma (negative deflection)
  • You can see early dendritic growth (positive deflections)

soma

dendrite

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If I highlight two neurons (blue and purple) you can see how the dendritic outreach (blue positive deflections) is heading towards the soma, and assumedly the axon, of the purple neuron

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~ 3-5 ms

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mind + behavior

E18 cortical neurons

BrainBits

Slow, easy to see, and culture wide

26400 electrodes

2x4 mm2 recording area

2.4µVrms low-noise

17.5 µm

HDMEA

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Learning in cultures

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moving into the virtual world

Nathan Wu - Yale

Viraj Chhajed - UCLA

Wes Clawson - Tufts

Trevor Sullivan - Tufts

Evan Kolberg – John F Kennedy

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graphic by: Alexis Pietak

Experimental Paradigm

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Closing the loop

Holistic

Train the whole tissue��

Agential

Collective of active agents (neurons)�

Learning

train tissue to test intelligence

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Closing the loop

Holistic

Train the whole tissue��

Agential

Collective of active agents (neurons)�

Learning

train tissue to test intelligence

H

A

L

https://project-hal.github.io/

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Friston, K. The free-energy principle: a unified brain theory? (2010)

Training with H.A.L.

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No stim

Random

Stim

Friston, K. The free-energy principle: a unified brain theory? (2010)

Training with H.A.L.

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Friston, K. The free-energy principle: a unified brain theory? (2010)

Training with H.A.L.

No stim

Random

Stim

Rightwards Burst

Leftwards Burst

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Friston, K. The free-energy principle: a unified brain theory? (2010)

Training with H.A.L.

Rightwards Burst

Leftwards Burst

No stim

Random

Stim

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Friston, K. The free-energy principle: a unified brain theory? (2010)

Training with H.A.L.

No stim

Random

Stim

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some current/future work

Chem A

Chem B

Chemical Stimulation

time

Goal state

2D world ~ dynamic state space

A

C

B

D

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some current/future work

  • What communication protocols are ‘best’ for task acquisition?

  • What tissues work best in what capacity?

  • How is learned behavior shared across a collective of collectives?

A

B

Stim B if A does X

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Bringing CDOs and ‘HAL’ together

This is/could be a CDO in the future

Using CD-HAL to understand biology and biological computation

Using CD-HAL as biological compute

why

how

what

how

what

why

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Bringing CDOs and ‘HAL’ together

  • Environment
    • “What perturbations produce xyz
    • “Is training signal A better than B?”

  • Body
    • “What would be good for task 4?”
    • “How best to combine behavior I and J?”

  • “Given this data, can you find systematic use of a given “?

how

what

why

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Library of Intelligence Tests

Catalogue of “bio-rithms”

CD

CD

CD

CD

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Thank you

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AFOSR Grant FA9550-22-1-0465 DARPA-EA-24-01-04-039

[your name here]

wesley.clawson@tufts.edu

Team Members:

  • Caitlin Grasso
  • Sydney Palmer
  • Serena Meng

Past Team Members:

  • Nathan Wu
  • Trevor Sullivan
  • Viraj Chhajed
  • Evan Kolberg

Levin Lab Members:

  • Devon Davidian
  • Juanita Matthews
  • Hamid Sediqi
  • Axel De Baat
  • Hananel Hazan
  • Franz Kuchling

Levin Lab Admin:

  • Bryanna Vacanti
  • Emma Taddeo
  • Robert Brucker