The Electrome: The Next Great Frontier For Biomedical Technology

Stephen Cass: Welcome to Fixing the Future, an IEEE Spectrum podcast. This episode is brought to you by IEEE Xplore, the digital library with over 6 million technical documents and free search. I'm senior editor Stephen Cass, and today I'm talking with a former Spectrum editor, Sally Adee, about her new book, We Are Electric: The New Science of Our Body's Electrome. Sally, welcome to the show.

Sally Adee: Hi, Stephen. Thank you so much for having me.

Cass: It's great to see you again, but before we get into exactly what you mean by the body's electrome and so on, I see that in researching this book, you actually got yourself zapped quite a bit in a number of different ways. So I guess my first question is: are you okay?

Adee: I mean, as okay as I can imagine being. Unfortunately, there's no experimental sort of condition and control condition. I can't see the self I would have been in the multiverse version of myself that didn't zap themselves. So I think I'm saying yes.

Cass: The first question I have then is what is an electrome?

Adee: So the electrome is this word, I think, that's been burbling around the bioelectricity community for a number of years. The first time it was committed to print is a 2016 paper by this guy called Arnold De Loof, a researcher out in Europe. But before that, a number of the researchers I spoke to for this book told me that they had started to see it in papers that they were reviewing. And I think it wasn't sort of defined consistently always because there's this idea that seems to be sort of bubbling to the top, bubbling to the surface, that there are these electrical properties that the body has, and they're not just epiphenomena, and they're not just in the nervous system. They're not just action potentials, but that there are electrical properties in every one of our cells, but also at the organ level, potentially at the sort of entire system level, that people are trying to figure out what they actually do.

And just as action potentials aren't just epiphenomena, but actually our control mechanisms, they're looking at how these electrical properties work in the rest of the body, like in the cells, membrane voltages and skin cells, for example, are involved in wound healing. And there's this idea that maybe these are an epigenetic variable that we haven't been able to conscript yet. And there's such promise in it, but a lot of the research, the problem is that a lot of the research is being done across really far-flung scientific communities, some in developmental biology, some of it in oncology, a lot of it in neuroscience, obviously. But what this whole idea of the electrome is- I was trying to pull this all together because the idea behind the book is I really want people to just develop this umbrella of bioelectricity, call it the electrome, call it bioelectricity, but I kind of want the word electrome to do for bioelectricity research what the word genome did for molecular biology. So that's basically the spiel.

Cass: So I want to surf back to a couple points you raised there, but first off, just for people who might not know, what is an action potential?

Adee: So the action potential is the electrical mechanism by which the nervous signal travels, either to actuate motion at the behest of your intent or to gain sensation and sort of perceive the world around you. And that's the electrical part of the electrochemical nervous impulse. So everybody knows about neurotransmitters at the synapse and- well, not everybody, but probably Spectrum listeners. They know about the serotonin that's released and all these other little guys. But the thing is you wouldn't be able to have that release without the movement of charged particles called ions in and out of the nerve cell that actually send this impulse down and allow it to travel at a rate of speed that's fast enough to let you yank your hand away from a hot stove when you've touched it, before you even sort of perceive that you did so.

Cass: So that actually brings me to my next question. So you may remember in some Spectrums editorial meetings when we were deciding if a tech story was for us or not, that literally, we would often ask, Where is the moving electron? Where is the moving electron?" But bioelectricity is not really based on moving electrons. It's based on these ions.

Yeah. So let's take the neuron as an example. So what you've got is- let me do like a- imagine a spherical cow for a neuron, okay? So you've got a blob and it's a membrane, and that separates the inside of your cell from the outside of your cell. And this membrane is studded with tens of thousands, I think, little pores called ion channels. And the pores are not just sieve pores. They're not inert. They're really smart. And they decide which ions they like. Now, let's go to the ions. Ions are suffusing your extracellular fluid, all the stuff that bathes you. It's basically the reason they say you're 66 percent water or whatever. This is like sieve water. It's got sodium, potassium, calcium, etc., and these ions are charged particles.

So when you've got a cell, it likes potassium, the neuron, it likes potassium, it lets it in. It doesn't really like sodium so much. It's got very strong preferences. So in its resting state, which is its happy place, those channels allow potassium ions to enter. And those are probably where the electrons are, actually, because an ion, it's got a plus-one charge or a minus-one charge based on- but let's not go too far into it. But basically, the cell allows the potassium to come inside, and its resting state, which is its happy place, the separation of the potassium from the sodium causes, for all sorts of complicated reasons, a charge inside the cell that is minus 70 degree- sorry, minus 70 millivolts with respect to the extracellular fluid.

Cass: Before I read your book, I kind of had the idea that how neurons use electricity was, essentially, settled science, very well understood, all kind of squared away, and this was how the body used electricity. But even when it came to neurons, there's a lot of fundamentals, kind of basic things about how neurons use electricity that we really only established relatively recently. Some of the research you're talking about is definitely not a century-old kind of basic science about how these things work.

Adee: No, not at all. In fact, there was a paper released in 2018 that I didn't include, which I'm really annoyed by. I just found it recently. Obviously, you can't find all the papers. But it's super interesting because it blends that whole sort of ionic basis of the action potential with another thing in my book that's about how cell development is a little bit like a battery getting charged. Do you know how cells assume an electrical identity that may actually be in charge of the cell fate that they meet? And so we know abou- sorry, the book goes into more detail, but it's like when a cell is stem or a fertilized egg, it's depolarized. It's at zero. And then when it becomes a nerve cell, it goes to that minus 70 that I was talking about before. If it becomes a fat cell, it's at minus 50. If it's musculoskeletal tissue, it goes to minus 90. Liver cells are like around minus 40. And so you've got real identitarian diversity, electrical diversity in your tissues, which has something to do with what they end up doing in the society of cells. So this paper that I was talking about, the 2018 paper, they actually looked at neurons. This was work from Denis Jabaudon at the University of Geneva, and they were looking at how neurons actually differentiate. Because when baby neurons are born-- your brain is made of all kinds of cells. It's not just cortical cells. There's staggering variety of classes of neurons. And as cells actually differentiate, you can watch their voltage change, just like you can do in the rest of the body with these electrosensitive dyes. So that's an aspect of the brain that we hadn't even realized until 2018.

Cass: And that all leads me to my next point, which is if you think bioelectricity, we think, okay, nerves zapping around. But neurons are not the only bioelectric network in the body. So talk about some of the other sorts of electrical networks we have, completely, or are largely separate from our neural networks?

Adee: Well, so Michael Levin is a professor at Tufts University. He does all kinds of other stuff, but mainly, I guess, he's like the Paul Erdos of bioelectricity, I like to call him, because he's sort of the central node. He's networked into everybody, and I think he's really trying to, again, also assemble this umbrella of bioelectricity to study this all in the aggregate. So his idea is that we are really committed to this idea of bioelectricity being in charge of our sort of central communications network, the way that we understand the environment around us and the way that we understand our ability to move and feel within it. But he thinks that bioelectricity is also how- that the nervous system kind of hijacked this mechanism, which is way older than any nervous system. And he thinks that we have another underlying network that is about our shape, and that this is bioelectrically mediated in really important ways, which impacts development, of course, but also wound healing. Because if you think about the idea that your body understands its own shape, what happens when you get a cut? How does it heal it? It has to go back to some sort of memory of what its shape is in order to heal it over. In animals that regenerate, they have a completely different electrical profile after they've been-so after they've had an arm chopped off.

So it's a very different electrical- yeah, it's a different electrical process that allows a starfish to regrow a limb than the one that allows us to scar over. So you've got this thing called a wound current. Your skin cells are arranged in this real tight wall, like little soldiers, basically. And what's important is that they're polarized in such a way that if you cut your skin, all the sort of ions flow out in a certain way, which creates this wound current, which then generates an electric field, and the electric field acts like a beacon. It's like a bat signal, right? And it guides in these little helper cells, the macrophages that come and gobble up the mess and the keratinocytes and the guys who build it back up again and scar you over. And it starts out strong, and as you scar over, as the wound heals, it very slowly goes away. By the time the wound is healed, there's no more field. And what was super interesting is this guy, Richard Nuccitelli, invented this thing called the Dermacorder that's able to sense and evaluate the electric field. And he found that in people over the age of 65, the wound field is less than half of what it is in people under 25. And that actually goes in line with another weird thing about us, which is that our bioelectricity- or sorry, our regeneration capabilities are time-dependent and tissue-dependent.

So you probably know that the intestinal tissue regenerates all the time. You're going to digest next week's food with totally different cells than this morning's food. But also, we're time-dependent because when we're just two cells, if you cleave that in half, you get identical twins. Later on during fetal development, it's totally scarless, which is something we found out, because when we started being able to do fetal surgery in the womb, it was determined that we heal, basically, scarlessly. Then we're born, and then between the ages of 7 and 11- until we are between the ages of 7 and 11, you chop off a fingertip, it regenerates perfectly, including the nail, but we lose that ability. And so it seems like the older we get, the less we regenerate. And so they're trying to figure out now how- various programs are trying to figure out how to try to take control of various aspects of our sort of bioelectrical systems to do things like radically accelerate healing, for example, or how to possibly re-engage the body's developmental processes in order to regenerate preposterous things like a limb. I mean, it sounds preposterous now. Maybe in 20 years, it'll just be.

Cass: I want to get into some of the technologies that people are thinking of building on this sort of new science. Part of it is that the history of this field, both scientifically and technologically, has really been plagued by the shadow of quackery. And can you talk a little bit about this and how, on the one hand, there's been some things we're very glad that we stopped doing some very bad ideas, but it's also had this shadow on sort of current research and trying to get real therapies to patients?

Adee: Yeah, absolutely. That was actually one of my favorite chapters to write, was the spectacular pseudoscience one, because, I mean, that is so much fun. So it can be boiled down to the fact that we were trigger happy because we see this electricity, we're super excited about it. We start developing early tools to start manipulating it in the 1700s. And straight away, it's like, this is an amazing new tool, and there's all these sort of folk cures out there that we then decide that we're going to take- not into the clinic. I don't know what you'd call it, but people just start dispensing this stuff. This is separate from the discovery of endogenous electrical activity, which is what Luigi Galvani famously discovered in the late 1700s. He starts doing this. He's an anatomist. He's not an electrician. Electrician, by the way, is what they used to call the sort of literati who were in charge of discovery around electricity. And it had a really different connotation at the time, that they were kind of like the rocket scientists of their day.

But Galvani's just an anatomist, and he starts doing all of these experiments using these new tools to zap frogs in various ways and permutations. And he decides that he has answered a whole different old question, which is how does man's will animate his hands and let him feel the world around him? And he says, This is electrical in nature." This is a long-standing mystery. People have been bashing their heads against it for the past 100, 200 years. But he says that this is electrical, and there's a big, long fight. I won't get into too much between Volta, the guy who invented the battery, and Galvani. Volta says, No, this is not electrical." Galvani says, Yes, it is." But owing to events, when Volta invents the battery, he basically wins the argument, not because Galvani was wrong, but because Volta had created something useful. He had created a tool that people could use to advance the study of all kinds of things. Galvani's idea that we have an endogenous electrical sort of impulse, it didn't lead to anything that anybody could use because we didn't have tools sensitive enough to really measure it. We only sort of had indirect measurements of it.

And his nephew, after he dies in ignominy, his nephew decides to bring it on himself to rescue, single-handedly, his uncle's reputation. The problem is, the way he does it is with a series of grotesque, spectacular experiments. He very famously reanimated- well, zapped until they shivered, the corpses of all these dead guys, dead criminals, and he was doing really intense things like sticking electrodes connected to huge voltaic piles, Proto batteries, into the rectums of dead prisoners, which would make them sit up halfway and point at the people who are assembled, this very titillating stuff. Many celebrities of the time would crowd around these demonstrations.

Anyway, so Galvani basically-or sorry, Aldini, the nephew, basically just opens the door to everyone to be like, Look what we can do with electricity." Then in short order, there's a guy who creates something called the Celestial Bed, which is a thing- they've got rings, they've got electric belts for stimulating the nethers. The Celestial Bed is supposed to help infertile couples. This is how sort of just wild electricity is in those days. It's kind of like- you know how everybody went crazy for crypto scams last year? Electricity was like the crypto of 1828 or whatever, 1830s. And the Celestial Bed, so people would come and they would pay 9,000 to spend a night in it, right? Well, not at the time. That's in today's money. And it didn't even use electricity. It used the idea of electricity. It was homeopathy, but electricity. You don't even know where to start. So this is the sort of caliber of pseudoscience, and this is really echoed down through the years. That was in the 1800s. But when people submit papers or grant applications, I heard more than one researchers say to me- people would look at this electric stuff, and they'd be like, Does anyone still believe this shit?" And it's like, this is rigorous science, but it's been just tarnished by the association with this.

Cass: So you mentioned wound care, and the book talks about some of the ways [inaudible] would care. But we're also looking at other really ambitious ideas like regenerating limbs as part of this extension of wound care. And also, you make the point of certainly doing diagnostics and then possibly treatments for things like cancer. In thinking about cancer in a very different way than the really very, very tightly-focused genetic view we have of cancer now, and thinking about it kind of literally in a wider context. So can you talk about that a little bit?

Adee: Sure. And I want to start by saying that I went to a lot of trouble to be really careful in the book. I think cancer is one of those things that- I've had cancer in my family, and it's tough to talk about it because you don't want to give people the idea that there's a cure for cancer around the corner when this is basic research and intriguing findings because it's not fair. And I sort of struggled. I thought for a while, like, Do I even bring this up?" But the ideas behind it are so intriguing, and if there were more research dollars thrown at it or pounds or whatever, Swiss francs, you might be able to really start moving the needle on some of this stuff. The idea is, there are two electrical- oh God, I don't want to say avenues, but it is unfortunately what I have to do. There are two electrical avenues to pursue in cancer. The first one is something that a researcher called Mustafa Djamgoz at Imperial College here in the UK, he has been studying this since the 90s. Because he used to be a neurobiologist. He was looking at vision. And he was talking to some of his oncologist Friends, and they gave him some cancer cell lines, and he started looking at the behavior of cancer cells, the electrical behavior of cancer cells, and he started finding some really weird behaviors.

Cancer cells that should not have had anything to do with action potentials, like from prostate cancer lines, when he looked at them, they were oscillating like crazy, as if they were nerves. And then he started looking at other kinds of cancer cells, and they were all oscillating, and they were doing this oscillating behavior. So he spent like seven years sort of bashing his head against the wall. Nobody wanted to listen to him. But now, way more people are now investigating this. There's going to be an ion channel at Cancer Symposium I think later this month, actually, in Italy. And he found, and a lot of other researchers like this woman, Annarosa Arcangeli, they have found that the reason that cancer cells may have these oscillating properties is that this is how they communicate with each other that it's time to leave the nest of the tumor and start invading and metastasizing. Separately, there have been very intriguing-- this is really early days. It's only a couple of years that they've started noticing this, but there have been a couple of papers now. People who are on certain kinds of ion channel blockers for neurological conditions like epilepsy, for example, they have cancer profiles that are slightly different from normal, which is that if they do get cancer, they are slightly less likely to die of it. In the aggregate. Nobody should be starting to eat ion channel blockers.

But they're starting to zero in on which particular ion channels might be responsible, and it's not just one that you and I have. These cancer kinds, they are like a expression of something that normally only exists when we're developing in the womb. It's part of the reason that we can grow ourselves so quickly, which of course, makes sense because that's what cancer does when it metastasizes, it grows really quickly. So there's a lot of work right now trying to identify how exactly to target these. And it wouldn't be a cure for cancer. It would be a way to keep a tumor in check. And this is part of a strategy that has been proposed in the UK a little bit for some kinds of cancer, like the triple-negative kind that just keep coming back. Instead of subjecting someone to radiation and chemo, especially when they're older, sort of just really screwing up their quality of life while possibly not even giving them that much more time. What if instead you sort of tried to treat cancer more like a chronic disease, keep it managed, and maybe that gives a person like 10 or 20 years? That's a huge amount of time. And while not messing up with their quality of life.

This is a whole conversation that's being had, but that's one avenue. And there's a lot of research going on in this right now that may yield fruit sort of soon. The much more sci-fi version of this, the studies have mainly been done in tadpoles, but they're so interesting. So Michael Levin, again, and his postdoc at the time, I think, Brook Chernet, they were looking at what happens- so it's uncontroversial that as a cancer cell-- so let's go back to that society of cells thing that I was talking about. You get fertilized egg, it's depolarized, zero, but then its membrane voltage charges, and it becomes a nerve cell or skin cell or a fat cell. What's super interesting is that when those responsible members of your body's society decide to abscond and say, Screw this. I'm not participating in society anymore. I'm just going to eat and grow and become cancer," their membrane voltage also changes. It goes much closer to zero again, almost like it's having a midlife crisis or whatever.

So what they found, what Levin and Chernet found is that you can manipulate those cellular electrics to make the cell stop behaving cancerously. And so they did this in tadpoles. They had genetically engineered the tadpoles to express tumors, but when they made sure that the cells could not depolarize, most of those tadpoles did not express the tumors. And when they later took tadpoles that already had the tumors and they repolarized the voltage, those tumors, that tissue started acting like normal tissue, not like cancer tissue. But again, this is the sci-fi stuff, but the fact that it was done at all is so fascinating, again, from that epigenetic sort of body pattern perspective, right?

Cass: So sort of staying with that sci-fi stuff, except this one, even more closer to reality. And this goes back to some of these experiments which you zapped yourself. Can you talk a little bit about some of these sort of device that you can wear which appear to really enhance certain mental abilities? And some of these you [inaudible].

Adee: So the kit that I wore, I actually found out about it while I was at Spectrum, when I was a DARPATech. And this program manager told me about it, and I was really stunned to find out that just by running two milliamps of current through your brain, you would be able to improve your-- well, it's not that your ability is improved. It was that you could go from novice to expert in half the time that it would take you normally, according to the papers. And so I really wanted to try it. I was trying to actually get an expert feature written for IEEE Spectrum, but they kept ghosting me, and then by the time I got to New Scientist, I was like, fine, I'm just going to do it myself. So they let me come over, and they put this kit on me, and it was this very sort of custom electrodes, these things, they look like big daisies. And this guy had brewed his own electrolyte solution and sort of smashed it onto my head, and it was all very slimy.

So I was doing this video game called DARWARS Ambush!, which is just like a training- it's a shooter simulation to help you with shooting. So it was a Gonzo stunt. It was not an experiment. But he was trying to replicate the conditions of me not knowing whether the electricity was on as much as he could. So he had it sort of behind my back, and he came in a couple of times and would either pretend to turn it on or whatever. And I was practicing and I was really bad at it. That is not my game. Let's just put it that way. I prefer driving games. But it was really frustrating as well because I never knew when the electricity was on. So I was just like, There's no difference. This sucks. I'm terrible." And that sort of inner sort of buzz kept getting stronger and stronger because I'd also made bad choices. I'd taken a red-eye flight the night before. And I was like, Why would I do that? Why wouldn't I just give myself one extra day to recover before I go in and do this really complicated feature where I have to learn about flow state and electrical stimulation?" And I was just getting really tense and just angrier and angrier. And then at one point, he came in after my, I don't know, 5th or 6th, I don't know, 400th horrible attempt where I just got blown up every time. And then he turned on the electricity, and I could totally feel that something had happened because I have a little retainer in my mouth just at the bottom. And I was like, Whoa." But then I was just like, Okay. Well, now this is going to suck extra much because I know the electricity is on, so it's not even a freaking sham condition." So I was mad.

But then the thing started again, and all of a sudden, all the sort of buzzing little angry voices just stopped, and it was so profound. And I've talked about it quite a bit, but every time I remember it, I get a little chill because it was the first time I'd ever realized, number one, how pissy my inner voices are and just how distracting they are and how abusive they are. And I was like, You guys suck, all of you." But somebody had just put a bell jar between me and them, and that feeling of being free from them was profound. At first, I didn't even notice because I was just busy doing stuff. And all of a sudden, I was amazing at this game and I dispatched all of the enemies and whatnot, and then afterwards, when they came in, I was actually pissed because I was just like, Oh, now I get it right and you come in after three minutes. But the last times when I was screwing it up, you left me in there to cook for 20 minutes." And they were like, No, 20 minutes has gone by," which I could not believe. But yeah, it was just a really fairly profound experience, which is what led me down this giant rabbit hole in the first place. Because when I wrote the feature afterwards, all of a sudden I started paying attention to the whole TDCS thing, which I hadn't yet. I had just sort of been focusing [crosstalk].

Cass: And that's transcranial-?

Adee: Oh sorry, transcranial direct current stimulation.

Cass: There you go. Thank you. Sorry.

Adee: No. Yeah, it's a mouthful. But then that's when I started to notice that quackery we were talking about before. All that history was really informing the discussion around it because people were just like, Oh, sure. Why don't you zap your brain with some electricity and you become super smart." And I was like, Oh, did I like fall for the placebo effect? What happened here?" And there was this big study from Australia where the guy was just like, When we average out all of the effects of TDCS, we find that it does absolutely nothing." Other guys stimulated a cadaver to see if it would even reach the brain tissue and included it wouldn't. But that's basically what started me researching the book, and I was able to find answers to all those questions. But of course, TDCS, I mean, it's finicky just like the electrome. It's like your living bone is conductive. So when you're trying to put an electric field on your head, basically, you have to account for things like how thick is that person's skull in the place that you want to stimulate. They're still working out the parameters.

There have been some really good studies that show sort of under which particular conditions they've been able to make it work. It does not work for all conditions for which it is claimed to work. There is some snake oil. There's a lot left to be done, but a better understanding of how this affects the different layers of the sort of, I guess, call it, electrome, would probably make it something that you could use replicability. Is that a word? But also, that applies to things like deep brain stimulation, which, also, for Parkinson's, it's fantastic. But they're trying to use it for depression, and in some cases, it works so-I want to use a bad word-amazingly. Just Helen Mayberg, who runs these trials, she said that for some people, this is an option of last resort, and then they get the stimulation, and they just get back on the bus. That's her quote. And it's like a switch that you flip. And for other people, it doesn't work at all.

Cass: Well the book is packed with even more fantastic stuff, and I'm sorry we don't have time to go through it, because literally, I could sit here and talk to you all day about this.

Adee: I didn't even get into the frog battery, but okay, that's fine. Fine, fine skip the frog. Sorry, I'm just kidding. I'm kidding, I'm kidding.

Cass: And thank you so much, Sally, for chatting with us today.

Adee: Oh, thank you so much. I really love talking about it, especially with you.

Cass: Today on Fixing the Future, we're talking with Sally Adee about her new book on the body's electrome. For IEEE Spectrum I'm Stephen Cass.