Jesse Gray

Jay found a Star Trek clip and in this clip kind of gives you a taste of the medicine of the future, of what it could be. And in this clip, it’s a it’s a clip where the executive team of Star Trek goes back to the past. The doctor Bones runs into this patient that’s kind of struggling and he’s what what’s wrong? And she says, kidney dialysis, dialysis. My God, what is this, the dark ages? He pulls a pill out of his pocket and he says, “here, take this and if you have any problems, just call me.” And then the scene continues and they’re running around the hospital. And when they’re running back, he goes by and she says, thank you, doctor, I grew a new kidney.

Amity Addrisi

Science fiction is only fiction until it becomes science. But a pill to regrow an entire kidney? We’re still a long way off.

Liz Dueweke
This is, however what scientists at the Seattle Hub for Synthetic Biology, or Seattle HUB are investigating how to bend biology, designing and controlling living cells to revolutionize our understanding of illness, disease and ultimately discover new treatments. I’m Liz Dueweke Dwicky.

Amity Addrisi

I’m Amity Addrisi and this is Lab Notes.

Jay Shendure
The mission of C hub is to make cells programmable we want to program them to be able to record their own histories. We want to program them to be able to act autonomously, and we want those programs to operate with the same level of predictability and reliability that we get from software.

Liz Dueweke

That’s Jay Shendure, lead scientific director for the Seattle Hub for Synthetic Biology, or Seattle Hub, a collaboration between the Allen Institute, University of Washington and Chan Zuckerberg Initiative. Its goal is to track and record the entire living histories of individual cells at a molecular level.

Jesse Gray
Another way to put it would be like, imagine a computer without a hard drive. It would be tough, right? And but if you’re programming the cell, it’s kind of the same thing. You’re going to need that cell to be able to keep track of things and store information about what happened. And so you got to be able to use the genome like a hard drive.

Amity Addrisi
Scientists at Seattle Hub are genetically modifying cells to record their own experiences in their DNA. This includes how they react to their environment and the genetic changes this may cause. Stephen Quake, former head of science at the Chan Zuckerberg Initiative, says the core of synthetic biology lies in the ability to customize biologic systems.

Stephen Quake

So synthetic biology is an effort to bring engineering principles and tools to biology to actually not just take what nature has given you, but to actively design biological systems to do things that you want. We believe that we are on the precipice of a revolution in the biomedical sciences where we are increasingly going from a paradigm where we’re primarily trying to understand biology to 1 where we’re trying to redirect biology.

Amity Addrisi

So where are we on this transformative path? Jay Shendure offers a fascinating perspective comparing our current position to the dawn of the industrial age.

Jay Shendure

You could argue that we’re in the the steam engine era, right? And the possibilities that lie ahead are enormous, right? If we can kind of enable this to go to the next level. Once you understand the basic principles of electricity, you can design circuits, etcetera, right? So, you know, are we at a similar tipping point where we can move from investigation to to engineering, so to speak, with all the possibilities that opens up?

Liz Dueweke

Jesse Gray, executive director of Seattle Hubs Strategy and Platform, says finding our way to the medicine of the future will require us to change our fundamental thinking about biology.

Jesse Gray

Today, when we even try to design just basic pieces of DNA, we’re we’re usually copying fragments from here and there and we’re usually trying to change as few things as we can because we don’t really understand the rules. And so it’s a different way of thinking to try to build entire DNA sequences that make cells behave in new ways. And, and it feels like the very beginning of it. And that’s what’s so exciting here.

Liz Dueweke
According to Stephen Quake, the potential applications and benefits of synthetic biology for human health are almost limitless.

Stephen Quake

Creating engineered cells that will come in and help cure disease in our bodies and help tell us what’s going on. And so the span for human health is just enormous. We’ve seen on the human health side, things like the cellular therapies, our T cells, those sorts of things. That is a form of synthetic biology where cells have been taking out our person’s body, reengineered to attack the cancer and then put back in. And that’s already saving lives. I think, you know, those types of cellular therapies were just at the dawn, at the very beginning of them. They’re relatively speaking, quite crude. And, you know, you look at the sorts of things that are going on in academic research in cellular biology, and you can see that there’s so much potential to do bigger, more complicated, more impactful things beyond cancer to other diseases. I think it’s it’s got a very bright future.

Amity Addrisi
Past studying a cell with a high-powered microscope meant killing the tissue, but synthetic biology means moving beyond what we can see with microscopes into the unseen world of living tissues. Imagine being able to capture live data from millions of cells, like how their DNA is changing in response to their environment, and not just in a Petri dish, but within a whole organism.

Jay Shendure

We’re really good at measuring biology when we can see it right? So we’ve got amazing microscopes, we can label proteins or other things of interest with fluorescence, and we can watch what happens over time. So that, that’s great, but when you can’t see it, right, if it’s, if it’s inside a tissue or, or inside a womb or whatever it is, our options are more limited. So the paradigm here is can we leverage the fact that the genome DNA is effectively a digital substrate to be where we make recordings, but also where we program our recorder.

Liz Dueweke

This is done using technology known as a DNA typewriter. Like a traditional typewriter laying down letters one at a time from left to right to spell out words and sentences, the DNA typewriter lays down molecular barcodes on a strand of DNA that correspond to events that happened to a cell, such as how it responded to a drug or when it began to divide.  This sequence of barcodes creates a living history, a chronological record of what happened to that cell.

Jay Shendure

The little snippets of DNA that we write can be assigned to meanings. So they can, they’re not random necessarily, but they can be triggered by certain biological events. And once they are written, they’re stable. So if that cell then divides and as a daughter cell, it passes on its recordings to that daughter and if that daughter experiences more biology and makes it’s more recordings, that passes those on to their daughter and so on and so forth.

Liz Dueweke

The cellular recording technology being developed at Seattle Hub allows scientists to monitor and capture biological information in real time.

Stephen Quake

I’m incredibly thrilled with how things are going at C Hub. You know, it’s 1st at one level, just organizationally awesome to see how the Allen Institute and UW are kind of meshing together. And then the work around engineering the cellular recorder Jay’s been working on, you know, you can see they’re just in the brink of being able to put into an animal and I just can’t wait. I’m very excited about that.

Amity Addrisi
The goal is to make sure all the pieces of this new technology work reliably while building full versions that can be easily used in lab cells and animal models

Jay Shendure

So driving to completion in terms of distributable products as well as data is a key goal. And then I I think a second key goal is starting to think beyond simply recording or perturbing and into how do we not only engineer cells or organisms in a way that will tell us what happened? How do we also get them to redirect their futures?

Amity Addrisi

Part of that plan is to create a special mouse called a recorder mouse, which will help them test and use their new biologic recording technology in a living animal.

Jay Shendure

So mice and zebrafish are phenomenal models for human biology. An enormous proportion of what we know about human biology, probably the majority, comes from our study of model organisms.

Liz Dueweke
Researchers at Seattle Hub are also pioneering the use of artificial intelligence to model and understand biology. A key mission is creating a virtual cell, an AI model of a cell that captures in molecular detail what the cell is doing and what happens when you disturb it. Both Jay Schinderer and Stephen Quake believe AI will change the face of science.

Jay Shendure

One of the core beliefs of our team, which, you know, we share with with many other groups in the current moment, is that there is an opportunity to build AI models that capture broad swaths of human biology.

Stephen Quake
You know, right now biology is 90% experimental and 10% computational. You, you don’t have like the equations of biology like you do for physics that allow you to predict what’s going to happen. And we think AI is going to provide a route to something like that, where in 10 years biology could maybe be 90% computational and 10% experimental.

Amity Addrisi

Other forms of artificial intelligence are already incredibly useful in science. AI is used for literature synthesis. It’s like having a colleague who can quickly read and summarize huge amounts of research. And it’s absolutely necessary for making sense of very complex and massive data sets that humans can’t easily process.

Stephen Quake
It’s a tool that lets you understand the structure of very complex data in ways that the human brain cannot. And so it provides insight like human brain is good at looking at 2 dimensions and three dimensions, but a lot of this data we look at, for example, from the cell atlas that that Cole is generating is 20,000 dimensional data. And like our brains explode at that. But the AI is very good at helping us understand the relationships in that very complicated data set. And those tools are going to continue to get more powerful.

Amity Addrisi

But Jesse explains that unlike ChatGPT, which uses the entire Internet, synthetic biology requires specific data on what each gene does.

Jesse Gray
The internet’s not going to work. We, we actually need something like this, this kind of data where what, what is each gene actually doing? In some sense, you need to know what each gene is doing if you’re going to be able to design a program for a cell or an Organism to boldly go where no man has gone before.

Liz Dueweke
So how close are we to that Star Trek future? Jay and Jesse say the importance of investing in science is paramount and the timeline for success depends on us. And Jay believes we’re at a critical moment.

Jay Shendure
I think if you zoom way out, one is hard pressed to identify any place or moment in human history when so much has been successfully invested in scientific progress. And at least to me, the fruits of that are overflowing.

Amity Addrisi

The cutting-edge Science of Seattle hub is paving the way for a transformative future bridging the gap between science fiction and reality.

Jesse Gray

It’s primarily about mastery. Like, let’s, let’s bend biology to our will and let’s make it do things. Let’s wrangle it and the and all the puzzles that that entails.

Amity Addrisi

By taming and controlling biology, we may be able to reshape how we diagnose and treat disease. I’m Amity Addrisi

Liz Dueweke

and I’m Liz Dueweke Dwicki.

Amity Addrisi
Thank you to Stephen Quake, Jay Shendure, and Jesse Gray for sharing their incredible insights on the Seattle hub for synthetic biology.

Liz Dueweke
This episode of Lab Notes was produced by Amity Addrisi, Peter Kim, Liz Dueweke Dwicki and Rob Piercy.

Jesse Gray

Jay found a Star Trek clip and in this clip kind of gives you a taste of the medicine of the future, of what it could be. And in this clip, it’s a it’s a clip where the executive team of Star Trek goes back to the past. The doctor Bones runs into this patient that’s kind of struggling and he’s what what’s wrong? And she says, kidney dialysis, dialysis. My God, what is this, the dark ages? He pulls a pill out of his pocket and he says, “here, take this and if you have any problems, just call me.” And then the scene continues and they’re running around the hospital. And when they’re running back, he goes by and she says, thank you, doctor, I grew a new kidney.

Amity Addrisi

Science fiction is only fiction until it becomes science. But a pill to regrow an entire kidney? We’re still a long way off.

Liz Dueweke
This is, however what scientists at the Seattle Hub for Synthetic Biology, or Seattle HUB are investigating how to bend biology, designing and controlling living cells to revolutionize our understanding of illness, disease and ultimately discover new treatments. I’m Liz Dueweke Dwicky.

Amity Addrisi

I’m Amity Addrisi and this is Lab Notes.

Jay Shendure
The mission of C hub is to make cells programmable we want to program them to be able to record their own histories. We want to program them to be able to act autonomously, and we want those programs to operate with the same level of predictability and reliability that we get from software.

Liz Dueweke

That’s Jay Shendure, lead scientific director for the Seattle Hub for Synthetic Biology, or Seattle Hub, a collaboration between the Allen Institute, University of Washington and Chan Zuckerberg Initiative. Its goal is to track and record the entire living histories of individual cells at a molecular level.

Jesse Gray
Another way to put it would be like, imagine a computer without a hard drive. It would be tough, right? And but if you’re programming the cell, it’s kind of the same thing. You’re going to need that cell to be able to keep track of things and store information about what happened. And so you got to be able to use the genome like a hard drive.

Amity Addrisi
Scientists at Seattle Hub are genetically modifying cells to record their own experiences in their DNA. This includes how they react to their environment and the genetic changes this may cause. Stephen Quake, former head of science at the Chan Zuckerberg Initiative, says the core of synthetic biology lies in the ability to customize biologic systems.

Stephen Quake

So synthetic biology is an effort to bring engineering principles and tools to biology to actually not just take what nature has given you, but to actively design biological systems to do things that you want. We believe that we are on the precipice of a revolution in the biomedical sciences where we are increasingly going from a paradigm where we’re primarily trying to understand biology to 1 where we’re trying to redirect biology.

Amity Addrisi

So where are we on this transformative path? Jay Shendure offers a fascinating perspective comparing our current position to the dawn of the industrial age.

Jay Shendure

You could argue that we’re in the the steam engine era, right? And the possibilities that lie ahead are enormous, right? If we can kind of enable this to go to the next level. Once you understand the basic principles of electricity, you can design circuits, etcetera, right? So, you know, are we at a similar tipping point where we can move from investigation to to engineering, so to speak, with all the possibilities that opens up?

Liz Dueweke

Jesse Gray, executive director of Seattle Hubs Strategy and Platform, says finding our way to the medicine of the future will require us to change our fundamental thinking about biology.

Jesse Gray

Today, when we even try to design just basic pieces of DNA, we’re we’re usually copying fragments from here and there and we’re usually trying to change as few things as we can because we don’t really understand the rules. And so it’s a different way of thinking to try to build entire DNA sequences that make cells behave in new ways. And, and it feels like the very beginning of it. And that’s what’s so exciting here.

Liz Dueweke
According to Stephen Quake, the potential applications and benefits of synthetic biology for human health are almost limitless.

Stephen Quake

Creating engineered cells that will come in and help cure disease in our bodies and help tell us what’s going on. And so the span for human health is just enormous. We’ve seen on the human health side, things like the cellular therapies, our T cells, those sorts of things. That is a form of synthetic biology where cells have been taking out our person’s body, reengineered to attack the cancer and then put back in. And that’s already saving lives. I think, you know, those types of cellular therapies were just at the dawn, at the very beginning of them. They’re relatively speaking, quite crude. And, you know, you look at the sorts of things that are going on in academic research in cellular biology, and you can see that there’s so much potential to do bigger, more complicated, more impactful things beyond cancer to other diseases. I think it’s it’s got a very bright future.

Amity Addrisi
Past studying a cell with a high-powered microscope meant killing the tissue, but synthetic biology means moving beyond what we can see with microscopes into the unseen world of living tissues. Imagine being able to capture live data from millions of cells, like how their DNA is changing in response to their environment, and not just in a Petri dish, but within a whole organism.

Jay Shendure

We’re really good at measuring biology when we can see it right? So we’ve got amazing microscopes, we can label proteins or other things of interest with fluorescence, and we can watch what happens over time. So that, that’s great, but when you can’t see it, right, if it’s, if it’s inside a tissue or, or inside a womb or whatever it is, our options are more limited. So the paradigm here is can we leverage the fact that the genome DNA is effectively a digital substrate to be where we make recordings, but also where we program our recorder.

Liz Dueweke

This is done using technology known as a DNA typewriter. Like a traditional typewriter laying down letters one at a time from left to right to spell out words and sentences, the DNA typewriter lays down molecular barcodes on a strand of DNA that correspond to events that happened to a cell, such as how it responded to a drug or when it began to divide.  This sequence of barcodes creates a living history, a chronological record of what happened to that cell.

Jay Shendure

The little snippets of DNA that we write can be assigned to meanings. So they can, they’re not random necessarily, but they can be triggered by certain biological events. And once they are written, they’re stable. So if that cell then divides and as a daughter cell, it passes on its recordings to that daughter and if that daughter experiences more biology and makes it’s more recordings, that passes those on to their daughter and so on and so forth.

Liz Dueweke

The cellular recording technology being developed at Seattle Hub allows scientists to monitor and capture biological information in real time.

Stephen Quake

I’m incredibly thrilled with how things are going at C Hub. You know, it’s 1st at one level, just organizationally awesome to see how the Allen Institute and UW are kind of meshing together. And then the work around engineering the cellular recorder Jay’s been working on, you know, you can see they’re just in the brink of being able to put into an animal and I just can’t wait. I’m very excited about that.

Amity Addrisi
The goal is to make sure all the pieces of this new technology work reliably while building full versions that can be easily used in lab cells and animal models

Jay Shendure

So driving to completion in terms of distributable products as well as data is a key goal. And then I I think a second key goal is starting to think beyond simply recording or perturbing and into how do we not only engineer cells or organisms in a way that will tell us what happened? How do we also get them to redirect their futures?

Amity Addrisi

Part of that plan is to create a special mouse called a recorder mouse, which will help them test and use their new biologic recording technology in a living animal.

Jay Shendure

So mice and zebrafish are phenomenal models for human biology. An enormous proportion of what we know about human biology, probably the majority, comes from our study of model organisms.

Liz Dueweke
Researchers at Seattle Hub are also pioneering the use of artificial intelligence to model and understand biology. A key mission is creating a virtual cell, an AI model of a cell that captures in molecular detail what the cell is doing and what happens when you disturb it. Both Jay Schinderer and Stephen Quake believe AI will change the face of science.

Jay Shendure

One of the core beliefs of our team, which, you know, we share with with many other groups in the current moment, is that there is an opportunity to build AI models that capture broad swaths of human biology.

Stephen Quake
You know, right now biology is 90% experimental and 10% computational. You, you don’t have like the equations of biology like you do for physics that allow you to predict what’s going to happen. And we think AI is going to provide a route to something like that, where in 10 years biology could maybe be 90% computational and 10% experimental.

Amity Addrisi

Other forms of artificial intelligence are already incredibly useful in science. AI is used for literature synthesis. It’s like having a colleague who can quickly read and summarize huge amounts of research. And it’s absolutely necessary for making sense of very complex and massive data sets that humans can’t easily process.

Stephen Quake
It’s a tool that lets you understand the structure of very complex data in ways that the human brain cannot. And so it provides insight like human brain is good at looking at 2 dimensions and three dimensions, but a lot of this data we look at, for example, from the cell atlas that that Cole is generating is 20,000 dimensional data. And like our brains explode at that. But the AI is very good at helping us understand the relationships in that very complicated data set. And those tools are going to continue to get more powerful.

Amity Addrisi

But Jesse explains that unlike ChatGPT, which uses the entire Internet, synthetic biology requires specific data on what each gene does.

Jesse Gray
The internet’s not going to work. We, we actually need something like this, this kind of data where what, what is each gene actually doing? In some sense, you need to know what each gene is doing if you’re going to be able to design a program for a cell or an Organism to boldly go where no man has gone before.

Liz Dueweke
So how close are we to that Star Trek future? Jay and Jesse say the importance of investing in science is paramount and the timeline for success depends on us. And Jay believes we’re at a critical moment.

Jay Shendure
I think if you zoom way out, one is hard pressed to identify any place or moment in human history when so much has been successfully invested in scientific progress. And at least to me, the fruits of that are overflowing.

Amity Addrisi

The cutting-edge Science of Seattle hub is paving the way for a transformative future bridging the gap between science fiction and reality.

Jesse Gray

It’s primarily about mastery. Like, let’s, let’s bend biology to our will and let’s make it do things. Let’s wrangle it and the and all the puzzles that that entails.

Amity Addrisi

By taming and controlling biology, we may be able to reshape how we diagnose and treat disease. I’m Amity Addrisi

Liz Dueweke

and I’m Liz Dueweke Dwicki.

Amity Addrisi
Thank you to Stephen Quake, Jay Shendure, and Jesse Gray for sharing their incredible insights on the Seattle hub for synthetic biology.

Liz Dueweke
This episode of Lab Notes was produced by Amity Addrisi, Peter Kim, Liz Dueweke Dwicki and Rob Piercy.

Amity Addrisi

For more episodes in Science Research News, visit our website alleninstitute.org.

Liz Dueweke

Thanks for listening.

Amity Addrisi

For more episodes in Science Research News, visit our website alleninstitute.org.

Liz Dueweke

Thanks for listening.