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Welcome to BIOTECH NATION !!! With understandable interviews requiring no background in science, BTN attracts a wide global audience. From everyday people looking for hope in treatments in development, to bioentrepreneurs interested in the experience of their fellow travelers, to venture capitalists looking for possibilities in cutting-edge breakthroughs, to scientists simply interested in the work of others, BioTech Nation is the voice of human endeavor, driving science to new realities for everyone. These interviews are drawn directly from the public radio program, "Tech Nation", which also can be heard in numerous global radio and podcasting venues.
What would you do if you had 1,000,000,000 of dollars and could use it to really make a difference in the world? What would you do? What do you believe in that would really make a difference? While the obvious is to give it to one truly deserving person or organization after another, which is laudable. What about building something that could create solutions in and of itself that could bring innovative groups together to be even more innovative, that could build new databases and even unprecedented computers to solve problems that cannot now be solved.
Dr. Moira Gunn:And that just may make the creation of new medicines faster, less risky, and more effective. And as a result, less expensive. Well, that takes a whole different vision. Today, I speak with doctor Steve Quake, the head of science at the Chan Zuckerberg Initiative, which was founded by Facebook, now meta's Mark Zuckerberg and his wife, doctor Priscilla Chan. And now, doctor Steve Quake.
Dr. Moira Gunn:Well, doctor Quake, welcome to the program.
Dr. Steve Quake:Thanks, Moira. It's great to be here.
Dr. Moira Gunn:Now the Chan Zuckerberg Initiative or CZI, we call it, was founded by Mark Zuckerberg, who we know from Facebook, now Meta, and his wife, doctor Priscilla Chan. And while we also know they committed some 99% of the Facebook slash meta stock to this philanthropic endeavor, Everything from there forward is different than anything I have ever seen. You are the head of science there. This is not just a philanthropy that is giving away money to deserving scientists. This is much more than that.
Dr. Moira Gunn:So start anywhere you would like. What is Chan Zuckerberg trying to achieve and how's it going about it?
Dr. Steve Quake:Well, we have the extraordinary goal of trying to help find, cures, ways to prevent, or ways to manage all human disease over the course of the next 100 years. It's an amazing mission. It's very unusual to be able to think in a 100 year time scale. Very few funding organizations, philanthropies do that, and it's very liberating in some ways, exciting in others, and, it's awesome to be a part of.
Dr. Moira Gunn:Now you've got biohubs. You've got institutes. You've got programs. Let's go there.
Dr. Steve Quake:Yeah. So our approach to philanthropy and implementing this mission is with 3 strategic levers. We call it build, fund, do. Do is doing science, and we founded a number of institutes to do science, including the Biohubs. And we now have Biohubs in San Francisco, Chicago and New York City.
Dr. Steve Quake:We've also started an imaging institute here in Redwood City and funded an institute for artificial intelligence at Harvard University. That's due. Fund is giving grants to support science, and we support the brightest, most creative scientists we can find anywhere in the world. We've given more than a 1,000 grants in our short history in 34 different countries around the world. And that's built an extraordinary community of scientists.
Dr. Steve Quake:And we encourage them to collaborate. We bring them to CZI on a periodic basis, get them to work together and really believe that the whole is greater than the sum of the parts. And finally, build is building open source software to accelerate science. We've got a team of 110 software professionals here at CZI who've been doing amazing things to build software tools to help scientists all over the world do their work faster and more efficiently.
Dr. Moira Gunn:So you were saying you've got Biohub's in San Francisco, Chicago, and New York, an institute, actually in Cambridge, in Boston. Why there? Why those four places?
Dr. Steve Quake:Well, the Boston went at Harvard. Mark and Priscilla went to Harvard and
Dr. Moira Gunn:They know where it is.
Dr. Steve Quake:Very fond and grateful for the experience they had there. Exactly. And they wanted to give back. And so that one was very personal for them. Harvard is, you know, okay.
Dr. Moira Gunn:Yes. I'm just joking.
Dr. Steve Quake:It's a wonderful university with amazing scientists and engineers, and we're very proud to be able to support them. The first Biohub in San Francisco was how I got involved with Marc and Priscilla. I was the founding co president of that. I led it for half a dozen years and, and was able to help recruit and build it. And, you know, it started as a and it is a collaboration between Stanford, UCSF, Berkeley, and the Biohub.
Dr. Steve Quake:We really decided we wanted to partner with the great universities in the Bay Area, and put this together as an opportunity to take on big projects that they wouldn't do on their own. And that's how we made the Cell Atlases, which we'll talk about a little later, I think. And that worked so well. And as I mentioned, collaboration is kind of a hallmark of our philanthropy. We decided to try to see if we could replicate it and capture lightning in a bottle again asking universities to apply to host the next Biohub.
Dr. Steve Quake:And, we required there be at least 3 universities who wanted to work together who were in the same city or geographic area. And we were overwhelmed with the interest, deluged with applications. It was a super challenging and rigorous review process. And out of that, Chicago and New York emerged as our next 2 biohubs. In Chicago, we partnered with Northwestern University of Chicago and University of Illinois.
Dr. Steve Quake:And in New York, we've partnered with Rockefeller, Columbia, and Yale.
Dr. Moira Gunn:Well, this is just another indicator of how unusual it all works. When we first met, we met at the, Lake Nona Impact Forum. And you said, well, you know, what we're trying to do can't be done in conventional environments. Well, this is an indicator. I've never heard of any major effort coming together between 3 universities geographically located.
Dr. Moira Gunn:If you did if you don't hang around, usually you say, I'm gonna find a university just like me, probably not next door. Nope. We want you together. We want everybody to work together to bring all that together. That's just one of those examples, if you will.
Dr. Steve Quake:Oh, yeah. It's been tremendous. And, you know, universities can be quite competitive with each other, especially when they're in the same city because they're competing for faculty, for students, for grants and whatnot. And sometimes they lose sight of the fact that, you know, the whole can be greater than the sum of the parts, and we we've tried to encourage that. And it's been a great success for everybody thus far.
Dr. Moira Gunn:You mentioned the the human cell atlas here. Let's talk about the virtual cell. We need to spend some time here developing this as to where it's going and why it's so important. So let's start. What's the virtual cell?
Dr. Steve Quake:Yeah. This is a project we've launched here at CCI to try to apply the latest advances in artificial intelligence and machine learning to the complexity of biology, and trying to develop models not of language, but of biology. We have spent the last 7, 8 years, really 2 decades of my career when I think about what I was doing before I joined with Mark and Priscilla, developing the technologies and the tools and then the experimental programs to build cell atlases, which are molecular characterizations of all the cell types in the human body. As a short detour here, I'll just say this is very distinct from the genome. The genome is sometimes described as the blueprint of the organism or of the human.
Dr. Steve Quake:It really isn't a blueprint because you can't build a human from just the genome. Every different cell type in your heart, in your brain, in your liver, in your lung, they all have the same genome, but they're very different in what they do as cells. And, right now, there's no way to predict that from the genome, the even the existence of those cell types. So we went and measured it all experimentally, and that was a huge endeavor. It was the first big project to the San Francisco Biohub.
Dr. Steve Quake:It was a giant team science effort involving many professors and even more students, postdocs, and staff. I think in the end, it was 160 authors on the paper. But we did build a rough draft characterization of all the cell types of the human body. And we wanna use that now to teach artificial intelligence models exactly what how those cell types are made, how they're connected to the genome, and how they've evolved, how new cell types can be made for therapies, cellular therapies. We think this could be a tremendous tool.
Dr. Moira Gunn:Now how many cell types are there in the human body?
Dr. Steve Quake:You know, 1,000, I think is the fair number. Most are in the brain. That's the most complicated part. And we're still, as a community, I think, getting to the bottom of the diversity of the brain. But in the rest of the body, I mean, roughly 7, 800.
Dr. Moira Gunn:Just 7, 800. You know? But we're talking about all of the characteristics of them and how they, in fact, interact with all the rest of them. And, of course, all of them are starting from a single cell. So it's amazing.
Dr. Moira Gunn:That's the
Dr. Steve Quake:miracle of biology, isn't it? We all start from a single cell and grow into trillions of cells, and somehow it all works. Apparently.
Dr. Moira Gunn:You and I are talking together.
Dr. Steve Quake:That's the mystery we wanna understand.
Dr. Moira Gunn:Whoever's listening is listening as well. Now here's where I'm kinda going with this. It's like all of these people, the 100 and 60 people you mentioned and all the people that helped them and the and the labs that helped them, it had to start in biology. It had to start in biological labs that we cross the line in to describe it digitally. That's the big step forward.
Dr. Moira Gunn:Because once you get to digital, then now you got something to work with.
Dr. Steve Quake:You're absolutely right. It was a huge step. And, you know, biologists weren't used to thinking digitally or even quantitatively. There are lots of jokes about that in the field. But, you know, the field of biology has now made that transition, not just to being digital but to being information science.
Dr. Steve Quake:And the way we make the Atlas is quite literally by counting molecules as, you know, we count them as individual, you know, digital entities, from each cell.
Dr. Moira Gunn:And this is the first time we're really doing this. So we're actually picking out what we think is gonna actually work. We're really still learning as we're going here.
Dr. Steve Quake:We're learning so much along the way. And as I said, at the moment, it's not a finished atlas, it's a draft. There's a ton left to do, and that work is gonna continue as an endeavor by the whole scientific community.
Dr. Moira Gunn:The exciting part for me is 2 part, frankly. Not just what we can go forward with, but anything we go forward with, we can always bring back to the lab and look at knowing that we're on the right path. But let's talk about that going forward. When you start taking these thousands of cells, how they may interact, all the data you're collecting about each of them. You know, we actually move into the artificial intelligence realm simply because of its size and the number of connections.
Dr. Moira Gunn:And this is so big that you anticipate having to build a new computer.
Dr. Steve Quake:That's right. So, you know, each cell is so complicated. We're measuring roughly 20,000 different numbers for each cell. Those are the different kinds of molecules that we're characterizing. And humans have a hard time trying to visualize something living in 20,000 dimensional space, So we need the help of computers to do that.
Dr. Steve Quake:And, we, at the moment, are going through this amazing revolution in large language models and artificial intelligence, which is making the computers and the and the algorithm even more powerful at helping us, manipulate and understand relationships of these very high dimensional, spaces. And so at CCI, we have decided to build one of the world's largest supercomputers used for basic science research in this field. It's been sort of a challenge for everybody to see all the amazing advances happening in the field more broadly being led by industry, where it's done, you know, behind closed walls. You don't have access to it. The cost of the compute is enormous.
Dr. Steve Quake:Universities have not been able to build that same kind of infrastructure, be resourced that way. At CCI, we can't do it quite at the level of industry, but we can do it at a level beyond most universities. And so we decided to build this tool and share it with, with the community.
Dr. Moira Gunn:And you're anticipating just one computer here?
Dr. Steve Quake:We're starting with 1. Yes. With 1,000 with a 1000, GPUs in it.
Dr. Moira Gunn:I have to say, this is not about just driving over to Best Buy and say, could we have a 1,000 of your little computers? This is a major architectural feat here to get this together, which addresses the problem of being able to query these. And, many people say, well hey, well so you could model it. What difference does it make? Well, if we have the the the perfect interaction, say.
Dr. Moira Gunn:And let's say I have a cell that is diseased or a cell that is compromised, that will actually change every cell in your system potentially.
Dr. Steve Quake:Well, the cells all interact. Exactly. And the impact of a disease cell goes well beyond that cell in many cases. And those interactions are just crucial to understanding disease for sure. And it's not just the cells that we have in our body that exist naturally.
Dr. Steve Quake:There is a whole field of people designing unnatural cells that are there to cure disease. It's called celliotherapy, and it's had remarkable results in cancer. And we think that these virtual cell models are gonna be essential in helping broaden that field and design new cellular therapies.
Dr. Moira Gunn:Now right now, if I have a good idea, even for a cellular therapy or any kind of therapy, I have to go through everything. My company has to go through everything to bring it to commercially available product that people can actually use. It takes years, 1,000,000,000 of dollars. It's a lot. How will computational power like this and the data behind it help make that possible?
Dr. Moira Gunn:So we know that it's successful. Right now, we only have 1 out of 9 attempts successful. And how can we shorten that endeavor? Will this help?
Dr. Steve Quake:Oh, I hope so and I believe so. Right now, I mean, there's so much trial and error involved in bringing new therapeutics into the clinic. And there's trial and error in the therapeutic mechanism and figuring out, does your approach really cure the disease? And there's trial and error in the unexpected unintended side effects that might happen with a new therapeutic, and so called toxicity. And these models and these cell atlases are gonna help with both.
Dr. Steve Quake:We're already seeing people using the cell atlases to explore this toxicity question. If you've designed a drug that's aimed at, that's aimed at a particular cell type in a particular tissue, you can ask the Cell Atlas, oh, is that target being used by other cell types in the body? And if it is and if you drug it, will bad things happen? That would be toxicity and not good. If you learn that early on, you can decide, well, maybe that's not a good target, and maybe I shouldn't invest 100 of 1,000,000 of dollars in making a drug and developing and putting in humans only to find out that it has this unintended consequence.
Dr. Steve Quake:So, I think we'll see a lot more of that.
Dr. Moira Gunn:Well, I like that because phase 1 is about toxicity as an example. It's like phase 1, we could have a 100% in phase 1 if we could model it before we got in there. We certainly would do that. So this brings shortens the time and certainly, decreases the expense. Who would be able to use this, new computational power and Human Cell Atlas?
Dr. Steve Quake:Well, you know, at CCI, we have very strong ethic towards open science and sharing everything we do. So all the data we generate from our projects is shared openly for anyone in the scientific community to use. All the Cell Atlas data is out there for everyone to use. And the models we build, they'll be out there for people to use as well. So we we wanna lift all boats.
Dr. Steve Quake:And we already see them being used by scientists all over the world, both in universities and in research institutes and in pharma companies. And so we're very excited about that.
Dr. Moira Gunn:Well, this brings, me to a second question. And you discussed it in, the Carl Zimmer article, The New York Times article, that this must be used for good. How do you envision that it might be used for bad?
Dr. Steve Quake:Well, you know, any technology is developed. You know, people can use it for good or for bad. We've seen that many, many times over the last centuries. You know, there is worry that people will use, AI tools for things like bioweapons research and things like that. And, you know, it's it's it's something that is I think responsible scientists, we have to worry about and discuss and and have ways to mitigate.
Dr. Steve Quake:That's a worry that I think many people share.
Dr. Moira Gunn:Well, I think you said some things there that I thought were were interesting in the article about you and and other scientists got together and saying, well, perhaps we should regulate or perhaps we should develop guidelines. Do you have any sense for how that might work? Or is that an open question that people are all working together? I know the scientific community very well, and they're totally organized to want to do something to make sure that it is not used for bad.
Dr. Steve Quake:Absolutely. And we have great mechanisms for that in science. And, you know, we have tremendous organizations such as the National Academies who convene experts, provide guidance the government for how to set regulations, and those allow input from the whole scientific community. Everybody can air their concerns. Very smart, experienced people can kinda synthesize and weigh in, and that is sort of in the best tradition of giving advice to government regulatory agencies about how to handle new technologies.
Dr. Moira Gunn:This really pushes mankind forward in its knowledge of of who we are and and what biology is all about.
Dr. Steve Quake:It sure does. You know, there's been questions we've wondered about since ancient times. How do humans develop? How are they made the Greeks thought about that? They knew a lot about human development, actually.
Dr. Steve Quake:I mean, their knowledge of of human biology was truly spectacular. And, you know, a good chunk of it was right. Some of it has been disproven over time, but large parts have survived. And that's because they're just very keen observers of of the world around them and, you know, how humans developed and aged. And what we've been able to do since then is really understand the molecular basis of development and aging.
Dr. Steve Quake:And and, you know, we now understand we're composed of cells, and we understand the molecules in the cells that interact to do things, such as help us grow from a single cell to a a full fledged human being. I sometimes wonder what the agent Grinks would say if we could teleport them in the present and say, this is what we figured out. You know? I mean, they had the idea the universe was composed of atoms, and now we can say humans are composed of individual, components such as cells, and we really understand all of them in some deep sense. It's an amazing time in science is all I can say.
Dr. Steve Quake:It's an amazing time.
Dr. Moira Gunn:It certainly is. And if if we could transport those Greeks, I'd wanna know what they did instead of video games. I just, you know, every there's always something. They were humans too. They were humans too.
Dr. Steve Quake:They debated with each other. They like to debate and argue.
Dr. Moira Gunn:That hasn't changed. That hasn't changed. Well, doctor Quake, this has been terrific. I do hope you'll come back and see us again.
Dr. Steve Quake:I'd love to. Thank you so much for having me today.
Dr. Moira Gunn:Doctor Steve Quake is the head of science at the Chan Zuckerberg Initiative and the president of the czBiohub Network. More information is available at chanzuckerberg.com.