Oh sure, he’s a Professor of Biomedical Engineering at the University of Florida, and he has his neuroprostheses lab, and he’s dedicated to his work, but that’s not what I mean. His wife, Elizabeth Nunamaker, is the Assistant Director of the University of Florida’s ACS as well as a Clinical Assistant Professor and Doctor of Veterinary Medicine. I’m going to guess that their son is no stranger to the UF campus and his parents’ labs and offices. I know first-hand that Young Otto made an appearance at one of our EMBC soirées before he could even walk. Otto lives, breathes, and is married to neurotech.
I know a lot of people with highly technical jobs. In my experience, their families do their best to understand and support their work and their passion, but often times shop talk is endured rather than reciprocated. That’s not the case at the Otto-Nunamaker home. “I can’t imagine it any other way,” explained Otto. “It very much suits me to be able to talk through things with my wife.”
It seems that Otto has a history of blending his work and home life. Two of his three grad school roommates were also colleagues in the Kipke lab. “We did experiments during the day and analyzed data at night – usually having breaks for foosball and refreshments,” he said. “I enjoy that immersive aspect. There’s home that happens at work, and work that happens at home. If you like all aspects of it then you’re lucky.”
As an undergrad at Colorado State University, Otto studied chemical engineering. He went on to Arizona State University to obtain his masters and Ph.D. in Bioengineering. While at ASU, he was working with Daryl Kipke, who moved to the University of Michigan in 2001 – the end of Otto’s fourth year. It’s not unheard of for a professor to relocate, but his or her students are usually left with two choices: move or find a new advisor. Or the third option, you could quit. “I was pretty invested in the line of research and excited to continue working with Kipke, so for me, it was an easy decision to finish my thesis with Kipke,” Otto recounted. “I didn’t think I had enough data so that was a big part of what drove me to move 2,000 miles to Ann Arbor. In the end, none of the data that I collected at Michigan ended up in the thesis.
“It was a very interesting and major life change. However, I can tell you that in the end, the move was honestly one of the best things that ever happened in my career. It wasn’t that Michigan was necessarily a significant improvement over Arizona, but a move like that adds diversity to your program and adds diversity to your contacts. It infuses the lab with a lot of new resources.”
History was bound to repeat itself, but this time Otto was the professor and it was his turn to ask his students to make the leap with him. After eight years at Purdue University as an Assistant Professor and then an Associate Professor, Otto would again traverse half the country to the University of Florida. Having been in the situation his own students now faced, their fate was a considerable factor in his decision. “I knew what decisions they were facing,” he recalled. “I told them that I was not doing this lightly, that it was something that I had thought a lot about.”
Of the six PhD students Otto had at the time, three made the move to Florida. “I had guessed that about half would make the move, but I incorrectly guessed which three it would be,” he laughed. Otto counseled his students with the voice of experience, he had been exactly where they were now. He acknowledged that personal reasons cannot be discounted and that wasn’t a bad thing at all. “You have to be happy to do good science. Sometimes happiness is in Indiana, and sometimes happiness can move.”
Otto calculated the value proposition of moving to Florida to be a net positive. Of course, it didn’t hurt that in the year of the move, Indiana suffered back-to-back polar vortexes. Otto accepted the position at Florida in late January or early February and told his lab in early March – while the students were still defrosting a little. It’s hard to ignore the siren call of a Cheeseburger in Paradise when your bundled up in a parka. (You’re welcome for the earworm.)
What does Otto’s lab look like now? He has eleven project leaders in the lab drawing from five different departments. As the field draws its talent from a growing number of areas, Otto’s lab is a good preview of how this diversity will change the composition of labs in the future. “I find that having academic diversity in the lab is really important,” remarked Otto. “It makes everyone think at the group level. It helps to make them better teachers, and to think about problems from beginning to end, instead of assuming everybody jumps in for their part in the middle. They’re all anxious and eager to learn about other complementary approaches. The intellectual diversity really helps. I hope we continue to expand our talent pool. Chemistry is becoming more and more important. Biotech and genetics and molecular biology. I don’t think there’s a limit to who will contribute.”
Cross-training among contributors to the neurotech field is not new, but the disciplines and specialties continue to grow. While biomedical engineering and electrical engineering were once the traditional training routes, we’ve grown to increasingly include materials science, computer science, machine learning, molecular biology, genetics, ethics, and more. “A great example from our field is Kip Ludwig; he was an English major,” Otto noted. “It turns out that really helps make him a great writer. I’ve written with him and he’s fantastic. There’s no limit to the talent pool we can draw from.”
Otto’s lab embraces academic diversity to address the wide range of research he does. Each of his ten grad students and one postdoc is a nearly independent research arm. This breadth is requisite in order to address the dizzying scope of Otto’s research interests. His is one of the few labs that I know that works in both the central and peripheral nervous system. In general, his focus is, well, everything. For brain implants he is focused on higher channel counts, higher information rates, and longer implant times. Each advance comes with its own difficulties including fabrication, programming, usability, and stability. Changes to any of those inputs forces one to ask how it impacts the other dimensions.
“We’ve recently started partnering with a lot of fabrication experts that are making increasingly smaller devices out of novel materials that are expected to, well hoped to be able to last in the body for a long time with high performance,” he said. Otto’s group then puts each device through a series of rigorous validation tests including electrochemistry and electrophysiology, endurance, histology, and provides feedback to the fabrication teams about how the device is really working, if it’s lasting, and where improvements can be made. Otto finds excitement in the material science and fabrication advancements that are allowing the field to contemplate hundreds or thousands of channels of information.
Another area of interest within the Otto lab is applying their learnings from the central nervous system to speed up research in the peripheral nervous system. “The current clinical standard in the peripheral nervous system is the cuff electrode,” Otto noted. “Which in the brain is the equivalent to an Ecog device; you get information, you can give information, but it’s very low channel count. It’s not a very faithful way to communicate with the nervous system and it’s not how the nervous system works. There’s a drive in the periphery to be closer to the neural elements that you want to stimulate, have more channels, which means you have to be implantable. That’s the current physics.”
Otto applies learnings from the central nervous system to work in the PNS. He argues that perhaps the PNS is more challenging because there is less known about the PNS compared to the brain and because movement is more of an issue when working outside the skull. The lab is looking at nerves and new devices, new approaches, and new surgeries. They ask the ongoing questions about the impact of different stimulation paradigms and evaluating what their ripple effects might be.
“I find it so exciting to be pulled into the world of bioelectronic medicine. We can add so much impact to what we do and that adds to the potential for our work to help people. I have personal reasons for that drive, but I have a hard time giving up on the brain. I feel like we have a lot to learn and contribute,” he commented.
Otto’s work across two separate but integrated systems underscores his ongoing theme of downstream effects. What we do in one spot will have an impact on the other. If you’re stimulating in the periphery, it’s going to have an effect in the brain and vice versa. Everything works in concert and there are no soloists. Missing the integration step can be the failure of achieving a functional closed loop system. Even the most optimized components will fail if they are not tested at the systems level. “The first challenge is that if any of the individual components fail in a feedback loop, the whole system fails,” Otto opined. “At least you’re getting efficacy standardized to a point where you’re not going to have component failure. That’s step one.
“Step two is improving the performance of the component. Step three is system integration to see if your component performance improvement has helped with the system improvement. There are not a lot of people working in entire closed loop performance, although that is changing.”
To date, the field has largely been combining components to try to cobble together a closed loop system. Companies like CorTec are building platforms that are designed to be closed loop from inception. This approach should help to address the component failure problems and allow people like Otto and others to make significant advances in their research.
In examining what could be the best or most impactful use of a fully optimized closed loop system, Otto pointed out that the best system is the one that solves your personal needs. “The best implementation for an individual is the one that makes them better. If you’re a diabetic, the best CL system is the one that controls your glucose. If you’re epileptic, it’s a system that stops your seizures.” Otto evaluates the import of a potential system on how well that system addresses the needs of a population, what is the new quality of life? These are the questions that allow you to assign significance.
There probably is not a more high-profile closed loop system in the last few years as the one promised by Neuralink and Elon Musk. When asked to comment on Neuralink’s 2019 announcement, Otto stuck to the themes of integration and iteration. “They may not have presented anything I’d never seen before, but they took the best approach from fabrication, implantation, standards, and machine learning, and they’ve iterated on it, and incredibly fast, too. The chip design is impressive,” he noted. “Between the white paper and the July presentation they showed a lot more validation than they had ever shown before.
“They didn’t show longitudinal data last summer. Then, in the white paper, they showed some excellent data from a lot of channels. As soon as we see graphs with time on the X axis, I think it will be really important to show you their approach and the validity over time. Putting it all together for a long time is going to be important. But I think the other important thing about Neuralink’s summer presentation is where they’re taking the field. If they could figure out a way to put some systems into research labs that it could push the science – if they’re willing to do that. If you look at what the BrainGate trial did, and is still doing, it has led to a change for the entire field. Neuralink has that potential as well… as long as it does end up in researchers’ hands.”
The Neuralink event certainly stimulated interest from the neurotech field and way beyond. They were blunt about the event’s purpose being to stimulate recruitment. In Otto’s view, it was much more than that. “I was looking at the posts during the broadcast and more than a few times I read comments like ‘Today, I’m proud to be an engineer.’ What that kind of enthusiasm and spectacle does for the field is immeasurable. It helps us all to recruit. It builds excitement for the field the way that “The Matrix” did for me twenty years ago.