The Hundred-12 months Historical past of Electrical energy in Drugs

We in medicine are generally aware of how important electric devices are — and were — to understanding the function of the heart and brain.

Thanks primarily to work by physicists who sought to tame electricity by distilling it down to a handful of equations and parameters, clinicians have been tinkering with electrical devices for well over 100 years. And they’re now used in an array of technologies, from pacemakers to deep brain stimulators to transcutaneous nerve stimulators, to treat pain.

But there’s another side to this story originating in the 18th and early 19th centuries, when tinkerers, called “electricians”, were utilizing electricity with no idea how it worked. Their experiments depended as much on identifying innate biological sources of electricity as they did on harnessing its outside sources for potential medical applications. 

“Even in the field of bioelectronic medicine, in which we make use of the physics of electromagnetism, the biophysics of neurostimulation, and the principles behind merging the two phenomena, we often forget how the study of biological and nonbiological electricity emerged together,” notes Stavros Zanos, MD, PhD, assistant professor and head of the Translational Neurophysiology Lab at Northwell Health’s Feinstein Institutes for Medical Research in Manhasset, New York. “Looking back to the 18th century, the time of Franklin and Cavendish, researchers were literally shocking themselves with Leyden jars and electric fish, out of sheer curiosity, little aware that they were laying the foundation for our understanding neurological, muscular, and cardiovascular electrophysiology, and for so much of the technology on which physiology and medicine depend.”

Luigi Galvani

There are exceptions to this characterization of 18th-century research. Signs of their influence can still be seen today in Bologna, Italy, where a statue of the physician and all around polymath Luigi Aloisio Galvani (1737-1798) looks out over the piazza named in his honor, and to the northwest, at the University of Pavia, where Galvani’s archrival, physicist Alessandro Volta (1745-1827), also stands proudly carved in stone. Hundreds of years on, many in northern Italy can take you through the abbreviated highlights of these two men’s work: Galvani harnessing electricity to make frog legs twitch; his disagreement with Volta causing the latter to invent the battery; and Galvani’s nephew, Giovanni Aldini (1762-1834), adapting that battery design into something bigger and more powerful in order to electrify dead people, thereby immortalizing himself as the historical inspiration for Mary Shelley’s (1797-1851) novel Frankenstein.

Alessandro Volta

For many Italians, the fame of these experiments rivals that of those conducted here in America by Benjamin Franklin (1706-1790), with his iconic kite in a thunderstorm. In fact, as explained by physicist Jim Al-Khalili in his 2011 BBC documentary “Shock and Awe: The Story of Electricity” — and is likely equally apparent to any emergency physician who’s managed lightning injuries — it’s doubtful Franklin’s story ever happened. It’s much more likely that the proof that lightning was electric came from a safer experiment conducted in the French town of Marly-la-Ville in 1752, while Galvani and Volta were just children, involving a tall metal pole, which no one made the mistake to be caught holding during the decisive strike. This lightning experiment galvanized (pun intended) Franklin’s concept of positive and negative charge, a major insight in the discussions of electricity leading to the Galvani–Volta rivalry later in the century. 

Statue of Luigi Galvani in his eponymous piazza in Bologna.

To get a local perspective on the legacy of Galvani and Volta, I spoke with Matteo Cerri, MD, PhD, professor of physiology and researcher on the neuroscience of hibernation at Bologna University, where Galvani also spent his career. Chatting from nearby Galvani’s statue, Cerri noted how, at first glance, his image appears to be staring downward at a book, but closer examination shows that it’s a frog on a dissecting plate that draws his gaze. It’s a fitting scene, as it also proved the initial dividing line in the researchers’ philosophical feud.

As a physician and anatomy professor, Galvani was fascinated by electricity, which researchers of his era had attempted to harness to treat a patient who was paralyzed. Treatment entailed imparting to the patient a shock from static electricity, then the only type of electricity that 18th-century electricians knew how to generate. They did so using hand-cranked devices that rotated glass globes against woolen cloth, the same principle that generates carpet shocks from your shoes, but more efficiently.  

Not only could cranking the globe build up a much higher charge than even the shaggiest carpet, it could be delivered through a wire to people or objects, causing a spark, or to a Leyden jar, a crude capacitor invented by Dutch scientist Pieter van Musschenbroek (1692-1761) in the 1740s, which could store a charge for hours to days.

Print of an early Leyden jar.

Although most 18th-century electricians squandered the mysterious force for party tricks, like making people’s hair stand up or igniting a glass of cognac, the attempt to utilize sparks as therapy for paralysis proved inspirational to Galvani. He set about conducting experiments where he would dissect out the femoral nerves of freshly sacrificed frogs and shock them with a wire connected to one of the spinning static electricity generators, causing the leg muscles to twitch.

In Galvani’s mind, the electricity from the machine was not moving through the frog, but rather was emanating from the brain, through the nerves and muscles, causing them to contract. Galvani believed this to be a spiritual force, which therefore could not be manufactured by humans. This was Galvani’s religious take on “animal electricity”, a hypothesis that biology could produce electricity, a different type of electricity from what humans could generate and store in Leyden jars.

Lightning in a Bottle

As van Musschenbroek had learned the hard way, a Leyden jar could impart a rather uncomfortable shock if it was held in somebody’s hand while being charged, and then the wire coming out of the top was touched by that person’s other hand. In contrast was the torpedo fish (Torpedo marmorata), a creature whose bite felt strangely similar to a shock from a Leyden jar. Today, it’s known commonly as the marbled electric ray, but some 18th-century thinkers doubted that it was electric at all, because, unlike Leyden jars, the sting of T. marmorata did not cause a spark.

Henry Cavendish (1731-1810) of England tested Leyden jars of varying sizes and worked out that a shock could be characterized by the “degree of electrification” and by an independent parameter he called the “quantity of electricity”. Inspired by the internal anatomy of the fish that featured a series of chambers, Cavendish built a kind of torpedo fish simulator: several Leyden jars, linked together to hold a high “quantity of electricity”, because of the high number of jars, while keeping the “degree of electrification” low by charging the jars to just a fraction of their capacity. When touched, the device produced a strong shock, but with a spark visible only through a magnifying glass, leading Cavendish to conclude that the real fish did indeed produce electricity. He distinguished this from the standard Leyden jar in that the fish produced a higher “quantity of electricity” with a much lower “degree of electrification”. In today’s terminology, Cavendish meant that Leyden jars delivered low charge and high voltage, while T. marmorata delivered high charge and low voltage.

The Birth of an Electric Rivalry

Cavendish’s insight occurred in the mid-1770s, when Galvani and Volta were rising stars. The animal electricity hypothesis became all the rage, triggering a debate over the source of the muscle twitching in Galvani’s dead frogs.

In contrast to Galvani’s belief that a shock delivered from a static electricity generator to a femoral nerve didn’t do anything but awaken some remnant of spiritual forces, Volta, a freethinker of the Enlightenment, proposed that the electrical fluid from the spinning generator used to shock the nerve was itself driving the twitching.

Considering Volta’s idea tantamount to religious heresy, Galvani published further observations that stimuli other than generators could evoke the same twitching. Such stimuli included shocking from a Leyden jar, which Volta retorted was evidence against animal electricity, not in support of it, and mere contact with two different kinds of metals. Curiously, Galvani found that when he suspended his frogs from an iron wire, then ran a copper-containing wire from the iron wire to the exposed femoral nerve, the frog legs would twitch. With nothing attached that could supply electric charge to the nerve, Galvani believed he now had stronger evidence that the twitching was from an internal power, an idea supported by still another observation: he could stimulate the twitching by touching the exposed femoral nerve with another animal nerve, using no metal at all.

Galvani might have continued experimenting, but he lost his academic position and all sources of income when he refused to swear an oath of loyalty to the Cisalpine Republic, a French satellite state that held sway over northern Italy beginning in 1797 and whose legislative body was packed with academics of the Enlightenment, including Alessandro Volta! In a spiraling decline, Galvani died, destitute and depressed, in late 1798.

Volta continued in science for three more decades, motivated to shed light on Galvani’s finding that the wires of two different kinds of metals provoked the muscle twitching. Putting two different metals in his mouth simultaneously, Volta found that he could taste the electricity, but it was too weak to measure with an instrument. Thinking about the multiple chambers in the torpedo fish, however, and how Cavendish had simulated them, Volta piled up alternating discs of copper and zinc, separated by disks soaked in dilute acid. In 1800, he found that this layering amplified the effect, proving that Galvani’s wires themselves had produced electricity. As a result, Galvani is remembered for being wrong about animal electricity. But this isn’t an altogether fair reputation.

The First Battery

Volta’s legacy got an additional boost because his discovery was also an invention, the first battery, which people could appreciate concretely, as it generated the age of electricity with lightning speed. Using a Voltaic battery scaled up to room-sized proportions, England’s Humphry Davy (1778-1829) would demonstrate electric arc lighting in 1808. The electromagnet would enter the scene within Volta’s lifetime, leading to generators, electric motors, and the telegraph within two decades of his death. Yet dependent on all this innovation was Galvani’s initial animal work.

“We should remember that behind every scientific endeavor, there’s always a person who deserves credit regardless of the result,” notes Cerri. “This was true with Italy’s two giants of early electricity research, just as it’s true with so many scientific thinkers today. In real sense, the interplay between Galvani and Volta and the differences in their legacies parallels the current struggle between basic and applied research.”

The ironic twist to the story is that bioelectricity actually is different from electricity employed by our devices.

“Galvani’s intuition about electricity was more true than Volta’s in the broader sense,” says Cerri, alluding to how an action potential is effectively the movement of positive charge along the cytoplasmic surface of the cell membrane of axons and myocytes.

Franklin’s ingenious concept was that electrical charge, like a bank account, could be in surplus or deficit (which he called positive and negative, respectively). This explains the shock of Leyden jars as the need for positive charge to travel through the body of the jar holder to cancel out negative charge on the other side of the glass. The convention for electric current is that it’s a positive charge moving through wires and circuits. That’s backwards when it comes to our devices, where the negatively charged electrons are what’s moving, but it’s correct for our biological currents carried by positive ions!

In much the same way, Galvani and Volta may have moved in philosophically opposite directions, but their theories still provided the initial sparks that lit the way for interventions used to this day in modern medicine. 

Warmflash is a freelance health and science writer living in Portland, Oregon. His recent book, Moon: An Illustrated History: From Ancient Myths to the Colonies of Tomorrow, tells the story of the Moon’s role in a plethora of historical events, from the origin of life, to early calendar systems, to the emergence of science and technology, to the dawn of the space age.

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