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

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

Five decades on 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 [1]. 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 [1].

👉 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 [1].

How did a drug like that come to exist? Not from a drug program. It started with pure curiosity [1]:

  • 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 had its clinical lead in hand within six months — a cardiac-myosin inhibitor optimized from chemistry licensed from Cytokinetics. What they lacked was the why: HCM mutations didn’t make each myosin stronger. In 2014 that answer came to Spudich in a dream — the mutations increase the number of myosin heads pulling, a “mismatched game of tug-of-war” [2]. The dream explained why the molecule they already held could work.
  • The medicine. That inhibitor — designed to take the excess heads offline — became mavacamten. Bristol-Myers Squibb bought the company in 2020; the FDA approved mavacamten (Camzyos) in 2022 for adults with symptomatic obstructive HCM — roughly $1 billion and fifty years after a curiosity about slime-mold motion [1].

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 treat hearts. Five decades later, it helped produce the first mechanism-targeted therapy for obstructive HCM 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 [3].
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) [4].
1971 Actin purification (Spudich–Watt) A clean, single-band actin prep still standard 50 years on — the reagent under nearly every myosin experiment [5].
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 [6][7].
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 [8].
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 [9].
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 [10].
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 [1].
2012 Lasker Award Shared the Albert Lasker Basic Medical Research Award with Sheetz and Vale for cytoskeletal motor proteins — often called “America’s Nobel” [11] [12].
2012 → 2022 From mechanism to medicine Co-founded MyoKardia (2012) → mavacamten, first-in-class cardiac myosin inhibitor, FDA-approved 2022 for symptomatic obstructive HCM [1]. (Earlier co-founded Cytokinetics → the myosin activator omecamtiv and the inhibitor aficamten (Myqorzo), FDA-approved Dec 2025 [13].)

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 turn into testable hypotheses — which interfaces a mutation perturbs — before a protein is ever expressed. They don’t yet replace measuring head availability, SRX occupancy, or force; they narrow what to measure.
  • One mutation → all of them. Protein language models and variant-effect predictors can prioritize thousands of MYH7 variants for expert review and functional testing — turning a one-at-a-time bench program into a genome-wide triage, with pathogenicity still established by mechanism, structure, and clinical evidence.
  • 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

  1. Stanford Medicine, Krista Conger, “Innovation in bloom: How curiosity, collaboration and public funding grew into a lifesaving therapy” — https://stanmed.stanford.edu/mavacamten-heart-drug-power-discovery/
  2. Stanford Medicine News, “Mystery novel and dream spur key scientific insight” (2019) — the story behind the 2014 tug-of-war insight — https://med.stanford.edu/news/all-news/2019/03/mystery-novel-and-dream-spur-key-scientific-insight.html
  3. Stanford Medicine News, “Lasker Award goes to biochemist James Spudich” (2012) — biographical spine (PhD with Arthur Kornberg; postdoc with Hugh Huxley at Cambridge) — https://med.stanford.edu/news/all-news/2012/09/lasker-award-goes-to-biochemist-james-spudich.html
  4. Thin-filament structure — Spudich, J.A., Huxley, H.E. & Finch, J.T., “Regulation of skeletal muscle contraction. II. Structural studies of the interaction of the tropomyosin–troponin complex with actin,” J. Mol. Biol. 72(3):619–632 (1972) — https://pubmed.ncbi.nlm.nih.gov/4349760/
  5. Actin purification — Spudich, J.A. & Watt, S., “The regulation of rabbit skeletal muscle contraction. I. Biochemical studies of the interaction of the tropomyosin–troponin complex with actin…,” J. Biol. Chem. 246(15):4866–4871 (1971) — https://pubmed.ncbi.nlm.nih.gov/4254541/
  6. In-vitro motility (1983) — Sheetz, M.P. & Spudich, J.A., “Movement of myosin-coated fluorescent beads on actin cables in vitro,” Nature 303(5912):31–35 (1983) — https://pubmed.ncbi.nlm.nih.gov/6682486/
  7. Kron–Spudich motility assay (1986) — Kron, S.J. & Spudich, J.A., “Fluorescent actin filaments move on myosin fixed to a glass surface,” PNAS 83(17):6272–6276 (1986) — https://pubmed.ncbi.nlm.nih.gov/3462694/
  8. Kinesin: Vale, Reese & Sheetz, Cell 42:39 (1985) — https://www.cell.com/cell/abstract/S0092-8674(85)80099-4
  9. Single-molecule force — Finer, J.T., Simmons, R.M. & Spudich, J.A., “Single myosin molecule mechanics: piconewton forces and nanometre steps,” Nature 368(6467):113–119 (1994) — https://pubmed.ncbi.nlm.nih.gov/8139653/
  10. Stanford Bio-X history & timeline — https://biox.stanford.edu/about/biox-history
  11. Lasker Foundation, 2012 motor-proteins citation — https://laskerfoundation.org/winners/motor-proteins-that-contract-muscles-and-enable-cell-movements/
  12. Stanford Bio-X, “Lasker Award goes to biochemist James Spudich” — https://biox.stanford.edu/highlight/lasker-award-goes-biochemist-james-spudich
  13. Cytokinetics, “FDA Approval of MYQORZO (aficamten)…” (Dec 19, 2025) — https://ir.cytokinetics.com/press-releases/press-release-details/2025/Cytokinetics-Announces-FDA-Approval-of-MYQORZO-aficamten-for-the-Treatment-of-Adults-with-Symptomatic-Obstructive-Hypertrophic-Cardiomyopathy-to-Improve-Functional-Capacity-and-Symptoms/default.aspx

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

CiteSung, J. (2026). "From a Slime Mold to a Heart Drug — and What AI Does Next." LatentCell. https://latentcell.ai/posts/slime-mold-to-heart-drug

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