---
title: "Substrates Unbound"
description: "Laura Tripaldi asks what a \"substrate\" is once living neurons and silicon electrodes are wired together in a single computing device."
type: "reading-notes"
authors:
  - "Laura Tripaldi"
published: "2025-11-21"
original_url: "https://substrates.antikythera.org/"
doi: "10.1162/ANTI.5D07"
canonical_url: "https://antikythera.wiki/work/journal/substrates"
md_url: "https://antikythera.wiki/md/work/journal/substrates"
last_updated: "2026-08-23"
site: "Antikythera Wiki"
---

# Substrates Unbound

> Independent, unofficial reading notes from Antikythera Wiki (https://antikythera.wiki). Written with AI from the published text, with citations; not by the work's author and not affiliated with Antikythera (https://antikythera.org). Read the original at the link below.

- **Authors:** Laura Tripaldi
- **Published:** 2025-11-21
- **Kind:** Journal · Journal article
- **DOI:** https://doi.org/10.1162/ANTI.5D07
- **Original:** https://substrates.antikythera.org/
- **Length:** 11k words
- **This page:** https://antikythera.wiki/work/journal/substrates
- **Notes generated:** 2026-08-23

## Summary

[Laura Tripaldi](https://antikythera.wiki/people/laura-tripaldi) asks what a "substrate" is once living neurons and silicon electrodes are wired together in a single computing device. Her answer is that the substrate is not the passive floor beneath a function but a participant that shapes which functions are possible at all. She reaches it through two figures a thousand years apart: the alchemical homunculus, a synthetic human grown from sperm, blood, and minerals in a sealed vessel, and DishBrain, the 2022 device in which cultured cortical neurons learned to play Pong. Both confound the line between natural and artificial, and both make intelligence depend on the particular matter it runs on. Tripaldi argues that the two inherited ways of relating organisms and machines, technomorphism ("the cell is a computer") and biomimesis ("the computer is a faulty copy of the brain"), each erase the agency of substrates, one by making all substrates interchangeable and the other by fixing the natural substrate as the only real one. She proposes a third position, an agential materialism in which the interface between substrates is a site of co-construction.

## The argument

Tripaldi opens with the observation that contemporary technology proceeds by "mutual contamination" of natural and artificial realities, both in the traffic of models and metaphors between biology and engineering and in hybrid devices that physically interweave organisms and machines. Two problems follow: the machine/organism binary has become harder to draw, and the role of substrates in these hybrids is unclear. Her central move is to treat these as one problem. The word "substrate" (sub stratum, that which lies below) already encodes subservience, and conventional computing formalises it in the separation of hardware from software. Once that separation is accepted, each side of the AI debate uses the substrate to settle the ontology. Both sides miss the substrate's capacity to reshape function.

The next step is genealogical. Following William R. Newman's history of alchemy, Tripaldi reads the homunculus as the first speculative artificial-intelligence project: alchemy sought to replicate natural processes materially rather than imitate them mechanically, and the homunculus was its hardest case because it required a rational soul as well as a body. She then turns to synthetic biological intelligence (SBI) and shows in technical detail how DishBrain's learning depends on substrate-specific facts, from induced pluripotent stem cells to a training protocol derived from Friston's free-energy principle that works only because neurons respond to predictability. SBI, she argues, does not simulate cognition but materially enacts it.

With the two cases in hand, Tripaldi excavates the paradigms they disrupt. Technomorphism is her name for the stance, running from La Mettrie's clockwork man through the information-theoretic biology that Evelyn Fox Keller documents to Liberman's "molecular computer" and [Blaise Agüera y Arcas](https://antikythera.wiki/people/blaise-aguera-y-arcas)'s claim that DNA is literally a program, in which the machine becomes a universal archetype under which organisms are subsumed. Its cost is substrate indifference. Biomimesis, exemplified by Searle, is the opposing stance in which nature is the archetype and technology a simulation that can never duplicate it. Its cost is a frozen, essentialised substrate. Tripaldi credits technomorphism with dissolving the old hierarchy but argues it installs a new one.

Her constructive proposal comes through the notion of interface. In materials science an interface has properties that belong to neither bulk material, and its constituent terms emerge only as products of the encounter. The interface operates epistemologically, in Keller's sense that modelling brains on computers and computers on brains changes both, and ontologically, producing new bodies for new machines. Luciana Parisi's "hypernature," in which the technical and the natural become continuous through matter's own powers of association, names the resulting horizontal ontology. The final section calls this a substrate ontology, contrasts the homunculus with the golem (clay animated by a word, the ancestor of substrate indifference from Wiener's telegraphed human to the OpenWorm project), and identifies two features of SBI that no silicon computer has: nano-intentionality, borrowed from Tecumseh Fitch, and onto-/phylogenetic diversity, seen in DishBrain's different behaviour with mouse and human neurons. Biological computers point to a third substrate ontology in which matter is neither indifferent carrier nor preordained host but actively engenders differential forms of intelligence.

## Section by section

### Introduction

Tripaldi sets the frame: natural and artificial realities contaminate each other epistemologically and ontologically, computer hardware is blending with neuron cultures, and the old hierarchies no longer hold. A machine ontology that overcomes the artifice/nature binary without privileging either side must, she says, recognise substrates as holding intrinsic agency. The analytical work is on the word "substrate": its etymology encodes passivity, the hardware/software split reproduces that passivity as design philosophy, and AI's critics and defenders share the framing while disagreeing about which substrate deserves metaphysical credit. The natural/artificial line and the substrate/function line, she argues, cannot be questioned separately.

### The Homunculus Problem

Tripaldi recounts two recipes: the tenth-century Liber vaccae, in which human sperm is deposited in a cow, the skinless offspring is buried in a powder of sunstone, sulfur, magnetite, and zinc oxide, and after a year begins revealing "all things that are absent"; and the sixteenth-century De Natura Rerum attributed to Paracelsus, in which sperm sealed in glass and incubated in horse dung grows into an all-knowing being. Through Newman's Promethean Ambitions she argues that alchemy, unlike the mechanical tradition of automata, aimed to replicate nature's own processes, accelerated in the laboratory.

The claim that gives the section its title is that the homunculus problem was already a problem of artificial intelligence. Spontaneous generation of animals was uncontroversial after Aristotle; generating a rational soul was not, and its makers held that this required working with the material complexity of natural processes rather than mechanical mimicry.

### Brains in a Dish

Neural interfaces begin with Hans Berger's EEG measurements in the 1930s. Tripaldi separates in-vivo brain–computer interfaces such as Neuralink ("internalization of the computer") from in-vitro cultures ("externalization of the brain") and restricts the essay to the latter. The first "neurochip," announced by a Caltech group in 1997, placed rat embryonic neurons by hand into silicon wells with sixteen electrodes, where they survived no more than two weeks.

The turn came in 2006 with induced pluripotent stem cells, which revert adult cells to a pluripotent state and can be differentiated into cortical neurons, together with high-density arrays packing tens of thousands of electrodes into a few square millimetres. DishBrain, published in Neuron in 2022 by Brett Kagan's team at Cortical Labs, cultured a single layer of human and rat cortical neurons on such an array; the electrodes delivered "sensory" signals encoding paddle and ball position, the neurons' activity moved the paddle, and the loop closed in real time.

The training protocol carries the philosophical weight. It applied Friston's free-energy principle, on which a neural system tends to reduce its exposure to unpredictable stimuli. Successful interceptions were rewarded with predictable stimulation and misses punished with chaotic patterns; performance improved within minutes and not at all without feedback. Tripaldi's point is that the software is shaped by the substrate's physiology, since feedback must be biologically meaningful. Beyond the engineering case (lower energy, shorter training), SBI's plastic organisation "materially enacts" cerebral processes rather than modelling them.

### Technomorphism and Biomimesis

Statements like "the brain is a computer" span a spectrum from loose analogy to strict ontological equivalence, and usually conceal a hierarchy in which one term is the archetype for the other. La Mettrie's L'homme machine (1747) extends Descartes's bête-machine from animal physiology to the human mind. Tripaldi quotes the springs and "the human body is a clock" and isolates the real move: "machine" and "clock" stop naming artefacts and become placeholders for a metaphysical idea of which both organisms and machines are instances. This is technomorphism, and substrate indifference is both its premise and its consequence, since a category covering both nuts and bolts and blood and flesh must be independent of embodiment.

She follows the stance into the twentieth century through Keller's Refiguring Life. "Genetical information" made DNA the primary agent in biology and the rest of the cell passive, the "discourse of gene action"; Keller's objection, which Tripaldi endorses, is that Shannon information has no place for meaning, while a single base-pair change can be "the difference between life and death." Liberman's 1970s theory of the cell as a stochastic "molecular computer" ends in the claim that cells and brains are universal computers equivalent to any other. Agüera y Arcas's What Is Intelligence? is its most recent descendant: because any computer can emulate any other, differences between cells and Von Neumann machines are ontologically inconsequential, and calling DNA a program is "literally the case."

Tripaldi declines to call this reductionism. Her objection is narrower: the continuity is bought by erasing the substrate's capacity to shape which functions are possible, so that hybrid devices would change nothing about machine ontology. Biomimesis gets shorter treatment: the Aristotelian position that art imitates nature, underwriting the "substrate-bound" view of mind, with Searle's passage about simulated digestion not digesting pizza quoted as the exemplary statement. Her verdict is symmetrical. Biomimesis declares the natural substrate fixed, technomorphism renders all substrates interchangeable, and neither can account for actual hybrids.

### Material Interfaces

The substrate's power, Tripaldi says, is one of "unbinding": loosening matter from subordination to function and undoing the artifice/nature divide together. The concept she builds on is interface. In materials science the interfacial region exhibits behaviours absent from either bulk material, and contemporary readings treat it as a zone in which two substrates have their properties redefined by the encounter; the paradox is that the interface is conceived as a union of two prior terms, but the terms emerge only as its product. On the epistemological level, Keller's claim that scientific language is performative means that modelling the brain as a computer changes both brain science and computer engineering, an open loop rather than a mirror. On the ontological level, interfaces produce "new bodies for new machines," and the direction of that contamination is contingent rather than convergent on any ideal form.

Parisi's Abstract Sex supplies the final piece. Where Haraway's cyborg deconstructs nature as a locus of purity, Parisi argues that substrates have always exceeded their own nature at the molecular level, as bacterial cloning, horizontal gene transfer, and endosymbiosis show. Her "hypernature," a "machinic phylum of unnatural associations," naturalises technology rather than projecting technology onto nature. Tripaldi prefers it to the cyborg for devices like DishBrain. Agential materialism, she says, can be translated as "letting the substrate speak."

### Substrate Ontologies

The alchemist had to wait for the homunculus's skin to grow: acceleration could not abolish the durations dictated by the material. This yields Tripaldi's definition of a substrate ontology, the vision of how natural and artificial divide and what role materiality plays in negotiating that boundary, which every design approach presupposes.

The golem is the homunculus's counter-figure. Formed from clay and animated by the inscription of emeth on its forehead, reverting to dirt when the first letter is erased to leave meth, it demonstrates the power of verbal magic rather than biological process. Tripaldi quotes Newman's contrast between the golem's "hard" world of robotics and AI and the homunculus's "wet" world of IVF and genetic engineering, and reads the golem as the forerunner of substrate indifference. Wiener's suggestion that a human could be sent over a telegraph line and the OpenWorm project's cell-precise digital twin of C. elegans are its descendants.

Against this she names two properties of biological computers. Nano-intentionality, from Fitch, is the capacity of every eukaryotic cell to perceive its surroundings and respond by changing its morphology, which Fitch takes to be the evolutionary root of intentionality and the "missing link" absent from silicon, whose transistors are engineered not to change. Tripaldi's addition is that DishBrain shows nano-intentional devices can be designed: its neurons formed functional connectivity across spatial distance in response to training. Onto-/phylogenetic diversity rests on Kagan's finding that mouse neurons played better at first while human neurons learned faster and moved more exploratively under identical inputs, so that intelligent behaviour in SBI retains a contingency tied to each culture's physiology and history.

Tripaldi concludes that these features transfigure what a computer is. Technomorphism treats intelligence as substrate-indifferent, biomimesis as substrate-bound, with the function either present or absent but never transforming with its support. Biological computers suggest a third ontology in which substrates actively give rise to parallel forms of intelligence shaped by embodied difference.

## Key concepts

- **[Substrate Agency](https://antikythera.wiki/terms/substrate-agency)** — The capacity of a material substrate to shape not only how a function is performed but which functions are possible; Tripaldi's central claim, opposed to the etymological passivity of "that which lies below."
- **[Technomorphism](https://antikythera.wiki/terms/technomorphism)** — The stance, from La Mettrie to Agüera y Arcas, that raises technical reality to a universal archetype covering both machines and organisms, at the cost of treating all substrates as interchangeable.
- **Biomimesis** — The opposing stance, Aristotelian in origin and exemplified by Searle, that art imitates nature and can never duplicate it, which makes intelligence "substrate-bound" to the brain.
- **Substrate indifference** — The assumption shared by technomorphic positions and the golem myth that matter is a passive carrier of a disembodied function, so that any computer can emulate any other without ontological consequence.
- **[Substrate Ontology](https://antikythera.wiki/terms/substrate-ontology)** — The implicit vision, presupposed by any design approach, of how the natural and artificial divide and what role materiality plays in negotiating that boundary; the homunculus and golem stage two competing ones.
- **[Synthetic Biological Intelligence](https://antikythera.wiki/terms/synthetic-biological-intelligence)** — Kagan's term for devices such as DishBrain in which live neurons are interfaced with electronics and learn within a simulated environment; for Tripaldi, cognition materially enacted rather than modelled.
- **Interface** — A material zone of co-construction whose properties differ from those of either substrate and whose constituent terms emerge only as its product; operative at both epistemological and ontological levels.
- **Hypernature** — Parisi's name for the space in which technical and natural realities become continuous through matter's own powers of association; Tripaldi adopts it as a horizontal ontology preferable to the cyborg.
- **[Nano-intentionality](https://antikythera.wiki/terms/nano-intentionality)** — Fitch's term for the capacity of eukaryotic cells to perceive and adaptively reshape their own morphology, which Tripaldi argues biological computers show can be designed into a device.

## Connections

- [What Is Intelligence?](https://antikythera.wiki/work/book/what-is-intelligence) is the essay's named antagonist. Tripaldi quotes Agüera y Arcas's claims that computability is universal "regardless of how it's done" and that DNA is literally a program, and treats them as the current form of technomorphism.
- [Organoid Array Computing](https://antikythera.wiki/work/journal/coginfra/organoid-array-computing), within [Cognitive Infrastructures](https://antikythera.wiki/work/journal/coginfra), covers the same DishBrain experiment and the wider design space of organoid intelligence from an engineering standpoint. The two agree on the facts; Tripaldi supplies the philosophical framing that paper leaves implicit.
- [Cognition With and Beyond the Brain](https://antikythera.wiki/work/journal/coginfra/cognition-with-and-beyond-the-brain) and [Modes of Cognition](https://antikythera.wiki/work/journal/modesofcognition) share Tripaldi's interest in cognition arising from non-brain substrates, though they are less committed to the materialist ontology she draws from Parisi.
- [Recursive Worlds](https://antikythera.wiki/work/journal/recursiveworlds) and [The Long L](https://antikythera.wiki/work/journal/longl) describe intelligence as information propagating across substrates over time, which is closer to the technomorphic pole Tripaldi criticises. Walker's account makes selection the agent and the material its carrier; Tripaldi makes the material itself agential. The tension is real and neither work addresses the other.


## Terms used

- [Computation](https://antikythera.wiki/terms/computation)
- [Functionalism](https://antikythera.wiki/terms/functionalism)
- [Generalized Biomimesis](https://antikythera.wiki/terms/generalized-biomimesis)
- [Life](https://antikythera.wiki/terms/life)
- [Machine Phase](https://antikythera.wiki/terms/machine-phase)
- [Nano-intentionality](https://antikythera.wiki/terms/nano-intentionality)
- [Polycomputation](https://antikythera.wiki/terms/polycomputation)
- [Predictive Intelligence](https://antikythera.wiki/terms/predictive-intelligence)
- [Substrate Agency](https://antikythera.wiki/terms/substrate-agency)
- [Substrate Ontology](https://antikythera.wiki/terms/substrate-ontology)
- [Synthetic Biological Intelligence](https://antikythera.wiki/terms/synthetic-biological-intelligence)
- [Technomorphism](https://antikythera.wiki/terms/technomorphism)

## Related works

- [Cognitive Infrastructures](https://antikythera.wiki/work/journal/coginfra)
- [Modes of Cognition](https://antikythera.wiki/work/journal/modesofcognition)
- [Existential Technologies](https://antikythera.wiki/work/journal/existentialtech)
- [Antikythera](https://antikythera.wiki/work/journal/research)