LatentCellBio × AI Weekly

From a Slime Mold to a Heart Drug — and What AI Does Next

Jul 22, 2026 · #drug-discovery#protein-design

Over six decades at one question — how do muscles move? — chased from a slime mold all the way to an FDA-approved heart drug.

Jongmin Sung with James Spudich at his lab, Stanford
With James Spudich — my scientific root and hero — at his lab, Stanford.
Book cover: They Called Me Mad by John Monahan
They Called Me Mad — genius, madness, and the scientists who pushed the edge.

TL;DR

A 31-year-old cattle rancher can play with his kids again because of mavacamten, an FDA-approved drug for a thickened, overworking heart. Its story starts in 1971, with James Spudich studying how a slime mold moves. That fifty-year arc — from an obscure amoeba to a first-in-class cardiac drug — is also a blueprint for AI: every step along the way was a measurement problem, and measurement is exactly where AI now compounds.

Start here: a story worth reading

Stanford Medicine magazine (Stanmed) has a piece I keep coming back to — “Innovation in bloom: How curiosity, collaboration and public funding grew into a lifesaving therapy,” by Krista Conger.

👉 https://stanmed.stanford.edu/mavacamten-heart-drug-power-discovery/

It’s the rare science story that earns the word beautiful: a fifty-year line that runs from an obscure amoeba in a Stanford lab to a pill that lets a young rancher play with his kids again. Read it. Then come back — because the arc it tells is, quietly, also a blueprint for how AI is about to accelerate biology.

The beautiful story, in short

The article opens not with a molecule but with a person: Jack Gardella, a 31-year-old cattle rancher diagnosed at 21 with hypertrophic cardiomyopathy (HCM) — a thickened, overworking heart. By 2024 he was short of breath doing ordinary things. Then he started mavacamten. His words: “I feel a lot better. I am not short of breath.” He could play with his children again.

How did a drug like that come to exist? Not from a drug program. It started with pure curiosity:

  • 1971 — an unlikely model organism. James A. Spudich chose Dictyostelium, a slime mold, because it was easy to grow and genetically tractable — “so far flung from what might today be considered important for drug discovery,” yet perfect for studying how actin and myosin generate motion.
  • A happy accident. A grad student stumbled onto homologous recombination in Dictyostelium — meaning the lab could now swap myosin genes and watch what mutations do. Biochemistry married to genetics.
  • Watching one molecule move. The lab learned to see myosin work directly — actin filaments gliding across a myosin-coated slide, then, with Nobel physicist Steven Chu, a laser trap measuring the force of a single motor. Spudich’s line: “Watching the actin filaments move across the myosin-coated glass at the same rate they move when your muscle contracts was a total wow moment.”
  • The turn toward the heart. A 1990 Harvard discovery tied myosin mutations to inherited HCM. But human β-cardiac myosin couldn’t even be produced in the lab until 2010, when Colorado researchers cracked it — finally letting Spudich study the human disease protein directly.
  • The puzzle and the dream. Founding MyoKardia in 2012, the team hit a wall: HCM mutations didn’t make each myosin stronger. In 2014 the answer came to Spudich in a dream — the mutations increase the number of myosin heads pulling, a “mismatched game of tug-of-war.”
  • The medicine. MyoKardia built a small molecule to take the excess heads offline. Bristol-Myers Squibb bought the company in 2020; the FDA approved mavacamten (Camzyos) in 2022 — roughly $1 billion and fifty years after a curiosity about slime-mold motion.

The magazine’s thesis is the part worth underlining: lifesaving drugs grow out of curiosity-driven, publicly funded science with no guaranteed payoff. Nobody funds “esoteric amoeba biochemistry” to cure hearts. It cured hearts anyway.

The man behind it: James A. Spudich’s achievements

Strip the story to its load-bearing beams and you get one of the cleanest bench-to-bedside careers in modern biology:

When Contribution What it was
early 1960s Undergraduate research with J. W. Hastings Got his first taste of the bench as an undergraduate with John Woodland “Woody” Hastings, a pioneer of bioluminescence and biological clocks — an early dose of curiosity-driven biology.
1968 PhD in the Kornberg lab Trained under Arthur Kornberg (DNA-polymerase Nobelist) in Stanford’s biochemistry department — where he absorbed the purify every part, reconstitute the whole ethos that ran through everything after.
1968–71 Postdoc with Hugh Huxley (MRC, Cambridge) With Hugh E. Huxley — co-author of the sliding-filament theory — he did electron-microscopy structural biology of the thin filament: how the tropomyosin–troponin complex sits on actin and swings to switch contraction on and off (Spudich, Huxley & Finch, J. Mol. Biol., 1972).
1971 Actin purification (Spudich–Watt) A clean, single-band actin prep still standard 50 years on — the reagent under nearly every myosin experiment.
1983–86 In vitro motility assay With Michael Sheetz, showed myosin + actin + ATP alone suffice for motion (1983); the Kron–Spudich assay (1986) made watching one motor routine.
1985 A scientific lineage → kinesin The reconstitution mindset radiated out: Ronald Vale (Stanford-trained in Spudich’s orbit), with Reese and Sheetz, discovered kinesin, the cargo motor of nerve cells.
1994 Single-molecule force With physicist Steven Chu — a laser-cooling Nobelist, whose optical trap is the very tool used here — they trapped one myosin in a laser and measured its force and step size (Finer, Simmons & Spudich), proving how the motor works by direct measurement.
1998 Stanford Bio-X Led the grassroots founding — pitched with Steven Chu to Provost Condoleezza Rice — of Stanford’s cross-disciplinary program, and became its first director.
2010 → Human HCM mechanism Once human β-cardiac myosin could finally be expressed (2010), he explained how point mutations cause HCM — by shifting myosin’s folded, auto-inhibited “super-relaxed” state and releasing too many heads.
2012 Lasker Award Shared the Albert Lasker Basic Medical Research Award with Sheetz and Vale for cytoskeletal motor proteins — often called “America’s Nobel.”
2012 → 2022 From mechanism to medicine Co-founded MyoKardia (2012) → mavacamten, first-in-class cardiac myosin inhibitor, FDA-approved 2022. (Earlier co-founded Cytokinetics → omecamtiv, a myosin activator.)

The through-line: purify the parts → measure the single molecule → understand the mutation → drug the mechanism.

Why this is now an AI story

Every step in Spudich’s arc was a measurement problem — and measurement is exactly where AI compounds:

  • Structure → mechanism at scale. The auto-inhibited/super-relaxed state Spudich inferred from biophysics is now something AlphaFold-class models and MD can render and perturb in silico, mutation by mutation, before a protein is ever expressed.
  • One mutation → all of them. Protein language models and variant-effect predictors can triage thousands of MYH7 variants for pathogenicity — turning a one-at-a-time bench program into a genome-wide screen.
  • One drug → a designed series. Generative design plus affinity prediction (FEP, ML scoring) aim to do for the next mavacamten what took a decade of screening: propose, rank, refine.
  • The harness. Agentic pipelines can chain these — read the literature, predict a structure, score a variant, propose a molecule. That automated loop is what a modern Bio-X looks like.

The lesson from Spudich isn’t the technology; it’s the philosophy: reconstitute from trustworthy parts, measure the smallest unit directly, let mechanism drive the medicine. AI is just the newest instrument on that same bench — and, like a slime mold in 1971, the payoff may come from somewhere nobody would fund on purpose.

Further reading

If the through-line here — obsessive curiosity pushing past what looks reasonable — is your kind of story, John Monahan’s They Called Me Mad: Genius, Madness, and the Scientists Who Pushed the Outer Limits of Knowledge (the book whose cover opens this post) is a fun tour of the same spirit — Tesla, Einstein, and a gallery of scientists who pushed the edge.

Sources

Canonical: https://latentcell.ai/posts/slime-mold-to-heart-drug