Bioelectricity: The Next Frontier

A deep dive into bioelectricity and how it will transform medicine

Today we’re going to talk about something revolutionary that’s been lurking in the shadows. And no, it’s not AI, VR, quantum computing, blockchain, or any of the other million buzzwords you hear all the time. It’s bioelectricity.

Wait, wait — what is that word? It may sound like something you’d banish to the pages of some obscure textbook or nod along to in a science documentary acting like you understand while you’re really just wondering if you should order takeout or try that new social media recipe for dinner tonight. But let me tell you this: bioelectricity is not just a cool word, it may hold the key to humanity’s wildest dreams, from curing cancer to eternal life.

Okay, I’m getting a bit ahead of myself. Before we start speculating about grand futures or growing eyes on our butts just for fun (we’ll get back to this later) let’s start with the basics. Let’s understand what bioelectricity is and why it’s probably the coolest thing you’ve never heard about.

So… What is Bioelectricity?

Before diving into bioelectricity lets remove the bio and talk about good-ole electricity.

Imagine you’re in line at your favorite place — airport security. The travelers (electrons) are shuffling about, dumping their possessions on the conveyor in a mad rush to get through to their flights. They go single-file through the metal detectors, flowing smoothly, creating what we call current. This flow of electrons is what powers all your electrical devices. If all goes smoothly there is lots of power, but if an electron is stopped for forgetting to take off his shoes or smuggling his favorite broken radio in his carry-on, the current slows, reducing the power.

But there’s more to power than just flow. See, electrons don’t like each other very much. When they’re packed on one side of security, they desperately want to get to the other side. Jostling around with all their pent-up energy and desire to move is what we call voltage. More technically, it’s the electric potential difference between two environments. The higher the “get me outta here” feeling, the higher the voltage, and hence, more overall power.

Great. Now that we understand electricity let’s introduce the bio component. See, each of our cells are actually like this bustling security line. However, instead of electrons our cells have ions — tiny charged particles like sodium, potassium, and calcium. And instead of the TSA agents and metal detectors they have membranes and ion channels.

These ions flow inside and outside of cells, creating what we call bioelectricity. The membrane is the metal detector which the ions must get through and the ion channels are the TSA agents selectively choosing which ions pass through and blocking the way for others. And just like in the airport, these ions have mounting pressure and desire to escape. On one side you may have crowds of positively charged sodium ions desperate to charge through the membrane, while the other side is relatively calm. This imbalance in ions creates the cells voltage, or more formally the membrane potential (VMem).

Bioelectricity is everywhere! Our bodies are electric. Every cell, from our neurons to skin cells, all carry an electrical charge. Why that’s just excellent! But, uhhh… so what?

A Shockingly Big Deal

So our bodies are electric — big deal. Well, turns out it actually is.

This VMem thing is not there only lounging out being cool. It actually turns out to be our bodies language for communication! It sends nerve cells firing, tells cells to start dividing, or triggers a muscle to contract. You can essentially think of it as DNA being our hardware, our fixed instruction set, and bioelectricity being the software. And if you’ve seen anything about software lately, you’d understand why this is a pretty freaking big deal.

You may be thinking “why, that surely does sound interesting, but what does our body’s software and communication really do? Is this useful to know?” Gee, thanks for asking! Indeed, there are so many roles bioelectricity plays. Let’s break it down through some key examples!

Regeneration

You’re a flatworm (just roll with it). Some people don’t like flatworms so they decide to slice you in half (ouch!). “Oof, this sucks” you think. But then you realize you’re a flatworm. You’re one of the most regenerative organisms around. Sensing the change in electrical gradients by the wound, you determine the polarity (read “direction”), decide a head must regrow on one half and a tail on the other; you then call out to your stem cells to start differentiating and producing the necessary proteins. A couple weeks of work and you’re now two healthy flatworms. Yay!

Alright alright, you may be thinking “that sure was fun imagining being a flatworm, but if you slice me in half I’m surely not going to regenerate like that.” You most certainly are right. But that doesn’t mean that bioelectricity doesn’t play a crucial role in human regeneration as well.

Turns out that we actually use these signals to regenerate too! When you get a cut on your skin the bioelectrical signals are disturbed and a similar process calls out to your cells saying “we got damage here! Reporting for help to regenerate this skin.” Often times the wound will heal completely, but when the bioelectrical activity weakens (aging just sucks) a scar may form. Other organs such as our liver and bones have an even greater regenerative capability.

By manipulating these bioelectrical signals, that’s when the magic happens. For example, it’s been shown that we can direct the bioelectrical signal in these flatworms in such a way that they grow two heads! And even better, if you slice them again, those progeny will also have two heads. For humans too we have shown that by applying electrical stimulation we can improve wound healing and other forms of regenerative abilities. Might we possibly be able to perform magical feats of regeneration if we can more precisely talk to our cells through bioelectricity? Only time (and science!) will tell.

Communication

“Duck!” the neuron frantically relays to the muscle cell.

“A duck. Where? Why are you so worried about a duck?” replies the muscle cell.

“No! A frisbee! It’s coming right at us!”

“Ahh, gotcha. But it’d heading for the head. Should I even bother?”

“YES! Just freaking duck already!”

“Alright alright, chill. I’m on it. See, we dodged it. You’re welcome.”

Conversations like this (okay, maybe not exactly like this, but you get the point) are happening constantly in your body. Cells signal for your muscles to contract, heart to beat, and reflexes to dodge frisbees.

It starts from the resting membrane potential (RMP), the baseline Vmem for the cell. When the neuron detects danger such as the frisbee approaching, it’s Vmem rapidly becomes less negative (a process called depolarization), until a critical threshold is reached. This triggers the neuron to send a message (via a synapse) to a muscle cell, which contracts to move you out of harm’s way. Meanwhile, the neuron resets itself by becoming more negative (hyperpolarization) to return to its RMP.

So yeah, that’s pretty neat. But muscle movements? Long-distance communication in our body? Pfff, we can do better. Surely bioelectricity has some cooler, more exotic things it communicates. And by golly, I wouldn’t be writing this article if it didn’t.

Remember earlier when we discussed growing eyes on our butts? Well, it turns out bioelectricity plays a role in allowing this phenomenon.

I’m sure you remember those days when you were just a single cell. You happily began growing, dividing, and your cells began to specialize. You see, just like humans became so advanced through specialization, our cells do the same. What starts as embryonic stem cells (the ultra-generalist class of cells which embryos mostly consist of) becomes all the cell types we know and love: blood, skin, muscle, bone, neurons, and a plethora more. But how do these stem cells know which cells to assign which role?

Excellent question indeed! This is a process in science we call cell fate determination. Many factors play a role (science is always a bit of a mess), but one of the key elements is that thing we discussed earlier: Vmem. Scientists discovered that different cell types have varying charges across their membranes, with cell like neurons being more negatively charged so they are more excitable, and something like blood cells being only a little negatively charged. This observation is pretty cool, but is the relationship causal? Let’s find out (but I’m sure you already suspect a certain answer).

If you were a scientist trying to answer this question, what would you do? Well, Michael Levin thought it’d be funny to see if he can can manipulate Vmem to grow an eye on the tail of a xenopus (what an epic name for an animal). And sure enough, when he depolarized the region in development that normally becomes eyes, those cells became malformed eyes, but when hyperpolarizing cells as far away as the tail, remarkably they formed into functional eyes. What a result!

To clarify, it wasn’t the bioelectrical patterns itself that formed the functioning eyes. It seems as though Vmem is a crucial upstream signal, communicating the necessary molecular mechanisms that must be recruited to accomplish the desired task. Now let’s see (pun intended) what’s the last role of bioelectricity.

Morphological Control

Ever wonder how babies are born looking more or less the same? One head, ten fingers, two lungs, eyes on their faces — it’s astonishing how consistent biology is.

Genetically they say we’re almost 99% identical to chimps, 70% with fish, even 60% with banana trees. However, I am yet to find a human with gills or that’s as tasty as a banana. Where is all this information coded? How is biology so consistent at making all these things that share so much genetically yet differ so much? I’m sure by this point it’s no surprise. It’s bioelectricity!

We can think of our bioelectric networks as the conductor in the grand orchestra of development. It’s responsible for high-level morphological control, allowing the developing organism to distinguish right from left, up from down, and one organ from another. Even crazier, if you mix up all the cells early on in the development, the bioelectrical pattern will adjust, making the necessary rearrangements to produce the correct target morphology. This shows us that it’s not hardcoded genetics that determines these things, but once again bioelectricity dynamically adjusts to reach it’s goals.

This theme of morphological control will play a vital role in many of the applications we will be discussing. Speaking of applications, enough talk about the roles it has, let’s explore some sci-fi applications!

Our Sci-Fi Future

Hundreds of years ago people turned to bloodletting and witchcraft as their medicines. Oh, how dumb we were. My prediction, however, is that humans in the future will look back on many of the ways we practice medicine now, even what it means to be a human today, with the same utter fascination, thinking “how stupid could those people have been?” This isn’t to take away anything from modern medicine, which has done an incredible job, but rather to highlight this grand future that still lies ahead. And I believe bioelectricity will play a central role.

To explore the vast landscape of possible applications, I’ll present ideas in the order of most possible to more radical ones that’ll have you questioning what substances I’ve been consuming (just cutting-edge science papers and maybe a hint too much sci-fi). Instead of doing it exactly in this order, however, I’ll take my artistic license and group them under broader umbrella applications, making sure to let you know when an application is more farfetched (but don’t worry, I’m sure you’ll be able to tell).

Regenerative Medicine

Did you know that humans can regenerate their fingertips? Don’t believe me? Go ahead, try it yourself! Take any sharp object, chop off your fingertip, and watch it magically reform all good and new. Or, on second thought, maybe just take my word for it.

While this has been shown to be possible, proving the regenerative capacity of humans, let’s focus on something more relatable: wound healing. When you cut yourself or burn some skin for whatever reason you would perform said activities, you will likely see the wound heal entirely on it’s own (with the help of some band-aids and creams) or potentially scar. Pause and think about this fact for a little. If that doesn’t blow your mind that this is a mundane, expected capability of the human body then you surely must have lost your mind. But maybe some of the bioelectrical interventions of the future will do the trick.

Experiments have already shown in labs the efficacy of electrical stimulation in accelerating wound recovery, as well as bone healing. In fact, DARPA awarded millions of dollars through their Bioelectronics for Tissue Regeneration (BETR) program to essentially make bioelectric band-aids that speed up the recovery of soldiers, who I’ll admit probably suffer from worse injuries than your average Joe. All this evidence points to bioelectronics to start being widely adopted in this domain of regeneration. However, rather than accelerating processes that we can already do or increase their efficacy, will we soon be able to perform completely novel regeneration tasks?

Axolotls, adorable aquatic salamanders with a top-tier name, are one of the best regenerators in the game. They can regenerate everything from a limb, heart, spinal cord, and even parts of their brain! Keep slicing off that axolotls leg, it’ll regrow hundreds of times to utter perfection. Wouldn’t it be cool for us to be able to do this too?

Before getting into how we may do this, lets think for a second why we heal the way we do. Imagine we’re hanging out 10,000 years ago, just two Homo Sapiens chilling, when suddenly a crocodile cleanly bits off your leg. As the great friend I am, I bat the crocodile away and try to help you. Now, let’s give you the choice. Would you rather have the wound scar within days, protect you from infection, and allocate little energy, or wait months to potentially regenerate it while maybe losing too much blood beforehand or die of infection. Yeah… scarring seems fine to me.

While that was the case when we evolved (just to clarify, the above is a hypothesis, not a known fact for why humans tend to scar instead of regenerate), now we can use antibiotics to prevent infection, clean and cover the wound effectively, and have the luxury to wait lots of time to regenerate that lost limb. Now if only there was a way to tell this to our body?

Aha! Time to have a good talking to with our bioelectrical circuits it seems. While definitely far off (we’re not even at the “hello world” stage yet), it may be possible one day to do just that: tell our body to regenerate entire limbs, possibly even organs, spinal chord, and parts of the brain (although brain regeneration in nature doesn’t grow back exactly how it was before).

The unlocking of precise bioelectrical manipulation has the potential to be absolutely transformative for regenerative medicine. Although other components such as gene editing and stem cell therapies may need to pair (biology never works in isolation), bioelectricity is a key component into making all humans regenerate like axolotls and Wolverine.

Brain-Computer Interfaces (BCIs)

Ever since the start of our species, you know how we communicated? Speech. Talking. Language. While the rest of the animal kingdom may find this impressive, I find it kind of lame. I mean we went from walking, to domesticating horses, to planes, trains, and automobiles, but we’re still talking with our old mouth. Yes yes, I get that we can text, call, and all that jazz, but where is telepathy? Wasn’t that all the sci-fi hype not too long ago?

Well, I got good news for you: telepathy is on it’s way. With the brain being the central hub of bioelectricity, scientists have been probing around to see if they can decode your thoughts. And sure enough, they were able to demonstrate 97.5% accuracy in a corpus of 125,000 words (way more words than I know)! The underlying signal used for this process is, yup, you guessed it, bioelectricity.

And no, don’t worry. It doesn’t seem possible for someone to wave some device in front of your face and decode all your deepest and darkest secrets… yet.

A more immediate application or decoding bioelectric signals from BCIs is to address paralysis. Before we regenerate those missing limbs it would sure be nice if there was a way to at least control prosthetics with our thoughts. Much progress in research labs has already been made in using BCIs for this exact task. Even companies such as Neuralink are now bringing this out of labs, allowing for faster-than-human cursor movement from thought. Soon the paralympics for eSports (if that’s a thing) be the most elite league!

Even crazier, we’re starting to build other organs such as eyes. Functional eyes! We use the same concept of getting sensory input, digesting it, and then translating it directly to signals that the brain can interpret. I see a marvelous future ahead.

Cancer

Cancer. What to do about it? The disease we’ve spent more than anything to fight. We tried destroying cancer with all our might. We’ve got so many fancy ways that we fight this war, getting us closer and closer to victory. But what if the way to win was to not fight at all?

Profound, isn’t it? I’ve learned from the great Suz Tzu’s saying “the greatest victory is that which requires no battle.” Smart guy. Smart as it is, cancer is trying to kill us. Seems like a good idea to kill it first. Unless…

Alright, a step back first. Before getting into my idea of how to cure cancer without fighting it, let us reflect on what cancer truly is. Cancer begins when a cell goes rogue, forget’s it’s part of the collective organism, goes on a mad multiplying fest, and gobbles you up (forgive the massive oversimplification). Cancer often seems evil since, well, it’s quite deadly. What if, however, cancer is more akin to a confused soldier who forgot what side of the battle they’re on?

The part I want to concentrate on is cancer’s loss of collective identity. Rather than function as part of the larger organism, cancer goes rogue. If only we had a way to alter the identity of the cancer cells, hmmm. But alas, we do! We discussed earlier how bioelectricity is a key player in determining cellular identity.

This new view of cancer will address how we can think about a cure. We can look at cancer as a disease where the cancer cells lose their identity tied to the collective. It’s not that the cancer is trying to kill us; we’re simply it’s environment and it’s trying to survive.

To get a better understanding of this idea, consider the analogy of humans with our environment. Humans, just trying to survive, seem to actively be destroying the surrounding environment, just as cancer slowly destroys the host organism. If some God came down and showed us that we’re killing this environment, that we need to live in tune with our environment to survive, then we better hope humanity would follow that path (the reality may look different). Now how can we do the same for cancer?

You see how in our analogy the humans don’t actively want to destroy the environment. It’s a byproduct of losing our identity within this world. Maybe there is a way instead we can talk to the cancer, just as the fictional God would talk to us, and give the cancer some perspective, some therapy, rather than war.

So we said before that the Vmem of cells tends to indicate cell type. Well, it turns out that cancer cells tend to be highly depolarized. Guess what that is familiar to. Embryonic stem cells! The cancer is basically saying it’s reverting to an embryonic stage and starting anew. We’re surely not going to allow that. How can we tell it otherwise?

Again, scientists are very bright creatures indeed. Since cancer cells seem to be too depolarized, let’s try hyperpolarizing them and see what happens. How are these studies conducted you may ask? Well obviously we would take genes called opsin from our ancient microbe ancestors, genetically engineer that into the cancer, then use light to stimulate those genes to hyperpolarize the cells. Sometimes it really seems like science is stranger than sci-fi. Anyway, this technique is called optogenetics and using it we have discovered that cancerous tumors, even once formed, can be suppressed.

Moreover, scientists came across a surprising result. Highly regenerative tissue, although similar to cancer in the sense that it multiplies rapidly and decreases the activity of tumor suppressant genes, are particularly resistant to developing cancer. Really seems like those tumor suppressant genes are helping, huh.

So where does this finding lead us? Well, if we can promote regeneration, perform targeted hyperpolaralization, and control the morphological state of our bodies, we may just have a new avenue to defeating cancer. But does this concept maybe extend even further?

Aging

Aging really sucks. If you’ve read some of my other posts you would know that me and aging don’t have the best relationship. Typically, aging is viewed as damage accumulation over the years; a breakdown of our body. But just like we did with cancer, what if we can view aging as a morphological disease?

We begin our life as an embryo, tasked with developing a perfectly formed human body reaching it’s target morphological state, basically a fancy way to say a normal body. That is, two arms, eyes, ears, a wonderful face, and all those other fantastic human features. However, once we reach that state, it’s not like the body can just stop. Cells are constantly dividing, dying, changing, and breaking down. We need constant maintenance on our body. Damage, and simply change, forces our body to constantly adapt. Just as bioelectricity is a key component in guiding the morphological progression during development, so too it’s critical in this maintenance role. If we can perfectly maintain this morphological state, might we live forever?

It’s time to turn back to our trusty friend, the flatworm. It turns our that more than just growing two heads, they actually have a potentially bigger perk from their bioelectrical abilities. They may in fact be immortal. Even though they have some of the most unstable genomes, their regenerative abilities and strong bioelectric error-correction abilities gives them this seeming biological immortality.

This idea of high regenerative abilities being tied to positive outcomes seems to keep coming up. From wound healing, to cancer, and now even aging itself, it all begins with bioelectricity. By seeing these diseases through this new lens, perhaps we can begin humanity’s journey to the next greatest scientific and medical breakthrough of all time.

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Parting Philosophy

If you haven’t noticed yet, I’m pretty excited about bioelectricity’s medical potential, but also as just a really cool new way to look at biology. To finish off this article, I want to share with you my general outlook for how the future of biology will take shape.

I’ve already stated that I view bioelectricity as the software of biology, while genetics is the hardware. While the hardware is critical, the last few years have truly shown us the power of software. Biology is poised to be the next field to take this leap.

Traditional software did not get this far from expertly crafted algorithms, precise rule-based systems, and intense micromanagement. Quite a lot of computer science was in fact done this way, with even the first chess engine to beat the best human chess player, Deep Blue, being a kind of expert system. While highly impressive, it took vast resources, many years, and plenty iteration to reach this massive accomplishment. However, no matter how amazing it can play chess, it was always limited to our human abilities, as we were the ones who programmed it. By learning to let go and focus on high-level control, by making AI systems which learn by themselves, we made chess engines that far surpass the greatest chess players. And they go from random moves to this level within hours! Hours!

Now, consider biology — immeasurably more complex than chess. Over billions of years, evolution has honed extraordinary solutions to life's challenges, solutions no single human can fully comprehend. Yet, despite our impressive strides in medicine, we’re still in the "Deep Blue" phase: solving only the problems we can grasp. Imagine what we could achieve if we embraced high-level control and allowed bioelectricity to function as a kind of self-learning system, guiding medicine into the superhuman era.

By leveraging bioelectricity, we could unlock revolutionary possibilities, communicating with and rewiring the very systems that define life itself. The landscapes of biology and medicine would be reshaped in ways we can scarcely imagine today.

So, as we look ahead, remember this: our future is electric.

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Sources:

1. We Are Electic by Sally Adee

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