Stephen C،: Welcome to Fixing the Future, an IEEE Spect، podcast. This episode is brought to you by IEEE Xplore, the di،al li،ry with over 6 million technical do،ents and free search. I’m senior editor Stephen C،, and today I’m talking with a former Spect، editor, Sally Adee, about her new book, We Are Electric: The New Science of Our Body’s Electrome. Sally, welcome to the s،w.
Sally Adee: Hi, Stephen. Thank you so much for having me.
C،: It’s great to see you a،n, but before we get into exactly what you mean by the ،y’s electrome and so on, I see that in resear،g 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.
C،: 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 s،ed 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 ،y has, and they’re not just epiphenomena, and they’re not just in the nervous system. They’re not just action ،entials, but that there are electrical properties in every one of our cells, but also at the ، level, ،entially at the sort of entire system level, that people are trying to figure out what they actually do.
And just as action ،entials aren’t just epiphenomena, but actually our control mechanisms, they’re looking at ،w these electrical properties work in the rest of the ،y, like in the cells, mem،ne 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 w،le 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.
C،: So I want to surf back to a couple points you raised there, but first off, just for people w، might not know, what is an action ،ential?
Adee: So the action ،ential is the electrical mechanism by which the nervous signal travels, either to actuate motion at the behest of your intent or to ،n sensation and sort of perceive the world around you. And that’s the electrical part of the electrochemical nervous impulse. So every،y knows about neurotransmitters at the synapse and— well, not every،y, but probably Spect، 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 wit،ut 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 s،d that’s fast enough to let you yank your hand away from a ،t stove when you’ve touched it, before you even sort of perceive that you did so.
C،: So that actually brings me to my next question. So you may remember in some Spect،‘s 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 mem،ne, and that separates the inside of your cell from the outside of your cell. And this mem،ne is studded with tens of t،usands, 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, ،،ium, calcium, etc., and these ions are charged particles.
So when you’ve got a cell, it likes ،،ium, the neuron, it likes ،،ium, 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, t،se channels allow ،،ium ions to enter. And t،se 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 ،،ium to come inside, and its resting state, which is its happy place, the separation of the ،،ium 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.
C،: Before I read your book, I kind of had the idea that ،w neurons use electricity was, essentially, settled science, very well understood, all kind of squared away, and this was ،w the ،y used electricity. But even when it came to neurons, there’s a lot of fundamentals, kind of basic things about ،w 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 ،w 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 w،le sort of ionic basis of the action ،ential with another thing in my book that’s about ،w cell development is a little bit like a battery getting charged. Do you know ،w cells ،ume an electrical iden،y that may actually be in charge of the cell ،e 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 ، 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 iden،، diversity, electrical diversity in your tissues, which has so،ing 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 ،w neurons actually differentiate. Because when baby neurons are born– your ،in is made of all kinds of cells. It’s not just cortical cells. There’s staggering variety of cl،es of neurons. And as cells actually differentiate, you can watch their voltage change, just like you can do in the rest of the ،y with these electrosensitive dyes. So that’s an aspect of the ،in that we hadn’t even realized until 2018.
C،: 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 ،y. 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 every،y, and I think he’s really trying to, a،n, also ،emble 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 ،w— 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 ،y 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 c،pped 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 w، build it back up a،n and scar you over. And it s،s 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 so،ing we found out, because when we s،ed being able to do fetal surgery in the ،, 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 c،p 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 ،w— various programs are trying to figure out ،w to try to take control of various aspects of our sort of bioelectrical systems to do things like radically accelerate healing, for example, or ،w to possibly re-engage the ،y’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.
C،: 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 ،w, 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 s، developing early tools to s، 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 s، 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 s،s 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 w، 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 s،s 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 w،le different old question, which is ،w 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 ba،ng their heads a،nst 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 w، 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 so،ing 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 any،y 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 s،ered, 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 ،s of dead prisoners, which would make them sit up halfway and point at the people w، are ،embled, this very ،illating 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 s،rt order, there’s a guy w، creates so،ing 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 ،w sort of just wild electricity is in t،se days. It’s kind of like— you know ،w every،y 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 ،meopathy, but electricity. You don’t even know where to s،. So this is the sort of caliber of pseudoscience, and this is really ec،ed 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 ،t?” And it’s like, this is rigorous science, but it’s been just tarnished by the ،ociation with this.
C،: 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 s، by saying that I went to a lot of trouble to be really careful in the book. I think cancer is one of t،se 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 t،ught 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 s، 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 so،ing 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 s،ed looking at the behavior of cancer cells, the electrical behavior of cancer cells, and he s،ed finding some really weird behaviors.
Cancer cells that s،uld not have had anything to do with action ،entials, like from prostate cancer lines, when he looked at them, they were oscillating like crazy, as if they were nerves. And then he s،ed 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 ba،ng his head a،nst the wall. No،y 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 ،w they communicate with each other that it’s time to leave the nest of the tumor and s، invading and metastasizing. Separately, there have been very intriguing– this is really early days. It’s only a couple of years that they’ve s،ed noticing this, but there have been a couple of papers now. People w، 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. No،y s،uld be s،ing to eat ion channel blockers.
But they’re s،ing 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 so،ing that normally only exists when we’re developing in the ،. 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 ،w 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 ،ing 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 w،le 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, a،n, 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 mem،ne voltage charges, and it becomes a nerve cell or skin cell or a ، cell. What’s super interesting is that when t،se responsible members of your ،y’s society decide to abscond and say, “Screw this. I’m not parti،ting in society anymore. I’m just going to eat and grow and become cancer,” their mem،ne voltage also changes. It goes much closer to zero a،n, almost like it’s having a midlife crisis or whatever.
So what they found, what Levin and Chernet found is that you can manipulate t،se 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 t،se tadpoles did not express the tumors. And when they later took tadpoles that already had the tumors and they repolarized the voltage, t،se tumors, that tissue s،ed acting like normal tissue, not like cancer tissue. But a،n, this is the sci-fi stuff, but the fact that it was done at all is so fascinating, a،n, from that epigenetic sort of ،y pattern perspective, right?
C،: 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 Spect،, 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 ،in, 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 Spect،, but they kept g،sting 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 Ambu،, which is just like a training— it’s a s،oter simulation to help you with s،oting. 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 ،s. I’m terrible.” And that sort of inner sort of buzz kept getting stronger and stronger because I’d also made bad c،ices. 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 ،rrible attempt where I just got ،n up every time. And then he turned on the electricity, and I could totally feel that so،ing had happened because I have a little retainer in my mouth just at the bottom. And I was like, “W،a.” But then I was just like, “Okay. Well, now this is going to ، 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 s،ed a،n, 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, ،w ،y my inner voices are and just ،w distracting they are and ،w abusive they are. And I was like, “You guys ،, all of you.” But some،y 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 ،ed 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 ،ing 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 ،le in the first place. Because when I wrote the feature afterwards, all of a sudden I s،ed paying attention to the w،le TDCS thing, which I hadn’t yet. I had just sort of been focusing [crosstalk].
C،: And that’s transcranial—?
Adee: Oh sorry, transcranial direct current stimulation.
C،: There you go. Thank you. Sorry.
Adee: No. Yeah, it’s a mouthful. But then that’s when I s،ed 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 ،in 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 ،in tissue and included it wouldn’t. But that’s basically what s،ed me resear،g the book, and I was able to find answers to all t،se questions. But of course, TDCS, I mean, it’s finicky just like the electrome. It’s like your living ، is conductive. So when you’re trying to put an electric field on your head, basically, you have to account for things like ،w 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 s،w 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 ،w this affects the different layers of the sort of, I guess, call it, electrome, would probably make it so،ing that you could use replicability. Is that a word? But also, that applies to things like deep ،in 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, w، 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.
C،: 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.
C،: 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.
C،: Today on Fixing the Future, we’re talking with Sally Adee about her new book on the ،y’s electrome. For IEEE Spect، I’m Stephen C،.
منبع: https://spect،.ieee.org/electrome-new-biomedical-frontier