From Earth orbit to the Moon and Mars, explore the world of human spaceflight with NASA each week on the official podcast of the Johnson Space Center in Houston, Texas. Listen to in-depth conversations with the astronauts, scientists and engineers who make it possible.

On Episode 240, Nicole Wagner describes an experiment that is using microgravity on the space station to test the manufacturing of a protein that could solve retinal blindness. This episode was recorded on March 29, 2022.

Transcript

Pat Ryan (Host): Houston, we have a podcast! Welcome to the official podcast of the NASA Johnson Space Center, Episode 240, “Seeing the Future.” I’m Pat Ryan. On this podcast, we talk with scientists, engineers, astronauts, and other folks about their part in America’s space exploration program, and today we’re going to look into an experiment on the space station that could change how some people look at…everything. We often talk about benefits derived from the International Space Station. There’s benefits to future deep space exploration, to international cooperation, to the commercialization of space and space research, and the benefits to people here on Earth – us, Earthlings, you know. Well, some of these benefits can seem pretty esoteric or at times farfetched, I get that; but some of the benefits are very easy to understand. How about developing the means to restore your vision, your eyesight, if you go blind due to macular degeneration or retinitis pigmentosa; that is a thing. There are no cures for these diseases today, but the biotechnology company LambdaVision of Farmington, Connecticut is developing a protein-based artificial retina that employs a protein activated by light, which it hopes will one day restore functional sight to people with these diseases. And their scientists are making use of the weightless environment in the laboratories of the International Space Station to make a better-quality protein for this task. The protein is called bacteriorhodopsin, and you’re going to hear a lot about it in this episode as the latest version of the experiment known as Protein-Based Artificial Retina Manufacturing is about to launch on the Crew-4 mission. Our guest today is the principal investigator of this experiment, Dr. Nicole Wagner, the president and CEO of LambdaVision. She studied biochemistry at Florida State University before earning a bachelor’s degree in molecular and cell biology at the University of Connecticut, and then a Ph.D. in biochemistry from UConn where her graduate career focused on the use of light-activated proteins for applications in devices, and she was very involved in the proof-of-concept experiments that helped found LambdaVision. The next step in artificial retinas; here we go.

[Music]

Host: Let me start with a gross oversimplification. I’m going to assert that most people go off to college with some particular field of study or, or some career in mind. Nicole Wagner, what got you interested in research on degenerative retinal diseases?

Nicole Wagner: You know, Pat, my journey to working on vision was a very serendipitous one. You know, I started off in high school loving science, but not really knowing what a scientist does. So when I started, I actually went from my high school in Oxford, Massachusetts, and went off to Florida State, where I spent one year studying in a pre-medical program. And so, while I was at Florida State in this pre-med program, I learned a lot about medicine because that’s where I thought I was going to be going, and, and not knowing what a scientist does. Fast forward, I got a little bit homesick living in Florida, and transferred back to Connecticut where I went to UConn, and my journey into science really started by trying to check a box on a medical school application. So I knew that research was important for going, you know, a lot of people who do medical school have to do research, or it’s advised that you do research, so I joined Bob Birge’s lab, which is where LambdaVision was founded, only to do research with the goal of ultimately going to medical school. And Bob Birge is a pioneer in studying light-activated proteins as well as vision. And so, it sort of fell into my lap a little bit. And so I had a great experience there and seeing what the research that he did, and you know, it sort of lended itself to, to this artificial retina technology that we’re developing now.

Host: What was it that had you originally interested in science, I guess, coming out of high school? Why, why into that, pointed that way, instead of into a, a liberal arts kind of education?

Nicole Wagner: You know, I think for me, I had a lot of really great science teachers, you know, I had some really great math teachers, we had a lot of really great engineering-type design programs. And then it was for me, really, my anatomy and physiology teacher that got me most interested in doing research and, and science, and actually was the reason that I went to Florida State: he went to Florida State and I wanted to sort of follow his footsteps.

Host: Ah, OK.

Nicole Wagner: So that’s, that’s my first introduction into, into science. And then, you know, I think one of the important things as you’re thinking about, you know, especially when I was in high school, is, you know, a lot of people don’t understand what, what a scientist does, myself included at the time. You know, people know what a nurse does, people know what a doctor does, people know what an engineer does. People don’t know what goes on in a research lab. I mean, it’s not, I don’t think it’s obvious.

Host: No, I agree.

Nicole Wagner: So it really took, it took me that opportunity to go into a research lab to see that they are doing cutting edge tech, you know, cutting edge research, and translating that into products. So, you know, it’s not all just mixing things in beakers all day long: there’s a lot of thinking about things, there’s a lot of roundtables, there’s a lot of discussions that’s happening. And then you get to see the other side of it as sort of building out this, this story and what, what you’re trying to do and how that can lead into, you know, even commercial products, which is where, you know, certainly I got more interested, in thinking about how we could take the research that we did and, you know, use it for, for applications that could benefit million, millions of people.

Host: Right. You, you started us on that story. Let me ask you to, to pick it up. You, you transferred back to University of Connecticut and you became involved with Dr. Birge’s research, right?

Nicole Wagner: Yes.

Host: Where, tell me this, where’s the story go from there? How does, how does that lead you into, the, these specific areas of research that you worked on?

Nicole Wagner: Yeah, so my story with, with Dr. Birge, so I, I transferred from Florida State. I go back to UConn; I joined Bob Birge’s lab, really just to check that box on the medical school application.

Host: Right.

Nicole Wagner: You know, and actually it’s, it’s a little funnier than that because when I joined his lab, I, I started in, you know, I was doing research in his lab; that’s what I loosely called it. But when I really started, I was a glass cleaner. I cleaned all the beakers of all of the other graduate students, you know, that they did at, at the end of the day they’d put them in the sink and I’d come in and I’d clean those glasses. I’d wipe down the bench tops and make sure that everything was sterile. I would go through and I would, you know, organize all of the, you know, journal articles and everything in the lab. Really, I was a glorified work study student that was helping out these, these graduate students. And I did that for a year, so I was a sophomore, and when I was trans, you know, going into my junior year, I said, you know, this is, it allowed me to see what was going on in the laboratories, and it also, you know, I wanted to do more, I really wanted to do some of the science.

Host: Sure.

Nicole Wagner: And so, at that time I asked Bob Birge at the time I said, you know, would it be all right if I did research the following year? And he said, you know, that would be great and he was excited for me to join the lab and get involved and, you know, paired me with another graduate student. And I sort of shadowed them for, you know, that my, my junior year. And so when it came time for me to think about going to graduate school or to going to medical school, because that was my initial intent…

Host: Right.

Nicole Wagner:…I said, you know, I talked to talked to Dr. Birge and he said, you know, Nicole, I really think he’d be great at doing research. He said, you know, you’re, you’re great in the lab, you have great hands, you should, you should really consider pursuing a Ph.D. And so I, I thought about it and, and that’s exactly what I did. So I put all my eggs in one basket and I said I’m going to apply to UConn, I am going to stay in Dr. Birge’s lab and I’m going to be a scientist. And I’m going to work on all these really cool applications for bacteriorhodopsin research. And I actually didn’t get into the Ph.D. program that year.

Host: Of course.

Nicole Wagner: So I ended up taking a year off, sort of doing a bridge year where I did some, you know, additional classes, and reapplied the following year. And I was really, really fortunate because Dr. Birge, he allowed me to stay in his research lab during that time, continued to get experience…

Host: Oh, great.

Nicole Wagner:…doing research, and then, you know, allowed me to reapply and helping me get in that following year. So when I joined in 2007, I joined the Ph.D. program in molecular biology and my goal was to work on optimizing light-activated proteins, like bacteriorhodopsin, which I can talk about in a little bit, for device architectures. So it was a really fun, you know, it was a challenging but certainly fun journey. And I’m glad, you know, that was my first step at, you know, going out and trying to be a physician, to joining a research group, to deciding I was going to stay in research, not getting in, and then, you know, eventually, getting into that Ph.D. program, which is where the technology was, was founded that where, which is where LambdaVision was founded.

Host: I’ve talked to plenty of other people who have a similar story where they had something in mind and got sidetracked by something that seemed just to happen by chance, which changed their outlook completely and, and had them off in a, in a new direction.

Nicole Wagner:You know, it’s a winding journey and you never know, you know, if you asked me where, ten years ago where I’d be, you know, I, I wouldn’t have predicted where I am now. So a lot of, of serendipity in my path.

Host: Let’s talk a little bit more about the details here and for all of those of us who may not remember everything we learned in high school, can you give us a short course on the role the retina plays in how we see, and how damage to the retina from the diseases that we’re going to talk about, how that, that causes people to lose their eyesight?

Nicole Wagner: Sure. So the technology that we developed in, in Dr. Robert Birge’s lab, this protein-based artificial retina, is intended to help patients that are affected by end stage retinal degenerative diseases. So what most people are familiar with is a disease called macular degeneration.

Host: Right.

Nicole Wagner: It’s the leading cause of blindness in people 55 and older, and it affects about ten million people in the United States. Our initial target will be a, a disease called retinitis pigmentosis, which is a, the leading cause of heritable blindness. And it typically affects, you know, about a hundred thousand people in the United States, about a hundred thousand people in Europe, and over a million people worldwide.

Host: And, and did you say that’s…

Nicole Wagner: And so, what’s unique about…sorry, go ahead.

Host: Did you say that’s inheritable? Like if you get it from your parents, like you get everything else?

Nicole Wagner: Yes. It is an inherited genetic disease.

Host: OK. So go ahead.

Nicole Wagner: So the diseases, what they do is they affect your photoreceptor cells in the eye. And so these are your light-sensing cells. So what I often have people think about as I’m describing how, how the retina works, I have everybody sort of imagining that they’re in their office, and what’s happening in your office right now is your eyes, your photoreceptor cells, are taking the light in that room and converting it into a signal that gets sent to the optic nerve, and then eventually to the brain. Now, if you have retinitis pigmentosa or macular degeneration, what happens is those cells that take the light energy and convert it into a signal that can be sent to the brain, they start to die. So your eyes become incapable of taking light energy and converting it into a signal that can be sent to the optic nerve, and into the brain. And so what our technology is doing is we have a, essentially it’s an artificial photoreceptor cell layer. So we have a scaffold that we coat with the protein, this protein absorbs light, and in response to light the protein is going to pump protons towards those cells, your bipolar and ganglion cells or the neural circuitry of your retina, and that’s what sends the signal to the optic nerve and to the brain. So we’re replacing the function of those damaged rods and cones in the eye.

Host: Ah, it is though, I knew, I was hoping rods and cones were coming in, because that’s something I did remember. You’re, these — the protein that, that we’re working on here, you said that’s going to help those cells transmit the light; is that right?

Nicole Wagner: Yes. So essentially what we’re trying to do, so those cells, those rods and cones, they’re responsible for taking light and converting it into, and basically, it’s an electrical signal that’s going to send an impulse to the brain.

Host: Right.

Nicole Wagner: And so, when those are gone your eyes can’t take that light and convert it into anything that’s meaningful to get a signal to that optic nerve and then to the brain. So what we do is where those cells would normally exist in the eye, we have our protein coated on the scaffold and that protein is going to absorb that light, and in response to the light it’s going to pump ions that then get picked up by receptors on your neural cells that’ll allow you to send a signal to the optic nerve and to the brain.

Host: OK. So that’s, it’s all chemical and electrical…is that the right way to think of that?

Nicole Wagner: I think that’s, that’s a fair way to think about it. I mean, when you’re thinking about some of the other technologies that people are trying to develop to treat these blinding diseases, I like to break them into two categories. So when I think about it, I think there’s a very true hardware-type technologies where you have these, you know, they really look like engineering, you know, engineering marvels, they look like a virtual reality headset.

Host: [Laughter] OK.

Nicole Wagner: Right? And so, you have of these big headsets, and what they’re doing is they’re really sending a true electrical signal to your neural cells and then that’s getting sent to the brain. And then there are these other types of technologies, which a lot of people are very familiar with, called gene therapy treatments. And so what these gene therapies are doing is, or these optogenetic-type gene therapies, is they are sending similar proteins in a viral vector directly towards the cell. And then the light again will be absorbed, and it will pump ions in a very similar way. So I’d like to think of our solution as, as sort of an elegant solution between a pure gene therapy approach and some of those hardware-type technologies, because one of the things that we can do is we get around some of the challenges of a gene therapy approach by the way that we actually manufacture this artificial retina, which is through this layer-by-layer approach, and that’s what, you know, certainly allows us to be able to absorb lower light intensities to stimulate that, the, the neurocircuitry of the eye.

Host: The protein that we’re talking about, and we mentioned a couple of times, it’s called bacteriorhodopsin. Am I pronouncing it right?

Nicole Wagner: You are pronouncing it correctly. I often call it BR, so if I say BR…

Host: That’s what you’re…

Nicole Wagner:…that’s bacteriorhodopsin.

Host: Tell us what that is and, and where it comes from?

Nicole Wagner: So bacteriorhodopsin, it’s a seven-transmembrane protein that is found in a salt marsh archaeon, so an organism in a salt marsh called Halobacterium salinarum. And what this protein does is it pumps a proton from one side of the organism to, or the other, and so that proton pumping is what we rely on to stimulate the, the neural circuitry of, of the retina.

Host: The proton pumping?

Nicole Wagner: Yes. Proton pumping. So it’s pumping hydrogens.

Host: And that is what helps carry the electrical signal?

Nicole Wagner: Right. So you can think about this, if you have, think about almost like a, like a battery…

Host: OK.

Nicole Wagner:…where you have a, a, a bilayer, and one side is more positive, one side is more negative. And so we are translocating a proton from one side to the other, and that’s creating a, a gradient that’s allowing you to stimulate, or you almost think of it as, as a, as a charge, the neurocircuitry of the eye.

Host: So it’s a naturally-occurring protein, but it’s not naturally occurring within your eye?

Nicole Wagner: Right. It’s doesn’t naturally occur within your eye. So you have in your eye rhodopsin…

Host: OK.

Nicole Wagner:…which is similar in, in structure to bacteriorhodopsin, but functions, functions differently. You know, the rhodopsin, what it does is it will, you know, you can use it to absorb light, and it has a chromophore, and that’s the reason it can absorb light, and allows all these, these gradients to, to promote vision. Bacteriorhodopsin, one of the reasons why we, it’s been so well-studied and well-characterized is because this protein is, is very, very stable, more stable than, than traditional rhodopsin, and that’s because the, the light-containing moiety, that chromophore, is actually bound in that binding pocket. And so, that’s what allows it to have the stability to be used for these device applications. And it also allows us to produce in very, very high quantities as well. So you, you couldn’t do that if you used the native rhodopsin in the eye.

Host: You say the stability of it allows it to be produced in large quantities?

Nicole Wagner: Well, the protein itself is, is very, very stable.

Host: Yes.

Nicole Wagner: And it’s very stable because, what I, maybe, I didn’t mention this before, but it was, it’s found in a salt marsh.

Host: Right.

Nicole Wagner: So what causes the protein to be expressed is very, very high light intensities, very low oxygen, and very, very high salt. So it’s an, it’s an extremophile. It grows, you know, it’s a, it grows in the halophilic organism.

Host: I’m sorry, a kind organism, tell me again, what kind of organism?

Nicole Wagner: Halophilic. So, salt-loving.

Host: OK.

Nicole Wagner: So it grows in these salt marshes, and that extreme environment, you know, allows it to be a very robust protein. You know, this protein survives in very, very harsh condition. And so it is, it tends to be very, very stable. It, you know, what, I, we often joke about this but I carry a vial of the protein with me in my wallet everywhere I go. So if we were sitting there, I, I would take the protein out for you to see. And what’s really cool is the protein itself is a very, it’s a deep purple color. So it’s, you can see it visually. And a lot of people who work with proteins are used to working with them in very low quantities, very low yields, and, you know, they often need to be refrigerated because they are not very stable, but ours grows in these extreme conditions which lends itself to some of that stability as well.

Host: Neat. Now, LambdaVision and the labs there that you worked in while you were a student, you’ve been working on the use of bacteriorhodopsin to treat these retinal diseases; give, give me a sense of, of how that work has progressed over the years?

Nicole Wagner: So my background is, well, what I did my Ph.D. in was optimizing bacteriorhodopsin for device architectures. So I worked on the protein for halography, photovoltaics, chemical sensors, and then it was really with the emergence of optogenetics that we started to think about ways that we could use this protein to restore neural function. So for me, what is, what is unique and how we’ve kind of, the work that I did in my graduate, during my graduate Ph.D. thesis is translated to this company, has a lot to do with getting this protein to be suited for device architectures, and how do you get it to bind to various substrates and scaffolds, so that we can, we can use this protein and the, the, you know, that incredible stability in the properties of it being able to pump protons, to function, in some of these other device architectures.

Host: Yeah.

Nicole Wagner: And so that’s where I spent a lot of my, my career. And then, you know, that’s kind of lends itself into some of the work that we’re currently doing now with NASA, which is, you know, on this layer-by-layer manufacturing in microgravity.

Host: Well, and that’s really kind of what I had in mind in asking that question, because you were doing this work since before you were ever involved with NASA. The question is, where does the idea come from to think about manufacturing this in space?

Nicole Wagner: So I, I mentioned that a lot of the work that, that I’ve done in my whole career has been built on, on a bit of serendipity.

Host: Right.

Nicole Wagner: So in 2016, we, LambdaVision, participated in a program called MassChallenge. And MassChallenge, for those who don’t know, is an accelerator program that’s good at helping startup companies sort of get off the ground. You know, there’s a fundraising component about it, but there’s also, you know, just general business and entrepreneurial development as well. And so in 2016, we participated in that program, and I was driving from Connecticut to Boston, south Boston, three to four times a week, which for those of you who don’t know that’s a good hour and a half drive on a nice day, but could be three hours or more depending on the time of day with, with traffic. So it was quite, quite a trip. But I happened to be in Boston one morning and sitting at the table, you know, and the, to give you a visual of what that table looks like, I mean, we were sitting, MassChallenge has sort of a Google-type atmosphere, or what I would imagine a Google atmosphere looks like, where it’s these open floor plans, you know, there’s a lot of people working really hard. People are talking across the table. There’s a lot of collaboration. And so, it’s just a very, you know, exciting environment to be in.

Host: Yeah.

Nicole Wagner: Where, and so, we were sitting there and we’re sitting at the table and, you know, one of the program directors comes around and knocked on the table and said, you know, there’s a presentation down the hall, CASIS (Center for the Advancement of Science in Space), which is ISS National Labs, is down the hall along with the partner Boeing, and they’re holding a meeting to, you know, to talk a little bit about the, the CASIS-Boeing tech in space prize. And so I said, OK, well, you know, I didn’t really have anything to do, and I said why not check it out. And so I went to the meeting, you know, really not knowing what I was getting myself into. You know I, I was thinking of when I thought of ISS National Labs, you know, in 2016, I associated it with NASA and I’m thinking Moon, Mars, lunar mission. I’m not thinking about, you know, how you can do research on the International Space, Space Station and how it can benefit people.

Host: Now you know, we, we want you to think that it’s associated with Moon and Mars, because it is, but not only.

Nicole Wagner: Well, that’s true. Well, that’s, that’s not only it when it’s, when it’s ISS National Lab.

Host: Right.

Nicole Wagner: You know, I didn’t know what, what I was doing there in terms of, of that piece, and so, what I was getting into. I was thinking, you know, how, how is LambdaVision going to do all those other pieces? And so, you know, was it a good fit for us, I guess, is really the question I had of the day.

Host: And it was worth, and I’m going to say it was worth going to listen to him and see if it had any, if it could have any impact for your company.

Nicole Wagner: Yes. Yes. So when we went there, what I did learn from that experience was the great work that was being done on the International Space Station, and, you know, some of the in-space manufacturing, which I was unaware of at the time, you know, there was 3D printing, there’s tissue on chips, there’s stem cell work, you know, there was fiber optics development, all of that was happening and, you know, I didn’t, I had, had no idea. And so, you know, after sitting there through this presentation, you know, it, it occurred to me, you know, the, that, that this might be very valuable to how we’re manufacturing our artificial retina.

Host: Right.

Nicole Wagner: What I knew going into MassChallenge, and one of the reasons we went there, was because we knew that we had a challenge in how we’re manufacturing our, our technology right now. One of the, the biggest challenges in how we manufacture it is that we have, gravity plays a big role in how, how these thin films are deposited and the stability of those thin films. And so, you know, prior to this, I wouldn’t have, wouldn’t have necessarily thought that we could do things on the International Space Station, not because it’s impossible but because how the heck do you get there, right?

Host: You didn’t have your own rocket.

Nicole Wagner: No, I, I did not have my own rocket, and, and honestly, I, I just had no idea how you would, how you start to do, you know, where do you start to do an experiment on the International Space Station? And even leaving that, that first meeting, I, you know, I, I left the meeting, I said, wow, this is pretty cool, you know, I think that they’re doing quite a bit on the International Space Station. There’s an opportunity here; how can we, we leverage that opportunity? And when I called my research advisor, he’s like, how, how are we going to automate this? We have to automate this whole process; the way that we’re doing it right now on Earth is, is not amenable to doing it in a microgravity environment. You know, we had an open beaker system; you can just imagine all these solutions floating around on the ISS.

Host: Nope, can’t have that.

Nicole Wagner: You know, so I’m sitting there and I’m, you know, I’m googling Raspberry Pis and, you know, how do we get all of these, you know, how do we automate this, and you know, NASA’s not going to let me just do something on the ISS, you know, security, how do you handle all the security to get to, you know, automate an experiment on the International Space Station? But fortunately, after going through that process of, of sort of internally thinking through all this, after sitting down again with the, the team at ISS National Labs and Boeing, they said, you know what, we have groups that we work with and they’re called implementation partners, and they help to handle a lot of that. And you know, what you do is you focus on what you’re good at, which is how do you, you know, manufacture this implant and the work that you’re doing? So, you know, while at MassChallenge we had an opportunity to get paired with Space Tango, who has been our implementation partner since 2016. And what they have done is they’ve done all of the automation to work with their CubeLab and Tango system on the International Space Station. And they helped facilitate the experiments that we’re doing on the ISS. So once we made that connection, once that match was made, it allowed us to really think about how we can conduct these, these experiments, and how we may be able to actually leverage microgravity to improve the quality of our thin film production.

Host: Yeah. All because you went down the hall to a lecture that you weren’t planning to go to.

Nicole Wagner: That’s it. I was it, I, you know, had I not been there that day, sitting there, this, this may not even be, you know, something that we’re talking about today, because this was really, up until this point I had no idea that, that it was even an opportunity for me.

Host: Does the process include research grants or other kind of seed money to help LambdaVision or, or similar companies get more involved in space station research?

Nicole Wagner: Well, so at MassChallenge there was a, you know, we had quite a bit of, of resources, you know, not just, not just funding from that initial program, but it was also, I, I think, you know, one of the things I talk about when, when we talk about the benefits of working on the International Space Station and working with NASA and the relationship we have there, is that our team instantly grew, you know, by being part of, of this research project on the International Space Station. You know, one of the biggest things when you start a business and people always say this, is that you, you go, you know, A — team, B — idea, and that’s it: I mean, we were, we instantly got paired with fluidics experts, you know, super scientists, engineers to think through our, our strategy and how we were going to manufacture this on the International Space Station. And I think that was, you know, one of, one of the biggest benefits that we were able to receive initially. You know, fast forward, so this is 2016, we had no idea what the experiment was going to look like. We were paired with, with again, I mentioned Space Tango.

Host: Right.

Nicole Wagner: We designed an experiment, and we won, we won the, the tech in space prize at the end of 2016, which allowed us to do our first flight to the International Space Station to look at the effects of microgravity on how we manufacture these thin films.

Host: Before we actually, before we actually launch, can you give me a, a more of a, of a, fill out the sense of what it takes to convert the research that you were doing in a one-gravity laboratory in Connecticut into something that was of the shape and size that it could fly to space?

Nicole Wagner: Yeah, it certainly was a, was a challenge. You know, I think first, before I, before I talk about how we, we miniaturized and, and got to that space, I think what’s important is, you know, then, a very logical question that we get asked very often is, how does a vision company get involved in space and, and why microgravity, right?

Host: Yeah.

Nicole Wagner: So I think it’s important to understand, you know, how we manufacture these, these thin films now, and why we, we thought that we could manufacture these on the ISS and some of the improvements there.

Host: Right.

Nicole Wagner: So the way that we actually manufacture these thin films — I, I use the word on Earth, or terrestrially — is through a process called layer-by-layer deposition. So what that means is, it’s really just a fancy word for layering proteins onto some sort of a scaffold or substrate material. And so, that process on Earth happens in a hood. So think of an entire hood in, in a laboratory. And what it looks like is we have a scaffold — think of a scaffold as a tightly-woven piece of gauze, suspended by a string — and that is sitting on top of a solution, it’s floating on a, on a solution that’s filled with a purple, and that purple is the protein that we use.

Host: Right.

Nicole Wagner: Now, there’s six beakers in that hood. And this process, this deposition process, we move from beaker one to two, three, four, five, and six. And then we do that again; we do that over 200 times to generate our artificial retina.

Host: All right.

Nicole Wagner: Now, that process is very much subject to the effects of gravity. So anything in that solution wants to sediment out, so we get a gradient of solution. Things like evaporation are going to play an impact. That’s going to affect things like surface tension as well. And so you can imagine that on Earth, any imperfection that happens in a earlier layer is going to be compounded as you add more and more layers.

Host: Like if there’s a, if there’s a bump of something that, that causes your, the layer on top of it to be deformed, then subsequent layers will carry that same deformity.

Nicole Wagner: Yes, yes, very much so. And so that, you know, overall creates, you know, less usable areas for us, and it makes a lot of waste. So the process that we do terrestrially is just very inefficient. And we, we don’t get, you know, a lot of usable, usable area. So now we have to take that huge process that I just described, these open beaker systems, and translate it into a very small box that can be on the International Space Station. And so, you know, I talked about sitting there in that room, thinking, how the heck am I going to do this, how do you automate this process, how do you make it miniaturized: and so, we were paired with Space Tango and Space Tango was a group of engineers that helped us develop a flow-through system. So now rather than having our scaffold sit on the surface of a, think of it as a glass of water…

Host: OK.

Nicole Wagner:…we actually have it adhered to a chamber and we flow the solutions over that chamber. And so we do it very much the same way in terms of the, you know, the, the types of solutions that we’re using, but the approach is very, very different. And it’s been miniaturized, so that we can fit it in a very small box that can then be hooked up to the International Space Station.

Host: Yeah, very small? How small, how, what size is your experiment?

Nicole Wagner: So our, our box, our, our Tango lab, I would say is about, about a foot long, maybe eight inches wide. So it is, it’s, it’s tiny when you think of that as compared to an entire lab incubator.

Host: Oh yeah. It’s like a shoebox.

Nicole Wagner: That’s right. Yeah. It’s very much like a shoebox.

Host: OK. And you’ve taken your whole lab process and with the help of, of your partner you’ve helped condense it down into the size of a shoebox. And then, now you’re ready to fly? What, tell me, tell us about your first flight?

Nicole Wagner: So we, we miniaturized the process and, you know what, I think is, is important to, to think about here is it’s not just miniaturizing the process. So right there’s the technical piece of, you know, you need to get everything down, but it’s also as a, as a scientist, who does work on the ground, terrestrially, you know, it’s a very different thought process. So when you’re doing things in microgravity, you’re designing everything for, for one experiment. And so the, the thought process of how you automate it, what’s going on in that one experiment, the ground controls that you’re doing leading up to that experiment, are very, very different, than how we traditionally would do things. You know, if I was going to tell somebody in my laboratory to go do an experiment, I’d say, go do it, tell me if it works; you know, come back if it fails, go and do it again. You don’t necessarily have that same, same luxury for a microgravity experiment. So we certainly had to, to do quite a bit of ground testing, do a lot of experimentation. And so, while we were awarded the grant in 2016, our first flight took us til, about two years to prepare for.

Host: Wow.

Nicole Wagner: So we flew on SpaceX 16 at the end of 2018. And it was a super, super-cool experience. You know, it was like one of those, I, I describe it as a bucket list item. I didn’t know it was on my bucket list. I, we, me and my colleague, Jordan Greco, traveled to Kennedy Space Center, and we got to watch the launch at the space center. And we were in a room, you know, there were astronauts there, there was NASA leadership and ISS National Labs leadership there. And you know, there was like big countdown clock on the wall, like you’re counting down for, you know, the ball drop on, on New Year’s Eve. And it was just so, so cool to be there. And it was surreal to think that we had a project right now that was going to launch on a rocket to the International Space Station, and, you know, be carried out. And, you know, when we were in that room, what they told us is, you know, we’re all out there trying to take pictures and, you know, you want to videotape it.

Host: Sure.

Nicole Wagner: But they said, you know, don’t, don’t videotape it; go out there and sort of just take it in. And I think that was really great advice because, you know, you can go back and Google, you know, what the launches looked like, but you, you can’t, it’s very difficult to describe that experience of just being there and watching your, your work, your research, what you spent ten years in, in development of, and, you know, two years trying to miniaturize, now finally going to the International Space Station. It was, it was such a cool experiment.

Host: And you did get to go outside and feel it, right?

Nicole Wagner: Yeah. We were out, we were outside on the balcony watching, watching it, you know, launch; you know, we’ve got to participate in some of the, you know, media ahead of time. You know, what is also interesting, and I, I tell people this, too, in terms of experiments, you know, those rocket launches, don’t always go as planned. You know, we were supposed to fly one day, and the launch got shifted a few days. So while I intended my trip to be, you know, only a couple of days I think it extended, you know, a few more, but I, I certainly wasn’t going to miss it. I’m glad I didn’t.

Host: Right. How did the experiment do on the station that first time?

Nicole Wagner: So we had great results for the very first experiment. What we were able to do is demonstrate that we can lay our proteins in, in a microgravity environment. You know, we did have challenges, which is to be expected. That very first launch one of the biggest challenges that we had is that we developed a bubble, and so I’m sure there’s a lot of people that are, that are listening that are very familiar with the challenges of bubbles in a microgravity environment. So we did get a very pesky bubble. And so wherever that bubble was it prevented, prevented some layering. So we spent some time following that first launch thinking about how to reduce and minimize bubble formation in, in microgravity. So we, like I said, we flew on that SpaceX 16 mission, that was in 2018, we get some of those, that preliminary results. And then we applied for a NASA Phase I SBIR (Small Business Innovation Research), which we were awarded. That Phase I SBIR allowed us to look at, you know, some of, some of what we saw from that initial launch and do additional ground testing. And then we applied for a Phase II award, which we received. We’re currently still in part of that NASA Phase II SBIR program to do some additional launches. And so that’s, that’s what we just recently did. We flew, now we’ve flown four times to the ISS: so, SpaceX 16, we flew NG (Northrop Grumman) -14, NG-15, and just flew on SpaceX 24. So it’s been, been a lot of fun, a lot more launches since that first one, and we are looking forward to, Crew-4 launch, which is coming up in April of, of this year.

Host: Has it been the same in each instance where you’ve, you’ve been able to learn something from one flight and implement it or improve your, your hardware or your procedure or, or something so that the subsequent flight gets you better results, more of what you’re looking for?

Nicole Wagner: Right. We, we’ve certainly learned a lot from each flight. And you know, that’s, that’s the importance of, of doing this, and it’s also the importance of some of the ground testing that we’ve done as well. So I mentioned that first flight was SpaceX 16. The goal of that flight was, you know, just initial proof of concept, can we layer in a microgravity environment, you know, can we miniaturize this process, what does that look like? We then flew on NG-14. And the goal of that flight was to look at the protein. You know, a lot of people who do work on the International Space Station work on the, you know, they, they like to use microgravity to, to change proteins; we don’t want the protein to change. We want the protein to, to function this, the same way it does on, on Earth. And that’s important for the, the stability and the integrity of these, the, the function of the overall artificial retina technology. So we flew NG-14 to look at that. And the protein itself, you know, functioned the same, that’s what we were able to determine. We flew NG-15, which was an improvement on that SpaceX 16 flight in terms of some of the hardware and software. And then SpaceX 24 we, we just flew, and this was the first time that we were able, we were able to manufacture a 200-layer film in microgravity. So we were very, very excited about, about that and the results from that flight. And now as we move forward towards Crew-4 what we will be doing is flying some optimized parameters as well, so that we can get, you know, more efficient layering in this upcoming flight.

Host: Is, is 200 layers kind of a magic number for you?

Nicole Wagner: It is for us. You know, there’s a, there’s a tradeoff here. Like I said, the protein itself is this purple color, so think of this as almost painting a wall; we want the wall to be just purple enough so that we can absorb enough light that generates a signal that’s sufficient to stimulate those cells. And so, that’s where we’ve, we’ve settled in on that, that 200 layer.

Host: All right. And with, and with that, you say now on this, on this, this flight, you’re about to have, you’re, you’re, you’ve already gotten the 200 layer and on this next one, what improvements are you looking to make?

Nicole Wagner: So we’re able to do 200 layers on SpaceX 24. And this particular flight what we’re trying to do is we’ve, you know, some of the hardware has been swapped out so we have smaller, you know, smaller pumps, we have pumps that pump at different speeds to help control, you know, how we are filling and, and wasting different chambers, and we’re also changing some of the parameters in terms of, of, you know, how, think of it as how long that protein sits in the chamber or how long, you know, another, some of the other substrates or substances sit in that chamber. So parameters that affect layering. So we’re going to change some of those, and iterate based off of what we learned from SpaceX 24.

Host: Did I understand you, right, you said, you, you’ve, I guess, re-miniaturized what you’d already shrunken down?

Nicole Wagner: Well, you know, every time something, something changes a little bit; you want to fit as many things in that, that box. It’s not necessarily miniaturizing it anymore, but making sure that, like I said, you only get to fly one time so you want to make sure that, you know, you have some redundancy. You want to make sure that if, there’s a backup, so if something isn’t working you have another one so that you can carry out the experiment as you, you would expect it to, to be carried out.

Host: And, and in, in, in the case when you, when you fly these experiments, what is it that’s actually happening on the station? Are, are, are astronauts involved or is this something that somebody turns a switch and allows it to run autonomously for some period of time?

Nicole Wagner: All of our experiments are completely autonomous. We have everything automated, which is, which I think is, is nice. I mean, it’s one of the reasons why I think manufacturing in microgravity for our technology makes sense. So we can control — when I say “we,” the Space Tango team controls — you know, what’s going on in that, the chambers, they they’re automating it but they can also go and change parameters in real time if they needed to, so we can monitor that from a system on, on the ground in real time.

Host: Are you imagining that, is this your last needed flight, or do you have more experiment development that you want to do on subsequent flights?

Nicole Wagner: We have additional flights planned for this year.

Host: Oh, OK.

Nicole Wagner: We have some, we, we received some NRLA [ISS National Lab Research Announcement] awards, with ISS National Labs, to do some additional experiments; some additional parameterization-type experiments, and then, you know, moving forward some of the questions that we have now are, are starting to think towards scale. So, you know, as we continue to prove, you know, this proof of principle in terms of the layering, you know, how can we generate more thin films, you know, what does that scale start to look like, and how can those be used for some of the work that we’re eventually going to need to, to do, both in terms of preclinical testing, you know, and hopefully as we move forward, you know, clinical trials at some point.

Host: Well, and I was going to ask about that, there, we all have heard that, you know, new drugs or new procedures or new equipment, medical stuff, all takes a long time to develop, and this is not the end of the road for LambdaVision?

Nicole Wagner: No, certainly, certainly not. But you know, all, all these things are, are worth working for. I mean, there’s a huge unmet need here, to develop these technologies. So our, you know, where we are right now, we are working on the manufacturing for this, the artificial retina, and, you know, doing that all in accordance with what is sort of termed good manufacturing practices. So we’re doing it with a lot of quality standards in mind, reproducibility in mind, and a lot of documentation, because one of the things that we’re doing on the ISS is to make sure that we can eventually use these on, on the ground as well. So that’s something that we’ve been thinking quite a bit about. And then, you know, once we have those thin films, the next step is to continue doing some preclinical testing, to, to demonstrate the safety and efficacy of our artificial retina, in, in animal models, before moving towards the clinic.

Host: And is the, is the idea then that you ultimately would be able to develop up an artificial retina that would all have been grown in space?

Nicole Wagner: Yes, yes.

Host: Yes.

Nicole Wagner: So ultimately, you know, if we continue to, to see success and improvements in microgravity environment, and how we’re manufacturing this, this thin film, long term we, we would envision ourselves to continue doing that on the International Space Station.

Host: And not just the International Space Station. There are, are other labs in space that are on drawing boards into the future.

Nicole Wagner: That’s right. I mean, that is, you know, that’s actually the, the very exciting part, is to see what the future holds for, for low-Earth orbit. You know, I recently just came, came back from South by Southwest, where I was on a panel thinking about the future of space in 2050. And we had one of, you know, one of the moderators was, was from Axiom, which is one of the commercial space stations that’s being developed. And so, you, you know, it’s cool to think about, you know, what, what the future can hold in, in 2050, and what, you know, manufacturing is going to, to look like. And you know, how many more astronauts can be there to help carry out some of these experiments. So this is certainly an exciting time to be in, in research, especially space-based research. And, you know, I, I, what’s, what I think is most exciting about it, too, is that, for people looking to get into space research, it extends now beyond, you know, engineers. You know, I think space is, is a group for biologists; you can be in space now, if you, you know, you’re a nurse, you could, and anything you want to do. You know, there’s, there’s an opportunity there: marketing, film, and it’s, it’s just great to see space be such a, you know, at the forefront of, of all these different fields.

Host: And the, I can hear your excitement about your own, you know, processes in your voice, but it, it extends to other people that you’re not even a, a part of their group.

Nicole Wagner: Yeah. I mean, I think for me, you know, I, it’s, it’s fun to see, you know, more and more people get excited about space, getting excited about research that’s going on in space. And, and to see, you know, these new commercial space stations start to be developed. For me, I think, I think that’s great. I, I love it. You know, I, I love following the news and seeing what, what all of these new, new groups are doing. And it’s exciting for me. I have, I have three children, I, a daughter that is six, a daughter that’s four and a, a son that just turned six months. And, you know, my daughter came home one day from school and she said, you know, Mom, I know you’re going to be proud of me – because you’re always proud of your kids — and I, I said, OK, I said, yeah; she goes, but today you’re going to be really proud of me. And I said, why? She said, well, today, Mom, I helped NASA. And I said, oh you did, what did you do with NASA? And she said, well, we built rockets — they built these Lego rockets — and they put tinfoil over them to shield them from the Sun so they could do more deep exploration.

Host: Right.

Nicole Wagner: So, you know, when, when I see that in my own home, it makes me really excited because it’s, it’s her seeing the future of, of what space-based research can be like.

Host: That’s excellent.

Nicole Wagner: And, and that’s, that’s the, that’s so fun for me.

Host: It is. The, the prospect of, of your success with artificial retinas that could help so many people is, is also pretty outstanding, too.

Nicole Wagner: That’s, that’s it. I mean, I think the other piece for us is, you know, this is a, you mentioned, you know, it’s a long journey; it is a long journey, but, and it’s, it’s not, not the easiest journey, right, but I think, you know, there are so many people that reach out to us day after day that say how, you know, how much of a need it is for them. You know, they have a family member that’s had macular degeneration…

Host: Right.

Nicole Wagner:…or they know somebody with retinitis pigmentosa, and they’ve lost, you know, they can’t drive their car anymore, or they can’t read the newspaper or watch their favorite sports team on, on television. So, you know, when you hear those stories it, it motivates me, you know, day after day to, to work harder to get this into, to patients as soon as we can.

Host: It’s very exciting to hear that, and, and, and, and nice to know that your, your company, like others, has been able to work with NASA to make these, to make these advancements. It’s terrific. Nicole, good luck with, with the ongoing experiments. Thanks for, thanks for sharing.

Nicole Wagner: Thanks a lot, Pat.

[Music]

Host: There was a time a few years ago — it was Election Day in 2016, so I’ll never forget it — I spent a good portion of that day helping a dozen or so friends with a major cleanup. There was so much stuff that hadn’t been moved in so long, we stirred up quite a dust cloud. And combined with my regular allergies I had some pretty violent sneezing fits that left me, seeing stars. Great big stars, floating in front of my eyes. On the way home that afternoon I stopped at my eye doctor and she immediately sent me to a retinal specialist who confirmed that I had a small tear in one retina. That same day I got a firsthand lesson in laser surgery on the eye. Well, nothing quite like it to make you realize how fortunate you are to have two functioning retinas, and to be able to see clearly even when corrective lenses are involved. The prospect of a solution for retinal blindness is heartening, and another feather in the cap of science in space on the International Space Station. I will remind you that you can go online to keep up with all things NASA at NASA.gov. In fact, if you go to NASA.gov/subscribe, you can sign up for the NASA newsletter and all the news from NASA will be delivered to you. And when you go to our sites you can use the hashtag #AskNASA to submit a question or suggest a topic for us; just make sure to indicate that it’s for Houston We Have a Podcast. You can find the full catalog of all of our episodes by going to NASA.gov/podcasts and scrolling to our name. You will also find all the other cool NASA podcasts right there at the same spot where you can find us, NASA.gov/podcasts. Very convenient. This episode was recorded on March 29th, 2022. Thanks to Alex Perryman, Gary Jordan, Heidi Lavelle, Belinda Pulido, and Jayden Jennings for their help with the production; to Nicole Rose for helping make the arrangements, and to Nicole Wagner for helping us look into the future of treatment for retinal blindness. We’ll be back next week.