The Solution to Human Regeneration May Hang in a Long-Neglected Branch of Science

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Electricity, not DNA, could be the key to unlocking a medical breakthrough.

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A plate from the De Bononiensi scientiarum et artium instituto atque academia commentarii, produced between 1731 and 1791 (BibliOdyssey).

One night in the late 1700s, Luigi Galvani, an anatomy professor at the University of Bologna, strung up butchered frog legs on his balcony. This in itself was not unusual - they were, in all likelihood, awaiting the dinner plate. But on this night, with the air crackling with electricity from a storm, Galvani noticed something odd: when he touched the legs with a pair of scissors, they twitched. The professor's curiosity was piqued. Soon thereafter, he hung some dissected frogs legs in his laboratory - where, as it happened, he also kept a newfangled machine that captured static electricity, known as a Leyden jar. Anytime the jar was on and someone touched the legs with a metal scalpel, they jumped. It was almost as if they were possessed. 

Galvani wondered if this strange phenomenon could be related to electrical currents. Perhaps the limbs contained some sort of charge, an "animal electricity" essential for life. He thought that this charge was undiscovered biological juice, and, while he was wrong, Galvani was perhaps the first person to purposefully stimulate exposed nerve cells with electricity. Years later, he noted his achievement in a book that recounted more than a decade of such research: "And still we could never suppose that fortune were to be so friend to us, such as to allow us to be perhaps the first in handling, as it were, the electricity concealed in nerves, in extracting it from nerves, and, in some way, in putting it under everyone's eyes."

In the years that followed, Giovanni Aldini, Galvani's nephew and former assistant, went further. In 1802, he connected a primitive battery to a recently severed ox head. It was as if the animal came back to life: its eyes flew open; its ears wriggled; its tongue jerked. Aldini attempted a similar experiment on the corpse of a murderer who'd been hanged in London's infamous Newgate Prison. The effects were much the same: "The jaw began to quiver, the adjoining muscles were horrible contorted, and the left eye actually opened." 

These ghoulish experiments were well known in scientific and popular circles-- Mary Shelley used the notion that electricity could animate life as the foundation for Frankenstein--and interest in the effects of electricity on living creatures continued for the next 150 years. Many efforts were little more than quackery. In England during the 1800s, for instance, electricity was used to treat everything from hysteria to melancholia. Yet the flegdling field of bioelectricity was stalled by a rival branch of science, not fringe thinking. DNA was discovered in the 1950s. A tidal wave of interest followed, and it swept aside the studies that descended from Galvani's.

The search for the commands that shape our bodied became an investigation of the extraordinary interplay between genes and proteins. But as successful as the current approach has been, it does have limits. 

It is odd that electricity has been so negelected, because it is everywhere in our bodies. Ions flow in and out of our cells. Voltage pulses speed down our nerves. We are, in effect, walking electrical networks. The significance of this is readily accepted when it comes to the nervous system and the heart - think of the electrical pads used to revive someone after a heart attack. But in many ways, we remain stuck in an eighteenth century mindframe, aware of the electric signals that course through our bodies but oblivious to the ways in which they could play a subtler, and more profound, role in our development.

Not all of the blame for this is the result of the focus on proteins and DNA. There's also the legacy of bioelectrical research, which has teetered between genuine scientific insights and frivolous nonsense. It would take someone who knew little about the field's reputation, and who wasn't concerned about how his interests would appear to colleagues, to pick up the line of inquiry, and return to the question of regeneration.

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Michael Levin, director of Tufts University's Center for Regenerative and Developmental Biology (Kathi Bahr).

Modern medicine clutches at a number of dreams. Some, like developing an AIDS vaccine, can seem tantalisingly close. Others, like curing cancer or preventing the ravages of aging, have frustrated great minds for so many years that we've learned to temper our expectations.

And then there's regeneration. The idea that humans could regrow missing or diseased organs or limbs often feels like fantasy. But why? There are, after all, many species that can accomplish the task with ease. A decapitated flatworm will grow a new head, replete with a new brain. For the first week of their lives, tadpoles can replace lost tails. And the axolotl, or Mexican salamander, has the ability to regenerate everything from its limbs and tail to its spinal cord and skin, all without any evidence of scarring. Even some mammals have limited regenerative abilities: every year, deer regrow exact replicas of the antlers they shed, and in some circumstances, young mice and rats can lose a leg and grow it back.

Humans hang onto a sliver of regenerative ability as well. If a child experiences a neat slice through the end of his fingertip, that tip will grow back -- a talent that disappears sometime between the ages of seven and eleven. The Greek legend of Prometheus, the god who was cursed to have an eagle peck out his liver each day, only to grow it back every night, contains a grain of physiological truth: were you to lose part of your liver, it would, in fact, regenerate. With the exception of our skin, it's the only human organ that has that capability.

But what if we could go further than skin and liver cells? What if we could signal to our bodies to regrow damaged retinal tissue - or even to regrow an entire eye? What if we could regrow lost limbs? Michael Levin doesn't think this is an outlandish fantasy: in fact, he thinks he may be on the path to figuring out how to do precisely that.

Levin is director of Tufts University's Center for Regenerative and Developmental Biology in Medford, near Boston. His thinks that the key to regeneration  -- the key to pattern, to shape -- may be found in the electrical signals that are transmitted among all our cells, much like the ones and zeros that zip along a computer's hard drive. Manipulating these electrical signals has already led to results that seem more suited to X-Men than a scientific journal: Levin's lab has produced four-headed flatworms and grown an eye from scratch on a tadpole's belly. Over the course of the next year, Levin will begin experiments on mammals. Success could make human regeneration a reality in our lifetimes.


This is an exclusive extract from Electric Shock, the new article from MATTER, an online publisher focused on long-form science and technology writing. Visit readmatter.com to purchase the full article. 

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Cynthia Graber is an award-winning print and radio journalist who covers science, technology, agriculture and more. She’s currently a Knight Science Journalism fellow at MIT.

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