The new medical innovations that could change everything - The Engineers, BBC World Service

Hello, I'm Caroline Steel. This is the BBC World Service. And welcome to The Engineers.

This year I'm at the Royal Geographical Society in London and with our partners, the Royal Commission, 1851, we've brought together three world leading pioneers navigating the body in new ways and breaking fresh ground in biomedicine. And here to help me explore the work of these fascinating engineers. We have a delightful audience.

Audience, give yourselves a round of applause. Thank you. Surgery can be invasive.

Pills are a blunt tool. But what if we could borrow the body's neural pathways and electrically nudge its responses to MS or diabetes? And what if we could guide drugs through our veins to deliver them exactly where they're needed.

And paralysis can leave some people with locked in syndrome where they can't communicate. What if there was a non-invasive way to turn their thoughts into words? Thanks to our three world leading engineers, these scenarios are becoming new realities.

Tom Oxley, originally from Australia, is a neural engineer and professorial fellow at Melbourne Medical School. He is also founding CEO of Synchron, which has successfully implanted brain computer interfaces in ten patients worldwide.   Eleanor Stride is from the UK.

She is Professor of Biomaterials at the University of Oxford, specialising in the creation of tiny devices for targeted drug delivery. Her innovation of delivering drugs via bubbles in the bloodstream is going to human trials later this year. Khalil Ramadi is from the United Arab Emirates.

He is assistant professor of bioengineering at New York University. His electroceutical pill, designed to deliver nudges from the gut to the brain, is being developed at his Ramadi Lab for Advanced Neuroengineering and Translational Medicine in Abu Dhabi. Please do join me in welcoming them all.

Tom, your first experience of a patient with Locked in syndrome went on to inspire the rest of your work. Could you tell me a bit about that? Yeah, so I work in the field of brain computer interfaces, BCI, implantable BCI.

There's a very famous company you probably heard of where a famous entrepreneur driving this field forward. But we've actually been doing this a little bit longer, and we set out on a mission to find a way to deliver electronics into the brain without disturbing the local natural architecture of the of the head and the body. And yeah, so in my early clinical career as a, as a, in my neurology training, Uh, I had a young man around my age, now early 40s, who had a family of three, and he had a stroke.

And the stroke was actually a stroke in the part of the brainstem called the pons that carries all the motor fibres out of the brain. About 20% of your brain is made up around controlling the movement of your muscles. I'm using my mouth.

I'm using my body. And if you cut that fibre, then you can't control your body. But the rest of your brain is working.

And so he it was horrific because and that's still happening now. There's no therapy for people who have major strokes. There's no treatment for broken nervous systems.

So I think the great hope with BCI is that this technology can bypass the failed body, where the brain is still active. Um, yeah. Very clever.

Thank you. Tom. Elena, you've developed a new approach because the conventional means of pills and injections isn't super efficient, is that right?

That's right. So if you take a pill or you have an injection, you are putting the drug everywhere in your body. Your bloodstream is there to carry material around, which if it's food and oxygen is a good thing.

Um, unfortunately, that means the amount of a drug that actually makes it to a particular target site is less than 1%. That aim might not be enough, and obviously the rest of your tissue is absorbing that drug. And with very toxic drugs such as these for treating cancer, that can give you very severe side effects.

And one solution for that might be bubbles, right. Why are bubbles a solution? Well that's what we're hoping.

So what we're actually doing is repurposing the bubbles as drug delivery systems. Um, so these are tiny little bubbles of gas. They're, um, about a 50th of a human hair so they can safely go through your blood vessels because they are so tiny, we have to stabilize them.

So they've got an outer coating of a protein or some very biocompatible material. And we use that to also encapsulate drugs. So you've got this little ball of gas.

It travels through the bloodstream. The drug doesn't do anything. And then we focus the ultrasound at the target site to break the bubble open, and we release the drug just in that site.

So we're hoping to get much more of the drug to the right spot and minimize the risk to the rest of the body. Okay, so the bubbles travel all the way around the body, but you just burst them at the exact right point. So you're not sort of exposing everywhere to something potentially harmful.

Exactly. Ah. Very clever.

Khalil, your interest in engineering the brain led you to look at the gut. Some people might find that surprising. I understand where that comes from.

Colloquially, the gut is known in our field as the, quote unquote little brain. It has the second largest number of neurons in our body, after our brain. And essentially you can disconnect these neurons from the brain.

And they actually your gut can still function. You can still digest things. You can still you don't feel hungry quite as well or feel full.

Some of that feedback is lost, but at least the gut is able to function entirely with its own little brain. From an engineering standpoint, that's also really attractive to us because all of a sudden there is no hole, right? We swallow pills every day for therapeutic purposes, and those pills basically come into contact with the gut lining, which has all the neurons.

Very clever. Thank you. Tom.

Your brain implant is called Stentrode and it detects changes in brain activity. And like Eleanor, you're making use of our blood vessels. Could you tell me about the non-invasive way that you get this implant into people's brains?

Yeah. So the motor cortex, command centre of the brain, the brain is pretty well understood in the way it controls movement. So if you have a small enough sensor above a certain region of the brain, there's a part that controls your mouth, part controls your hand part controls your foot part controls various parts of your body.

So if you have a sensor over that part of the brain, you see the brain looks like a lightning storm in voltage potential. So its electrical activity in the brain so detected with a voltage sensor. You can then train an algorithm to know that, oh, in that moment you're trying to say open and close your hand.

Once you've trained an algorithm on that, you can then pull it out and send commands like through Bluetooth, to a system that would push a cursor around a screen or make selections on a screen. How do you do that? In a not very invasive way?

Because sort of instinctively hearing, you know, device in a vein on the top of your brain, that sounds like it's going to be pretty invasive. What's the way that you insert it? So our first generation is just targeting the safest, largest, most accessible blood vessel called the superior sagittal sinus, the one running down the middle.

We enter the jugular vein in the neck, thread the device up through a catheter, and then connect the lead that's coming out of the neck to a device that looks like a pacemaker box that sits under the skin in the chest and communicates the brain information out of the body. Great. Thank you.

And if Tom used the back door to the brain, your way is sort of similarly surprising. Could you tell me a bit about the early experiments which showed potential for influencing the brain via the digestive system. We did a series of early experiments.

We started just zapping little pieces of stomach, and then we looked at blood levels of different GI hormones. And the one that popped out really interestingly was this robust increase in a hormone called ghrelin. So ghrelin is a hunger promoting hormone.

Basically, the minute you take a bite of something, it tanks all the way to zero. And then as you get hungry and hungrier or more time has elapsed since your last meal, ghrelin goes up telling you to go eat. We were able to deliver this stimulus to the stomach and get repeated and robust increases in the short term of this hormone, ghrelin, which was really, you know, I think, validating some of our approach.

And so that led you to create your pill, your little device called flash. So what's it look like? Could you kind of paint a bit of a picture for us?

Yeah. So if you, uh, I'm sure some people in the audience take supplements. If any of you take your omega three capsules so you can think of it as about that size, but instead of containing chemicals, it contains electronics and so on the outside.

What you see in the picture are circumferentially wound electrodes, basically tiny metal wires. And inside we have a battery, some electronics to basically shape what the pulse that you receive there are like micro zaps that you basically can't feel. You swallow this.

It has about enough energy to stimulate for about 30 minutes and then it passes along its way. That's fascinating inspiration. And Eleanor, you were tasked with including oxygen in the bubbles which you're using to deliver drugs.

Why is oxygen important and why was that such a challenge? Yeah. So one of the challenges actually in a lot of diseases, but cancer particularly is because tumours grow very quickly.

You end up with a rubbish blood supply. There aren't enough blood vessels in the tumour. And so areas get completely starved of oxygen.

And the problem when you starve cells of oxygen is they start behaving very strangely. They start going effectively into a zombie state and it's very, very difficult to kill them. So them.

So drugs don't work. Radiotherapy doesn't work. Our own immune system can't kill these cancer cells.

So if we could deliver oxygen simultaneously with the drug, we could temporarily reverse that and hopefully make the cancer cells easier to kill. That's sort of counterintuitive, because in a way, you're sort of trying to boost the cancer cells, wake them up in order to fight them. Yes, exactly.

So the reason it's difficult is that oxygen is a very, very small molecule. It's very soluble. We, uh, have a very, very good way throughout the body of distributing it, um, which is exactly the opposite from the types of gas we usually put in our bubbles, we usually use something incredibly inert, incredibly heavy that isn't going to go anywhere.

I gave my poor PhD student many months of misery in the laboratory, as we desperately try to keep this gas inside our bubbles, and they didn't. Every time we made them, they just fell apart immediately. That's so interesting, because you'd think putting oxygen in a bubble is easier than putting some complex drug in a bubble, but that's actually where things got really difficult.

Yeah, and luckily, after many months and a lot of brainstorming in the entire team, we figured out, well, right, we need to completely change the coating. We've got to make it much more gas tight so we keep that. And actually, in the end, what we started doing was making the bubbles the old way with our very heavy gas and then partially substitute the oxygen.

And actually, it turned out the gas we've been using is a really, really good solubilizer of oxygen. And it was holding it all together. Tom, your team became the first in the world to receive approval for human trials of a permanently implanted brain computer interface.

Could you give me an example of a patient that you've worked with, than what you've been able to do with them? It's been a it's been a journey of different users doing different things. Rodney has most recently been, as well as Mark in Pittsburgh, has been using the latest Bluetooth profile, which we have worked on with Apple.

A new human interface device, which is a language for Bluetooth. So there's an HID for a keyboard. There's an HID for a mouse, there's an HID for an eye tracking system.

There's now going to be an HID Bluetooth for brain control. So up to this point, we've been tricking the computer into thinking the brain signals coming in were coming from a keyboard or a mouse. Now we have a ability to build different features that are truly brain derived.

Thank you. Tom. Audience.

It's your turn. Does anyone have a question about something that we've discussed so far? Okay, we've got quite a few hands.

Let's start with the lady in the middle. Thank you so much. Hello.

My name is Cheryl. Um, I would like to know if with the bubbles, you've targeted them at other cells in the body besides cancer ones. Eleanor, I think that's one for you.

Yep. Absolutely. Um, yes.

So we're increasingly looking at treating stroke. Um, so actually delivering the drugs that are clot busting because those are also horribly, horribly toxic. Um, and we've got a big project on delivering antibiotics, um, because again, antibiotics are fantastic, but they wipe out all the bacteria in your body, and most of the bacteria in our body are really, really important and really useful.

So if we can target that delivery. So hopefully next year we're actually going to be trialling this in chronic wounds with antibiotics. Anyone got a question for Khalil or Tom.

The person over here on the left. Thank you. Thank you very much.

My name is Ruchi. Um, it's a question for Khalil. You've got the pills.

Um, presumably you recover them as they come out. Do you foresee a time when they're going to be able to be dissolved, you know, dissolve in some way or something like that? Yeah, that's my favourite question.

Yes. Retrieval is a problem. So right now most of the electronics that we have are very much inorganic materials that don't necessarily degrade very well in the body.

Um, and essentially you either have to retrieve them or flush them down the toilet. And so that obviously poses issues, especially when you think about scaling up the there's a sort of parallel push towards making electronics that are not just ingestible, but edible. And so there you are trying to sort of make these same tools, but from food grade materials.

And so you can imagine how that is a lot more conducive to what you're describing right now. Those two fields are starting to talk to each other. Thank you so much for your questions.

Elena, your bubble technology is going to human trials in October. What are you hoping for? That's the plan.

This is. This is subject to paperwork, as always. Um, so we have tested the safety of the bubbles already, so we're fairly confident.

But this will be the first time actually with a chemotherapy drug. This will be in breast cancer. So these are patients who are going to have surgery anyway.

So they take the tumours out and actually quantify whether we have succeeded in delivering more drug. And hopefully whether that's led to more cancer cell deaths. So that's fingers crossed.

It's very exciting and could, you know, save many, many lives. How far off this being available to the general public do you think we are? This is a super question.

Um, so I think 15 years ago, I thought we were five years away at least. Now the gap is closing. We're probably looking at ten years.

Another ten years. Okay, great. Thank you very much.

Khalil, your invention is slightly less far along, but the implications of it could be huge. Could you tell me a little bit about the different conditions that this pill could be used to treat? So the gut is this fascinating organ that so many other organ systems overlap in.

Uh, we have our metabolic system, our endocrine system, our hunger and satiety system, our immune system. And so what that means from a disease implication, it means different conditions, different eating disorders, potentially obesity. Those are all sort of indications that we are we are looking at, you know, Ozempic watch out.

Uh, if you go a little bit further down in the gut, you get to the small intestine. That's a little more where metabolism happens. And so there are indications potentially Like diabetes become slightly more relevant.

Obviously super complex disease depending on where we go. I think the indications are a little varied. Thank you Tom.

So far we've focused on how Stentrode can help with conditions like locked in syndrome. What are the other possibilities for it? Where do you see Stentrode going in the future?

So if the first wave of implantable BCIs is in the domain of motor control, then the spectrum of conditions that cause motor impairment could potentially benefit. So neurodegeneration, motor neuron disease, stroke, multiple sclerosis, cerebral palsy, spinal cord injury, head injury, severe arthritis. There are many conditions that stop you being able to engage in the physical and technological world.

So I think as the technology moves towards other cortical domains, it will move into the domain of speech, into the domain of vision hearing. And then what I think is really interesting is emotional, emotional content. So a lot of a large portion of your frontal lobe is made up of reacting to the world.

Uh, what annoys you? What makes you happy? What frustrates you?

All of those emotions that are embedded in non-verbal communication. And there are many conditions, such as autism and many others where the, uh, challenge of, uh, communicating your emotional state, uh, is could potentially this technology could really help. Eleanor, we've talked a lot about chemotherapy, but do you see your bubbles helping with other areas of medicine?

Absolutely. So I think I mentioned earlier, antimicrobial resistance is a really, really terrifying problem that we need to do something about quickly. The other sort of allied challenge with bacterial infections is, um, bacteria grow these horrible things called biofilms.

So if you scrape your teeth, it's the horrible goo that comes off on your fingernail. Um, bacteria live in these biofilms, and it's really hard to get the drugs into them to actually kill them off. So again, using the bubbles, you get this mechanical effect.

You can actually break up the biofilm to get the drug into the bacteria and kill them as well. So that's something we're very excited about. I'd say we're hopefully testing this next year.

So fingers crossed. Fingers crossed. Tom, you must be aware of the ethical issues with interpreting people's brainwaves.

I mean, a large proportion of the population already think that we have microchips in our brains. How do you deal with those ethical concerns? So I think about this a lot.

I think there are concerns. The first thing I'll say on privacy, if anyone's watched Black Mirror, I think it's the Brits are to blame for Black Mirror. Um, the dystopian narrative on where BCI goes in society, uh, has some elements of truth to it.

I think it's in a long horizon. But the irony around the privacy concern with BCI is that the people in need right now have the exact opposite requirement, because they don't have. If you become paralyzed, you lose your privacy because you now become dependent on someone else.

And that's ironically what they're looking for. So you have to give up your brain access to enable this. Okay, that makes sense.

And just back to that Black Mirror episode, which I've seen, there are examples where something goes, something small goes wrong in someone's brain, but it has hugely devastating consequences. And they have a chip put into their brain, I guess, not massively dissimilar to what you're doing, Tom, and it is able to completely transform their brains. And, um, people are able to live as normal after having had a stroke or something like that.

Um, but the issue is people become reliant on a technology that they don't have total control over. And I guess this is probably something that you're considering. You're going to have people dependent on this technology.

What safeguarding is in place. How do you ensure that they're still able to use it in 5, 10 years time? So this issue has come up over several decades in other medical device applications.

The first one was probably the cardiac pacemaker, uh, which in the 70s and 80s, when it first appeared, needed multiple iterations and needed lots of support. Um, probably more recently, uh, there was a widely reported, uh, well, company that was doing a cortical vision implant, and the company, for whatever reason, wasn't able to continue and was people were left with implants that were no longer supported. So it's a challenging issue.

Um, there is the risk that the, uh, companies no longer exist, so there's no easy solution when we consent people, uh, we talk about it, so we talk about it in the consent. I think in a future state, if the technology. Um, I heard Alex Wang, the Scale AI last week made a comment that he didn't want to have children until they could get an implantable BCI, because otherwise they'll be, uh, they'll be disadvantaged.

And Steve Bannon has been talking about this a little bit in his, um, when he's referenced Neuralink that in the future, the question is, will there be now a subclass of humans, not a subclass, a different class of humans that have elected to take a technology for the purpose of augmentation? And does that mean they can then participate in society at a level, uh, superior? Yeah.

In some way advantageous relative to not. And what will that mean? What will that mean for society?

So from that perspective, if there's discrimination on the side of, um, who can't afford the technology, and then there's discrimination on the side of what will it mean for cultural divisions? Thank you. It's the turn of our audience again, who has a question on anything we've discussed so far.

The man over here in the aisle. And then afterwards, we'll go to the lady at the back. Thank you.

As someone that lives with left front lobe epilepsy, The delivery of drugs. You've all spoken with the brain and the gut. Is there a correlation between implants bubble and the gut?

Could. Could the three work together? Is this the.

Is this a moment for a collaboration? What do you think? Who wants to take this one?

Khalil. Could we work together? Absolutely.

I think the I mean, we met each other a few hours ago. Just full, full disclosure here. And, uh, and let's just say time flew by.

Just in terms of when you put geeks together, we just end up. Having. Interesting conversations.

I don't want to speak for sort of all engineers, but I will say that one thing that really excites me is where there is a problem that is unsolved. And I think that's sort of just kind of the engineering hat. So most of the projects that we embark on, start off with what is a problem that is currently underserved or where there is an opportunity to have an impact?

And then do we think that we have a novel enough idea to actually think that we can make an impact. Thank you. And we're going to go to the lady in the centre here.

Hello. This is question for Elena. What happens to the bubbles and the drugs inside them that aren't burst when they're targeted at the target organ?

Thank you. It's a very good question. So, um, the gas eventually just leaks out and you're left with a tiny little crumpled balloon, essentially, um, which gets processed by the liver.

Perfect. Thank you. I see a few young faces in the audience.

Does anyone of our younger members want to ask a question? There's someone keen over there in the back wearing a hoodie. This is quite a lighthearted question, but could you use neural implants to do more realistic VR gaming?

Oh good question. I think that'll be one of the first groups that are early adopters for this technology. I'm not joking.

And I think the reason it's going to be attractive is and it's, by the way, a US defence. That's why US defence is interested, because you can engage with systems in a more responsive way than what your body can. So you get down your reaction times for technology control.

Uh so gamers maybe. You what interest has it been from us defence. Tell me a little bit more about that.

Well, actually, the field of the field of BCI started with several hundred millions of dollars from US defence from DARPA. That was where our first funding came from. Then over the course of ten to 15 years, that that funding went away.

Trump came in and there was more of a focus on soldiers weapons. So there's less investment now from US defence. But there's been, uh, the initial the initial defence interest was helping people who are coming back from desert warfare who'd lost arms, legs and arms to restore control of prosthetic limbs and then also to understand post-traumatic stress from head injuries.

So that's the origin. Fantastic question. Thank you.

Thank you so much for your questions, everyone. I wish we could take more, but I'm afraid we're out of time. That's it for The Engineers exploring the human at the Royal Geographical Society in London.

I'm Caroline Steel on behalf of the BBC World Service, our partners, the Royal Commission, 1851, and my producer, Charlie Taylor. Please join me in giving a warm round of applause for our pioneering engineers Eleanor Stride, Khalil Ramadi and Tom Oxley. Thank you.

Very much.