Spanda
Under research

Life, by conservation.

Spanda is a virtual cell that cannot break the laws of thermodynamics — and from that single, unbreakable constraint, growth, homeostasis, and death emerge on their own. It is the first whole-cell model where free energy is conserved at every event.

70%
of reactions violate detailed balance
50,000×
error the invariant exposes
13–17%
reversed — across 3 organisms
Living cell · fed · live alive
50%
energy charge
10
transporter
0
entropy ↑
Drive it — starve it, knock out a gene, poison it

Not a recording — the real 13-reaction thermodynamic engine, running live in your browser. Detailed balance holds at every event.

The one law
kf/kr=e−ΔG°/RT

One reference rate per reaction, split symmetrically by free energy. The forward and reverse directions can never disagree with thermodynamics — so the simulator can produce or consume energy only through the bath, never from internal inconsistency.

Why it's a different kind of model

Most cell models are fitted. This one is derived.

A model you tune until it matches the data can be tuned to show you almost anything. A model where the behaviour of life falls out of one unbreakable law is making a real, checkable claim — and that is what makes it worth trusting.

Every other whole-cell model
  • Forward and reverse rates are set independently, from different databases — so the model can quietly manufacture free energy.
  • Life-like behaviour is fitted or hand-coded to match the data it was built from.
  • Growth, a cell cycle, division, death — each one has to be scripted in by hand.
  • Predictions quietly inherit whatever inconsistencies are hiding inside.
Spanda
  • One reference rate per reaction — free energy is conserved at every single event.
  • Growth, homeostasis and three modes of death emerge on their own — nothing is scheduled.
  • Turn the law off in a null control and the life-like behaviour disappears.
  • It cannot cheat thermodynamics — so what it predicts can be trusted.
What “emergent” means

We write down thirteen reactions and one conservation law — and nothing else. The cell that grows, holds itself steady, and dies three different ways is never coded; it appears as a consequence of the rules.

Why it's the harder test

A fitted model can be tuned to reproduce anything you already know. An emergent one is falsifiable: break detailed balance and the behaviour collapses — a null control we actually run.

Why that makes it superior

Fitted models interpolate; a derived model predicts. Emergence is the evidence the physics underneath is right — and right physics is what makes a virtual cell worth believing.

The idea

Treat free-energy conservation the way a physics engine treats momentum — as a law that cannot be broken — and a cell starts to behave like a cell.

Every whole-cell model ever built specifies each reaction's forward and reverse rates as independent numbers, pulled from different databases. Nothing forces them to agree with thermodynamics. Spanda forces it: one reference rate, split symmetrically by ΔG°, so detailed balance holds at every event. From that single constraint, two things follow — life-like behaviour emerges for free, and the errors hiding in everyone else's models become visible.

01

One conserved law

Forward and reverse propensities are derived from a single reference rate via k_f = k₀·e^(−ΔG°/2RT). The simulator can produce or consume free energy only through the bath — never from internal inconsistency. Parameterised entirely from eQuilibrator standard Gibbs energies.

02

Emergence, not scripting

A 13-reaction proof-of-concept produces a non-trivial steady state, positive energy charge, strictly-positive entropy production, and three distinct death modes — starvation, gene knockout, waste poisoning — with no scheduler and no death logic. The biology falls out of the chemistry.

03

An audit of the field

Run the same check against the best published cell models and 70% of reactions violate detailed balance; 27% point the wrong way. The pattern is universal across the prokaryote–eukaryote divide — and statistically far from random, so it reflects real database structure, not noise.

04

A falsifiable prediction

The thermodynamic model says JCVI-syn3A should pool lactate over pyruvate 564 : 1 — consistent with known Mycoplasma fermentation; the existing model says the opposite. One metabolomics run settles it. Science you can disprove is the only kind worth selling.

What the invariant reveals

Three findings, all reproducible.

All findings
01 · The audit
70%of reactions violate
detailed balance

In the leading minimal-cell model, 27% of reactions with data (21 of 77) run the wrong thermodynamic direction at standard state — including 5 of 10 glycolytic steps. Median violation: 12-fold.

02 · The prediction
50,000×disagreement on
one reaction

For lactate dehydrogenase, thermodynamics says syn3A should pool lactate over pyruvate 564 : 1 — matching textbook Mycoplasma fermentation. The published model says 0.011 : 1. One metabolomics run decides it.

03 · The universality
13–17%reversed, in
every organism
JCVI-syn3A16.8%
E. coli iML151516%
S. cerevisiae · Yeast-GEM v913%

Prokaryote to eukaryote · 7,181 reactions audited · far from a shuffled-K_eq null (40%).

Intellectual honesty

What's emergent, what's engineered.

The interesting claim is that biology emerges from the physics. So we keep a ledger — and label exactly what we built in versus what fell out. The honesty is the product.

Engineered
Detailed balance k_f/k_r = e^(−ΔG/RT)
The central axiom of the framework — by construction, not emergent.
Emergent
Metabolic bistability (persister-like states)
Appears with the invariant ON; disappears under a detailed-balance-violated null control.
Emergent
Three death modes (starve / knockout / poison)
No death logic is written; collapse follows from the chemistry — reproduce it live in the simulator.
Emergent*
~105-min cell cycle
Division at the Young-Laplace instability from measured constants — but timescale calibration is uncertain; reported with two options side-by-side.
Emergent
Cross-organism universality of violations
Independent datasets (syn3A, E. coli, yeast); significant against a shuffled-K_eq null.
Partial
Gene-essentiality correlation
Partly recapitulates the proteomics used to initialise it; quantified with a uniform-IC control.
Not yet
Dynamic ribosome biogenesis
Ribosome pool is held static in this version; a dynamic module is built but not yet wired in.
Not yet
FtsZ division-ring dynamics
Implemented separately; not yet coupled to the main cell-cycle loop.

* Emergent, but with calibration uncertainty — reported with two options side-by-side. Full detail on the findings page.

The bet

A virtual cell as trustworthy as a physics engine.

Drug discovery, strain design, and basic biology still run on wet-lab cycles measured in months and millions. A whole-cell simulator you could actually believe — one that can't violate the second law, that you can perturb and query in silico — would compress those cycles the way computational fluid dynamics compressed the wind tunnel. Spanda's bet is that thermodynamic consistency is the missing foundation: get the physics exactly right at the smallest scale, and the biology becomes predictive. We start with the minimal cell because it is the one place this is tractable today — and build outward.

Back the research

This is the stage where backing matters most — before revenue, while the science is still being settled. The decisive next experiment is one metabolomics run, not a wet lab of our own.

See how to support

Sponsorship & partnership — not equity. There is no product yet, and we won't pretend otherwise.

स्पंद · the pulse

Don't take our word. Drive the cell.

Feed it, starve it, knock out a gene, poison it — and watch life and death follow from the chemistry alone.