The Engineers: Exploring the human

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25:14I'm Caroline Steele and this is the Engineers Exploring the Huben. I'm joined by three world-leading engineers in the field of bioengineering. Tom Oxley is professorial fellow at Melbourne Medical School and CEO of Synchron. Eleanor Stride, OBE, is professor of biomaterials at the University of Oxford. And Khalil Ramadi is assistant professor of bioengineering at New York University and head of the Ramadi Lab in Abu Dhabi.

25:47Eleanor, your bubble technology is going to human trials in October. What are you hoping for? That's the plan. This is subject to paperwork, as always. 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. So we're going to be looking just to triple check that, first of all, no one to all defects. and then we are actually quantifying the amount of drug we've managed to deliver. So this will be in breast cancer, so these are patients who are going to have surgery anyway, so we'll 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 death.

26:27So that's, fingers crossed. All clinical trials, the first number one is safety, so that's really the primary outcome for us. It's very exciting and could save many, many lives. how far off this being available to the general public do you think we are? This is a super question. So I think 15 years ago I thought we were five years away. At least now the gap is closing. So you do your first trial, it's a small number of patients, fingers crossed, everything goes well. You then have to go to phase two and then you have to go to phase three and the number of patients and the cost and the time increases.

27:03after that, provided everything has gone well and everything has worked sufficiently well, that's when you would then apply to get it approved for the NHS or in different healthcare. So we're probably looking at 10 years. Another 10 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. We have our metabolic system, our endocrine system, our hunger and satiety system, our immune system.

27:43And so what that means from a disease implication, it means that if we look at the stomach, for example, that's the primary organ which relays hunger, as you heard earlier, to the brain. And so different conditions, different eating disorders, potentially obesity, those are all sort of indications that we are looking at. You know, Zempick, watch out. 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, indications potentially, like diabetes, become slightly more relevant. Obviously, super complex disease. It's not as simple as I'm describing it.

28:20But these are the types of circuits that we have in our body and where they overlap. And then the colon, if you look a little further down, that's where water regulation happens. There are some studies to show that you can sort of boost immunity one way or the other, depending on if you want to tone down inflammation or if you want to sort of upregulate the immune system, put it on hyper alert. And so 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?

28:54Where 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 the first wave of motor system devices will affect that. that but 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 emotion emotional content so a lot of a large portion of your frontal lobe is made up of reacting to the world what annoys you what makes you happy what frustrates you all those emotions that are embedded in non-verbal communication.

29:59The brain takes up a surprising amount of neuronal activity controlling that unspoken language. And there are many conditions such as autism and many others where the challenge of communicating your emotional state could potentially, this technology could really help. So with emotions, could it get to a stage where maybe I'm feeling frustrated but finding it hard to articulate it, there might be a way of sort of getting that feeling out of my body and communicating it to someone else. That's exactly what I think will happen. And, you know, maybe you don't want that, where maybe you don't want your partner or knowing, or maybe they're having trouble picking it up.

30:41But I think if you're engaging with technology that is now physically able, which I think is coming in the next five to 10 years, then it could be really important that that technology knows how you feel in that moment. So maybe you're having small emotional reactions and the technology is reacting around you. I can't tell if that's going to solve or cause lots of arguments. Definitely one of the two. 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 overuse of antibiotics is one of those problems so if we can target the antibiotics much more effectively or we can use other drugs hopefully we can reduce the acceleration of resistance that we're seeing because at the moment we give antibiotics far far too much to humans and to animals so if we can find a way of targeting it that would be great the other sort of allied challenge with bacterial infections is bacteria grow these horrible things called biofilms so if you scrape your teeth it's the horrible goo that comes off on your fingernail 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 and 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 brain waves i mean a large proportion of the population already think that we have microchips in our brains.

32:15How do you deal with those ethical concerns? I think about this a lot. I think there are concerns. The first thing I'll say, so, and I think about things in three principles, privacy, autonomy, and discrimination. The first thing I'll say on privacy, if anyone's watched Black Mirror, I think it's that the Brits are to blame for Black mirror. The dystopic narrative on where BCI goes in society has some elements of truth to it. I think it's on 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. If you become paralyzed, you lose your privacy because you now become dependent on someone else.

33:02And that's ironically what they're looking for. So you have to give up your brain access to enable this. But in a future state, the question becomes, well, how do you, especially if you move into the domain of subconscious engagement, if it starts to engage with things that your brain is doing at a subconscious level. So I think if that happens, then there's a real question around how you handle privacy and consent, and you're starting to give up what could be very intricate parts of yourself. So I think that's a major consideration and there has to be agency and sovereignty to the systems. And when you say BCI system, just to clarify, you're referring to part of, you're partly referring to the device that you're implanting into people's brains.

33:45I'm talking about a situation where you have a implant and it's able to understand some of your cognitive processes and it's engaging with layers of technology around you. 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 liver's normal after having had a stroke or something like that.

34:24But 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 five, ten years' time? So this issue has come up over several decades in other medical device applications. The first one was probably the cardiac pacemaker, which in the 70s and 80s, when it first appeared, needed multiple iterations and needed lots of support. Probably more recently, there was a widely reported company that was doing a cortical vision implant.

35:05And the company, for whatever reason, wasn't able to continue and people were left with implants that were no longer supported. So it's a challenging issue, given that the companies emerging are not government-funded. They're companies that are having to stand on their own two feet and create successful businesses. There is the risk that the companies no longer exist. So there's no easy solution. When we consent people, we talk about it. So we talk about it in the consent. Probably an important thing to mention is that you offer a certain level of functioning and then if there are upgrades, well, what happens then?

35:47How do you continue to upgrade? It's challenging to upgrade systems that have been implanted in the body. What matters is that at the moment in time, you've talked about the user that you're offering a level of performance that is better than what they had before. Now, yes, things are going to keep getting better in front of you, but that's an aspect of life that's unavoidable. But we have that conversation. and what's been extremely humbling and inspiring is that most of the people we've worked with have a life-threatening disease, mostly motor neuron disease and their motivation to do this is the belief that they're going to have made a contribution to a system that's going to help people after them.

36:29And you mentioned discrimination. Could you tell me a little bit more about that concern? So discrimination, I think in a future state, if the technology... 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 disadvantaged. And Steve Bannon has been talking about this a little bit when he's referenced Neuralink, that in the future the question is, will there be 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 superior, in some way advantageous relative to not, and what will that mean for society?

37:19Great, thank you. Khalil, one last question from me. How would you feel if your pill went on to be used as an appetite suppressant, as something to help people lose weight as its primary function? That is a mechanism that we would love to be able to identify, because right now we can do the opposite. And I think... To make us really hungry. You get it. It would be great if we could suppress appetite. The biology is not so simple. And we have some hypotheses about maybe how we might activate certain appetite-suppressing circuitry. We're not quite there yet, although some preliminary data looks promising, so we'll see.

38:03But I do think that that's probably the biggest indication that we might be able to have this work for. Thank you. This is The Engineers, exploring the human from the BBC World Service. We've discussed bubble drug delivery, brain implants for communication, and electrical pills which tackle disease from the gut. It's the turn of our audience again. Who has a question on anything we've discussed so far? We've got a question down here at the front. Hi, my name's Tim. It's a general question, really. We've heard a lot in the last 12 months about the exponential growth in artificial intelligence. And I just wanted to pose the question to the three experts in turn.

38:45To what extent do you think AI will have a positive impact on your relative areas of research, or possibly even a negative one? So we'll have really quick, short, snappy answers from everyone, if that's okay, starting with Eleanor. So I think a very positive area is in rapid diagnosis. So I think in being able to process lots and lots of medical images very quickly, very efficiently, the radiographers don't get tired, we can detect diseases earlier, we can treat them much more effectively, I think that's where. The problem with all AI, if you don't have good data, and you are using the wrong statistical processing, you will get rubbish answers and that's I think where the danger lies so we've just got to be super careful where we apply it.

39:27Tom next. In the good instance integration with AI and BCI is in a sense needed because the ability to make sense of the huge amount of data in the brain will be best served by AI and it will enable interaction between brain activity and technology but on the flip side, from what we've already seen, the algorithms that start to please humans from a corporate commercial perspective have already playing on human systems that are very vulnerable and they're primarily dopaminergic because they're addictive. So what I worry about is how that plays out over time. And finally, Khalil. I'm going to answer your question very practically, which is that as a researcher, these LLMs are fantastic for exploring ideas, drafting things, and I think it's very much changing the way that researchers sort of start to generate ideas and collectively brainstorm.

40:23So I think that's sort of a really positive one. Negative is that maybe we'll all end up having the same ideas. I don't know. I think Eleanor has something she wants to add. I think another thing we also need to be crucially aware of is just how much energy these things take. So again, in being very careful what we apply them to because they consume electricity and water like nothing we've had on the planet. Any more questions? So we'll start with 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 always put with the brain and the gut, is there a correlation between between implants, bubble, and the gut.

41:04Could the three work together? 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 disclosure here. 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.

41:50And 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 a question for Eleanor. What happens to the bubbles and the drugs inside them that aren't burst when they're targeted at the target organ? Thank you. No, it's a very good question. So the gas eventually just leaks out and you're left with a tiny little crumpled balloon, essentially, which gets processed by the liver. Now, that does mean not all of the drug is getting to the target. it there are two things we have to take into account there first of all we are typically using a hundred times less drug than you would normally give systemically so that the risk of side effects is still quite substantially reduced um the other thing though is we try and engineer the coating so the drug stays passivated it doesn't do anything and it's passed out so hopefully that's that's a way of dealing with that great thank you next question hi there panel um primarily for tom There's been a lot of discussion about the use of the implants for treating these degenerative diseases.

42:58Is there any way there could be potential for tracking onset and worsening of the conditions? The use of the implants for diagnostic purposes is fascinating. Lots of potential, especially in epilepsy. The challenge is that they're very expensive and they've got risk. So the field of diagnostics, especially with a permanent implant, you've got a very high burden for justification for putting it in. I think probably one of the most compelling areas that is emerging is in the domain of epileptic seizure cycle detection. Because otherwise, neurologists have very little way of understanding when seizures are happening, apart from the patient recounting, but the seizure makes you lose memory.

43:47So there is no mechanism right now of knowing when your brain is going into abnormal patterns or not, and that can inform therapy. Thank you. I see a few young faces in the audience. Does any one 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.

44:19I 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, 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. So gamers, maybe. What interest has it been from US defence? Tell me a little bit more about that. Well, actually, the field of BCI started with several hundred millions of dollars from US defence from DARPA. That was where our first funding came from.

45:00Then over the course of 10 to 15 years, 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 the initial defence interest was helping people who were 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. Thank you very much. Fantastic question. Thank you. Gentleman there. Hi, I'm Michael of Laherty. It's a question about engineering, really. Swallowing in a battery is never a good idea.

45:38Have you looked at alternative sources of energy to power your capsule? Yeah, great question. Swallowing a battery, for the record, is not a good idea. I don't recommend... Do not try that at home. I absolutely agree with that. We encapsulate it. That's why it's okay. But I think the two options that you have otherwise are you either generate the power locally or you deliver it wirelessly. Wireless powering, if anyone has obviously used it to charge your phones, you know that it's really good up close, but the minute you go more than a few centimeters away, it doesn't work. As that gets better, that could be an option.

46:11And then obviously the body has tons of sources of energy too. You have chemistry, so you can play around with local ions and acids. You can harvest mechanical energy. The catch there is that if you take the energy out of a contraction, then the contraction doesn't actually do its effect. So there's a sweet spot there as well. But yes, I mean, I think you bring up a fantastic point. There's a couple of different options. I think as our colleagues in electronics and electrical engineering also get better at powering things, so too will some of the options we have available to us. Great, thank you.

46:42Next question. Thank you. And does your work with BCIs be a very small step towards a world of Terminator?

47:00Terminator was robots walking around controlled by Skynet, which is a little bit different to a human system that has an electronics implant. So, no. Let's rephrase the question. Would it set up a world where you have computer-controlled humans versus your regular biological human. Yes, you could see someone maybe being at a disadvantage if you're not one of the people with this implant. So just to make the point, the idea is to send the control of the brain out, not to have the control coming in. So there's that. But I think we're already in a world where computers are beginning to control us.

47:49TikTok is an example of an algorithm that is very addictive, that has a huge influence on culture in a not always positive way. I believe that BCIs will enable understandings of ourselves better than what we have right now. So my hope is that actually this technology helps us become more human. Great, thank you. Khalil, similar to that, could you see your pill ever being used for nefarious purposes? I think, as with all medicines or technologies that we have, there's always sort of the security component. It can be as simple as counterfeit medications that are labeled in one way but in fact carry something else.

48:32And the minute you introduce electronics which are, let's just say, adaptable after they are manufactured, I think that also opens the door towards active manipulation as opposed to just source manufacturing manipulation. So yes, I mean, I think security is a huge component of it. And honestly, in part, why some of these things are so expensive to develop is that you have to take all of this safety and security into account. Thank you. And yes. Hi, this is a question for Tom. I was wondering in terms of what you're most excited to experience or see coming forward from the technologies you're developing now in terms of brain interfaces and where that will develop from there.

49:14What I'm excited about on a long-term perspective is this technology, assuming it's safe and it's effective, you've got a mechanism to transmit information from the various cognitive domains of your brain. and I think in a future state this is probably a couple of decades away but if we have the device streaming from multiple domains of your brain I think we're going to realize like the you know that you can have multiple ideas going in your head you can multitask you can have parallel streams of things happening in your brain you might actually be only actively consciously working on one of them but if this technology enables streams from multiple domains of brain into various technology layers, then you could potentially be working in multiple streams of consciousness at once.

50:07Thank you. And yes, thank you very much. Hello, my name's Sarah. I'm a diagnostic radiography student. My question would be, as part of mammography in the section that we do there, would rolling out your ultrasound be something that you would look to put in within our department and something eventually we would be able to do as a routine course that we do? I promise I didn't plant her in the audience. Absolutely. And something we've been really keen to do is try to ensure we're using existing clinical ultrasound systems so that we don't have to use very high-powered devices or develop anything new.

50:46So absolutely. And the idea is this will be user-friendly and something that you see the disease, you can treat very, very quickly with the same system. Thank you. Very exciting. Thank you so much for your questions. everyone. I wish we could take more, but we are out of time. That's it for the engineers exploring the human at the Royal Geographical Society in London. I'm Caroline Steele. 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.

51:21Thank you very much.

51:30You've been listening to The Engineers exploring the human for the documentary from the BBC World Service.