Episode One Slug
Bioelectronic Medicines – What’s in a name?
“Tis but thy name that is my enemy;
Thou art thyself, though not a Montague.
What’s Montague? It is not hand, nor foot,
Nor arm, nor face, nor any other part
Belonging to a man. O, be some other name!
What’s in a name? That which we call a rose
By any other name would smell as sweet;
So Romeo would, were he not Romeo call’d,
Retain that dear perfection which he owes
Without that title. Romeo, doff thy name,
And for that name which is no part of thee
Take all myself.
For those of us in the field, we know conceptually what bioelectronic medicine is, but we’ve also spent a few years trying to clearly define it as it pertains to the larger fields of neurotechnology and neuromodulation. We all have an opinion. A theory. A thought. But in the end, which matters more? What we call it or what it is?
In our Bioelectronic Medicine Series, we will endeavor to build consensus around a definition for Bioelectronic Medicine while digging into the history, opportunities, and future. We’ll start today with some background and an overview that will allow new listeners and people outside of the field to join us for another amazing Skraps journey.
So, as Tim Dennison is fond of saying (while toasting with an appropriate pint of suds) “Here’s to neuromodulation, in all of its forms.”
JoJo, Arun Sridhar
Hey, this is Michael walls. I’m a biomedical engineer and neuro tech consultant. I like SKRAPS because it reminds me of those great conversations you have, while grabbing a bite and a beer with colleagues or mentors at a conference. It gives me a front row seat to conversations, I wouldn’t necessarily be privy to, and learn things I wouldn’t normally get elsewhere. If you like the podcast as much as I do, don’t forget to subscribe and rate it in your preferred app.
Arun Sridhar 00:28
Hey, this is Arun.
And this is JoJo. And this is SKRAPS bioelectronic medicines. This is your podcast where we on your behalf find amazing sparks of scientific brilliance. And if you’re wondering where SKRAPS came from, it’s the word sparks spelled backwards.
Arun Sridhar 00:46
This season we’re calling our series as SKRAPS: Bioelectronic medicines, where we explore the stories of medicines that quite literally get on your nerves. Before we go any further, can we ask you to do a couple of things. Please visit our website, skrapspodcast.com and subscribe to our newsletter. We promise to not share your details with anyone else. And more importantly, the newsletter is a place where we can share with you extra content, ideas and information that doesn’t always make it into the episodes.
Once you’ve complied with Arun’s request. It’s my turn. Go ahead and unlock your phone once again and open up the podcast app that you’re listening to right now. Please submit a rating and leave a review for us.
Arun Sridhar 01:40
And before we start, can we stayed up front that we are not here to sell a product or sell an agenda, but merely to report on the state of the art to inform, educate and engage you, our dear listener who has decided to lend your ear drums to us for this episode. We rely on donations for a production and have a commitment that 100% of the donations will be used for the production of the new episodes.
Okay, Arun. Can we get back to the topic today?
Arun Sridhar 02:10
And what are we telling our audience about today?
Arun Sridhar 02:14
We are going to tell them about medicines that quite literally gets on their nerves.
Arun, that sounds like some kind of a leech or even an ex boyfriend that gloms on like some rabid dog and latches on so hard that you can’t shake it off.
Arun Sridhar 02:32
Oh, no, not quite that dire! You’ve been spending far too much time reading about what only the general public are talking about Elon Musk and mind control. So do one thing. Take a deep breath.
Really deep breath? Yes. Okay, here we go.
Arun Sridhar 02:47
Breathe out and refocus once again.
Okay, that felt good. Great. What was I saying before?
Arun Sridhar 02:54
So we’re going to talk about how our body is so intricately wired, yet most people are so conditioned to think only about the molecular medicines. But there is a whole axis of control in our body that we have just learned to ignore.
Ignore. Nope, not me. I don’t ignore anything. Not a single thing. Not once, have I ever ignored anything. Except maybe a parking ticket. Or my mother’s advice. Or maybe even the little voice inside my head that tells me to put down that last cookie.
Arun Sridhar 03:34
Well, by ignore, I mean, kind of brainwashed to believing that only molecular medicines that target the cellular processes are the ones that are key to treating disease, but there is a whole different mechanism that exists. Want me to give you an example? Yes, please. I think that would help me. Okay. Why do you think a person starts breathing deeply even before they feel breathless, while running up a flight of stairs, or most of us who are so conditioned to being on the zoom the last couple of years, will know very well as to why the first meeting after a heavy lunch on a weekday is the time that they feel extremely comatose.
Food coma. I like that example. I’m very familiar with that example,
Arun Sridhar 04:18
Exactly! In both cases, it is the nerves in the body that suss out what the demands of the body are and is what the demands are going to be and send signals to the brain in response to a physical activity in the context of running up a flight of stairs, or having a full meal. Those signals modify our body state slightly to ensure that we meet our demands.
So you’re saying that even before I get breathless, then my nerves make me breathe deeper and maybe even faster. And I have my nerves but not tryptophan to blame for feeling sleepy after heavy meal. Yes.
Arun Sridhar 04:57
When you have a heavy meal, the blood flew in the body gets rerouted to the gut, to aid digestion, while transiently reducing blood supply to the brain. When that happens, the carbon dioxide levels build up very transiently and makes one feel extremely sleepy.
Love it. Next time, you know, I’m gonna nerd out on my kids with this one. They’re all grown up now. And they just love it when I explain things like this to them. But why I want to make sure I get it right. So what you mean to say is that by electronic medicines is all about these nerves. But I just want to clear this up. You didn’t mention the brain or the spinal cord. Everything that I know from being in the field, this is what people will use as the prototypical examples. So what are you hiding around? Oh,
Arun Sridhar 05:45
I didn’t say that at all. In fact, it is the opposite. The reason why we wanted to do the season, as you know Jojo is because we wanted to ensure that every single aspect of how nerves control the human body, and its bodily functions are addressed. So what most people will describe as the traditional neuromodulation is very much part of the conversation.
Okay, so what about neuroprosthetics? I mean, you got to rank a system that makes a person with a spinal cord injury able to walk pretty high up there. I mean, that that rates highly right, of course,
Arun Sridhar 06:19
But Can we pause for a second? And rather than get into the flow about throwing in a bunch of terminologies and jargon, make a concerted effort to help people understand the field?
Yeah. When we first discussed this, it was just mind blowing. I mean, what was extremely exciting to me was how we decided to organise it. Because honestly, no one is even doing it. And everyone comes up with their own definition.
Arun Sridhar 06:43
So what did we do that got you so excited?
You know, me? I got excited about our definition. Of course,
Arun Sridhar 06:48
No, JoJo. Oh, come on.
No, we came up with our own framework to organise the field that helps to make sense, can we share it with everyone now? I can’t wait.
Arun Sridhar 06:57
Good. Got a small piece of paper. And for those who don’t go to the episode description, and click on the link to the schema,
wait a second, though, before we go any further we have to add, the previous instruction only applies to people who aren’t driving or performing surgery.
Arun Sridhar 07:14
I see what you did there. Well done JoJo.
Okay, go ahead. Let’s get started. Okay.
Arun Sridhar 07:20
So let’s start with the most basic definition of what bioelectronic medicines, our nerves are the information superhighway in the body. Whether you like it or not see it or not hear it or not, the nerves do their job, and are needed for both voluntary and involuntary functions.
So by voluntary, you mean like I want to swallow my delicious piece of chocolate cake. And involuntary is something like breathing as we will all breathe, whether we’re awake or asleep, right?
Arun Sridhar 07:55
Okay, everyone knows about the brain and how the brain controls many of the emotional and cognitive aspects of our life. The brain regions constitute the central nervous system, and the ones outside the brain like the spinal cord, and every other nerve trunk that emanates from the spinal cord is part of that autonomic nervous system. And the basic underlying principle that governs the functioning of our nervous system is electricity. Yes, electricity produced by small ions, and these ions, like sodium potassium, move in and out of the nerves. And this is propagated like a wave, like what the fans do at a sporting event, a Mexican wave from one part of the body to another. So the field of bio electronic medicines is one which uses electricity to modify body functions.
Arun Sridhar 08:46
Absolutely. And one needs to understand how these electrical signals are in health and disease. So it can be modified.
So hang on, what you’re telling me is eerily similar to molecular medicines. Like you can have a type of stimulation to increase signalling, like an agonist in pharmacology or reduce molecular processes and prevent a function from happening. Like an antagonist. You got it? Yeah. Okay. All right. So explain this in the context of existing devices to start with.
Arun Sridhar 09:18
Okay, let’s let’s take the first example. Deep brain stimulation, in its very simplistic form, stimulates areas in the brain that have reduced neurotransmitter levels called dopamine. And this is usually the area in the brain called basal ganglia. And stimulating this region reduces the tremors that are associated with Parkinson’s. spinal cord stimulation, on the other hand, uses parameters that prevents the pain signals from going to the brain and therefore perform electrical trickery to tell the brain that everything is okay. And no pain signals is travelling towards the brain. And that’s how it reduces pain.
Awesome. This makes sense. We’re gonna make the first category of bio electronic medicines, deep brain stimulation and spinal cord stimulation devices. But I must say what you said sounds awfully similar to a cardiac pacemaker.
Arun Sridhar 10:13
Bingo. They did evolve from the cardiac pacemakers. A few cool clinicians and engineers decided that if it works for a beating heart, or heart that doesn’t beat enough, it must work for the brain and spinal cord. So I always refer to them as hammers looking for nails approach. Why? Because they had a tool, and they went about looking for use case and history. His thought is that, that once these devices are proven to be safe, in one indication, the manufacturers will fund research studies for almost any other indication trying to find the use. So it is a hammer, searching for a nail without differentiating if what it is going to hit is going to be a harder nail or a Phillips head screw or a hex screw
And by design, these are open loop meaning that they stimulated a given parameter, frequency, current, etc.
Arun Sridhar 11:10
Yes, or no hardware is being improved to make them sends what is going on in the brain and stimulate accordingly. Much like how some of the latest generation pacemakers was able to increase the heart rate in response to exercise. But for the sake of simplicity, let’s refer to them as devices that evolved from the cardiac pacemakers.
Okay, I got that one. But I have another question about Elon Musk. What is the crazy thing that he’s apparently trying to do? Is he trying to control how people are feeling? I mean, it seems like Bill Gates in the COVID vaccine.
Arun Sridhar 11:49
Stop following Zuckerberg into the metaverse Jojo. Honestly,
I was only kidding. But seriously, I mean, part of these people are what we call the Musketeers.
Arun Sridhar 12:01
Oh, is that what we’re calling them now?
Yeah, why the hell not? Okay, go on.
Arun Sridhar 12:06
You know more about them? Well,
I’ll tell you what I think I know. Brain computer interfaces, or brain machine interfaces were discovered for the first time in 2006 by Leigh Hochberg and many others who work to improve the lives of people with tetraplegia. They use electrodes implanted in the brain, specifically the cortex to enable people to communicate with the external world to translate their thoughts into actions.
Arun Sridhar 12:32
And you refer to them as Musketeers, because….
well, I mean, because I was on Facebook, of course. Now, I’m just kidding. I call them musketeers because nobody’s come up with a better name yet. And because Elon Musk decided that he’s in the game to implant chips. But the way he has gone about it has irked quite a few people in the area. While trying to perform a publicity stunt for hiring. He has also become the butt of many jokes, and means,
Arun Sridhar 13:01
but there are some very cool companies in this space, though. And this area seems to be quite hot in terms of investment that some of the Silicon Valley VCs have made.
Yes, so the two that we covered is the hammer looking for the nail pacemaker like devices, and the Musketeers was the third.
Arun Sridhar 13:19
Remember, I said that there were some existing device companies that have learned to modify their current systems to enable them to read the brain signals and differentiate from what is good from the bad, the healthy from the diseased and therefore, have the brain pacemaker react to the recording data, rather than provide stimulation like the way they used to do like a horse with blinkers on.
And this is the third group where machine learning and artificial intelligence is being used to enable closed loop therapies. Starting with the neurological disorders, like Parkinson’s is a good example.
Arun Sridhar 13:55
Yes, these are what I call the self proclaimed cool kids. No one really knows whether they are cool enough or not. But they are currently faking it until they can make it. There are some really good examples of fantastic technology, or there are some really good examples, but time will tell how it pans out for things beyond deep brain stimulation.
And these companies and research groups are developing apps and software they compare with an existing hardware. And the software and algorithm are offered as as a SaaS model. SAS as in software as a service. Yep. Holy crap. There’s already so much diversity in bioelectronic medicine, but hang on there still more.
Arun Sridhar 14:39
So the fourth category is what I call as target practice, which is throwing darts at the dartboard in World Championship and seeing which one will stick in the right point zone. Jokes apart. Everything that I’ve mentioned so far deals with electrical stimulation, literally current sent via a wire to excite The nerves are a bunch of nerves. But this category uses targeted modalities that can be applied non invasively ultrasound and magnetic stimulation comes to mind immediately. These are already reasonably well examined projects in neurology space. And it’s promised to help some very difficult to treat disorders that traditionally have deserted even biopharma. We have some really cool episodes on this in this series, so we won’t take much time on this. Beyond that right now.
So this group is the non electricians, but the Dr. Meg nietos, and the Dr. Sonic hedgehogs of the world. Okay, so what’s the next category?
Arun Sridhar 15:39
The last category of vertical in the electronic medicines framework here is what I call as novel therapeutics. Remember, it used to be called electrosurgical JoJo for just one day before before a copyright claim came crashing down after the release of the nature commentary published in 2013.
Oh, yes, we got that cease and desist order to.
Arun Sridhar 16:01
So since then, these folks have claimed the moral term of bio electronic medicines, and have been coy in sharing it with others. But honestly, this is the one that has the most potential, bigger patient impact and much bigger economic and societal impact potential.
Okay, before we get on to the impact part of this, I do want to talk about the definition of bio electronic medicines. And how, because when we got the cease and desist orders, same time you guys did, we were also launching the journal, which we were going to call electro SUTA Khals. And then the cease and desist order came in. We had like three hours, because we had to submit it to pub line. We had three hours to come up with a name. So that’s, that’s part of the backstory on that one. Chris Czura. Margo puerta. I think Mark Lambert was there. And I we all sat there and we had tequila shots. And just like this name, no, this name no, this name no, this name! But another part of that exercise and launching that journal included a definition or an attempt at a definition for bioelectronic medicine. And I hope that’s something that we can take a look back and review. Now seven years later, and and see what it looks like and how it compares to how people defined by electronic medicine today. And I hope I hope it’s I hope it’s a good foundation. But I also hope that it’s evolved since then.
Arun Sridhar 17:31
Absolutely. And that is exactly what we will do during the course of this series and test drive this framework to see if the definition that is already existing out there encompasses it, or if that needs to be modified in a certain way to include some of the more recent breakthroughs and technologies and innovations
And the people too, because they’re important, but I diverted from from where we were going with this you were about to tell us about the bigger impact on society and the economy, and what bioelectronic medicine is going to mean therapeutically. So please continue.
Arun Sridhar 18:10
Think about the potential of having a nerve to a certain organ. And the way to selectively target one specific function, either because the nerve that you’ve chosen is selected for just that particular organ, or you figured out a way to selectively target one particular function. For example, in the earlier season of scraps, we discussed a therapy where a variable one on the hand, was used to stimulate the median nerve that ultimately helps treat essential tremor. Or other examples like stimulating the pressure sensors in the body to treat heart failure, and many others.
So does vagus nerve stimulation for arthritis count?
Arun Sridhar 18:53
Yes, it does. We have some comments reserved for it when the time comes.
So essentially, we’ve outlined five major pillars of bio electronic medicines. The Hammer looking for the nail drill, which is traditional deep brain and spinal cord stimulation, the Musketeers or brain computer interfaces. The self proclaimed cool kids in data and digital the Dart throwers, in targeted stimulation and novel therapeutics. Are you working on the last vertical in your previous role? Yes, that’s
Arun Sridhar 19:24
correct. Yeah. Okay, so
where does neuro technology fit in?
Arun Sridhar 19:28
This is a very interesting question. I think the field of neuro prosthetics required a whole set of technology to be developed to make paralysed individuals to operate their bodily functions.
Finally, tonight, President Obama had an unforgettable handshake this past week in Pittsburgh, when he met with a pioneer on the frontiers of medicine and technology. President Obama shook this robotic hand. 30 year old Nathan Copeland could feel the firm grip as if it were his own hand. Copeland is paralysed from the chest down after a car accident in 2004 injured his spinal cord, lots of things are hard, picking cups, regaining the ability to do things can really change someone’s life. President Obama was clearly impressed. never fully grasp what’s going on and didn’t exchanging a fist bone. Both men could feel a sense of history. Sensation is such an important part of figuring out what it is we’re touching and how to touch it. Is it soft? Is it hard? Is it hot? Is it cold, and the next step is to miniaturise all of this for eventual use outside the lab.
Arun Sridhar 20:40
And some of the most foundational work for the field was done in this area in the last 30 years. A lot of our understanding in how we stimulate nerves comes from this area.
That’s so true. The traditional area of neural prosthetics has now morphed into neuro technology where multiple aspects of engineering, including material science, signal processing, electronics, they’ve all come together to make a device that would help develop a neural prosthetic. So one of the best examples is the network neuroprosthetic are the NNP from Case Western Reserve University’s Biomedical Engineering Centre,
Arun Sridhar 21:18
absolutely. A fantastic achievement, and it only took them 20 years or so to get it through regulatory approval, and the five verticals that we refer to all use certain or most elements of neuro technology secret sauce. However, the recipes might be different for each of the vertical. I hope it makes sense. Yeah, I
think it does. A brain computer interface might require a different set of neuro technology ingredients, to a non invasive targeting methodology, to a novel therapeutics that targets a new nerve about two millimetres or less in diameter. Now let’s add to the mix, that the devices need to be made much, much smaller. What we’re looking at today, and a device that was recently developed is 27 times smaller than the original spinal cord stimulators, and those resemble a pacemaker. So all of this is neuro technology. And we qualify neuro technology as a platform technology to enable the verticals that we described.
Arun Sridhar 22:18
Okay, we promised something at the beginning that we haven’t addressed as yet. We said that there will be something in this for the investors. But so far, we’ve only described things from a scientific strategy perspective. Can we talk about it from an economic perspective? Jojo?
Yes, yes, yes, and I’m much more comfortable with economics. What I really like about the model that we’re proposing is that it solves two conundrums in the area. One, most of the companies we know and have that have been successful so far in the area, overlap with more than one vertical. For example, a brain computer interface company might develop a novel neuro technology to interface with specific regions of the brain. So that’s neuro technology. But then, that same company has to be focused on one type of disease population, and also be heavily grounded in data for closed loop. So you can see how the verticals can actually merge. But in reality for a given company at any given stage, one can make a clear determination using our framework, what type of investment is needed, and how that investment will be used? How this investment will be used will be dictated by what type of efforts are needed? Is it to build the hardware or build data systems or go into disease populations, so they can justify and describe how the company is structured at any given stage? That raises an interesting question. Did the venture capital investors really understand this area? Well,
Arun Sridhar 23:54
that is a loaded question Jojo. You know why? Because the medical device venture capital is an offshoot of the traditional Silicon Valley investor model from the 70s in the 80s forfeited to the biopharma model, which takes far too long, and is too risky, with low return on investment to then being forced fitted to a shorter time window based model for medical devices like cardiac pacemakers and catheters.
So you’re telling me that investors don’t entirely appreciate the nuances of bio electronic medicines?
Arun Sridhar 24:30
Oh, it’s much more than that. I spend truckloads of my time talking to investors. And it is super interesting. The biopharma investors think by electronic medicines as a remit of the medical device, venture capital investors, the medical device or med tech investors want data on humans as quickly as possible, because that’s how the medical device world works. For example, a pacemaker is a pacemaker is a pacemaker and Same is true for a heart valve. Once you know, or once you’ve proven that a pacemaker or heart valve works in a particular way, then the new innovation is predominantly in engineering and design. And it is about making the prototype smaller, faster. And then ultimately making it safer and testing it in the clinical studies, the traditional med device ecosystem. But then when you pair it with a novel therapeutic, targeting a huge population with a key unmet need, that nerve stimulation can treat. But then you take a novel therapeutic, targeting a huge population with a key unmet need, and enough stimulation approach using a novel nerf target that can treat this huge unmet need. No one really understands about who goes about funding them. This is a big problem in the area. And then on top of that, if you add data and technology, I think it becomes a deep tech meets Life Sciences problem. A scenario that blows everyone’s mind and is so different from what everyone else knows or has heard of so far,
but this hasn’t stopped investments in this space has it? Oh, heck no. Okay, then let’s tell you about some big movers and shakers. There are three primary indicators. There are more companies that have IPO in the last five years than ever before in the history of medical devices. And the ones with the biggest market caps are bioelectronic medicine companies
Arun Sridhar 26:28
that are done on investment on a successful exit and future market cap is eye wateringly clear, an investment of around $80-100 million in total, to take a product through two pivotal trials rakes in approximately 10 to 12 times its value in the first IPO
Early stage investments in bioelectronic. Medicine companies, which is mostly novel therapeutics, has shot up dramatically by two to three times. The average series A pre money valuation is much higher in the last two years than ever before.
Arun Sridhar 27:03
On the two additional pharmaceutical companies, as you mentioned, have realised that bioelectronic medicines is the way to go for them, as an additional innovation arm and have invested what one can suspect, close to 50 to $70 million in one case, and a straight out acquisition for over $300 million of a technology that barely finished preclinical validation, as most people believe in the area.
This makes it an interesting and to be honest, a little puzzling to the onlooker. While the world is focused on what Elon Musk is saying and doing the actual experts in the field seem to be working on a different dimension undeterred by this viewpoint, and in totally tangential direction that the world has barely taken notice of. We’re here to change all of that. Starting with this season. Scraps will create the first compendium of information for the field that has not yet existed before. And via that process. We hope to educate, inform, and engage each one of you about this new exciting area of medicine that we have been privy to for quite a while.
Arun Sridhar 28:10
Let’s lift the veil shall we? It starts from Episode Two.
And if you liked what you heard, please support us by leaving a rating and more importantly, sharing information about us via your network. You can send us questions that you want us to address during the season, send them to scraps firstname.lastname@example.org. We’re so grateful for our sponsor coretec for their invaluable support. Scraps is a volunteer run organisation that depends on donations to bring these episodes to you. If you would like to know more about how to support us, go to our support page at scraps podcast.com/donate. So that’s it for now. We’ll be back in the next episode with some really cool ways in which bioelectronic medicine is impacting an area that even pharmaceutical companies deserted a decade ago. Now there is new hope with bio electronic medicines. Stay tuned.