Biofabrication w/ Ritu Raman
EPISODE #64
Summary
Biomedical engineer Ritu Raman shares her insights on designing biological robots, how new developments in tissue engineering may allow us to grow organs, and what biofabrication means for the future of food and medicine.
Guest Bio
Ritu Raman, PhD is the d’Arbeloff Career Development Assistant Professor of Mechanical Engineering at MIT. Her lab is centered on engineering adaptive living materials for applications in medicine and machines. The Raman Lab’s current focus is building neuromuscular actuators to restore mobility and power robots. Prof. Raman has received several recognitions for scientific innovation, including being named a Kavli Fellow by the National Academy of Sciences and being named to the Forbes 30 Under 30 and MIT Technology Review 35 Innovators Under 35 lists. She is the author of the upcoming MIT Press book Biofabrication. She is passionate about increasing diversity in STEM and has championed many initiatives to empower women in science, including being named a AAAS IF/THEN ambassador and founding the Women in Innovation and STEM Database at MIT (WISDM).
Show Notes
Transcript
Luke Robert Mason: You're listening to the FUTURES Podcast with me, Luke Robert Mason.
On this episode, I speak to biomedical engineer, Ritu Raman.
"If you had the ability to build anything you wanted with biology, what would you do? What is that extra organ or sense that you would give yourself or another human being? What is something that we could give to, say, a surgeon to make them better at their jobs and better at being able to patch together very tiny blood vessels together? And then work backwards from that."
- Ritu Raman, excerpt from the interview.
Ritu shared her insights on designing biological robots, how new developments in tissue engineering may allow us to grow organs, and what bio-fabrication means for the future of food and medicine.
Luke Robert Mason: Your new book looks at the exciting new developments in the way in which we design tools and technologies by using the natural world as our inspiration. I guess the obvious question is: what is bio-fabrication? How will it transform the way we think about innovation?
Ritu Raman: That is a great starting point for the conversation, for sure. I think, you know, a lot of us probably have some very traditional view of what an engineer might be or what they might do. Most of the time, you're thinking of an engineer maybe as somebody who puts together different pieces of different materials and maybe makes a machine. It could be a phone, it could be a train or a plane. I think that concept of fabrication is something that we all maybe have an intuitive idea of. Bio-fabrication is really just saying, in addition to all of the materials that we already use like metals, plastics, or ceramics, could we also start thinking about how we might start using biomedical materials, like living cells, as functional components in the machines that we build?
The reason that we might want to do something like this - apart from that it's just cool science sometimes, and that's an okay reason - is that biological systems like our bodies and our natural world that surrounds us have this really innate, adaptive ability where they're able to sense different things that are changing in their environment and respond to it in some way. We can do things like exercise and get stronger, or heal from some sort of damage that we might experience in our environment. But a lot of the machines that we interact with in our daily lives, like our laptops, for example, can't do things like that. They are what they are until they break.
Bio-fabrication not only asks: is it possible to build machines with living materials? But, what kinds of new machines and capabilities might that give us that might help us address some of the most challenging technical problems that we face?
Mason: So ultimately, do you believe that building with biology is our future?
Raman: I think it's definitely part of our future. Sometimes if you talk to people who are more biologically oriented, they'll be like, "Biology is everything. It's better than humans." I rained as a mechanical engineer. I'm a professor of mechanical engineering at MIT and I do think that there are some materials, that we've designed and built that are not naturally present in our environment that are amazing. We can send things out into space sometimes that we can't build using our natural biological materials because they have special capabilities that help them be functional in that robust environment.
So I think building with biology is something that kind of just adds an additional set of materials to our toolbox. There are times and places when we might need a biological material to give us a bit of an edge.
Mason: What are some of those cases? What are some of the most important use cases for something like bio-fabrication?
Raman: I think probably the most - maybe this is very obvious - but I think the most useful and exciting place to use a biological material or machine is inside the body. This is more like if you think of different types of implants or devices that we might put inside of our bodies, like an insulin pump that might be helping people with diabetes or perhaps some sort of surgical procedure that we're subjecting somebody to who might have a cancerous growth or tumour, you might start thinking, well a lot of the things that we're putting inside people's bodies, whether a pacemaker or something else, is a battery. It's a hard, metallic compound. It's something that's designed to maybe work for most people that it's put inside but it's not really individualised to the needs of a patient.
If we could create an implant, for example - if we go back to this idea of an insulin drug pump - wouldn't it be better to have something that could sense what the needs of the individual person are, at the moment in time and one day, and then secrete the amount of insulin that that person might need at that moment in their lives. It's very individually tuned. It's adaptive. If they have other kinds of diseases or things going on in their lives, they might be able to adapt to them. I think that's one of the most exciting places for me, in terms of biological use.
But I also think beyond medicine, there are places - say just in traditional robotics - where bio-fabrication can be wildly interesting. You might have seen some cool videos from Boston Dynamics or other places of these cheetah-like robots that can navigate very natural environments. Maybe that would be great for going and sniffing out bombs and diffusing them. Actually, those robots look really cool in the videos but they're nowhere near as amazing as we are at navigating unpredictable environments and not falling over or tripping. If we could make robots that use living muscles and the same kind of neural feedback mechanisms that we use to sense and feel around our world, then I think there could be some really exciting uses for bio-fabrication there, as well.
Mason: I'm always reminded when I hear these sorts of things about Rossum's Universal Robots. That was a Czech play that originally gave us this idea of this thing called the robot. Initially, it was this biological entity. In that play, it's not silicon, it's almost like silicone. It's biological material that gives rise to these things. Weirdly, it feels like what you're talking about is not creating robots at all. It's not creating artificial intelligence, but forms of artificial life. We come up against that boundary, don't we, when we start talking about things like bio-fabrication? At what point is this process creating neo-forms of life?
Raman: That is such a good philosophical question. Unlike you, I didn't come to that question from reading. I actually came to that question when I was sharing some of my research with a bunch of 10-year-olds as part of an outreach programme. At the end of this talk, I'm like, well, I hope I explained my PhD research correctly to these children. This little girl raised her hand and was like, "Well, I have a question and it's to say..." basically, she said, "If you make something out of living materials, does that mean it's alive?" which is, I think, the question that you're getting at as well. It was truly a stunning question to be asked by a child at the end of an outreach event.
You're right. I think sometimes if we think of a living cell just as a functional component in a machine and we're saying, "Okay, well it's sensing these certain types of signals. It's processing it in some predictable way. Then it's creating some output response." Well, that's the same thing as, say, a lightbulb that I can turn on or off based on an electrical signal. But part of what we're saying is exciting about these systems is that adaptive behaviour. They might lead to some sort of unpredictable outcomes or perhaps learned behaviours and outcomes. That then starts becoming something that we might think of more as having some sort of consciousness or perhaps some sort of moral consideration.
It really depends on how complex the system would have to be, but I always try to go back to...if we had some general consensus definition of what a living being might be - so something that yes, senses and responds to its environment, but also perhaps does that in some kind of autonomous way. Perhaps it's autonomously seeking some food and metabolising that food, converting one form of energy to another. Typically, most living beings need to reproduce, right, and keep their form of life going. I think we can start to narrow down when have we created something that maybe checks off all of these boxes and falls into the category of some sort of lifeform that deserves moral consideration.
Mason: I mean in some cases, as a scientist, do you think that matter matters? Is it about how many cells and how much material is there before we start acknowledging something as life? These sorts of conversations always remind me of bio-artist Oron Catts, who would create these biological artworks. Part of his process would be to kill the artwork at the end of the gallery exhibition. He had to deal with the fact that his artwork was biological material. Was this thing alive? Was this thing not alive? Was it a form of A-life - artificial life - and he didn't know how to deal with the removal of this lifeform that he'd created; this neo-life, as he was calling it.
Do you think it's about the amount of cellular material, perhaps? Or is it about what that cellular material expresses or does?
Raman: You ask the most interesting questions. I think maybe I would say it's less about the amount and more about the provenance and the type. There are sometimes when we're building things, say, with mouse cells versus things that might be derived from human cells, versus something that might be derived from an insect. I think in our heads and as a society, we've sort of established a hierarchy. Different people fall on different parts of the spectrum. We might say we have a certain set of standards for when we do animal research with insects versus a non-human primate like a monkey. We've decided that one of those is worth more of our moral consideration. I think if you're using cells from those different types of organisms, the same type of rules might apply.
I say, "might" because that falls into the second of what type of cells we're actually using. I tend to do a lot of work with muscle cells. We're kind of just connecting an electrical stimulus to a piece of muscle tissue and watching it contract for a variety of reasons. There, most of the time I think we can kind of devoid or cut off any kind of thought that this muscle is a being on its own.
Eventually, we want to start doing things like integrating neurons that tell that muscle when to turn on or off, or perhaps sense something in its environment to make a decision about when to turn it on or off. I think once you start thinking about types of cells that we associate more with feelings or consciousness, or decision making, then again you start falling into this realm of, well, that seems like maybe it's a little bit more of a grey area. I would say something that's just insect and muscle - maybe you're not thinking of it as a particular living being. But once you start thinking, actually, I'm using cells from a primate and I'm putting some neurons in there - then I think you'd see a lot more people start thinking of that as worth more, morally.
Mason: Well, I'm fascinated by closely your work touches on issues such as personhood. Specifically zygotic personhood. For example, the debate around what point a zygote might be considered a potential person. That often depends on how much cellular material exists. I'm interested to know if these sorts of debates impact the way you think about the assemblage of cells that make up a bio-robot.
Raman: I think it's sort of inextricably tied to a lot of these types of questions. Primarily because - going back to what we were talking about, about the origin and the provenance of cells - a lot of the time with these sorts of debates about when life begins, you're thinking about something as...you'll say like a 'heartbeat law'. When the heart cells start beating. Yet heart muscle is one of many different things that we need to survive. I work primarily on skeletal muscle and nobody is really talking about what is this special phase of skeletal muscle development, at which I consider a clump of cells more than a clump of cells.
I think it's inextricably tied to our work. I don't know if that necessarily gives me more insight into the answer. I think a lot of times when I think about this debate, I figure that most of the people that spent the most amount of time understanding stem cells and understanding where life comes from and how we originate and grow don't have an answer. Which, to me implies there's not a clear answer. Perhaps continuing to work on this and keeping in mind that different people are going to have different opinions is one way to do it.
One thing I try to be very careful about it in my work is to not be dismissive of varying viewpoints on this issue. It just doesn't really get us anywhere as a society. I only want to work on things that I believe have value and that people will care about. I try to focus on solving problems - whether in health or in robots - that I think will advance human health. I try to check in with the general public every once in a while to be like, "Do you think I should be doing this? If not, okay - there are plenty of other problems we can work on."
Mason: Uh-huh. I mean part of it is the language that's used when we talk about this form of science. When we create organs on chips, for example - something you mention in the book - we use embryonic stem cells to do that sort of work. People hear 'embryos', "Embryos!? Stem cells!? God, they're using baby cells!" You're like, "No, no no no - it's a completely different sort of thing." How do we make sure that people understand the science behind these sorts of processes?
Raman: I think part of it is through podcasts and books, and getting people through the media where they are. I had the opportunity when I was at the University of Illinois for my PhD to have a relatively short conversation with Mahatma Gandhi's grandson - great-grandson, who happens to be a professor there. I was talking to him about, how do we have conversations with people that we disagree with, or who might have a very strong opinion about who we are or what we do. He said it was very important to always think about winning over a person, rather than winning an argument.
For me, I think there are times when I think I've managed to share something about my work or perhaps change somebody's opinion through the media. I think that's a great way to engage with people. A lot of times, these kinds of conversations and the sort of bottoms-up learning happens through our personal connections. Sometimes with our personal connections is when we tend to be the most dismissive and the most snippy. My parents are both engineers - they weren't trained in biology - and they'll ask a question sometimes about a vaccine or something. I think I tend to be very snippy with them in a way that I wouldn't be with other people.
I think one of the best things we can do is - those of us who have spent a long time learning about these things - have the patience and compassion to share that with the people in our lives, and sometimes repeat ourselves more often than not. We can remind them that maybe, actually, induced pluripotent stem cells come from adult human skin, and not from babies.
Mason: Well, I love the way in which you talk so enthusiastically about the wonderful possibilities of this research. I thought it was just a little important that we went through that process of just understanding that, hey, what we're talking about is something that has the potential to really help human beings, even though the science sounds kind of scary when we use these words like 'life' and 'embryonic stem-cell', and 'pluripotent stem-cell'. It's like, what's going on here!?
But you say in the book, so wonderfully, that perhaps the most powerful application of bio-fabrication is in preserving and prolonging human health. That really feels like the core of your interest in this field. There are so many wonderful, inspiring examples of how bio-fabrication is really being used in healthcare. You mention some of those implantables, those insideables, those ingestibles, those swallowables, for example. What sort of medical devices have you been working on and developing in this space?
Raman: You know, we work on - as you said - preserving and promoting human health. I think of human health specifically through the lens of mobility, and the quality of life that being able to navigate our worlds through some sort of conscious motion helps. One of the things that we do is build models of the neuromuscular system in the lab. We make these little bitty worm-looking things, that are made out of muscle cells and sometimes mouse cells. We're trying to transition to human cells right now. They're controlled by motor neurons that essentially tell the skeletal muscle when you turn on or off. This is the same thing that happens in our bodies, but we try to recreate miniature versions of this in little Petri-dishes in the lab.
What this allows us to do is to say, say somebody has a very traumatic injury. Perhaps they're in a car accident and they use an arm. Perhaps they have a nerve crush injury that happens as some other part of the trauma. Perhaps they have ALS and they're having some degeneration that's causing motor symptoms and an inability to control their movements in the way they used to. We can essentially recreate that in our Petri-dishes and if we use human cells, we can even use cells from the specific human we're asking the question about. We can say that this is what's going on with this person. Let me understand how this disruption or this disease impacted their way to control their muscle using their nerves. Let me design a new therapy - whether that's something like a new surgery or a specific therapeutic drug that we give that person and that's tailored to that person's individual needs. You can test it out in the lab and then have it tested on the person themselves. Hopefully, that would give us a greater likelihood of success.
That's kind of, I would say, some of the lowest thresholds to entry work that we do, but we also do other things related to sometimes when you lose large chunks of muscle in your body, you're not able to regenerate it in the way that you would after, say, a smaller tear or an exercise injury, or something like that. We start thinking, okay, we know how to make muscle in the lab using cells now. Can we just make a large chunk of muscle tissue, essentially like a piece of meat that's kind of alive, and stick that in your leg or wherever you've lost this tissue, and have that integrate with the surrounding muscle tissue in your leg as well as the surrounding vasculature - so your blood vessel network and nerves. So eventually, it should be indistinguishable from the rest of your body and help you restore your ability to move and walk around.
We've done this in mice, which is always the key answer in everything. You can do it in mice. Now we're thinking about how we might be able to translate that work in a way that's more impactful to human beings.
Mason: I mean, are you ultimately talking about growing new limbs and growing new organs in the lab?
Raman: Yes. I think that would definitely be a huge goal that not only us but everybody in this broader field that we call tissue engineering and regenerative medicine has been working towards for decades. There is a range of technical challenges that are roadblocks in the way of us getting there, but we have gotten much farther than we used to be. Science progresses in many small steps.
Mason: What are some of those technical challenges? Do you mind me asking what it is that's holding us back from being able to replace our organs ad infinitum?
Raman: It's a great question. I think part of it is the fact that to make a human or any significant portion of a human, you need billions and billions and trillions of cells. Part of it is a manufacturing challenge. Typically the sorts of things we're making in the lab might have millions of cells. That actually ends up being very tiny. It's something that's microscopic or millimetres in scale. You need to very rapidly produce billions or trillions of cells.
Once you have all these cells, you need to put them together in this very complex 3D architecture. The great thing about the body is it has this very hierarchical organisation. For example, in muscle, you have a few muscle cells that fuse together to form a fibre. Then you have thousands and thousands of these fibres. Then each, say, set of a hundred of one of these fibres is innovated by one neuron. Running through all of this is a range of blood vessels. In those blood vessels, there are immune cells that are coursing through. You have all these different types of cells at many scales, that are patterned in this very complex way. You need a machine - whether that's a 3D printer or some other kind of manufacturing device - that can very precisely and also very quickly put together all of these different cells into this complex architecture.
Once you have all of that, you need to stick it inside a person and have them not immediately reject it because their immune system is like, "What is going on? Why have you done this to me?" Then assuming they don't reject it, they need to form functional connections with it. A blood vessel that was already in your arm might then need to go and attach to the appropriate backend blood vessel on the new part of your arm that we're adding on.
You can see that just from some of these technical challenges, each piece requires somebody working on, say, manufacturing, somebody working on fabrication and patterning, people working on different types of cell sources, people working on the immune response - and people are. People are working on every aspect of this. It just takes time for all of these things to work in synergy.
Mason: I'm sure you're always asked about HBO's 'Westworld'. The opening credits to their TV series show these bodies that are being printed by robots. It's a wonderful and visceral vision of what the potential future for this could be. In reality, that stuff is much more likely to happen through processes like xenotransplantation, isn't it? Where non-human animals grow organs and then we transplant those organs into humans. Can you tell us a little bit more about xenotransplantation and why this looks like a possible way to grow new organs for humans, certainly in the near future?
Raman: Yeah. I think this really captures the trend of the fact that these are not new ideas. These are probably things that for centuries or for millennia, we've been dreaming of. Especially when faced with disease or damage in our own lives or those people we care about. We say, "What? Somebody had a heart attack? I wish I could give them a new heart." It's the first thought that pops into your head. Over time, we eventually said, "Well, it turns out that if somebody passes away and they donate their organs, and they are a good immune match, then maybe we can put their heart in our hearts." We're like, okay, that sounds good. We figured out how to do that, such that it works most of the time. Then we're like, well, you can't always rely on someone to die and donate their organs. Why not start thinking of other ways? The very long-term way is what I was talking about of taking that person's cells and putting together the exact right organ for them.
There is an intermediate path and it's this one. You can think of animals like pigs or other animals that we have some very strong similarities to - not just in terms of hearts - our gastrointestinal systems might look fairly the same but they often tend to be fairly the same size, as well, which is often very important. Then the question becomes: oh no, they're pig cells. You can't just put pig cells in a human being and expect the body to be okay with it.
You've all these people who are working on ways to genetically engineer these cells such that they don't present as pig cells to our bodies. Essentially, they look close enough to what a transplant from another human being who's maybe not super different to us might look like, so that we can kind of essentially resolve this supply chain issue. It's completely possible that this will be good enough, and maybe people will say, "This is fine. Let's just keep doing this. Let's keep farming pigs for organs." I think there are many cases where we might say, "Well, it's probably not a perfect match. The perfect match is what you originally had and the closest we can get back to that, the better your quality of life might be."
Then there might be other reasons why we might not pursue this route. It could be animal farming - especially if done irresponsibly - it can not be great for the environment, and for getting more and more concerned about sustainability and climate change. You might say, "Okay, well what are other better ways or more efficient ways to produce these organs over time?" With all these things, I think there are multiple ways of getting to our end goal. That's the great thing about science. I know that even if everything I do for the next several decades fails, someone else will probably succeed. That's a good thing.
Mason: Well, let's hope that everything you do over the next decade doesn't fail. I really do, for everybody's sake. But we're talking about this idea of creating organs outside of the human body. We already do that, don't we? You mention in the book this idea of organs that exist not within the body or elsewhere in a 3D printer, but organs that exist on a chip. What are organs on a chip and what are they used for?
Raman: Organs on a chip are essentially very tiny versions of an organ. It could be something that is, say, sub-millimetre scale, that lives within a little plastic device or chip, that has some fluid flowing through it, that keeps these living cells alive and warm, and happy. The interesting thing about these organs-on-a-chip devices is that you're basically reducing down something as complicated as the heart to what is the basic functional unit of the heart that I can re-create in the lab, that still captures many of the important or interesting characteristics of the heart at a larger scale.
This gets back to the idea of the fact that biology and the human body are hierarchical. Most of the time, it's, "Here's a very small version of a thing. Now I'm going to make a thousand of those. This is muscle." A thousand muscle fibres. Really, maybe you could look at one or two muscle fibres and get an idea of what the whole muscle might do. Why you might want to do something like this is for high-throughput drug testing. You're going in and you're saying that the old way of testing drugs like a vaccine or something like that is to say, "Okay, I made something in the lab and I tried it at a bunch of animals. They didn't die. They seem to maybe sort of kind of get better. Now I'm going to try it on 10 people. They didn't die so now I'm going to try it on 100 people. They didn't die. Now I'm going to try it on 10,000 people. Okay, now we're ready to give this vaccine to everybody." That's certainly a way that works. We've done it for a long time. But there are many, many times that something works on animals and then we put it into those first 10 humans and either they don't get better, or worst case scenario something terrible happens to them. They get very sick, or they get sicker, or they die. We want to minimise that happening as much as possible. We're doing this to help people, not to just do crazy experiments.
Then the question becomes, how do we test something in the lab in a way that maximises that chance of success? It goes back to this idea of 'probably not in animals’. I'm not a mouse. There are many things that work in mice that aren't going to work in me. If we could create a miniature version of human tissue or an organ - and particularly if we could use mice cells, even better - then we would have the most perfect model system of something we could try in the lab. It's so small that we could test very low cost. Maybe a hundred different versions of a drug on a hundred different versions of my muscle tissue. We could say, "That's the one. That's the one that helps her." It could be something that helps us translate from just going from organs on a chip straight to humans, with greater success than doing something in mice first and then hoping that it works in human beings later.
Mason: What you're talking about there sounds like it's the burgeoning effort towards something like personalised medicine. If we could all have a version of our organs on a multitude of chips then surely we can optimise medicine itself for the perfect outcomes for our bodies.
Raman: Yes. I think the specific point you brought up about little versions of our bodies - it's not just about little versions of organs, right? I always talk about muscle because it's the only thing I know. But there are tonnes of other people that are working on, say, an eye on a chip, or a lung on a chip, or an intestine on a chip.
Then there are people thinking about how we connect all of these chips together into some sort of integrated system, such that we know there are many times that you can, for example, kill a cancerous tumour by putting a whole bunch of toxins right on it. Of course, that would work. The reason that doesn't work in human beings or why chemotherapy ends up being different is that it's actually really important for the rest of the tissues in our body. If you could create many of these organ-on-a-chip tissues that were connected in some way that was representative of our body, it would also give us an idea of the impact this drug might have on us as a whole. I think that concept of personalisation then just ends up being even more important.
At the end of the day, I don't know if we'll ever get away from clinical trials in saying, "This is what works for most people." But I think we all know as individuals and humans - both from our experience and those of our families - that what works for most people doesn't always necessarily work for us. Having something that is as close to you as possible is maybe the best way to get something that can help you feel better.
Mason: It sounds like that's a wonderful way to deal with the unintended consequences of certain drugs and certain treatments - to be able to identify them before they affect the body seems to be such an important way in which we can help people get better. But your work looks at muscle and it looks at the different ways in which we can use muscle as a material. The one thing, especially, that the FUTURES Podcast audience always seems to be so excited about is how we can use these burgeoning and emerging technologies to do things like longevity research, to increase our healthspan. I don't want to say 'lifespan' - but increase our 'healthspan'. What are some of the exciting ways in which fabrication can be used to help advance longevity science?
Raman: I love that you said 'healthspan' and not 'lifespan'. I do think that's sort of an emerging idea in the field.
Mason: Everybody's like "How does this help me live forever?" I'm like no, no, no. Hold on. It's about agelessness. It's not about living forever.
Raman: Exactly. It's about having the strength and vitality you had in your 20s when you're 90. That's the thing that we're really excited about. I think there are many ways. On a health level, there are some very obvious things that we could say. Typically muscle tends to waste away, or you might be more susceptible to neurodegenerative diseases as you get older. These typically result in a reduced ability to navigate our world. With rare exceptions, you don't see people in their 90s running marathons or racing up the stairs. I don't do that now, but I'm sure I'm going to be better at doing that now than I'm going to be when I'm 90.
So one of the ways we can do this is by creating models of, say, sarcopenia - age-related muscle degeneration in our little tissues that we make in the lab - and testing out a different set of ways, perhaps through targetted exercise or through some new therapeutic drug that we might be able to preserve that vitality of tissue over a longer period of time which will make us feel stronger as we get older.
I think on a broader scale, one aspect of the book that I think we haven't talked about is the potential impacts of bio-fabrication and sustainability. If we could make big pieces of muscle that are alive, we can also just kill that and call it meat. That's what meat is. There are ways or potential calculations that show that that way of creating meat might be more environmentally sustainable or efficient or healthy for us in terms of nutrient production than traditionally farmed meat.
In that way, you can also think about our quality of life as not only the life in the body that we're living but the world we're living in as well. There are ways that I think bio-fabrication can impact our health and our environment that will increase our health span over time.
Mason: That's an area that people get very excited about as well - this idea of lab-grown meat. The promise of murderless meat. The meat we can create doesn't require an animal in the process. It requires the extracting of some form of cellular material to grow that meat in a lab. Do you think there are some nutritional advantages over developing bio-fabricated foods and meats? Despite those nutritional advantages, do you also think there are some challenges in trying to go down that particular route for the future of food?
Raman: Yeah, I think there are definitely some nutritional challenges - or nutritional opportunities, I should say. It could just be that you're growing cleaner meat. You're going to have less of an ability to have pathogens or other types of bacteria be present in the system because you're inherently making it in a very sterile, lab-like environment where you're controlling the conditions. The second part is that there are many things that are traditionally in meat that might be good for you or bad for you. But there are also some nutrients that we don't typically get through a variety of different mechanisms - or maybe some of us are better at getting them than others - and other ways that you could toss in some of those nutrients as part of the engineered meat that you're making so that you can essentially have, in the same way, that we have fortified orange juice, fortified steak or chicken breast. I should mention that I'm a vegetarian so my topic knowledge should be very questioned on this issue.
I think there are also opportunities in terms of interesting flavours and things we can do. We're very comfortable talking about things like craft beer or cheeses that come from a specific farm in this one place in Switzerland. Isn't that the greatest thing ever? I think there are so many things that we could do. If we had smaller batch productions of people making different kinds of meat, maybe mixing different cell types or different types of nutrients, cooking them in new and interesting ways - perhaps there could be some exciting culinary innovations as well.
Now the challenges associated with this end up being a lot of the manufacturing challenges that I mentioned with organs before. You just need billions of cells. In this case, you need to be able to produce them very cheaply. Especially in America, we tend to be comfortable, or at least we know the idea that sometimes medicine just costs a lot, but you don't expect food to cost a lot typically. There is not really a way to subsidise that. You need something that matches the pricepoint of traditionally grown food whilst also being manufactured in this very novel way. I think that's one of the biggest challenges we'll face.
Mason: But the one thing that always surprises me when I look at these sorts of future foods is that they always attempt to replicate the texture, the look, and sometimes even the taste of animal-based meat. If we have all of these bio-fabrication tools, why can't we create entirely new forms of food? Is it just the limitation of our imagination or is it the expectation of the consumer that's limiting us to just create things that kind of look like hamburgers, or look like steak, or look like mincemeat?
Raman: I don't know if it's a lack of imagination. I think part of it is the fact that a lot of these companies are developing essentially plant-based substitutes for animal-based meat. They're typically going after a market that's like, "Oh, my daughter turned vegan because she's 12 and she watched a documentary. Now I have to do this." or, "I feel guilty about the environment so I have to do this." But it's people who are maybe raised eating traditional meat and they're just trying to replace that thing in their diet. A lot of the time, those end up just kind of falling flat on their face because they're made of different materials and for people like me who have never had actual meat, it's meaningless. I'm like, "I'll just eat a carrot." It's an interesting thing, it's a cool fad, and it's probably going to go far and satisfy one niche of the market.
I think once we satisfy some of the technical challenges of actually being able to make something with animal cells so it really is meat, just not from an animal, then I think you'll see the first wave of companies probably just saying, "Here's a steak. It's exactly like the other steak. Isn't that great?" Everyone is going to try it, and they're going to say, "Yeah. Unlike some of the plant-based alternatives, this really does make me feel like a steak." Once that wave subsides and people are like, "Yeah, I know I can get this already.", then you have to match the evolving needs of the consumer. Then they're going to say, "Okay, I had a steak. Now I want steak 2.0, or 3.0. I want you to mix cells from different types of animals. I want you to add new flavours. I want you to be more creative about this product you're giving me." I think that's when you'll start seeing some of the creativity and innovation that you're talking about.
Mason: Yeah, wasn't there a frog burger at one point? I think that was an art project where they used cells from a frog.
Raman: Ooh, was there?
Mason: Again, Oron Catts, the bio-artist who looked at generating a small amount of meat from a frog. It seems like suddenly, the entire animal kingdom is potentially ours to taste, which is terrifying in so many ways. These things do extend the possibilities of the imagination, I guess. I'd like to see more scientists collaborate with chefs and see what could be potentially created. What's the science behind this? How do we create these things? How does it all ultimately work? What are the various manufacturing technologies that are used for something like bio-fabrication?
Raman: Typically you need two things in order to make something like meat or an organ. To think about that, you just think, what are these things? They are essentially an assembly of living cells in some sort of complex shape. The first thing you need is a way to grow cells in the lab. How we've done this for a very long time is essentially using things like plates or Petri dishes in a very clean environment. We have these cells growing on these glass or plastic surfaces. They're usually immersed in some sort of liquid that has a tonne of amino acids or sugar that kind of replicates their native environment. They grow and proliferate, and we can make more and more of these cells.
For some of these really large manufacturing applications like meat or organs, people are developing bio-reactors. These are essentially these big machines where instead of having one person pipetting silly in a lab, you're having billions of cells floating around in these machines and being cultured automatically by some sort of robotic system. That's the first thing - you have the cells.
The second part is, how do you actually put those cells together? This is where some of the manufacturing technologies come into play. Cells are usually not just bound to each other. They're sitting in this sort of jelly-like goop of proteins that are called the 'extracellular matrix' - essentially just the thing that holds it all together. We replicate this in a variety of ways. We'll get different sorts of proteins from animal sources or sometimes even plant sources. We mix these up with the cells to form this slurry. Then you can either mould them, print them or pattern them in some sort of way so that they resemble a 3D structure. Essentially, it ends up kind of being like making jello in your home. The same kind of way that we would manufacture anything else in our lives, except instead of using a synthetic material, we would use a combination of these cells and proteins.
Mason: With what you're describing, are there any kinds of economic advantages to doing that? Are there environmental implications of doing that? It sounds very kind of industrial. It sounds very expensive.
Raman: I think it is very expensive now, in the sense that a lot of times - as we've seen many times in the Industrial Revolution - the first time we're figuring out how to make something it takes a lot of trial and error. It takes a lot of time to figure out how to reproducibly create the same thing over and over again. Once you know the steps, the next question is, okay I want to make a million of these and it can't cost more than 10 dollars. How do I do that? That comes with bio-reactors and new types of factories, and new ways of sourcing that material. Or just the fact that the demand for them is more and so we can make them in larger batches. As a result, by the economies of scale, the raw goods end up being a little bit cheaper. I think that's part of it and I'm hoping that eventually, we'll get to the point where making and manufacturing these things does happen. If not cheaply, then at least in a way that is comparable to the advantages it might have.
The second part that you asked about was the sustainability aspect. I think that's really interesting. My first instinct when I was writing the book and thinking about this topic was to be like, of course, it is. It's new technology so of course, it's greener and better for the environment. I think it's worthwhile to really take a step back and think about whether that's actually true. The reason I took that step back was that I was following one of my old friends on Instagram who started a regenerative animal farm. They're kind of pushing back on this big tech narrative which says that's the only way to create a sustainable future. You could raise a small number of animals in a sustainable way, use all of the meat within that animal - not just part - and only serve your local community. Maybe that would be a relatively sustainable way of eating meat. I think that's perfectly valid and true. I think for a lot of people, that may not be accessible. We don't really live in that kind of environment or we might not be able to afford that kind of price point. I think it's also okay to say, "I don't want to eat that part of the animal." if that's not something you're into.
Then it raises the question of if we could create these sorts of things at a cost advantage - something that might be affordable for many people - to me, it seems to make sense that the cost required to grow steak is much less, environmentally than the cost required to grow the cow. That's a calculation that many folks in the environmental engineering space have done. They've said that actually, a lot of the energy that goes into growing these cows, pigs or chickens is just wasted keeping this animal alive for a long time until we're ready to sacrifice it. If you only grow the parts that you want, that's one more efficient and sustainable way.
That also goes downstream to transport. Then you're not shipping whole animals or livestock in trucks, planes or boats, or however, they get from place to place. You're only shipping the part that you actually want. I would never say it's a hundred per cent it's true that it'll be more sustainable, but there are some indicators that it might be. It's worth continuing to ask those questions.
Mason: This was a bio-fabrication we've been talking about. It suddenly feels like it's the type that borrows from nature. It looks at nature, it looks at the environment and it goes, "Wow, look what biology can achieve." It tries to take that learning and bring it to the lab. Beyond bio-inspired examples, there are these bio-hybrid examples of using machines as we traditionally understand them and combining them with biology. In what way is a bio-hybrid machine different from a bio-robot?
Raman: I think they would fall all along a spectrum. This again goes back to the idea that I am not a biologist. I am an engineer - a mechanical engineer - and I think there are some great synthetic materials out there that we should absolutely keep using. The question becomes...you could make something that is fully biological and it just replicates what we see in nature. We could create a worm that looks like another worm. In an ideal scenario, we would have the technologies to do this.
But often we have to ask ourselves, maybe we want to send a robot into a very extreme environment. We want to make a biologically powered robot that can go and explore Mars, which is a very intense territory that no lifeform on Earth might be able to do. Then we can start asking and answering questions. There are some materials that are biological that might help us do this, like muscles that can sense changes and craters, and rocks on the Mars environment and help this robot navigate it without knowing ahead of time what's going to be there. You might also want a metal exoskeleton or some electronic sensors that are taking images and pictures and upload them back to NASA or whatever other organisation has put this robot on Mars.
I think bio-hybrid really falls into this realm of imagination. Of saying, okay, I have these biological materials. I can put them together in some sort of predictable way. I have the possibility of reverse-engineering what already exists in nature. There are some situations where I might want to forward engineer something that doesn't exist in nature, but could solve some big challenge that we're facing in society. That's where I would say this bio-hybrid terminology fits in.
Mason: You also have this wonderful term in the book called 'hypernatural functionality' - adding new biological or bio-fabricated constructs to pre-existing machines. Where have you seen some wonderful examples of part biological, part synthetic bio-hybrid machines being used to augment the existing tools and technologies that we have in our lives?
Raman: Where have I seen it? In my dreams, perhaps? I think we're still in a very nascent portion of the field. I don't know if I can right of the bat think of some real-world applications. There are some things that are happening in clinical trials, for example, where you are creating something like an artificial pancreas or something that you're putting in a diabetic patient, that might be secreting insulin as they need. We haven't really been asking and answering a lot of those questions because the ability to do them has been so far away.
This goes back to maybe some of the examples you brought up in science fiction, books, media and stories. I think we should all ask ourselves. If you had the ability to build anything you wanted with biology, what would you do? What is that extra organ or sense that you would give yourself or another human being? What is something that we could give to, say, a surgeon to make them better at their jobs and better at being able to patch together very tiny blood vessels together? And then work backwards from that.
I think we haven't really let ourselves - at least in science - ask these questions because they felt so far out of the way. Maybe if we got back in touch with some of our more imaginative writers and liberal arts friends, we'd be able to open up some of these application areas.
Mason: Do you think there's any good science fiction that really captures the sorts of visions that you have for bio-fabrication? When I was reading your book I was thinking of James Cameron's 'Avatar' - the ability to create these big blue pieces of biotechnology. The weird thing about that film though is that the gentleman who gets his consciousness ported into the big blue piece of biotechnology no longer has the functionality of his legs. You are sitting there thinking, why can't they grow new legs but they can grow these massive blue beings? There was kind of a weird scientific disconnect. But beyond that, do you think there is science fiction out there that has really, in a nuanced way, captured the sorts of uses of bio-fabrication that we may see in the near future?
Raman: I think my favourite kind of science fiction is the sort of superhero genre; the comic-book genre. Part of that is because, again, being a muscle person, when we think of someone who is a superhero, yes sometimes they have these wild and wacky superpowers but a lot of the time, what is that fundamental need or desire that it's tapping into, in human beings? It's the ability to be stronger or more special than another person. Not being afraid, because you have this ultimate strength. When I think of my work, for example, I say, "I'm making muscle so that people who have lost the ability to use their muscle or whose muscle is weak, I can restore it to their normal strength."
These kinds of comic books and movies make me ask the question: that's what I'm doing, but surely it's possible that somebody else might say, "Why can't I make muscle that's even stronger and put that into somebody?" Then would you create somebody that's a superhero type of person, maybe that is transmittable to the next generation versus not - and if you did that, what's stopping an average person whose muscles are working perfectly fine to just throw a whole bunch of money at making themselves stronger? Then you're just going to have a bunch of rich, very strong people, and a bunch of poorer people who aren't as strong.
These kinds of questions are asked, answered, and thought through in some of these superhero stories and narratives in these very complex ways. I think it helps me process the ethical implications of my work in a way that I don't know I would be able to do on my own. That's maybe my favourite. I think sometimes it gives me ideas. You'll have something like a replaced organ, or somebody's sick but then we upload their consciousness to a new thing and we're able to bring them back to life. Then it also pushes you to think about the fact that just because you have good intentions, it doesn't mean that everybody else does. That doesn't remove your moral culpability from the work you're doing. I like that those kinds of stories push me in that way.
Mason: As I'm hearing you talk I'm thinking of the supersoldier programme. You're building Captain America by enhancing different muscles. When we start talking that way with the multitude of possibilities that science makes available to us, we have to start asking the question of just because we can, should we? Do you think as this ability to build with biology becomes more mainstream, do you feel like we need global guidelines, perhaps? Global ethical guidelines on how we use this new form of emerging technology.
Raman: Absolutely. I think that global guideline needs to be global not only geographically, but global in the sorts of people it includes. In the past, we've had these symposiums or summits to talk about things like gene editing or to talk about things like artificial intelligence. This isn't the first time we've had this conversation. We've had this conversation since the dawn of technology. What often happens is you have a very specific type of person in the room. That person is a scientist and that scientist typically comes from a place of a lot of economic and social privilege, and often tends to be a man, and look a certain way.
It's not enough to just think about diversifying the population of scientists that we bring to the table, but also say there are probably philosophers, science fiction writers, members of the general public, people who are writing the laws, and people whose jobs might be affected by the automation of certain types of technology who should also be here and have a voice in the sorts of guidelines we're making. I think that should hopefully be the path that we pursue. I think the more inclusive we can be at that time point of making the rules, the more invested the larger community will be in doing the research and enforcing that rule. When you see people not wanting to do something or not following a rule, it's because they weren't in the room when that decision was made in the first place. I think global guidelines that are truly global and incorporated diversity along multiple dimensions would be the best path forward.
Mason: I guess the problem with biology compared to something like digital technology is that biology is hard. There are so many unintended consequences. There's so much that we just don't know when it comes to biology and we won't know unless we do it. Do you think we should take a precautionary approach to this sort of research or do you think we should be more proactionary? Let's just develop some of these tools and technologies and find out what happens. By finding out what happens, biology and nature might start asking some of the questions that we had when we started developing these things.
Raman: I think maybe that's a question that different scientists would have a different answer to. I tend to fall...for me, and maybe it's because I'm an engineer and also I'm at MIT which is very much based on the practical application of science and engineering, I always want to be doing something because I hope that I'm solving a problem that people I care about are facing, and that there's a real positive impact that I can have on the world through making this problem. I tend to focus on asking questions where I can see some sort of path to either a therapeutic goal or some goal that I feel will enhance human health or the sustainability of our planet.
That being said, that's often not how some of the most interesting science in the world has been done. We've funded some very basic science and exploratory research that then, a hundred years later, ended up leading to, say, the semiconductor revolution. That was never what was originally planned. For example, at the lab where I did my post-doc, I worked with Professor Robert Langer at MIT who's a co-founder of Moderna. Some of the foundational technology that led to the Moderna vaccine was stuff they were working on in the lab 40 years ago. I can't imagine that those people had a very clear vision of how many lives they would be able to save by that thing they were working on then. That's maybe something that I need to work on a little bit - kind of balancing my unwillingness, or maybe my precautionary tendency with this idea that sometimes, exploratory research can have very strong positive outcomes as well. it's important to keep that in mind.
Mason: Do you think also that talking this way about biology and seeing the similarities between biology and machines - does that certainly change the way we think about what a human being is? I find it always problematic when people go, "Oh yes, the human body is just a form of machine. It's just a form of machine, and biology is just this machinic process." I can't help but feel that human beings are so much more complicated than that. We can't be reduced to machines. Talking this way kind of does us a disservice, almost.
Raman: You're right. Maybe I'm one of those people that tends to say that because I want to reduce everything down to saying here's a cluster of cells that communicate mechanically and chemically. If we could reproduce it, we could make something that's a machine. Maybe that doesn't get to the point that when we say 'machine', or 'device', or anything - we built it for a reason. We built a car because we wanted to get from point A to point B more quickly. Why do humans exist? There's no answer to that. Maybe that could be the philosophical distinction that you're looking for. If there's a creator or there's not a creator, we don't necessarily know why we were put together in a certain way or what purpose we're intended to serve, if at all. That's maybe what separates us from machines.
Mason: Yeah, it does go back to that philosophical notion that to understand something, we have to build it. The reason we're pursuing this form of research is to build other humans. To borrow a phrase, 'to build things in the image and likeness of us'. The only way we will truly understand the complexity of us is by trying to do that design process of creating us. Then not realising that we have a way to create ourselves, and that's called procreation. Biology is doing very well at that, thank you very much, so we're kind of in this weird, weird trap there.
It does get to the point at which I think, are we just going to fundamentally realise that in this process of trying to create humanoid-like robots, we're just going to realise that nature worked it out all along. We're going to end up back where we began. The real drive for a lot of this stuff comes from what you were saying previously - is a certain form of demographic - men in labs, going, "Well if we can just get rid of the womb, then we can create bio-reactors. A womb is just a bio-reactor, isn't it?" That's kind of the mindset we're trapped in which is why we're pursuing certain forms of ways of doing this thing.
Raman: That's a wonderful way of thinking about it. Also, even as a woman who has seen some of my friends go through some very traumatic birth experiences, I've often been like, "Why can't I strap a backpack to my stomach instead and have that sorted out?" I think a lot of this research maybe goes back to this fundamental human nature and instinct of being obsessed with this process of understanding everything that happens and asking why. When we figure it out, we're just going to dive deeper and ask another question. I don't know if we'll ever fully arrive at a scenario. I think maybe once we get to the point where we can fully recreate humans, we'll be asking some questions that we can't even imagine in this conversation here. Then we'll keep saying, "I'm going to keep working towards that. When I get there, that's when I'll stop." But we'll never stop, right? It'll always be an endless process.
Mason: It will always be an endless process. Part of your endless process seems to be that one day, you might go to space. I was excited to hear that one of your original aspirations was to become an astronaut. Do you think the sorts of innovations inside bio-fabrication will ultimately help aid us in space exploration and could a bio-lab in space be something that potentially you develop?
Raman: I would love that. You've done some very deep digging, here. Maybe not that deep, I think maybe I tell everybody this. A very famous scientist that I met once said that most people who are scientists are here because when they were five they were really into space, or really into dinosaurs. Those were your two options. That's how you end up at MIT. That's certainly true of a lot of people. It's impossible not to look up and be like, "What's out there? I want to go there." We feel that way about going to Switzerland and posting it on Instagram so of course, now we want to push that even farther out in our imagination.
To me, a lot of the work we do, part of it is certainly just thinking about the astronauts' health and mobility. Their muscles, bones and nerves might atrophy in space. What are ways that we can learn more about that process and help them preserve their mobility when they come back to Earth? That's one thing. Eventually, if we start establishing communities in other places, on the Space Station or on other planets, potentially, we're going to need to farm there. We're going to need to create food. We're going to need to produce different aspects that help us navigate that new environment. Perhaps biological materials and machines and biologically derived food that's engineered could be and has to be a part of that community and process.
Hopefully, there are many potential aspects I have looked up. Now, space travel has been somewhat 'democratised' - if you have the money. Initially, back in the day, I did look up the things that you might need to be an astronaut. I think I matched the height requirement and I have a PhD so I'm like, I am basically almost there. I still throw up in the car but we can pretend like that's not going to impact.
Mason: Well, I hope one day we will see you running a bio-lab on Mars. It certainly feels like this is the way it's going to go. It's going to be so much more efficient to send a few meat cells into space rather than the whole animal, although the idea of pigs in space sounds like a wild vision. I know it's not going to be pigs in space - it'll be tiny little cells that we'll grow into bacon.
Ritu, I just love how you talk about this stuff with such enthusiasm. On that note, I just want to thank you for being a guest on the FUTURES Podcast.
Raman: Thank you so much for having me. I think these were some of the most fun questions I've ever been asked in an interview, so really appreciate it.
Mason: Thank you to Ritu for showing us how we can overcome technological challenges by building with biology. You can find out more by purchasing her new book, 'Bio-fabrication', available now from MIT Press.
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Producer & Host: Luke Robert Mason
Assistant Audio Editor: Ramzan Bashir
Transcription: Beth Colquhoun
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