We may be on the cusp of a revolution in medicine, thanks to tools like AlphaFold, the technology for Google DeepMind, which helps scientists predict and see the shapes of thousands of proteins. How does AlphaFold work, what difference is it actually making in science, and what kinds of mysteries could it unlock? Today’s guest is Pushmeet Kohli. He is the head of AI for science at DeepMind. We talk about proteins, why they matter, why they’re challenging, how AlphaFold could accelerate and expand the hunt for miracle drugs, and what tools like AlphaFold tell us about the mystery of the cosmos and our efforts to understand it.
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In the following transcript, Derek and Pushmeet Kohli discuss what gives humans, essentially “bags of water” their humanity.
Derek Thompson: I’m grateful you’re here. I’ve wanted to have this conversation with you for a while, and I would like to start at the highest possible level before we dive into the details of proteins and artificial intelligence and the weird and hopefully wonderful future of AI in medicine. So life. The universe is just a random distribution of atoms in space and some of those atoms form inert rock. And some of those atoms have gotten together and somehow formed entities that live and strive and procreate and fight and laugh and even understand themselves in relation to their environment. And this fact that conscious life emerges from some of the same simple elements that would otherwise be cold rock, might be one of the most profound mysteries of the universe. To you, what is so complicated about life?
Pushmeet Kohli: It’s such a very interesting thing that you and me are having this conversation. And if somebody was to chemically analyze us, we are essentially water. A majority of our body is just water. We are just bags of water floating around. And so what is it that makes me be able to speak what I’m speaking, for you to be able to make sense of it, think about it, rationalize it? And so the magical stuff in this bag of water are these small tiny things called proteins. These are the machines of life. They allow us to see the world. They allow us to reason. They control how energy is transformed in our body.
It governs all the processes of life. And yet there are only 20,000 of these basic building blocks, 20,000 proteins in the human body, and that’s for everyone. So these are the Lego blocks. They’re composed of amino acids and they sort of build every single tissue in our body. And so how does from an embryo, we are able to create such a complex system that can exhibit so many different properties? And how do we go from understanding what these molecules do, how they interact, and how can we explain the behavior that we exhibit? That’s a key grand challenge of life.
Thompson: And to give people a sense of some of these behaviors and functions of proteins that they might’ve heard of. Hemoglobin transports oxygen in red blood cells, insulin regulates blood sugar, collagen provides structure and some tissues. Keratin provides structure to hair and nails and skin. What’s so interesting about proteins is when you look at them up close, as I have in some of my reporting on your work, they look like little balls of string. Like if you cut maybe six inches of string and you rolled it between your fingers and you put it on a flat surface that the string knot sort of loosened a little bit, what you’ve built there is very close to many of the protein structures that I’ve seen. You said that these proteins are built out of very basic stuff and that it’s important to understand the shapes of these proteins. Why does the shape of the protein have such significance?
Kohli: So the shape is so important because it governs the function of those proteins. You gave the example of hemoglobin, right? If there’s mutation in any of these proteins, even a single mutation for instance, can get you a disease like sickle cell anemia. So there are these mutations called missense mutations in your genome, which lead to changes in the proteins that is expressed, and that changes the function of the protein. So it’s really important to understand what is the structure of that protein because it governs, it gives us hints as to what the function would be. And also these proteins interact with other proteins to form larger complexes. And so it’s really important how they geometrically align and interact with each other. And that’s why protein structure prediction has been a grand challenge of biology.
This excerpt was edited for clarity. Listen to the rest of the episode here and follow the Plain English feed on Spotify.
Host: Derek Thompson
Guest: Pushmeet Kohli
Producer: Devon Baroldi
Subscribe: Spotify
