César Ramírez Sarmiento

different allergic reactions to even like treatments for cancer so the idea is to develop like this very very tiny proteins that you can use as a pharmaceutical as a drug and that would be a better solution that 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

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 like a sphere as a protein, then they have like a little hole on the surface that is called the active site.

And the chemical reaction actually happens in that site and that site 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 like a year ago were like pretty bad at the enzyme design.

And 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.

Yeah, I mean, a lot of people talk a lot about 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 our cells.

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 hard-fought decisions

But fortunately, there have been different approaches from governments and also from companies to try to assess the risk of these 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.

So a bunch of scientists, including myself and other very well-known scientists in the realm of artificial intelligence for 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 biodesign 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 handful potential when you release them to the public.

For now, you still need 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 like different thresholds for determining whether it's a very high risk and we have to do something about it or it's like very low.

And then we do have to keep an eye on it, but without oversight.

I mean, I think, yeah, there is 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 like step on these things and try to take the lead.

So my country, actually, Chile is like leading for a while.

an initiative to ascertain 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 US 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 protein design.

My name is César Ramírez Sarmiento.

I'm based in Santiago, Chile.

I think that arts and science have been always on my mind.

When I was seven, I had the unfortunate reality of my dad passing away.

And after that, I remember that in high school, I kind of struggled a little bit.

So my mom decided to...

I'm a protein engineer and designer.

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 eight or nine.

And yeah, 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.

Proteins are macromolecules which are composed of amino acids.

And so for me, arts and science are huge spaces for creativity.

You can try to push the boundaries of what you can do, expand your horizons in terms of what you can create.

Arts and science, I see them as similar programs for 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

They are made of 20 different types of amino acids.

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.

I love that.

They are represented by letters.

I don't know.

I think that after the pandemic, I'm always scared about, oh, what's going to come next, right?

So 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 like we're very forgetful.

So you can imagine an alphabet of amino acids.

And we might forget that we were like, 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.

So 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 you can imagine that these amino acids are connected to each other like beads on a string.

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.

Happy to be here.

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 in cells.

They allow us to digest food.

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 do what they do now.

But when it comes to problems that are important for humankind, like plastic contamination, carbon dioxide, problems in health, we want to make them better.

We just don't have a thousand years to wait for it.

We have to do it now.

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 protein.

We can use different tools for that.

We can use experimental approaches.

We can use computational approaches.

But overall, what they're doing is that they are changing this sequence of amino acids that compose proteins in order to improve these properties.

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 would work.

Now with the advent of AI, we see about 10 to 20%.

So if you now take your 100 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 of 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 work on these problems.

We are actually working on how to educate the next generation of scientists from Latin America on 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.

Hey, how are you doing?

Thanks.

Me too.

Very excited to talk about different things today.

Yeah.

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.

For me personally, it was a sleep talking.

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 a huge fan base right now.

They're exploding and they're like a really cool show to see.

Yeah, I mean, something that's 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&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 like 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 like 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.

Yeah, actually, one of the things that we were thinking about a lot with one of my colleagues in Chile is 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 trying to recover different minerals using biotechnological solutions.

And those are kind of the things that it's like...

Try to combine very disparate scientific endeavors into one piece and then 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 in the 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, and these proteins that perform chemical reactions are called enzymes.

And enzyme design is a problem of its own that is 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 like 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 would be like great for humanity and how does it work exactly can you tell us a few more details

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 brain 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 real-case scenarios, such as a pilot plan for plastic degradation

in animal models for testing for like how to cure a disease.

Yeah.

Yeah, that was kind of a funny thing that happened when I was younger.

I think maybe I was like...

eight 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.

Yeah.

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're 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 like very harsh chemicals and so trying to develop new technologies using enzymes for achieving the same result which is like treating these ways for like 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 like a biological mean for that.

We have been discussing with a few colleagues in Chile that we can try to pursue.

I'm very excited about Chris Boltz, another TED fellow, his company, AI Proteins.

And what they're developing in his company is that these 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 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 have like a piece that is long enough, then you can fold it.

So proteins also fold upon themselves.

And so they're making these very, very tiny proteins that actually fold upon themselves so they have 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