The third episode of CIONIC’s podcast Superpowering the Human Body, features a conversation with Shriya Srinivasan, Postdoctoral Fellow at the MIT Langer Traverso Labs.

Shriya shares with us her incredible work to restore sensation and mobility to individuals with limb amputations, through optogenetics and advanced prosthetics. We also discuss how design thinking and collaboration between academia and business can accelerate solutions for human mobility.

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The full transcript is below, edited for readability.

Jeremiah: Hi, my name is Jeremiah Robison, founder and CEO of Cionic, where we build bionic clothing to enhance human performance and overcome disability. Welcome to another episode of our podcast Superpowering the Human Body, where we explore the science and technology of human augmentation. I’m so excited today to have on the show Shriya Srinivasan, a postdoctoral fellow at the MIT Langer Traverso Labs, who’s working on the future of prosthetics. Shriya, thank you so much for being here.

Shriya: Thanks so much Jeremiah. It’s my pleasure.

Jeremiah: Well, I’m really excited to talk to you about your work, but I want to start first with the patient journey, and I know that you are a big proponent of design thinking in approaches to healthcare. Why don’t you start us off with that patient journey — what the challenges and opportunities are for someone with the future of prosthetics; take it away.

Shriya: Yes, increasingly our research field is relying on design thinking, or this framework of user-centric design or patient-centric design. Where researchers actually try to get involved and understand what that patient’s day-to-day experience is. What they have available to them today in terms of therapeutics or rehabilitation devices or lifestyle accommodations. And then, further try to get a sense of what do they really want? What is feasible? What would make their lives better? A lot of times engineers can sit in their own bubble and think of very cool or fancy ideas, but In reality patients may not want or need them — or be able to use them. And so, having these two spheres come together; I think engineers are increasingly more able to incorporate the patient’s story and their needs into their design process and build on that. So I think that that’s a very important place for engineering to trend towards. And I think for patients, it also helps them to become a part of the processes and machines out there that can actually develop tools and innovations that will increase the quality of their lives.

Jeremiah: Absolutely. When we think about prosthetics, we think about advancements in control systems; the ability to interface the machine to the human body. Talk about your work in making more natural interfaces into those machines.

Shriya: So my research focused on exactly this — the interface between the human body, and specifically residual limbs for people with amputation, and the prosthesis that they’re able to control. Today, there’s a lot of prosthetic devices out there that have multiple joints, many degrees of freedom. There’s hands that have individual finger control, there’s legs that actually have actuated ankles — but despite all of these technological advancements, very few patients actually use them. And, the patients that I’ve talked to that actually use them say, “yeah, it’s kind of useful, but I only use it maybe once a week” or “it mostly sits on my shelf”. And, this sheds light on a very interesting and critical problem in the way that these devices have been built. We’ve come a long way on the technological front, but the ability for those human limbs to actually communicate information or receive sensory feedback from them, is still very crude. And for that reason, a lot of patients don’t prefer to use these advanced devices, because they add a lot of weight without adding functionality.

So my work focused on improving the actual residuum; the ability for those nerves and those muscles to communicate with the device, and more importantly, receive sensory feedback. We did these specifically by actually changing the amputation paradigm itself. At the time that the limb is created, we go in and we connect the agonist and antagonist muscles — so the muscle pairs, like your bicep and tricep — -and we make sure that that sliding motion and the paired way for it to actually signal to the brain that you’ve moved your joint so much, we keep those mechanisms alive. And then we also make special regenerative graphs that allow us to send feedback from the device. So, say your prosthetic arm touches a surface…we can electrically stimulate the appropriate component within the residual limb that your nervous system would be able to recognize and say “ah, my hand has touched the surface”. And so by orchestrating all of these new architectures and structures at the time of amputation, the innovation here is that the limb is actually ready to be interfaced or ready to communicate with advanced prosthetic devices.

Jeremiah: My understanding is that that starts right at the point of surgery where the amputation occurs. What are you doing to the body itself to expose that interface?

Shriya: You’re right. We do this at the time of either an elective amputation, or if a person’s already had amputation, a revision surgery. So at the time we go in, and we take the muscles that normally work in pairs — your agonist and antagonist muscle. So say you take your arm, — you only know how much your arm has been stretched because your bicep and tricep work together. With current amputation that pairing is actually severed. And so when your bicep contracts your tricep doesn’t stretch in the amputated residuum today. In the new model that we’ve worked on, we actually reconnect those muscles together. So, they kind of tug and pull through a pulley system within the limb and that recreates neuromuscular signaling patterns that the body is used to having. For nerves that are normally orphaned or just transected and severed and left in the residuum, patients often experience a lot of phantom pain. And so at the time of surgery, we now go and put in small regenerative muscle graphs — these are just one to four centimeter graphs. And these muscle graphs can be taken from anywhere in the body or perhaps the piece of the limb that is being discarded, and then we graph these on to those hanging nerves. So it’s almost like these live wires are being given something to hang on to and to signal in and out of the body with. Then, we use all of those pieces as kind of the transducers to really communicate with the prosthetic limb.

In addition to this, at the time of surgery, a lot of focus is given to how the residuum is padded, so that it’s comfortable in a socket. In patients today, as you age all of that muscle bulk tends to kind of atrophy away and thin down. Patients that are 10 or 20 years away from their last operation, they often have a lot of their bone coming up and chafing on their skin, and that can become really uncomfortable. In the new amputation paradigm that we developed, we made sure that we were really padding those boney spots with a lot of muscle to protect it and give it additional padding. And, specifically because these muscles can continue to work and take on forces, they can actually atrophy and help this limb stay a good size as a person ages and all of these decrease the pain and discomfort that these patients feel.

Jeremiah: That’s incredible. Once you have added these graphs to the body, how are they then exposed to the machine — the prosthetic — and how does the prosthetic influence that graph?

Shriya: Currently, we can use surface electrodes to take out and put in signals. In the future though — and actually we’ve already started working on this — there are also implantable electrodes that can be tunnelled through osseointegrated, or tunnels in the bone, to be situated on these muscles and that’s how we communicate with the prostheses.

Jeremiah: Wow, that’s really powerful stuff. I know that recently you have looked not just at the electrical stimulation of muscles, but also optogenetic stimulation of these nerves. Can you describe what optogenetics is and how it works and what the differences are between that and electrical stimulation?

Shriya: Optogenetics is the use of a special protein that is activated by light. We can genetically engineer this protein into the muscle or nerve of interest, and then if you shine even a simple LED through the surface of the skin, you can actually turn on or turn off these protein channels that allow the nerve or the muscle to fire. So, as long as these structures are superficial or close enough to the skin, we can get enough light to turn them on and off. Using optogenetics, we genetically engineered and functionalized nerves in the hind limb of an animal model and then we used light to basically orchestrate walking or movement patterns. What we saw was that with enough controls, we could actually get the leg to walk in whatever pattern we dictated, and we see that we can control the leg with greater fidelity than we can with electrical stimulation.

If you’ve ever tried a TENS [transcutaneous electrical nerve stimulation] unit, you’ll know that after a point your muscles start fatiguing very quickly — — and it’s because electrical stimulation goes out there and activates those oxygen-hungry fibers that are first needed say for a sprint, you need those big, big fibers. But when you’re sitting in a chair doing something that doesn’t require that much power, your muscles actually use the small fibers first. So optogenetics can actually use those smaller fibers first and then start to recruit those bigger fibers as it needs. We’ve seen that through the research with optogenetics, there’s a lot less fatigue that’s felt by these muscles and you’re able to get them to operate for longer periods of time with the desired movements.

Jeremiah: So I’ve got to ask, how did someone discover that this could be done?

Shriya: This protein came from a bacteria in algae, and people started using it mainly for neuroscience research — to look at the brain and see ”if I stimulate here where else in the brain does it start signaling to?” We looked at this and said, “okay, it’s just something that turns on and off a neuron. Let’s use it in the peripheral nervous system and think about rehabilitation, paralysis”. All of these conditions where a nerve has completely lost function and if you were to use electrical stimulation, either you need a really invasive approach with implanted electrodes and stimulators, or you apply stimulation at the surface and, say your nerve is over here, you’re stimulating everything that comes in the path and that can often be painful or annoying or just it simply won’t work.

Jeremiah: Yes. The ability to selectively target individual fibers in the electrical domain — we’ve worked on different patterns, different frequencies of electrical stimulation. I’ve seen in your research that you’re also looking at different wavelengths of light and engineering those proteins, those bacteria, to specifically activate at different light waves. So describe what Is possible today and where the future of those engineered optogenetic systems are going.

Shriya: So far, it looks like blue light opsins seem to be the most responsive in the peripheral nervous system. The challenge though, is that blue light is absorbed by the body. And so in theory, you can only access those structures that are very close to the skin, unless you implant a fiber or some sort of light source, which is potentially possible. Researchers are working on getting other colors, like red, which are not as easily absorbed by the body — to be functional in the peripheral nervous system. We’ve looked at different frequencies of stimulation. We tend to see that if you keep the light on for too much of a duty cycle, then the opsin starts to fatigue or doesn’t have time to recover. And so there are certainly constraints there. I think the biggest challenges though for us to get from where we are today to a patient, are two things. One is the immune effect: these opsins could potentially mount some sort of an immune response; the body could say “hey, this looks pretty abnormal…what’s going on” and nuke them. The second one is that this requires genetic modification. There are today about 200 clinical trials ongoing for the type of genetic modification that this would be, but nevertheless that’s still a step we have to think about and whether those potential side effects are worth the benefit.

Jeremiah: I went on to the Stanford optogenetics website and saw that I could order about 200 different variations of this with the full genetic sequencing and everything else. It’s really incredible how the scientific community shares this information and these findings, and also an inspiration, I think, for companies like ours that are working to take some of this science that we see coming out of these research institutions and really packaging it up in a consumer-friendly fashion to hopefully, do what commercial companies do. Which is to create it at a price point and a reproducibility that can apply across many different individuals. And we’re seeing more of this.I think that the valley, technology companies, and the industry as a whole are taking on bigger challenges and learning to partner with these research institutions. And you see that in everything from companies like neuralink, which did their big demonstration with their pig walking and being able to track that, to more and more companies operating in this space. Talk about how commercial companies can better partner with research institutions both from how do we facilitate new types of research and how do we commercialize new types of findings?

Shriya: You bring up a great point. The innovations that neuralink has really pioneered in the last two years would have taken academia just so much longer. And it’s because academia is not structured to carry out manufacturing, or design. We’re not funded to the same extent that a company like neuralink can take an idea and just push it ahead with the right volume of engineers and engineering expertise. This field is growing in a direction where the technology and our ability to get very high resolution signals or stimulation is going to be the barrier to making discoveries and innovations in neuroscience. And so really we do need companies and industrial firepower to propel the things in academia and vice versa. I think on the academic front, we have a lot of niche findings from research, that if properly combined with industry we could turn that into a product. And that process of productization will allow us to reveal all the small challenges that we really have to think about and scientifically overcome to get these things to market. So both from a funding perspective as well as an idea exchange perspective, we do need increased communication between these two spheres.

Jeremiah: Absolutely, and I think for us at CIONIC as we are building out our product, we are building out a platform. And the first consumers of our platform today have been researchers — and we have a study going on with a couple of different universities — where they’re taking our technology and using it in the context of their studies, not for our benefit but to help in their own investigations. Part of our goal there is, when we think about the platform for human innovation, the fidelity of your prototypes — of what you’re able to build in the lab — especially when we talk about body-worn devices that we want to get out into people’s homes; we feel like a lot of these labs just keep recreating the base fundamentals of the hardware so that they can then do the research. So how can we actually commoditize that for them so that most of the time is spent doing research? And then once that research is done, can we help to take it and commercialize it and get it out to folks?

Shriya: I think another big bottleneck is the ability for researchers to create such devices at scale. If we want to scan 100 patients or 50 patients often we can’t do that because we just can’t create the hardware in a replicable manner. But that’s somewhere where industry could partner with us and help drive that forward. I think there’s also a lot of data that could be gleaned on the academic side and used — big data or machine learning type approaches — to perhaps even screen for an early diagnostic type scenario. You have a lot of VR/AR type modules that are now being developed. What if we took all of that muscle data or all that EMG control data and looked at whether you can see signs of certain diseases in formation? So I think there’s a lot of overlap we could have there between things that are more geared towards being products versus, pure research based data as well.

Jeremiah: Yes and really trying to make it a continuum, so that the gap between early pioneering research like what you’re doing and market accessibility is a shorter path. If we can start to build on some of the same platforms, if we can share out the data as you said, nd human data is not a proprietary to a single company but is out there for the benefit of all I really hope that we can accelerate getting solutions to human body. Our company was really founded from a personal experience with my daughter, who has Cerebral Palsy and the total lack of any innovation. The best that science has to offer is crutches, canes, walkers wheelchairs. We have cars that can drive themselves down the road and yet this is the best that we can do for humans. Now, the human body is tough, but I think it’s also time. And it took time for us to get to a place where we had the confidence to do this and the resources. Like you said, the ability to go and build at-scale, devices that can live with a human and interact with the human. When you look down the road 30 years from now, what does that marriage of the human body and machine look like and how ubiquitous will this be?

Shriya: Great question. I think we will have many more custom devices that are built towards each person’s needs and desires. I think artificial intelligence is all going to play a big role in permeating every type of device or therapeutic that’s built from now on and it’s going to be a much more data-driven healthcare process. At the same time, I think we have to think about the balance that we have in the future about how much data is really good. If you find out you’re going to be predisposed to a disease or some sort of degenerative condition when you’re 30, is that really useful? Can you do anything about it? And is that going to be useful for your mental and emotional well-being or is it is it okay if we just diagnose that at the time that it becomes very symptomatic?

The other thing I think that’s going to start to emerge a little bit more, and we already see this, is that with these types of devices that so seamlessly integrate with the human body — you have cars that drive themselves like you were mentioning — I think it’s only a matter of time before we have small chips that we implant either in our muscles or potentially in the brain or spinal cord, that start to automate some of that functionality. Today, I could probably think about opening and closing my garage door or use some sort of muscle queue to trigger that; there’s really no new innovation we need for that to happen. But the ability for these types of devices and innovations to permeate the entire socio-economic spectrum, I think that’s going to be a huge thing that evolves in the future. There’s going to be disparities in access and the utilization of technology. I think it’s critical that researchers, industry and policymakers get together now and put in place some sort of thought processes or frameworks to bridge that gap so that we don’t have that issue in the future. Echoing one of the points you mentioned earlier, the reason we don’t have as much innovation as we should in some of these niche diseases is purely a funding issue. There isn’t a big enough market to devote x amount of funding to get this to market, whereas the science and technology is probably frankly there. It’s a matter of productization, taking that final step. And so and so we need to think about a way that healthcare has greater equity in the whole system.

Jeremiah: That’s an excellent point and I’m actually very excited about what I have seen recently with companies, like Open Bionics and others — Bill Gates Foundation — that are really trying to use productization, commercialization tools that are available to larger companies to drive down the cost and increase access to prosthetics. It’ll be really interesting to see, and I think that one of the best ways that we can get access across the ability spectrum is to create platforms — and platforms where it is not having to build from the ground up to get a new disease state — but it’s about optimizing. What we talk about is: can we make the delivery of a new therapy or a new function to the body as easy it is as it is to download an app to your iPhone? We’re certainly driving on that and I know a number of other technologists in this space; quite frankly it is so big with so much opportunity to do good, it’s really exciting to see all of the folks who are working on it, with more entrepreneurs and small companies taking on that task. I know that you were the co-director of MIT Hacking Medicine with a real focus on both design thinking that we talked about earlier and entrepreneurship in healthcare. Give us a little bit about how that organization works and how you mentor other individuals within your field to take on these big problems.

Shriya: Sure. So, MIT Hacking Medicine was formed around the idea that we need to apply more design thinking within the healthcare space. As you know, design thinking is just a framework for analyzing the problem and designing an effective solution to it, which holistically considers all the stakeholders. With our workshops, as well as our hackathons that are usually 48 to 72-hour events, we have a number of individuals come in from many different walks of life: engineers, clinicians, patients, insurance, policy makers, designers, business folks and the idea is to take a problem and really, really break it down into its root components and see where making an innovation would beat out the competition that there is in the market today.

And so we’ve done probably 180 events across the globe and we’ve been to about 30 countries and from these events and workshops, about 50 companies have actually spun out and raised $250 million in venture funding. Pillpack was one of our first companies that came out of it. So taking all of that experience in thinking about design thinking and coaching others to really integrate different perspectives, I’ve brought that into my research a lot and stress the principle of integrating the different parts of the spectrum that, for example, exist in amputation. Today people see a surgeon, a rehabilitation specialist, a prosthetist and an engineer, and all of these folks work in silos. In our research paradigm, we really try to integrate all of them. So we do have regular meetings with people from all of these spheres and ask how do we hand off the patient in this continuous fashion as opposed to a discreet experience, and make sure that the Innovation is actually touching each one of these aspects, and that we’re innovating in each segment. And I think using that type of a framework increasingly will be obviously useful to patients, to everybody involved.

Jeremiah: Yes, you really laid out a fantastic blueprint for what is necessary to integrate early research, science, development, the patient needs all the way through commercialization and access. It’s one of the things that is really exciting about working in this space: all the people who are willing to come together and share in both their knowledge and their opportunities and I really look forward to the future of an integrated healthcare system, in the future of technology’s ability to really provide some advancements to what the current state of the art is, because I know that we can, if we work on it together. I want to thank you for your time and all the wonderful work that you are doing in this space and I really look forward to continuing the conversation in the years to come and seeing the future of super powering the human body in the form that you’re bringing. So thank you so much.

Shriya: Thanks so much for having me.

Jeremiah: That does it for this episode of Superpowering the Human Body. You can subscribe to our podcast on Soundcloud or YouTube and never miss an episode until next time. This has been super powering the human body with Shriya Srinivasan, and we’ll see you next time.