Bioprinting In Microgravity with Dr. Michael Roberts ISS/CASIS

Gravity shapes every lab workflow we take for granted, and it may be the hidden constraint behind some of the hardest problems in regenerative medicine. We sit down with Dr. Michael Roberts, a microecologist who led bioregenerative life support research at NASA’s Kennedy Space Center and now serves as Chief Scientific Officer of the International Space Station National Laboratory, to talk about what microgravity is actually good for and why biomanufacturing in space is no longer just sci-fi.

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Transcript

Welcome And Guest Introduction

SPEAKER_00 0:00

Please listen to the disclaimer at the end of this podcast. Hello, hello. Welcome to the pod. Our guest today is Dr. Michael Roberts, a microbioecologist who took his science all the way to space. After leading bioregenerative life support research at NASA's Kennedy Space Center for long-duration missions, he's now the Chief Scientific Officer of the International Space Station National Laboratory and Vice President at CASIS. In that row, he's helping turning bioprinting in space from sci-fi into a real biomanufacturing ecosystem in low Earth orbit. Welcome to the show. Thank you, Ginny.

SPEAKER_01 0:43

It's an honor to join you today.

SPEAKER_00 0:46

So I have so many questions prepared for you, but one is how did a microbiologist now doing what you do, managing the space station?

SPEAKER_01 0:57

The short answer is people weren't watching the front door close enough, is one answer. The way I became involved with ISS National Laboratory was uh it was in part due to physical location. I had an opportunity to move to Florida and work at Kennedy Space Center, working for a NASA contractor. And I was there during the creation of an organization called the Center for the Advancement of Science in Space, which was awarded a cooperative agreement with NASA to manage the International Space Station National Laboratory. So through my experience, I had uh while at Kennedy Space Center, I was fortunate enough to be principal investigator on some flight investigations. The contract I worked on enabled me to write grants to do research not only on microbial ecology in the field, also to uh support NASA's exploration life support goals. So I had good exposure to NASA and flight research on shuttle and then on station, and had the opportunity to join this uh new organization, Casus, in its job to support research on the International Space Station. So it was truly too good of an opportunity to let go pass.

SPEAKER_00 2:12

I would say this is like a dream job for a lot of people. It almost like you are writing the sci-fi, not the other way around. But were you inspired somewhere that you decided instead of going to say pharmaceutical companies, you decided to go for this space?

SPEAKER_01 2:31

Literally. So uh I'm a I'm a late-stage baby boomer. I'm right at the end of the baby boom generation. So I certainly remember I was, I think, six years old at the moon landing. So I have memories of that, but it wasn't a spark in my mind at that time to say I'm going to be an astronaut or I'm going to be a scientist and do all this. So I sort of just fortuitously in my career found myself here and had the opportunity to do it. But you spoke about writing science fiction. I view it more as we myself and the organization I work for and our friends at NASA, we have the opportunity to work with the folks who are writing the science fiction. We get to witness it. We get to provide the tools they need in order to accomplish that. And to your point, it's an incredible job. I certainly enjoy the opportunities that I've had in our role, but most importantly, I'm so excited to see the advances that have been made and where we're going in the future. These are very dynamic times in space, and we look forward to the future, even though the International Space Station itself is on the back end of its career and its trajectory.

SPEAKER_00 3:47

We're going to talk a little bit about that at the end. But

From Microbes To Managing ISS Science

SPEAKER_00 3:51

now you're a strong advocate for biomanufacturing in space. Nobody, you know, I think not many people are thinking the space station is a place for manufacturing large quantity of stuff, either pharmaceutical or biologics. Where did that concept come from? And why do you think now is a good time?

unknown 4:13

Yeah.

SPEAKER_01 4:13

Now is a good time in short, because we have learned enough through 25 years of continuous human presence in space, how to live and work in the space environment. At the same time, the technologies that are built around biomanufacturing, regenerative medicine research, bioprinting have matured to the point, in addition to our improving but not foolproof fundamental knowledge about induced polypotent stem cells. We have this unique point in time where the technology maturation level matches up with opportunities in unique environments, which in this case is space and microgravity. So we are at this juncture in time where we've learned enough, we know enough, and we've demonstrated through peer-reviewed fundamental research to understand enough about the space environment that we can begin to utilize exposure to microgravity to actually improve health outcomes here on Earth. And biomanufacturing is a significant part of that. And to speak again to the highlight that you provided for International Space Station, International Space Station itself is not a good environment for manufacturing scale. It's designed as a multi-user facility. It supports multiple research investigations and international partners. It's visited quite frequently by visiting vehicles, things that you typically wouldn't do at a production facility other than at your loading dock. But it does offer opportunities for us to learn how to work in that environment and transition from research and technology development laboratory into the manufacturing realm. So that's what we're focused on the remainder of life of Station is helping translate what we've learned on Station into commercial platforms which are coming online as we speak.

SPEAKER_00 6:13

Wow. So,

Why Space Biomanufacturing Now

SPEAKER_00 6:14

Mike, do you remember some of the first projects that you manufactured or successfully manufactured on International Space Station?

SPEAKER_01 6:24

So the term manufacturing means a lot of different things to different people, but there's a program around protein crystallization, which predates the International Space Station. It even precedes the shuttle program. It goes back even farther than that in history. But you could consider that, right, one level of manufacturing in space and it's biologically oriented because most of that's focused on proteins and other biologics. With protein crystallization, the advantage originally was looking at uh the absence of gravity as a way to improve the size and physical homogeneity, how similar the crystals were, so that we could then bring those crystals back to Earth and use X-ray diffraction, which was the start of the time, to better understand the physical structure, right? And understanding the physical structure provides you opportunities to improve the safety and efficacy of your drugs. It also enables you to better understand the targets that you were going after. So we inherited a series of flight projects, uh, some of them sponsored by pharmaceutical companies, some of them sponsored by or originating with funding from the National Science Foundation or National Institutes of Health to explore ways to improve crystal production in space. And it wasn't only limited to the biological realm. Those experiments also touched on advanced materials that are now found in semiconductors and other things. So that's my first hands-on project where we were actually manufacturing something in space, making uh larger, more homogeneous crystals. And that science has continued to evolve over time so that now folks are not only exploiting microgravity to continue to improve the crystals, they're actually taking extant crystalline solutions, in this case, large monoclonal antibodies, that are already approved by the Food and Drug Administration for clinical applications. They're looking to use microgravity to understand ways to improve those crystalline substances and make their formulation more stable so that in some cases they can be delivered to the patient in different forms. And more importantly, better making those active pharmaceutical ingredients more amenable to understanding safety and efficacy. In many cases, those crystalline dis those crystalline substances and their formulation on Earth results in a community of different physical shapes and sizes that can affect the safety and efficacy of the drugs. And microgravity, you can have it can increase the level of control that you have there. And that is now that understanding of protein crystallography has already matured into platforms which now offer access to automated systems to do that in microgravity. And this led significant investment and research focused on biomanufacturing of tissues, organs, and expanding stem cell populations for research and clinical applications here on Earth.

SPEAKER_00 9:37

I think I saw a startup focusing on it in this area as well for protein crystallization. But the last study, you know, I'm not an expert in the space, obviously, because our audience, a lot of them are really interested in 3D bioprinting, which is something that you're also a strong advocate for. So I

Protein Crystals And Better Drug Design

SPEAKER_00 9:55

want to shifting, this is a perfect segue to talk about bioprinting in space. And also I want to allude to a paper that you have co-authored and talking about paradigm shift of biomanufacturing in low earth orbit. But I think a lot of our audience don't really understand the challenges and the difference, this paradigm shift. I'd like you to just teach us a little bit why there is a shift here. How do you think differently about bioprinting into space in microgravity environment versus here on Earth?

SPEAKER_01 10:30

Well, it begins with fundamental physical principles. As far as we know, all life evolved here on Earth, or perhaps we were seeded from Mars. We'll find out eventually. But all of that evolution that's occurred on Earth was in the presence of Earth's gravity, which is variable, but largely it's 1G. And we our entire physiology and that of all living organisms is derived from that 1G experience throughout the evolution of life. In microgravity, in the absence of that gravitational force, you have the ability to explore other forces that are masked by gravity here on Earth. And that in some cases has detrimental effects. So we're all familiar, uh, or most of us are familiar, with uh discussions of the astronauts' bones and muscles being weakened when they return from several months on orbit on the International Space Station. And there are countermeasures that are specifically designed that involve, in some cases, therapeutics, in all cases involve muscle resistive exercise in order to maintain that. Because in the microgravity environment on the International Space Station, for example, the astronauts' muscles and bones are not experiencing that 1G, so they're unloaded at that time. And as with all living systems, your uh our bodies adapt to that environment. They will, there will be a shift in fluids in the bodies, and there will be changes in the control of bone mineral density and control of muscle regeneration. So you have to consciously work towards maintaining that bone and muscle so that when you return to a 1G environment, you're still able to function. What we've learned most recently is that those changes, which are detrimental to human physiology, also offer accelerated models. So we're able to exploit those changes in bone and muscle, cartilage, immune system function to better understand aging and disease onset and progression here on Earth. That all feeds into other applications such as bioprinting in that space environment. In the absence of gravity in the freefall environment that exists as the International Space Station orbits the Earth, there's no issues with buoyancy. There's a lack of gravitational pull. So things that we take for advantage, if I'm holding a banana in my hand and I release the banana, I know that it's going to fall to the ground. In the microgravity environment, it's going to stay there unless I give it some other force to move it in another direction. You can take advantage of that when you're printing tissues and organs, in that you don't have to have a scaffold. So it offers opportunities to print biological structures which are structurally sound when they're mature, but in the printing process, they collapse upon their own weight. The way we get around that here on Earth is by using scaffolds and some other approaches. In the free fall environment of space, you don't have to have those scaffolds present. So it offers opportunities for 3D printing that are simply not possible. You also have the ability to use bioinks with very different viscosities, which are limited here on Earth either by nozzle size or by the viscosity of the inks themselves and their viability over the long term. So we have uh worked with companies that have developed different approaches to bioprinting in that environment. And they've taken different approaches that uh take different advantages of microgravity, but all of them seek a basic pathway is to utilize the absence of gravity to improve the structure of what they're manufacturing, and then they enable that, allow that to mature in space so that it can withstand re-entry into Earth's atmosphere and that return to 1G. So there are companies that are working very hard to develop essentially what amounts to a complete processing system, right? You would launch your bioinks and your cells and your printing device, execute a print of meniscus, a knee meniscus, or heart tissue for a cardiac patch, enable it to uh grow and mature on the space environment, at the same time physically challenging it, because we all know, for example, especially with cardiac tissue, that it needs to be physically stimulated to actually mature properly. You can complete all of that in the microgravity environment and then return that biological product back to Earth for, at this stage, research use, but one day perhaps for clinical utilization.

SPEAKER_00 15:34

Let's

Why Bioprinting Changes In Microgravity

SPEAKER_00 15:35

dig a little bit deeper on the technology side, because obviously we can't use a bamboo $100 printer in space. How do you have to re-engineer the printer itself to fit the flight and perform these experiments?

SPEAKER_01 15:54

Right. So fortunately, we work with a team of companies that in our parlance week, we refer to them as implementation partners and commercial service providers. So these are companies that uh provide engineering services built around executing research and technology development, uh, typically or historically supporting NASA and the other spacefaring agencies. But they offer decades of experience in taking research into the microgravity environment. So they've learned how to deal with the more difficult issues of working in a microgravity environment. Foremost among those is the ability to dissipate heat, understanding that you can't rely upon gravity to help you separate liquids and gases. You tend to, you have a very different physical process present in that environment. So especially with the focus on microfluidic systems, bubbles, dissolved gases, and liquids are a serious problem. It turns out that some of those problems, as we've moved into microfluidic systems for bioprinting, occur here on Earth as well at those types of scales. So there's a lot that we learn in the space environment from the experience of these companies trying to design a printing platform for space that have now actually directly translate into improved devices for use here on Earth. So those companies have uh developed over the years ways to support stem cell research experiments on the International Space Station. That led them into an interest in looking for ways to use biological materials in their printing devices. The first printing device that was available on station was focused on advanced materials research. And its primary reason for being there was to assist in the manufacture of tools and other things for use on the International Space Station as a model for what we would need, the capability that NASA would need to have to support humans as they move further from space. It's not possible to take everything with you that you would need, for example, on a Mars mission. So it would be advantageous for you to be able to take a printing device and be able to manufacture a tool that you may need or a particular part of another system that you didn't weren't able to take with you because of mass constraints as a replacement unit. So all of that knowledge about working in space, they've done that in collaboration with researchers, the research community. So as investigations came in, it's always based around a partnership between the scientists and the engineers at these companies. And they work towards a solution to address specific scientific questions. So as cell biologists came in looking for ways to study their cell systems in the microgravity environment, we improved our ability to culture cells. As technologies improved for printing in the absence of gravity, folks started to work with improving bioinks and looking at bioprinting as a possibility there. And then over the past about 10 years, those technologies have matured to where there are multiple approaches now being utilized on the International Space Station for bioprinting. They're all right now at research scale. These are primarily demonstration prints. There's certainly not anything at scale and not anything that would concern anyone or make anyone think of a manufacturing realm, but they have certainly pointed the ways to which of the bioprinting technologies work best in that environment. And they have generated most recently some very interesting constructs which are of great interest to regenerative medicine, for example, and being able to make large, thick tissue prints that are vascularized so that they can survive after implantation.

SPEAKER_00 20:04

So you mentioned several different approaches in bioprinting, but I'm assuming they're all extrusion-based, kind of foundational additive.

SPEAKER_01 20:14

They move beyond that now. So the biofabrication facility that uh was the first, one of the first bioprinters, the first bioprinter that was flown, was developed by a company called TechShot, which is now part of Redwire. So Redwire is the developer of that technology. It's based on that uh type of extrusion, linear FDM deposition and bioincrix. They've utilized that to produce both meniscus, knee meniscus, uh cartilage-like material, as well as cardiac tissue. They had also been funded through different elements of the Department of Defense and National Institutes of Health before to look at ways to improve bioprinting of cardiac tissues and other things. So they were simply trying to extend that in the microgravity environment. Most recently, uh folks have been using or the devices that have been used are based on SLA approaches, so stereolithography, but the subset of those that focuses on direct photo printing. So they're in that approach, they're able to utilize a mask so that they can start thinking about mass production, right? You have a very short exposure to the UV light in the space environment in order to effectively shape the organ of interest or cell of interest. So very recently, a company called Auxilium Biotechnologies that's uh working towards making a medical device for repair of peripheral nerve injury. They're able to make a device that improves the ability to repair long gaps and nerves uh induced by physical damage. They're looking to utilize microgravity as a way to improve their approach for manufacturing that. And they just this year completed their third round of printing of their neurospan bridge. They also worked with collaboration, worked in collaboration with researchers at the Wake Forest Institute of Regenerative Medicine to print kidney and liver tissue utilizing the DLP technology. So we're seeing a lot of innovation on the engineering side to improve the printing capability, and that's been coupled with folks from industry and from academia thinking about ways to improve throughput in those systems. As I mentioned on the International Space Station, the crew members are very busy executing the science. So in a typical six-month rotation, each crew member is supporting from 200 to 400 experiments over the course of six months. So the more automation you have in that type of environment, the better. The lower the mass involved in the system, the better, because it's still much cheaper than it used to be, but it's still a little bit expensive to get up into lower Thorbit. So those design criteria have driven companies to improve the engineering of their devices. And it turns out that those approaches, again, align with needs here terrestrially, about increasing the fidelity of bioprinting, having better understanding of the homogeneity of the cell populations that we begin that are involved in those bioinks. For in parallel with development of tissue chip systems, which we use quite extensively on the International Space Station. Folks are also looking at ways to improve our understanding of the biological media that those cells are in. We're looking for something that better approximates physiological media for multiple organ systems on a single chip. And that requires you to understand every single component so that you're not using biologically derived matro gel, for example, other things like that. So again, it's about this these advances and technologies are all coming together at the right time to make this possible.

Engineering Printers For Space Reality

SPEAKER_00 24:24

We're not really in space stations. It's really hard for people to listen to us to envision what it really looks like. Everybody knows the banana is gonna stay there. They understand that's microgravity, but we're talking about on a micro scale, you're not talking about a normal-looking cell culture anymore. We think it's looking different up there.

SPEAKER_01 24:44

It is, it is. Well, it it's truly three-dimensional, right? We all understand those of us who've worked in the cell culture before, even on the bacteriological side, as I did. You're taking uh an organism from its natural environment and placing it into what is essentially a sterile culture environment. So you're removing it from the whole environmental matrix. So we are all aware of to raise a child, it takes a village. To raise a cell, it takes a matrix, right? So you have to have that three-dimensional environment recreated. Uh, we've learned the space environment that we can induce cells to take on a more three-dimensional shape than in any bioreactor that we've recreated here on Earth. In part, there are certainly very innovative engineering designs that are able to suspend cells and get them out of direct contact with the surface of a growth vessel, whether that's glass or plastic. But those means to induce that buoyant state increase and expose the cells to hydrodynamic shear. They're able to sense that and respond to it. So it's in space in this absence of gravity, where the cells are literally just kind of hanging there, suspended in a fluid, where you can better replicate the environmental context and value of the cell that they would experience inside the body, inside an organ in that environment. So this ability to increase the three-dimensionality of the cells leads to important changes in their ability to respond to that environment and also offers us opportunities to improve our ability to understand what's going on at a cellular and a molecular level. So folks are now regularly flying tissues, cells from tissues that are isolated from patients with varying degrees of different diseases and exposing them to a gravity environment in the presence or absence of therapeutics. And they're able to get a more rapid answer, a quicker outcome from that three-dimensional cell culture than any device that they're able to use here on Earth at present. So essentially, we're able to, we believe, better recapitulate a whole organ system and the physical arrangement and communication that feeds each cell, each individual cell. People that are using organoids as their base models rather than simply focusing on cells, they see profound changes in the shape and organization of organoid models for liver, kidney, heart, a whole host of different tissue types in that environment, too. Now, again, those model systems for organoids don't faithfully replicate all of the function and structure of the mature organ, but being able to put them in that microgravity environment gets us closer to being able to recreate most of that. So it leads to accelerating the pace of discovery for using them.

SPEAKER_00 27:58

You mentioned

Organoids And 3D Cell Culture Gains

SPEAKER_00 27:59

that uh you have succeeded, or some company using International Space Station succeeded in vascularization, creating a vascularized tissue. Can you expand on that a little bit? Because I remember a couple of years ago, NASA actually had a vascularization challenge. It was a lot of money to offer to researchers to solve that problem.

SPEAKER_01 28:19

We were very fortunate to be peripheral to that challenge, not part of it directly. So the NASA Space Technology Mission Directorate uh funds these challenge programs every year to address technology gaps. And they're primarily focused on addressing gaps that relate to NASA's exploration program. Uh so historically, they focused on physical solutions to problems that we would encounter as we move farther and farther from Earth. A few years ago, going back to 2014, they released their first challenge, centennial challenge, that focused on seeking a biological solution to a problem. And that problem was if you have injury to crew members that requires tissue repair and you're a long way from Earth, is it possible to manufacture tissues that uh could be made ready to order to help repair that damaged tissue? The answer is no. It was no then, it's no now. But one of the primary problems that we continue to face in expanding our ability to bioprint tissues is to make them thick and fully functional, because that requires your ability to perfuse fluids to continue to sustain the cells, keep them properly oxygenated, and to remove waste as the cells are metabolically active. The challenge itself focused on seeking solutions to making what was a one cubic centimeter thick tissue slice from any organ of choice and demonstrate that the investigators were able to sustain that tissue by activity profiling, making sure that it was faithfully replicating a particular organ function and maintaining viability for 30 days. We at the ISS National Laboratory offered the opportunity for NASA to offer the institutions that were successful in that demonstration on Earth to take their technology to space to really get that last step of NASA's ultimate goal, which was might this type of technology actually work in the space environment? We were primarily interested in it because we had worked with National Institutes of Health and others to kick off stem cell expansion in the microgravity environment with the goal of one day supporting biomanufacturing and then environment and bioprinting. So those there were two teams that were selected and awarded the funding from NASA for their project. We at the ISS National Laboratory offered funding for them to execute their approach to bioprinting thick vascularized tissue on the space station. And then we partnered with uh a non-government organization, a philanthropic organization, to fund not only the winner but the runner up so that we could see in comparison how well they both they both worked. It turned out that both of those investigations came out of Wake Forest into regenerative medicine, but they were taking different physical approaches to their printing and utilizing different organ systems. So we haven't, uh I wouldn't say that we've achieved the ability to print vascularized tissue on orbit yet, but the teams have already learned quite a bit from their work on the ground and developing their experiments, and they have had two successful flights to date. And they've also been awarded additional funding from NASA through the InSpace Production Applications Program, which is at the same time that they're seeking to understand ways to improve the quality of the product, the manufactured tissue, they're also seeking ways to improve the devices that they're using in that space environment. In the same way that there's tremendous interest right now in standardizing the means of bioproduction and the materials and supplies that we use. And part of that now, you know, all feeds back into the FDA focus on new approaches and methodologies, right? So the focus by FDA on NAMS is again comes at a very timely point in our history where we're able, through access to space, offer accelerated models and approaches that can get you to an understanding if a particular therapeutic is safe, is it effective, and look at it not only in different tissues and different constructs made in space, you can actually start to approach personalized medicine so that you can take people from different ages, ethnicities, different uh metabolic states, whether they're diseased or non-diseased, and understand their individual responses to a particular therapeutic agent. And all that's been made possible by this accelerated onset and progression of physiological responses in the absence of gravity in space.

SPEAKER_00 33:29

And then out of curiosity for those uh winners, the Wake Forest winners, what organ system were they focusing on?

SPEAKER_01 33:37

Primarily liver. So liver, and they we've also had some recent success with kidney in the space environment. And it turns out I mentioned Auxilium Biotechnologies in their partnership with W Firm. W Firm, Wake Forces Hero Generative Medicine, has been pioneering in the improvement of bioprinting devices for research and for clinical applications. And they've taken several of their technologies all the way through to clinical approval and clinical application now. And then they're now working with Auxilium because Auxilium has, through their desire to improve the printing of their neurospan device, utilize that printing device in orbit. That's an interesting development because you have a single bioprinting platform which offers abilities not only to increase scale, because it uses a DLP process where you can rapidly use UV light to shape your print in microgravity. They're able to switch between different cell types and different prints very quickly because it's it's play it's utilizing the DLP technology rapidly exposed. So again, it's this interesting collaboration made possible by space and two institutions that I don't think knew of each other's existence until they learned they were both space focused and seeking to move forward with their individual missions.

SPEAKER_00 35:04

Well, first of all, I'm really happy that uh people with other additive processes are now exploring, putting DLP and NASA into space. I'm happy people were exploring because we do have just ongoing new processes every day. And number two, I think this is a perfect time to talk about the paper that you have co-authored with multiple organizations. Uh,

Vascularization Challenge And Thick Tissues

SPEAKER_00 35:25

it's titled as Biomanufacturing in Low Earth Orbit a Paradigm Shift. I really recommend reading this paper. It's a bit of like a manifesto kind of recap, what has happened and what are your hopes and wishes moving forward and what are the challenges. And you mentioned that a collaboration between two otherwise separate entities. I think what this paper also shown to me is that this does take a village, which is entire Earth's inhabitants, to really achieve. But it's not easy, as you can see, all kinds of dramas has had taken a place on the station almost, probably on a daily basis from your point of view. How do you think we should move forward with this kind of collaboration? How can we partner up? What are your strategies to bring all the stakeholders in? How do you connect these parties?

SPEAKER_01 36:22

Yeah, so we it's it's central to our mission at the ISS National Laboratory to establish partnerships. And we do that both with private industry as well as academic institutions, as well as with government agencies that fund research and innovation and technology development for improving particular outcomes, right? So we work in partnership with the National Science Foundation, supporting their efforts to increase fundamental understanding, to build that knowledge base about what's actually at the root cause of these changes that we see in this particular environment, and we actually recreating models that can recapitulate disease onset and progression. We work with the National Institutes of Health, several institutes at National Institutes of Health, to improve the development of organoid and tissue-based model systems, cell-based tissue chip devices, so that they can be used to accelerate our understanding of disease onset and progression in different organ systems for different diseases, as well as improve our understanding of aging. One of the things that happens with our immune system in the microgravity environment is over time, the astronauts' immune systems start to act more like those of someone advanced in age. As we age naturally here on Earth, our immune systems become less effective, right? Part of that is fatigue, right? Our immune systems become overwhelmed by all that they've been exposed to over time, and they start to lose the same level of effectiveness in combating infectious agents than they did when we were much younger. We see that accelerated in the space environment. So it's not that the crew members by any means are becoming sicker the longer they stay, but their immune systems are to some level less effective than they were when they were here on Earth. They recover those capabilities, their bodies recover over time when they get back to Earth, but those offer unique opportunities to study these in an accelerated model. So we seek to build partnerships with commercial companies and government agencies such as the ones I mentioned, so that we can further the technology and de-risk the technologies as we move into this next era of space. So when the international SN is deorbited in a few years, there will continue to be outposts in low Earth orbit to support research and technology development that's currently supported on station. And they will be able to more quickly and more rapidly address the needs of the market because they're going to be not government-owned and operated and serving the needs of a nation and many nations, they will be designed to service the needs of their customers and their community. And that opens up possibilities not only for more rapid iteration and rapid change, it opens up opportunities for scaling and manufacturing and other things that although the International Space Station has been, I think, a tremendous success that all of the international partners can take credit for and be very proud of, it is not a platform that enables you to begin adding new modules to begin manufacturing at scale. It's simply not designed or constructed to support that, but the new platforms will be.

SPEAKER_00 39:44

Absolutely.

Partnerships That Make The Ecosystem Work

SPEAKER_00 39:45

I'm kind of curious what what is going to happen in 2030? I think that's the time when the space station will be uh decommissioned then. What's going to happen to this collaboration? And you mentioned that it's going to perpetuate, but in a more private entity or entities. What about all these ongoing projects and partnerships?

SPEAKER_01 40:06

So get your popcorn and keep looking up to the sky and stay tuned in, right? So there have been articles in in Forbes magazine and others talking about every business needs a space strategy now that you know space is, I don't want to call it the final frontier, but it's another frontier, which is through the investments made by NASA and the technology developments offered by its partners in supplying the International Space Station. Here I'm speaking about SpaceX and Blue Origin and Northrop Grumman. They've driven down the cost of launch to the point where now it's possible for elementary schools to sponsor scientific research for those schools. The cost of getting small experiments up there has come down nearly two orders of magnitude over time. And we're moving into a realm now where we hope that those launch costs will continue to fall. But at the same time, industry is now developing new capabilities. There's a company, relatively young company called Varda, which has an op has built a platform that is not crew-tended, but is able to offer support for manufacture of protein crystals in the environment. So they can launch, execute protein crystallization experiments over weeks to months, and then they bring that back to Earth and send the samples off to the laboratory that donated them to them. So that's a different entry point for space. It reduces cost and other things and can offer more frequently, more frequent access to space. You may have heard that recently SpaceX has developed uh the Starfall vehicle, which is their ability to increase the ability to return mass from low Earth orbit. So they're also entering the market. And they're obviously SpaceX is a company that can operate that device at scale when you look at the number of Starlink satellites that have been added to low Earth orbit just over the past four years. So there's all this technology advancement that is meeting up with increases in demand that we see on the International Space Station side. So we remain very focused at the International Space Station in the remaining four or five years. It's possible that the International Space Station may be extended for a couple of years. There's been some interest expressed in that uh in the U.S. Congress, but the international partners haven't signed off on it yet. So maybe station will go to 2032 or slightly past, but even if it is deorbited at the end of 2030, an actual calendar year will be 2031, we believe that these commercial companies will have expanded their presence in low Earth orbit, and there will be several possibilities of different uh platforms that can support the research and technology development capabilities that we have on station. Now, I'm a, as a scientist, I'm a born skeptic, so I want to offer a little bit of caution there in that I do think it will take some time to build up the full capabilities of station, but you have the ability with these more purpose-built facilities and stations and the advances and approaches to space technology and increasing throughput and cadence, that they'll be able to arrive at the same capability as station much faster. Keep in mind that the International Space Station took over 10 years to assemble. It took about another 10 years in order to get the uh full science capability available on station. So even though we've been we've enjoyed a continuous human presence in space of 25 years, we've only had about five to seven years of fully focused research coming down from station, and it's been tremendously. Tremendous the science return we've seen from that. So are just uh continue that into the future as these new platforms come online.

SPEAKER_00 44:08

It seems like there is going to be acceleration. It's almost like a renaissance period is going to come for innovation in space from especially the life science perspective. I also I also thought when I was reading your paper, The Paradigm Shift, I read about these the epigenetic changes in cells and how cancer grow actually more rapidly in space. These are really fascinating, and you said is speed up aging. All of these subjects are very relevant to what we're really now interested in longevity space for healthcare.

SPEAKER_01 44:41

Absolutely.

SPEAKER_00 44:42

And it's almost like a kind of reverse engineering of why aging happens and the progression of cancer, which is one of the most scary thing topics nowadays. And I think that's really gonna, I'm looking forward to see some leaps forward in the therapeutic space from age for aging and also cancer at the same time, hopefully from a lot of the research findings from ISA.

SPEAKER_01 45:08

So I agree with you. It's a it's a very exciting time to be a scientist or to be a science communicator or to be a human. I mean, we all look around, or at least I'll speak for myself here. You look around and you think about how complicated life has become, and maybe we're not living at the best times, but there is tremendous advancement that's being made. We are seeing real promising results from a multitude of different technologies that are already moving into the clinic and affecting people's lives, especially in cancer research, cancer therapeutics, especially thinking about utilization of induced pluripotent stem cells for multiple different applications now. And that combined with increasing access to space and the democratization of space so that it's within the reach of even non-spacefaring nations now, we should see that pace of innovation continue to increase, which is which is a good outcome for sure.

SPEAKER_00 46:05

We

Post ISS Platforms And Lower Launch Costs

SPEAKER_00 46:06

have mentioned quite a few challenges during our interview so far. Of all the challenges, okay, let's talk about so from the biology side of things, logistics, quality control, and financials, which one do you think is the biggest blocker here for the industry?

SPEAKER_01 46:24

So I always certainly we deal a lot with logistics constraints. Until someone builds the space elevator, it is going to be more cost prohibitive to execute any experiment and certainly any manufacturing process in space than it is here on Earth. Although the International Space Station operates at about 225 miles above Earth, you can't use courier service to get your supplies up there and back. It requires a space rocket. And those, although they're much cheaper now than they used to be, are still expensive. And you have to have a docking port. And if you have humans involved in the system, which in some manufacturing environments you don't want humans there, in others you do, those are an added cost because you have to keep them well fed and uh able to survive in what is a very harsh environment in space. So logistics, and that relates back to cost is a player, certainly, and it's a constraint. But we hope to continue to see reductions in cost. We see many companies developing alternative platforms which offer cost savings that were not possible with the International Space Station, right? Our ability to return samples from station is connected to a launch vehicle that took supplies up there. There are multiple companies now that are developing these free flyer platforms, which could return mass from low Earth orbit safely using a paraglider system to any destination around the world at much lower cost than what it takes to get stuff up there. People are also working on ways to increase throughput in the same way. Uh we've seen this explosion in the ability in our ability to collect data from following cells and culture. We're seeing an explosion in ways to increase throughput in systems using microfluidics and artificial intelligence and machine learning that translate well to the microgravity environment. So we're going to be able to rapidly innovate as these platforms come online and people start addressing these new issues. So cost, logistics, those are the main ones. Regulatory environment is an unknown at this time. We haven't manufactured any products in space and brought them in, but there are promising developments there with the FDA Modernization Act. That sets the stage, certainly, for new approaches and methodologies that could involve manufacturing in space. The people who are designing these laboratories are not only thinking about research and technology development to serve the needs of NASA and other nations, they're actually thinking about a manufacturing environment, and that includes creating laboratories that are CGMP facilities that could mimic the cape the capabilities of manufacturing practices that are required for therapeutic manufacturing here on Earth. They're already thinking of those approaches and how they can bake them into their designs in the future.

SPEAKER_00 49:33

I

Biggest Blockers Cost Logistics Regulation

SPEAKER_00 49:34

know that through your row, you also interact with a lot of startups. And in fact, there is an accelerator program, Orbital Edge, that actually offers half a million to $750,000 plus International Space Station flight access, this program. You want to talk a little bit about that? And are there still opportunities for startups to get involved?

SPEAKER_01 49:57

There are. So thank you for mentioning that. So part of our focus in addition to these partnerships that I spoke about us building, we've worked with large pharmaceutical companies, we've worked with large manufacturing companies, we've worked with large consumer products companies. But we didn't want to leave out the engine that drives all this, and that's innovation of small business and innovation of startup companies. So for many years, we worked with the Mass Challenge Accelerator Program out of the Commonwealth of Massachusetts. And that is a cohort-built environment where small businesses can apply to participate in their ability to improve their business acumen in working with funders, improve their ability to build their business and accelerate the pace of development of their technology so they can actually survive the trials of getting it to market and then into production. And we've been very successful with that. That was designed around non-dilutive funding. So we partnered with Boeing Corporation to provide funding for companies that had an interest in taking their technology, their products to space. We expanded that just a little over a year ago to Orbital Edge Accelerator, which is specifically focused on a need to get to space to support it. And in this construct, we partnered with different venture capitalists who were able and willing and interested in providing funding for space-focused startup companies. So in this case, the funding that's provided to those companies is dilutive. It requires that those companies share some part of equity in order to get the space and receive the funding. But that is very informative for us as an organization at IS National Laboratory because it helps us understand how important space is and the need for access to low Earth orbit is to these companies. They're not going to give up their equity and their intellectual property simply to go to space to say that I've been to space and done it. They need to be able to be in it for the long run. And it's been very successful. We completed the first cohort last year. The second cohort is being selected as we speak. And we certainly plan to continue it next year and the years beyond. And we anticipate that the Orbital Edge Accelerator will uh last after station. We would like to see it continue to grow and provide access to capital for these small business startups long into the future.

SPEAKER_00 52:33

That's a very interesting angle. So these companies have to, it's almost a necessity for them to focus on space as part of their.

SPEAKER_01 52:43

So what we the reason we're involved in it, we seek to provide access and opportunities for science and tech dev to benefit Earth that requires access to station. As we move into an era where there are more platforms available than just station, we want to open up access to those two. But most importantly, we want to see that there is a continuing growth of the market for goods and services that come from space. Biomanufacturing is an important part of that. It's not the sole focus of that, but it's very important. And the way that the ability to attract capital works for those small businesses is many of those investment firms have different risk profiles. For the ones that can tolerate high risk, they need to have multiple companies in their portfolio and fund them for a short amount of time in order to see if they're able to accelerate their market capabilities as they mature. We don't have that in space. We can't fly hundreds of projects all at once to do that. And it's time and cost prohibitive to do that. It takes longer to get a flight experiment ready and fly it. So one approach is to have these companies self-select. They need to identify: hey, this is important to me. I need this access to space. It's important to the investors in that community because they're trying to identify technologies that they believe have the ability to scale and grow and offer them real return on their investment over time. So, and we've seen tremendous success with uh both the investment side of that portfolio as well as those interested in access to space to grow it.

SPEAKER_00 54:26

I'm absolutely interested in seeing who you select this year and future cohorts because it's such an interesting and growing space.

Orbital Edge And Advice For Builders

SPEAKER_00 54:35

Now, we have reached the end of this interview, Michael. Thank you so much for talking to us. Now, final question for you is for the for a young engineer who are listening or entrepreneurs are listening to us right now, do you have any advice for the future of life science in space? Just for them.

SPEAKER_01 54:57

Well, absolutely. Be excited and try to learn as much about it as you can as you go through your daily lives. So in the short time, although I'm I've been around for a while, the short time that I've been involved in this, I've seen such tremendous expansion of the community. It's now not only engineers who are focused on the material side of engineering and structural aspects. It goes beyond aerospace now. We have straight up bioengineering, biomolecular geneticists, all are important to this equation going forward. So if you have any interest in engineering, you should always look to space because there are opportunities there to do that. And from the entrepreneur side, I'm obviously a little bit biased as chief scientist of the national laboratory in space, but you need to think about space and how it feeds into what your mission is for your company that you want to build. There is not universally, but very likely some application or capability in space that offers you access to new markets or may offer you access to improve your product and your performance over the long term. That's simply not possible here on Earth. So you need to be as aware as you can be of what's going on in that particular sector and follow it.

SPEAKER_00 56:15

Absolutely. I think most of us do not think about space most of our days, but I hope this podcast can inspire some people to think differently because obviously there is a different paradigm out there pretty close by in the lower orbit.

SPEAKER_01 56:31

Thank you.

SPEAKER_00 56:32

Thank you so much, Mike, and hope to talk to you another time.

SPEAKER_01 56:36

Excellent, Jenny. Thank you. Good day to you.

SPEAKER_00 56:39

This

Closing Thanks And Disclaimer

SPEAKER_00 56:40

podcast is for educational and informational purposes only. The views expressed do not constitute medical or financial advice. The technologies and procedures discussed may not be commercially available or suitable for every case.