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- [00:01]
Elise Hu
This episode is sponsored by the new all Electric Toyota bz. A common myth is that switching to an electric vehicle means sacrificing capability or performance. The Toyota BZ proves otherwise. With available all wheel drive, you can get 338 horsepower and near instant torque for a powerful responsive drive going 0-60 mph in just 4.9 seconds. And with an EPA estimated range of up to 314 miles on front wheel drive models, you can go farther between charges and make the most of every drive. Learn more@toyota.com bz that's T O Y-O-T A.com bz the new all electric BZ Toyota let's go Places if you love.
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- [01:19]
Elise Hu
This show is brought to you by Dell introducing your new Dell PC. Powered by the Intel Core Ultra processor, it helps you handle a lot even when your holiday to do list gets to be a lot because it's built with all day battery plus powerful AI features that help you do it all with ease. From editing images to drafting emails to summarizing large documents to multitasking so you can organize your holiday shopping and make custom holiday decor and search for great holiday deals and respond to holiday requests and customer questions and customers requesting custom things and plan the perfect holiday dinner for vegans, vegetarians, pescatarians and Uncle Mike's carnivore diet. Luckily, you can get a PC that helps you do it all faster so you can get it all done. That's the power of a Dell PC with Intel inside, backed by Dell's Price Match guarantee. Get yours today@dell.com holiday terms and conditions apply. See dell.com for details. You're listening to TED Talks Daily where we bring you new ideas to spark your curiosity every day. I'm your host, Elise Hu. Today's talk is part of our new 2025 Ted Fellows films adapted for podcasts Just for our TED Talks Daily listeners, we'll be releasing these special episod showcasing our amazing Fellows on certain Fridays throughout the rest of 2025 and into the New Year, the TED Fellows Program supports a network of global innovators and we are so excited to share their work with you today. We'd love for you to meet protein engineer, designer and TED fellow Cesar Ramirez Sarmiento. What if we could take one of nature's fundamental biological building blocks, proteins, and redesign them to tackle some of humanity's biggest challenges? Cesar's lab is based in Santiago, Chile, and it uses AI to design new proteins with both therapeutic and environmental applications. His creative approach to protein design and AI shows why Latin America is emerging as such a leader in this space and why we should look to enzymes for everything from breaking down pet plastics to developing new healthcare systems solutions. After we hear from Cesar, stick around for his conversation with TED Fellows program director Lily James Olds. It's coming up.
- [03:42]
Cesar Ramirez Sarmiento
My name is Cesar Mezarmento. I'm based in Santiago, Chile. I'm a protein engineer and designer.
- [03:48]
Proteins are macromolecules, which are composed of amino acids. They are made of 20 different types of amino acids. They are represented by letters. So you can imagine an alpha Alphabet of amino acids. And you can imagine that these amino acids are connected to each other like beads on a string. And so that allows for them to come together in different geometries. And so they get a shape, they get a three dimensional structure that allows for them to dictate their functions. We have many different proteins with many different shapes that actually perform different biological functions.
- [04:21]
In cells.
- [04:22]
They allow us to digest food, they. They allow us to transport ions for electrical signals to go through neurons. They allow for the expression of different genes that regulate how our cells or how our body responds. Proteins are the workhorse of cells. They are like a toolbox for cells to do whatever they have to do. Proteins have been evolving for millions of years for performing functions that are important for cellular life. They have been perfected by nature to.
- [04:49]
Do what they do now.
- [04:50]
But when it comes to problems that are important for humankind, like plastic contamination, carbon dioxide, problems in health, we want.
- [04:58]
To make them better.
- [05:00]
We just don't have a thousand years to wait for it.
- [05:03]
We have to do it now.
- [05:05]
Protein engineering, in short, it's asking yourself if you can change the amino acid composition of your protein. And by doing so, if you can get improvements in some properties of that.
- [05:17]
Protein, we can use different tools for.
- [05:19]
That, we can use experimental approaches, we can use computational approaches. But overall, what they are doing is that they are changing this sequence of amino acids that compose proteins in order.
- [05:30]
To improve these properties.
- [05:32]
This is like giving nature a little push and that's where the use of artificial intelligence comes in. In the last five years, we have seen breakthroughs in artificial intelligence for designing proteins that we never imagined. They allow us for designing new protein structures, new protein shapes that encode bespoke functions for solving all types of problems. Before the advent of AI, the success rate for protein design was about 1% or less, which means if you created 100 proteins with 100 different sequences, maybe one of them will work. Now, with the advent of AI, we see about 10 to 20%. So if you now take your hundred sequences that you generated in the computer, about 20 of them will actually have the desired activity, and some of them will be actually better than the input sequences of the protein interest that you're working with. When I was a kid, I was interested in arts because it was allowing for a space for creativity. But then when I was in high school, I opted for science because I saw that I could provide much more for the benefit of society by pursuing science instead of arts in my case. But I think both disciplines are actually playgrounds for creativity for science. Artificial intelligence is another tool for coming with creative solutions for different problems. My dream future for protein engineering is that we have a strong community of protein engineers and designers in Latin America so that we can create solutions for problems that are specific to our countries. We are usually not fully aware of the advances of the use of artificial intelligence for protein engineering and design that is happening in other parts of the world. But at the same time, we have many people that are interested in creating new proteins. And so the idea of working in Chile is that we can actually create a critical mass of scientists that can.
- [07:23]
Work on these problems.
- [07:24]
We are actually working on how to educate the next generation of scientists from Latin American how to use these tools. I always had this belief that we had to come together to try to do something bigger than what we can do as individuals. We can think about other compositions of nature that we haven't seen before. In the case of proteins, we can navigate untapped terrain that nature hasn't explored yet. We can navigate through those landscapes of different protein structures, different protein sequences, and see whether those spaces that contain these protein structures and sequences are actually good for resolving the issues that are the most pressing problems for humankind.
- [08:09]
Elise Hu
And now a special conversation between Cesar and Ted Fellows program director Lily James Olds. Coming up right after the break. Today's episode is brought to you by Wayfair. With the holidays approaching, I'm already thinking about getting my house ready for guests and family gatherings. And Wayfair is my go to for making it all happen. I recently gave my kitchen a much needed upgrade with Wayfair's Non Slip kitchen mats. Got a colorful outdoor rug for entertaining. Everyone loves it, and I even snagged a cute little mirror vanity for my daughter. Everything arrived quickly with free delivery, and these pieces have made my spaces feel more functional and ready for the season ahead. Whether you're decorating with trees and wreaths, upgrading your kitchen essentials for those big holiday meals, or making sure your guest room is cozy and ready for guests, Wayfair has everything you need in one convenient place. There's something for every style and every budget with free delivery. Even on the big stuff like furniture and dining tables. Get organized, refreshed and ready for the holidays. For way less, head to Wayfair.com right now to shop all things home. That's W a Y F A I R.com Wayfair Every style, every home this episode is sponsored by Peloton. When I work out, I want to feel motivated and challenged, but sometimes I get bogged down with details like choosing the right weights or correcting my form. With the new Peloton Cross Training Tread Plus, I don't have to worry about that. Powered by Peloton iq, the Peloton Cross Training Tread plus offers endless ways to move and intelligent strength coaching that counts your reps, corrects your form and suggests weights so you get stronger skills, safer and smarter. With its swivel screen, you can go from running to strength or Pilates in one smooth spin, and it personalizes your journey with personalized plans. Peloton IQ builds a workout roadmap around your goals and energy so you stay motivated, not just today, but for the long run. So let yourself run, lift, sculpt, push and go explore the new Peloton Cross Training Tread plus at one Peloton.
- [10:21]
Lily James Olds
Hi Cesar.
- [10:22]
Cesar Ramirez Sarmiento
Hey, how are you doing?
- [10:23]
Lily James Olds
Welcome.
- [10:24]
Cesar Ramirez Sarmiento
Thanks.
- [10:24]
Lily James Olds
I'm so excited to talk to you today.
- [10:26]
Cesar Ramirez Sarmiento
Me too. Very excited to talk about different things today. Yeah.
- [10:29]
Lily James Olds
Wait, can you tell me where are you right now?
- [10:31]
Cesar Ramirez Sarmiento
Yeah, I'm in Louisville in Kentucky. I've been four days into a festival called Louder Than Life in which one of my favorite metal bands have played.
- [10:42]
Lily James Olds
So incredible. What's been the highlight so far?
- [10:46]
Cesar Ramirez Sarmiento
For me personally, it was a sleep token. I've seen them live once before in Germany and now I had the chance to see them again. They released a new album this year and they have. Yeah, they have a huge fan base right now. They're exploding and they're like a really Cool show to see.
- [11:02]
Capital One Bank Guy
Dude.
- [11:02]
Lily James Olds
These images from Sleep Token look insane. I'm looking at the photo, I'm, like, fascinated.
- [11:10]
Cesar Ramirez Sarmiento
Yeah, they're good.
- [11:11]
Lily James Olds
Okay, I got to listen. This is, like, pretty epic.
- [11:14]
Cesar Ramirez Sarmiento
Yeah. I mean, something that is very interesting about Sleep Token is that they combine different music genres into, like, one piece, right? They combine from, like, hip hop and jazz and soul and R and B and metal and deathcore. It's like everything just mixed into one piece of music. And I think of the work that we do in the lab and our collaborations with other people from my country and also from other countries as something similar that we're trying to put a lot of effort into combining different things to think out of the box and do something different from what we have done in the past, which has been only learning about proteins and then characterizing them. Now we're thinking more about, oh, what if we put this protein in a cell and then we do whatever we were thinking about doing with just proteins. Now we do it with, like, living cells, and we provide a solution for that.
- [12:09]
Lily James Olds
That's amazing. So you talk about how using AI for protein engineering is, like, I like how you say, giving nature a little push, you know, speeding up the process. Can you give me one or two concrete examples where AI engineered proteins are being used to help solve a problem and what impact they're having?
- [12:31]
Cesar Ramirez Sarmiento
Yeah, actually, one of the things that we were thinking about a lot with one of my colleagues in Chile about how to create new proteins to put them into cells that are very resilient to conditions in mining so that we can use them for bioleaching, which is like, try to recover different minerals using biotechnological solutions. And those are kind of the things that it's like, try to combine very disparate mineral scientific endeavors into one piece, and then try to try to see if that works or not. I think one of the cases that we're seeing a lot of impact right now is elimination of pollutants from the environment or trying to develop technologies to do so. And so there's a few companies that are working now on degrading plastic. These proteins that perform chemical reactions are called enzymes. And enzyme design is a problem of its own that is, like, very difficult to tackle. But there's one company in France and there's another company in China that are working on developing, with the use of AI, different enzymes that can actually degrade different types of plastics. And the idea behind it is that we are then using that plastic as a feedstock for creating new plastic afterwards. So the enzymes, what they will do is they will decompose the plastic into small molecules that you can use them for making new plastic afterwards, in the best scenario, will be like an infinite recycling process, and that will be great for humanity.
- [14:01]
Lily James Olds
And how does it work exactly? Can you tell us a few more details?
- [14:06]
Cesar Ramirez Sarmiento
So biological information goes from gene, which is on any living cell's genome. So that's DNA. And DNA encodes proteins. So we go from DNA to proteins. What you do in the computer is that you go from protein back to DNA. So you have different scenarios, and for them, you have different ways of working with them. And so the idea is that you can train artificial intelligence models on this information about the sequence of a protein, so the sequence of amino acids that compose a protein. Or you can train models on the structures of proteins, or you can train them on both. And then in the computer, after, like, a few days or weeks of work, you will have a set of different sequences that will encode these structures or these different protein functions. And then what you do after that is that you backtrack those designs from protein information into DNA information. So another form of Alphabet. And then you purchase those genes from these companies that synthesize your genes and then put them into different bacterial or animal cells for expression of these proteins, and then testing them out in the lab. And hopefully afterwards, you will test them out in, like, real cases, scenarios such as pilot plant for, like, plastic degradation, or in animal models for testing for, like, how to cure a disease.
- [15:29]
Lily James Olds
That's so wild and futuristic. To someone like me, who is not doing this every day in a lab, I'm thinking about a conversation we had before Cesar, where you spoke about kind of being inspired by snails and being inspired by natural processes and then putting that into your work in the lab.
- [15:51]
Cesar Ramirez Sarmiento
Yeah, yeah. That was kind of a funny thing that happened. When I was younger, I think maybe I was, like, 8 years old or something like that. My mom, she had some, like, plastic pottery for plants that she was, like, growing in the garden. And she said that the snails were eating through them. I was like, there's no way that that can happen. But the idea remained there for, like, a long time. I was, like, thinking, oh, maybe it's possible. But I just remembered that memory, right? And then when I was, like, in university, I was actually learning about biochemistry, like, learning about, like, proteins and enzymes and all of these things. And then we had a class about enzymes and how they perform, like, different chemical reactions. And one friend of mine said, oh, what if they degrade plastics and I was like, well, that doesn't exist. But little did I know that enzymes that could degrade plastics were being discovered. So the first one was like in 2003 or something like that. So that turned into my research topic when I became a professor. So it's kind of a cool origin story, I would call it.
- [17:01]
Lily James Olds
Yeah, I love that so much. I remember that with snails in the backyard as well. I'm curious, is there a particular local challenge in Chile or Latin America that you think protein engineering is especially well suited to tackle?
- [17:17]
Cesar Ramirez Sarmiento
Yeah, I mean, there's a few. So we have a huge fishing industry, right. And that fishing industry for some of the crustaceans that we are like extracting from the sea, a lot of it's not consumable, a lot of it's waste. And then almost all of the technologies for reutilizing those waste from crustaceans are typically treated with very harsh chemicals. And so trying to develop new technologies using enzymes for achieving the same result, which is like treating these waste for creating fertilizers or creating other types of solutions that can be used afterwards. But instead of using chemicals, using enzymes that will perform the same chemical reactions, but it will be like environmentally friendly because you're using a biological mean for that. We have been discussing with a few colleagues in Chile that we can try to pursue.
- [18:15]
Lily James Olds
And what's a new protein designer structure that you are really excited about right now and why? And what will it help to change or make better, do you think?
- [18:25]
Cesar Ramirez Sarmiento
Oh, I'm very excited about Chris Balz, another TED fellow. His company AI Proteins. And what they're developing in his company is that this very, very tiny proteins, very few amino acids, right? When you make them too short, they don't fold into like a shape. Imagine like if you had like a. A piece of rug and you want to fold it. If it's too short, you cannot fold it, right? But if you had like a piece that is long enough, then you can fold it. So proteins also fold upon themselves. And so they're making this very, very tiny proteins that actually fold upon themselves. So they have a shape. And that shape is complementary to different target cells that have proteins that are involved in cellular processes that are related to different diseases that can go from like different allergic reactions to even like treatments for cancer. So the idea is to develop like these very, very tiny proteins that you can use as a pharmaceutical, as a drug, and that will be a better solution than developing different chemical compounds that do not offer the same capabilities that these proteins have. So I'm really looking forward to see what they do with it.
- [19:35]
Lily James Olds
The advances that I've learned about from you are just so incredible. I'm. I'm curious with all of these examples you're giving, and how much AI is making protein design more successful? Where do you see the field of protein design in three to five years from now? Like, what do you think will be possible? You've outlined a little bit of that, but, like, what does that future look like in your best imagination?
- [20:01]
Cesar Ramirez Sarmiento
Yeah, that's an interesting question. So I think that I'm seeing a lot of advances right now in making new enzymes. So, enzymes are very difficult to make. They have very specific sites on the protein surface. So if you imagine that you have a sphere as a protein, then they have a little hole on the surface that is called the active site. And the chemical reaction actually happens on that side and that side alone, which means that there has to be very specific amino acids from your protein in very specific positions. So the methods that we had a year ago were pretty bad at the enzyme design. So before we will take an enzyme that we know it has some activity for some thing that we wanted to do. Like, there's a lot of enzymes that do plastic degradation. So we will improve the sequence, but we will never change the structure. But nowadays there's a lot of methods that actually can afford that. And so the idea is that you can create new structures that have never seen before in nature of enzymes, of new enzymes, and that allows for thinking about new chemical reactions that we can create from scratch. So that's very exciting. And I think that the field is moving forward very fast towards developing these new enzymes for new chemical reactions.
- [21:15]
Lily James Olds
I think the place that my mind, and I'm sure many others go is like, what are the risks and the dangers and unintended consequences of designing proteins that nature hasn't made before? Is this something that you're thinking about?
- [21:31]
Cesar Ramirez Sarmiento
Yeah, I mean, a lot of people talk a lot about the, the guardrails that we need for different AI technologies. So the risk with all AI technologies is their dual use. So you can use them for benefits or you can use them for harmful impact. So viruses are composed primarily of proteins, and they infect ourselves with all of these AI architectures for protein design. And you can think that somebody can take a given virus and then can use these AI models for protein design to improve their transmissibility or their infection rate. So those are like harmful decisions. But fortunately, there have been different approaches from governments and also from companies to.
- [22:23]
Try to assess the risk of these.
- [22:26]
Models with different evaluations and try then to make sense of what will be the risk that we can have when releasing these models to the public.
- [22:38]
Lily James Olds
Just to go a step further, how do we regulate it? I mean, obviously regulation always lags behind innovation. But I'm just curious, can you speak to the current relationship between your work and the policy and protections in place? And what do you hope this relationship will look like as this technology continues to grow that both allows for the innovation that is obviously creating the possibilities for incredible problem solving for humanity and also those dangers that you're touching on.
- [23:08]
Cesar Ramirez Sarmiento
So a bunch of scientists, including myself and other like very well known scientists in the realm of artificial intelligence for like everything about biology, not only about protein designs, signed some guidelines that were called responsible AI for biodesign that indicate that we will do significant efforts to identify risk in the different models that we develop for different types of bio design using artificial intelligence, and then try to indicate those risks whenever we release the models or try to do what people call unlearning, which is try to make models to somehow not capture this like, harmful potential when you release them to the public. For now, you still need like an expert scientist because they are not very easy to use. But if you combine them with these large language models that allow for having a conversation with your computer without having the expertise for creating something. So the risk over there is that any person can in principle ask to, for example, to one of these language models, can you please create a very harmful biological thing? Both the UK and the US and also the European Union have AI safety institutes. And what they do is that they evaluate the risk of using these different technologies. And so they have these different thresholds for determining whether it's a very high risk and we have to do something about it or whether it's very low. And then we do have to keep an eye on it, but without oversight.
- [24:48]
Lily James Olds
Yeah, I mean, obviously so much work still to be done, but it's always comforting to hear the things that are in place in terms of that kind of thinking and rigor. I guess that leads me to think also, you know, things are shifting so much obviously right now in the global landscape of science. You know, recent policy changes in the US around climate science and otherwise. The example that you just gave of, you know, who needs to be doing this work in terms of regulation around AI. Do you see this as an opportunity for other countries to kind of step in?
- [25:24]
Cesar Ramirez Sarmiento
I mean, I think, yeah, there's an opportunity for other countries to lead it. There's Efforts. I know in Europe, Denmark is putting a lot of funding into AI for biodesign. The UK is also investing a lot of funding into that. There's efforts, at least in Latin America, to also step on these things and try to take the lead. So my country, actually Chile, is leading for a while an initiative to asserting the risk and the ethical usage of artificial intelligence for different purposes. And so there is an opportunity for using artificial intelligence for protein design methods in the country and be like a leading country in Latin America for that. But yeah, since the youth has been experiencing some changes in the last year, yeah, there's a lot of countries that have been like, stepping up and trying to take the lead in improving this.
- [26:18]
Lily James Olds
Okay, I'd love to touch on creativity for a minute and the relationship between art and science a little bit, because I know it's something that's important to you. As you know, my background is also in the arts in theater, directing and film. And I'm curious, can you tell everyone a little bit about your background in the arts?
- [26:37]
Cesar Ramirez Sarmiento
CESAR I think that arts and science have, have been always on my mind. When I was seven, I had the unfortunate reality of my dad. That's, in a way. And like, after that, I remember that in high school I kind of struggled a little bit. So my mom decided to put me into a lot of classes outside primary school and high school, which will be a lot of arts. So the first thing that I did was to learn how to do oil on canvas when I was like 8 or 9. And yeah, I did for. I did that for several years until I was like 15 or something like that. I also started, like, learning how to play the guitar by that time I started also doing acting in high school. And so for me, like, arts and science are like huge spaces for creativity. You can try to push the boundaries of what you can do, expand your horizons in terms of, like, what you can create. Arts and science, I see them as like, similar programs for, like, exploring those boundaries in creativity and talking about proteins, like, between scientists is like, kind of easy, right? But it's very complex for the citizenship. And so I've been thinking a lot of that. Arts can be a very powerful tool for actually expressing what these very complex topics are. So I've been thinking about which artistic renditions can actually provide an understanding of what a protein is and what they do. I think that by connecting art and science together, you can push the boundaries even further.
- [28:26]
Lily James Olds
I love that. I think that's so fascinating. Okay, my last question is just what is something you're really scared of right now and what is something that's giving you hope?
- [28:37]
Cesar Ramirez Sarmiento
I don't know. I think that after the pandemic I'm always scared about, oh, what's going to come next? Right. So like, is there going to be another pandemic like that and how are we going to respond to that? Instead of being concerned about our capacity to respond to things, I'm more concerned about human behavior, which is we're very forgetful and we might forget that we were, at least in our case in Chile, we were in quarantine for a while and I don't want to be in that situation again. What I'm hopeful for is that there's a lot of investment and interest also from scientists to work on solutions. Biotechnological solutions for combating climate change and plastic degradation is just one example. But there's a lot of efforts for try to eliminate greenhouse gases. We know that there are some protein based solutions and also some cell based solutions and there's a lot of interest for investing on them. So I'm very hopeful that in the future and actually in the near future we will see a lot of startup biotechs that are working on climate change and successfully. So that's going to be great.
- [29:50]
Lily James Olds
That's really exciting. Well, thank you. As always, this has been a really fascinating and energizing conversation. So thanks so much Cesar.
- [29:59]
Cesar Ramirez Sarmiento
Happy to be here.
- [30:04]
Elise Hu
That was Cesar Ramirez Sarmiento, a TED 2025 fellow. To learn more about the TED Fellows program and watch all the TED Fellows films, just go to fellow and that's it for today. This episode was produced by Lucy Little, edited by Alejandra Salazar and fact checked by Eva Dasher. The audio you heard at the top comes from the short film made by Divya Gadangi and Owen McLean. Story edited by Corey Hajim and produced by Ian Lowe. Video Production manager is Searing Dolma. Additional support from Lily James Olds, Leone Horster and Allegra Pearl. TED Talks Daily is part of the TED Audio Collective. Our team includes Martha Estefanos, Oliver Friedman, Brian Greene, Lucy Little and Tonsika Songmarnivong. Additional support from Emma Tobner and Daniela Balaurazo. I'm Elise Hu. I'll be back tomorrow with a fresh idea for your feed. Thanks for listening. This episode is sponsored by the new all electric Toyota bz. A common myth is that switching to an electric vehicle means sacrificing capability or performance. The Toyota BZ proves otherwise. With available all wheel drive, you can get 338 horsepower and near instant torque for a powerful responsive drive going 0-60 mph in just a 4.9 seconds. And with an EPA estimated range of up to 314 miles on front wheel drive models, you can go farther between charges and make the most of every drive. Learn more@toyota.com bz that's T O Y O-T A.com bz the new all electric bz Toyota let's go Places Banking with.
- [31:59]
Capital One Bank Guy
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