Updated: Jan 22
On Sunday morning after my ritualistic run to Target, I noticed a building that had been hiding behind a recently pruned tree. “The Epiphany Center.” Only in San Francisco, right? Although I haven’t done the research to learn the purpose and the mission of The Epiphany Center (maybe they should include a side of motivation to go along with the epiphany offerings) but I immediately scoffed. Can you imagine - “Hi, I’m calling because I’ve stalled out in one of my experiments and I’d like to schedule an epiphany please. Do you have any openings on Tuesday - say around 2:00?” It seems just as ludicrous as making an appointment to find the love of your life.
I’ve asked a number of researchers where they find their motivation or where their best ‘aha’ moment was realized. For Nigel Lovell, Scientia Professor and Head of Graduate School of Engineering at the University of New South Wales, he finds clarity sitting on his surf board watching the sun rise. “You have those moments when you’re not actively trying to think about things and it happens more serendipitously,” said Lovell. “I don’t have one particular ‘Aha’ moment. You have plenty as you’re trying to design things and are trying to make things work. Things just come to you.”
He makes it sound so simple, so very Zen, so ‘see you on Tuesday at the Epiphany Center.’ Let’s be honest, asking the ‘aha’ question is a bit of a rookie move. (I’ve mostly stopped asking it), but I was a little intimidated sitting across from Lovell - the man behind the bionic eye (pause to appreciate, please - the Bionic Freakin Eye!), a man who has secured more than $80 million in research funding, and whose neuro family tree would make any royal blush with feelings of inadequacy. Don’t get me wrong, Lovell is a perfectly approachable person, a great buddy with whom to share a beer or three, but his body of work is quite intimidating.
I asked Lovell specifically about the $80 million he has raised to date and I was treated to a humble wave of the hand. “That comes from collaborations and the bionic eye, industry grants and government funding,” he dismissed. “‘Making a blind person see’ gains a lot of media interest and was quite well funded.” Lovell has been working in neural interface designs and implants for about twenty years (back when he had hair, he quips.) At approximately the same time he began running programs in telehealth to manage chronic disease and help the frail and elderly. He quickly admitted that deploying telehealth programs to help people avoid hospital readmission and to manage their meds to achieve a better quality of life isn’t such a sexy sell. “But if you look at the healthcare economic side, you’ll see that 80% of diseases are chronic and heavily impact the system in terms of the spend and the mortality. So you’re talking billions of dollars in Australia in the annual healthcare spend,” he explained.
What seem like two unrelated areas over Lovell’s last twenty years are now merging in an important way; we’re seeing that telehealth monitors are being combined with data from wearables and now from implantables, too.
“The area of neural engineering is starting to encroach on the area of telehealth,” noted Lovell. “We’ve got a holistic way of managing peoples health whether it’s from these implantables doing monitoring, or control of lost sensory function. We still need to understand how well they are working.” You could say that Lovell is closing the loop. In this case, that loop is at the treatment level and at the whole health service delivery level. He also acknowledges that closing the loop at the device level is critical.
“Many of the systems in the past operated as open loop systems and they weren’t optimal,” Lovell observed. Now you see particular devices like Saluda’s chronic pain device - it works so well simply because it works in a closed loop mode where it can figure out what levels of stimulation it needs to provide. If you can’t measure something properly, you can’t manage the thing properly.
“One of the areas that we’re focusing on in my lab is improved BCI - looking at means of better being able to read neural signals using optical techniques to close that feedback loop. A lot of the battles have been with the neural interface and the number of channels that you can concurrently read. I think that requires a disruptive technology. That’s what we’re trying to solve.”
Professor Thomas Stieglitz of the Albert-Ludwig-University of Freiburg, and co-founder and scientific advisory board member of CorTec GmbH, recently published a paper in Neuron 1 highlighting exactly the intersection in which Lovell now finds himself. “Ageing societies face challenges and associated health care costs in brain disorders including hearing loss that exceed those of cancer and cardiovascular disease by far,” Stieglitz explains. He further argues that support of translational neurotechnology research is necessary to bring the promise of neural implants into clinical practice. Novel neural technologies, when combined with telemedicine, such as is Lovell’s sweet spot, have the promise to address these challenges. I’d like to take a moment here to take credit for any future Lovell/Stieglitz collaborations.
Lovell hopes to improve the way in which we close the loop. “We’re working on a human trial on an augmented cochlear implant where we use gene electroporation. Literally we squirt in naked DNA - plasma DNA - and then we give some electrical pulses to transfect the cells locally,” Lovell explained excitedly. “This is a much safer way than using an AV viral vector transfection approach. In the cochlear we transfect the cells with a neurotrophic factor that causes neurite regrowth toward the cochlear electrode in a controlled manner and it reduces thresholds and improves, we hope, the actual performance of the device.”
Yeah. What he said. Nigel, you do know that I’m not a scientist, riiiight?
Ok, now at the JoJo-level, I think what he’s trying to say is that by improving the neural interface and increasing the number of channels that they are moving toward a closed loop scenario. It’s worked in guinea pigs and other animals so far, so the next step is to try it in humans. They are admittedly still a long way off, but they are using a similar approach for optogenetics to target brain and muscle in order to control those targets in a much more structured way.
Not satisfied with the success of the bionic eye and a national telehealth program that saves lives daily, Lovell remains at the bench (ha ha ha - get it? Because this is Behind the Bench - and he works at a bench... ahhhhh, I kill me.) He is currently working on optical techniques to passively transduce biopotentials. “It’s a new form of neural interface that grew out of technology developed in the EE department at UNSW that was intended for recording in mines and sonar,” he said while his low key brand of enthusiasm started to show through. “They have a special liquid crystal that if you place it in a sensing structure capacitor and then you put a voltage across the capacitor, then it changes the light reflectance and you can passively read out the change in voltage by the change in light intensity.
“I was looking at the technology with the inventor and asked ‘Why don’t we apply it to biopotentials and make not just one of them, but thousands or even millions?’” Why not, indeed? The Office of Naval Research has funded this work to try to use passive optical techniques to read out the biosignals. Lovell pointed out that this approach is devoid of electrical wiring problems and that the optical fibers provide a much easier means of measuring the signals.
As a veteran in the field, I was curious if Lovell thought that the disciplines that comprise the greater field of neurotech are integrating sufficiently in order to accelerate success in research?
“It’s still very much of a Chinese wall, and people are trying to break down those barriers, but the politics and funding don’t really facilitate that. In Australia it’s a classic case. There is no equivalent of the National Institute of Biomedical Engineering that sits in the gap between the basic science and clinical medicine.” (Ahem, please refer back to Stieglitz’s paper mentioned above.) “In Australia, we’ve got two funding bodies like the NSF and NIH equivalent, but they’ve got a sort of crevasse where each points to the other and says ‘you fund it.’ We’re struggling a bit and that makes it difficult to integrate the disciplines.”
Bridging funding agencies is a challenge. Everywhere. DARPA and NIH do the yeoman’s work in pre-clinical, but where does that leave the efforts moving to the commercial markets (hint: you’ll see a great push in this area in April - wink, wink, nudge, nudge.) But how about at the academic level? Does Lovell walk the walk? You betcha.
Through his various offices held within EMBS over the years, it is not unusual for Lovell to review about 3,000 papers in a single year. With that kind of exposure, he has a pretty good grasp on the breadth of work being done around the world across the dozen themes of the society.
“I’ve gotten to see so many cool things; every week I see something and think ‘Wow, I’d love to be able to work on that program or to work with this person,’” he noted. “In the area of biomedical engineering we have the opportunity to jump across disciplines, you think ‘Oh, gee, if I applied this in that area - wouldn’t that be cool?’
“There are some cool things that can happen between the molecular biology and the neurotechnology areas,” Lovell effused. “There are some cool things that come out of bridging the disciplines and applying one field to another field.”
Lovell’s lab is working with Gary Housely, Chair of Physiology in the UNSW School of Medical Sciences. Housely’s lab within the Translational Neuroscience Facility generates DNA plasmas that Lovell uses for optogenetics for neurite expression. They are looking for other constructs for changing the way that cells work. The big question is whether they can transvect the sensor organs in the cochlear to regenerate hair cells in order to reenact that mechanotransduction that’s been lost in the cochlear. So yeah, he’s walkin’ the walk; I’d almost call it a confident swagger.
Today, Lovell’s lab is adapting to respond to changes in technology development. He has scaled back the bionic eye group in recognition that making good improvements in functional activities requires more than tens or a hundred functioning channels in a visual prosthesis and that is a technology limiter for now. “That’s where we get back to disruptive technologies - improving the density and quality of the neural interface and the number of channels.”
And what about those youngins? Are our academic training programs on the right track? Are we adapting curriculum to reflect lessons learned and to ensure that trainees have the best foundation? What do today’s student’s need to succeed?
“I think that I benefitted from not having so many shortcuts. You have to do some things the hard way; you can’t be told. You have to toughen yourself up,” he said adamantly. “You should be able to draw on the skills from many disciplines. I think you give people in the field enough capabilities to do data analytics, signal processing - but you also want to make sure that you give them enough molecular biology or systems physiology so that they understand, not just at the micro or nano level, how systems interact to affect organs and organisms. The concept of understanding things across scales is important.”
Got it. Do the work. Toughen up. And learn a variety of stuff. Oh - and have a sense of humor.
“Students start out so serious. They need to understand the joy in the journey. It’s a long haul for the Ph.D. They’ve got to enjoy the journey and have some fun along the way, otherwise life can mistreat you.”
Wise words, my friend. Wise words.
1. Stieglitz, T. (2020) Of Man and Mice: Translational Research in Neurotechnology https://doi.org/10.1016/j.neuron.2019.11.030