The history
From Galen's pairs and Borelli's levers to a frog in a syringe and two papers that changed biology on the same day.
For two thousand years people thought muscles swelled with spirit sent down the nerves. Then a frog muscle in a glass tube showed nothing flows in, a mathematician treated bones as levers, and sparks showed the signal is electric. The twentieth century found the fuel, ATP, and the motors, actin and myosin, and in 1954 showed that they slide. Today the story is about genes, ageing and keeping muscles strong.
c. 500 peshi
Count of the body's muscles
Sushruta Samhita, India
c. 170
Muscles described as working in opposing pairs
Galen, Rome
c. 1660s
Proof that a contracting muscle does not swell
Jan Swammerdam, Netherlands
1680
Muscles analysed as levers
Giovanni Alfonso Borelli, Italy
1864
Muscle protein isolated (myosin)
Wilhelm Kühne, Germany
22 May 1954
Sliding filament theory
A. F. Huxley & R. Niedergerke; H. E. Huxley & J. Hanson, UK
600 BCE – 300
Sushruta counts muscles, Aristotle asks how animals move, and Galen shows muscles pull in opposing pairs.
600 BCE
c. 600 BCE to 300 CE (dates much debated)
The Sushruta Samhita, a Sanskrit surgery text, lists about 500 peshi (muscles), with 20 more in women, alongside bones, joints and vessels. Its authors learned anatomy by studying bodies softened in water.
Why it mattered. It is one of the oldest systematic counts of the body's muscles, not far from today's figure of more than 600.
350 BCE
c. 350 BCE
Aristotle wrote a short book asking how animals move. He saw that movement needs a fixed point to push against and something inside that pulls, though he thought the power came from the heart and "pneuma", a kind of warm breath.
Why it mattered. He framed the question every later muscle scientist tried to answer.
260 BCE
c. 260 BCE
Erasistratus dissected bodies in Alexandria and traced nerves into muscles. He thought a muscle shortened because it swelled with pneuma sent down the nerves, getting fatter as it got shorter.
Why it mattered. The "inflation" idea lasted for almost 2,000 years until experiments disproved it.
170
c. 170
Galen, doctor to Roman gladiators and emperors, wrote "On the Movement of Muscles". He showed that muscles act only by pulling, that they work in opposing pairs, and that cutting a nerve paralyses the muscle it serves.
Why it mattered. The idea of antagonist pairs, like the biceps and triceps, starts with him.
1500 – 1600
Leonardo and Vesalius draw muscles from real dissections, layer by layer.
1543
Vesalius published De humani corporis fabrica, a huge anatomy atlas based on his own dissections. Its famous "muscle men" plates peel the body layer by layer and correct many of Galen's errors, which came from animal bodies.
Why it mattered. Muscle anatomy became something you check by looking, not by quoting old books.
1660 – 1700
Steno's fibres, Swammerdam's frog and Borelli's levers turn muscle into mechanics.
1663
c. 1660s (published 1737)
Swammerdam sealed a frog's muscle and nerve in a glass tube with water and made it contract by touching the nerve. The water level did not rise: if anything it dropped a little. So nothing flows into a working muscle. His notes were published only in 1737, in Biblia Naturae.
Why it mattered. It disproved the old idea that muscles contract by filling with spirit or fluid.
1667
In Elementorum myologiae specimen, Steno described a muscle as a bundle of fibres joined to tendons, and explained contraction as a change of shape of those fibres, drawn with geometry.
Why it mattered. He put the fibre, not a mysterious spirit, at the centre of muscle action.
1680
1680–1681
Borelli's De Motu Animalium, published just after his death, treated bones as levers and muscles as the forces that pull on them. He worked out that muscles must pull many times harder than the weights they hold, because they attach so close to the joint.
Why it mattered. It founded biomechanics and is the reason chapter 4 of this box can work out your biceps force.
1780 – 1880
Galvani's frogs, Duchenne's electrodes, myosin, and red and white muscle.
1791
Galvani found that frog legs jumped when their nerves were touched with metal or sparks. He proposed "animal electricity" flowing from nerve to muscle. Alessandro Volta disagreed, and their argument led to the battery.
Why it mattered. It showed that the signal that makes a muscle contract is electrical.
1862
1855–1862
Duchenne stimulated single muscles through the skin with small electric currents to see what each one does. In 1862 he published photographs of faces made to smile and frown this way. He also invented a needle for taking tiny samples of living muscle.
Why it mattered. He mapped what individual muscles do and started modern muscle medicine.
1864
1859–1864
Kühne pressed a thick, sticky protein out of minced frog muscle and called it myosin. It was the first muscle protein ever isolated.
Why it mattered. Myosin turned out to be the motor that does the pulling.
1868
1861–1868
Duchenne described boys whose calf muscles looked big but grew steadily weaker, and examined their muscle under the microscope. The condition now carries his name: Duchenne muscular dystrophy.
Why it mattered. It began the scientific study of muscular dystrophies.
1873
Ranvier noticed that red muscles in rabbits contracted slowly and steadily, while pale muscles twitched fast. It was the first clear sign of slow and fast muscle fibres.
Why it mattered. Sprinters and marathoners differ in exactly this mix.
1880 – 1950
Calcium, lactate, heat, phosphocreatine, ATP and actomyosin.
1883
1882–1883
Ringer found that a frog heart kept beating in London tap water but stopped in distilled water. The missing ingredient was calcium: without it the heart muscle could not contract.
Why it mattered. Calcium, it turned out, is the switch that turns every muscle on.
1907
Fletcher and Hopkins showed that frog muscle builds up lactic acid when it works without oxygen, and clears it again when oxygen returns.
Why it mattered. It linked fatigue and oxygen to chemistry, and began a long, and often misunderstood, story about lactate.
1922
1922 (awarded 1923)
A. V. Hill measured the tiny amounts of heat a muscle gives off as it contracts; Otto Meyerhof linked oxygen use to the making and removal of lactic acid. They shared the 1922 Nobel Prize in Physiology or Medicine. Hill went on to study how fast runners use oxygen, the idea behind VO2 max.
Why it mattered. Muscle energy became something you could measure.
1927
1927–1929
At Harvard, Fiske and the Indian biochemist Yellapragada Subbarow discovered phosphocreatine in muscle in 1927 and, in 1929, ATP. Karl Lohmann in Germany found ATP the same year, and the Eggletons in London found "phosphagen" too.
Why it mattered. ATP is the energy coin every myosin stroke spends; phosphocreatine is the quick reserve behind a sprint.
1939
Engelhardt and Lyubimova showed that myosin is itself an enzyme that splits ATP. The motor and the fuel-burner were the same protein.
Why it mattered. It connected the fuel directly to the motor.
1942
In wartime Szeged, Straub purified a second protein, actin. Szent-Györgyi's team mixed it with myosin to make "actomyosin" threads, added ATP, and watched the threads shrink. Szent-Györgyi called it seeing motion, the oldest sign of life, in a test tube.
Why it mattered. Muscle contraction became chemistry you could do on a bench.
1950 – 1980
The 1954 papers, cross-bridges, troponin and the length–tension curve.
1954
22 May 1954
Two pairs of scientists, working separately, published back-to-back papers in the same issue of Nature. Watching the stripes of living and stretched fibres, both saw the dark A band keep its width while the light bands shrank. The filaments do not shorten: they slide past each other. The two Huxleys were not related.
Why it mattered. The sliding filament theory is how we understand every muscle today.
1957
Andrew Huxley proposed that side-pieces on myosin attach to actin, pull, and let go, over and over. The same year Hugh Huxley saw these cross-bridges in electron micrographs.
Why it mattered. The cross-bridge cycle in chapter 3 grew from this model.
1965
Ebashi discovered troponin, the protein on actin that grabs calcium and moves tropomyosin out of the way so myosin can bind. It explained how calcium turns muscle on and off.
Why it mattered. It completed the chain from nerve signal to calcium to cross-bridge.
1966
By holding single frog fibres at different lengths, they showed that force is greatest when actin and myosin overlap most, and falls when the fibre is stretched or squashed.
Why it mattered. It is the length–tension curve in chapter 3, and strong proof of sliding filaments.
1966
1962–1967
Bergström revived Duchenne's idea of a biopsy needle and used it on athletes. With Hultman he showed that muscle glycogen runs down in long exercise and that a high-carbohydrate diet refills it, the start of "carb loading".
Why it mattered. Sports science could now measure fuel and fibre types in living people.
1971
Lymn and Taylor timed each chemical step: ATP binding frees myosin from actin, splitting ATP re-cocks the head, and releasing the products drives the power stroke.
Why it mattered. It explains why no ATP means rigor mortis.
1985 – today
Dystrophin, sarcopenia, the myosin motor in 3D, myostatin and gene therapy.
1987
1986–1987
Kunkel's team found the gene behind Duchenne muscular dystrophy in 1986, and in 1987 identified its protein, dystrophin, which anchors the inside of each fibre to its outer membrane. Boys with the disease lack it.
Why it mattered. It turned a disease described in the 1860s into a target for treatment.
1989
1988–1989
Rosenberg proposed the word sarcopenia, from Greek for "poverty of flesh", for the loss of muscle with age. The next year a study showed people in their 90s could nearly triple their strength with 8 weeks of training.
Why it mattered. It made muscle loss something doctors measure and treat.
1993
Rayment's team solved the 3D structure of the myosin head, showing a motor domain that grips actin and a long lever arm that swings.
Why it mattered. For the first time the power stroke could be pictured atom by atom.
1997
Mice without the gene for myostatin grew two to three times more muscle. The same gene explains "double-muscled" cattle breeds.
Why it mattered. It showed the body actively limits muscle size, and opened research into treatments for muscle wasting.
2023
22 June 2023
The FDA gave accelerated approval to the first gene therapy for Duchenne muscular dystrophy, which delivers a shortened dystrophin gene, at first for some boys aged 4 to 5. In 2025, after deaths in treated patients, the FDA asked for its use to be paused while safety was reviewed.
Why it mattered. A disease once untreatable now has therapies aimed at its cause, though they are still being tested and carry real risks.
Did you know?
You have more than 600 skeletal muscles, and they make up about a third of your body mass.
The two 1954 papers that explained muscle were by two scientists called Huxley who were not related.
A muscle holds only about 2–3 seconds' worth of ATP, so it remakes it all the time.
Your biceps pulls about seven times harder than the weight in your hand, because it grips the forearm so close to the elbow.
The people
c. 129 – c. 216 · Physician · Pergamon (now Turkey), worked in Rome
Showed that muscles pull, work in opposing pairs and need their nerves.
1608 – 1679 · Mathematician and physiologist · Naples, Italy
Treated the skeleton as levers and worked out how hard muscles must pull.
1637 – 1680 · Naturalist · Amsterdam, Netherlands
Showed that a contracting frog muscle does not swell.
1806 – 1875 · Neurologist · Boulogne-sur-Mer, France
Mapped muscles with electric currents and described the dystrophy named after him.
1886 – 1977 · Physiologist · Bristol, United Kingdom
Measured muscle heat and won the 1922 Nobel Prize.
1895 – 1948 · Biochemist · Bhimavaram, India
Co-discovered phosphocreatine and ATP in muscle at Harvard.
1893 – 1986 · Biochemist · Budapest, Hungary
Made actomyosin threads contract with ATP in a test tube.
1919 – 1973 · Biophysicist · Derbyshire, United Kingdom
Co-author with Hugh Huxley of one of the two 1954 sliding filament papers.
1917 – 2012 · Physiologist · London, United Kingdom
Co-author of the other 1954 paper and of the first cross-bridge model.
1924 – 2013 · Molecular biologist · Birkenhead, United Kingdom
Saw the thick and thin filaments and their cross-bridges in the electron microscope.
Where it happened
Sources
Dates marked “c.” are approximate, and historians sometimes disagree about who was first. If you spot a mistake, tell us.
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