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WHEN first played back the footage, there was nothing to see. The tadpole had developed enough of a tail to swim out of shot, leaving only a blank screen. 鈥淥h well,鈥� she remembers thinking. 鈥淎nother one bites the dust.鈥� But the camera had been running all night, so she dutifully rewound the tape on the off chance it had caught something interesting. Interesting didn鈥檛 begin to describe what she saw. 鈥淢y jaw dropped, right to the floor,鈥� she says.

The video showed a frog embryo busily dividing to become a tadpole. Then, this tiny, smooth blob began to light up. Electrical patterns flashed a series of unmistakable images across it: two ears, two eyes, jaws, a nose. These ghostly projections didn鈥檛 last long. But 2 or 3 hours later, exactly where they had glimmered, the real things appeared: two ears, two eyes, jaws, a nose. Here, at last, was the proof she had been after in her role on a decade-long project undertaken by at Tufts University in Massachusetts. It showed that electrical patterns provide a blueprint that shapes a developing body, coordinating where to put its face and grow its other features.

Astounding as this sounds, it is just one of many roles that electricity plays in biology. There is mounting evidence that, as well as instructing development, electricity influences everything from wound healing to cancer. 鈥淏ioelectric gradients and communication are fundamental to being alive,鈥� says Levin. If we can map this 鈥渆lectrome鈥� and learn to decode it, some astonishing consequences for our health would only be the start.

If you have ever spared a thought for bioelectricity, chances are that you were contemplating the nervous system. We have long known that a neuron鈥檚 ability to relay messages hinges on electricity 鈥� specifically, a set-up that ensures different ions stay on different sides of nerve cell membranes. Neurons like to keep potassium ions inside and sodium ions outside. Both types of ion are positively charged, but, due to the vagaries of ion concentration gradients and head-exploding equations, the upshot is that the inside of a neuron is around 70 millivolts more negatively charged than the outside. This is called its resting potential.

Electric signalling

Although the resting potential is minuscule 鈥� around one-tenth the voltage that activates a transistor in the microchip that runs your phone 鈥� it is vital to the functioning of nerve cells. To maintain this voltage, the cell membrane is studded with tens of thousands of tiny channels through which sodium and potassium ions move, along with miniature pumps that kick out sodium interlopers. Stimulate a neuron and its ion channels open, potassium and sodium ions switch places and the voltage tumbles to zero 鈥� a process known as depolarisation. The pumps and channels rapidly restore the resting potential to 鈭�70 millivolts and the resulting voltage spike, called an action potential, moves along the nerve like a wave as other parts of the cell membrane become depolarised. This is how the nervous system relays all sensation and motion signals around the body, making action potentials fundamental to our ability to think, talk, move and perceive the world.

We used to believe that nerve and muscle cells were pretty much the only parts of the body that make meaningful use of electricity. But it turns out that the membrane around every one of your 40 trillion or so cells also acts like a little battery, using ion channels to maintain the cell鈥檚 tiny voltage. Over the past couple of decades, new tools and insights have revealed that this bioelectricity, dubbed the electrome, has a huge range of roles in the body.

There is no better example than the way electricity shapes a developing body. We all recognise a regulation-issue human or chicken or fish when we see one. But how do the cells in a developing embryo know where to go to make that body, rendering all those fingers and beaks and fins in the proper place and dimensions? Since the 1960s, researchers have suspected that are . This conviction only deepened with advances in genetics. Decades of research into genomes have turned up little that could account for key aspects of an organism鈥檚 shape. You will find plenty of genes coding for specifics such as height or the colour of hair, skin and eyes. But nothing tells you how many eyes. There is no gene for 鈥渢wo eyeballs, and would you mind popping them on the front of the head鈥�. The same is true for your legs, arms and ears. The genome alone can鈥檛 configure the placement of any of these features.

By 2009, it was clear that shifts in electrical voltages determine which identity cells and even organs assume in development. Levin suspected that they also shape the face. But how to prove that? Existing tools from neuroscience 鈥� implanted or surface electrodes 鈥� only track fast events like action potentials, and usually not in a way you can see with the naked eye. Development takes place over a much longer timespan and across a whole organism, not just in a single cell. More to the point, a lot of tools from neuroscience are too invasive and destructive to use to study a developing organism.

One alternative was to use . Such chemicals translate electrical differences into a gradient of brightness, with high voltages appearing as bright white, low ones as black and anything in between showing up in corresponding shades of grey. Levin and Adams chose one that could be harmlessly infused into a fertilised egg, allowing them to track each electrical step in every cell of a developing embryo in real time. Frogs were an obvious choice to test the dye on because their development can be observed without having to contend with a uterus 鈥� but what is true for frogs in this case turns out to be true for all animals, including us.

The result was extraordinary. As the team members watched their footage that morning in the lab at Tufts, the dye revealed that the voltage of each cell was the cue for it to assume its particular identity. Initially, all the embryo鈥檚 undifferentiated stem cells hovered around 0 millivolts, but, as the animal developed, its proliferating cells assumed a variety of voltages depending on the tissue they would form: 鈭�70 millivolts for nerve cells, a more forceful 鈭�90 millivolts for skeletal muscle, a flabbier 鈭�50 millivolts for fat cells and so on. These voltage changes, which could be seen as the ghostly glimmerings of facial features, formed the blueprint on which the developing tadpole was based.

Yet these shifts in voltage weren鈥檛 just maps, they were instructions. Subsequent experiments revealed that they turned on the genes that got to work to create an animal鈥檚 physical template. Messing with the electrical patterns disrupted the function of the ion channels and pumps that are crucial to maintaining the characteristic voltage of each cell type during development, resulting in radical physiological changes. Correcting the errant voltages during development . Alter a few of them deliberately and you can control body pattern: one study in frogs moved the place where the eyes grew .

Given the role of electricity in shaping a developing body, you might also expect it to be critical to maintaining that shape after an injury. This is indeed the case. The so-called current of injury 鈥� an electrical pulse produced when tissue is cut or otherwise damaged 鈥� was first reported in the 19th century, but ignored for more than 150 years. In 2011, , then at Old Dominion University in Virginia, built a device that could measure this current and found that it generates an electric field of around 120 millivolts per millimetre. This field acts as a beacon for the various cells that move in to repair damage and rebuild tissues. It is strongest right after an injury and wanes as healing occurs. People with a stronger current of injury heal faster than those in whom the signal is weaker. It also : you will have half the current at 65 that you had at 25.

Switching on healing

Meanwhile, other researchers, including , now at the University of California, Davis, and his colleagues, were doing experiments to manipulate the current of injury. They established its role as a control switch by demonstrating which gene networks it turns on, and they found that interfering with the relevant ion channels in cornea cells of the eye , whereas electrical stimulation could speed it up. Zhao now leads a to track and manipulate the bioelectricity of healing, which aims to halve the healing time of severe injuries. Clinical trials are set to begin in 2024.

Tweaking the 鈥榖ioelectric code鈥� has produced worms with second heads

The ultimate goal of this line of research isn鈥檛 just to heal an injury the way humans do 鈥� imperfectly, incompletely, with a scar 鈥� but to regrow limbs and organs the way some other animals can. This line of research is what Levin is best known for: tweaking the 鈥渂ioelectric code鈥� has helped him grow worms with second heads and regenerate frog legs at life stages when the animals can typically no longer regrow lost limbs. The work is now going on in mice and Levin has co-founded a start-up called Morphoceuticals with the aim of eventually adapting it to humans.

The potential benefits of understanding our electrome are even more dramatic when it comes to cancer. While working at Tufts with Adams and Levin, discovered it is possible to use a voltage-reporting dye to detect when cells turn malignant. Cancer cells . Notably, the transition from healthy cells is marked by a precipitous drop in voltage to around zero 鈥� similar to the lack of voltage that stem cells display. Meanwhile, at Imperial College London had discovered that the voltage of cancer cells oscillates, just like electricity in a nerve cell. 鈥淭hese were bog-standard action potentials,鈥� he says. It turns out cancer cells need these to communicate with each other about their environment, especially about metastasis 鈥� their spread around the body 鈥� which is the main way cancer kills.

快猫短视频s, including Djamgoz and Levin, hope to use ion channel blockers 鈥� currently the foundation of many heart medicines 鈥� to suppress these oscillations and stop cancers spreading. Indeed, new research suggests that people taking these heart drugs are . And Chernet has found that, in frogs, pushing cancer cells鈥� voltages back to those of healthy cells sends the malignancies into reverse. It is like an undo switch. Now, several compounds are in early-stage clinical trials with a view to .

But cell membrane voltage is only one part of the electrome. Since bioelectricity entered the limelight, researchers have identified myriad new avenues to explore. For a start, cells that become cancerous also emit strange . What鈥檚 more, a weakening membrane voltage in the mitochondria that power cells seems to .

Another surprise is that bioelectricity is involved in autoimmune conditions, including type 1 diabetes and rheumatoid arthritis, because of the way that nerves twine into our internal organs. to , with a view to figuring out whether tweaking the signals they carry might help with everything from to . The benefits to human health will only multiply as we expand investigations of the electrome beyond animals into other organisms (see 鈥淓lectrical nature鈥� below).

For her part, Adams is exploring the life-saving potential of the voltage-reporting dye that first allowed her to watch tadpoles taking shape. Chernet鈥檚 discovery that it can pinpoint cancer cells means that surgeons removing a tumour could use the dye to ensure they have excised all the malignant tissue. Currently, around 10 per cent of operations leave cancerous cells behind and it typically takes more than a week to detect these. Spotting stragglers before the wound is closed up would be a game changer. Adams has been trying to make this a clinical reality. If it works, she envisages also using the dye as an early-warning system for skin cancers, where quickly and cheaply distinguishing benign growths from malignant ones could save many lives.

Our understanding of the electrome has sharply accelerated since Adams first viewed that jaw-dropping video. But the real potential is still to come, she says. 鈥淭he research and insights emerging now will hopefully do for the electrome what molecular biology did for the genome: recognise its fundamental power in biology.鈥�

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Sally Adee is a freelance science journalist based in London. Her book