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.
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.
Not a recording — the real 13-reaction thermodynamic engine, running live in your browser. Detailed balance holds at every event.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Prokaryote to eukaryote · 7,181 reactions audited · far from a shuffled-K_eq null (40%).
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.
* Emergent, but with calibration uncertainty — reported with two options side-by-side. Full detail on the findings page.
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.
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.
Sponsorship & partnership — not equity. There is no product yet, and we won't pretend otherwise.
Feed it, starve it, knock out a gene, poison it — and watch life and death follow from the chemistry alone.