0:00[music] Daphne Koller is here.
0:12All right, 150 million people have benefited from her genius. I can't wait for you to learn what she's doing now, and it took 8 years to figure it out. And she's amazing and one of my most favorite people in the world. Daphne, she co-founded Coursera, which brought world-class education more than 150 people. That's 150 million people, not 150 people.
0:37And then took an even harder problem using AI to discover new medicines. 8 years after founding her company, and she's going to reveal it. It's first program is heading towards the clinic.
0:47So, I want to talk about the part of innovation we rarely see. How a breakthrough actually becomes something real. Now, people kind of wave their hands like, "Oh, AI is going to cure cancer and and figure out every hard problem." But you need a Daphne to figure out how to do that. And this panel is going to see if she's screwing it up or if she's leading and creating a new paradigm and showing a new way. Because it's, you know, I I I
1:16don't know if like the Nobel Prizes are going to be given out the same way now because everyone can work with AI. And we're in a new era where we need leaders to kind of show a path.
1:26So, I'm going to get into education later in this conversation, but please tell us what is the 8 year journey you've been on, and how's it going?
1:36So, it's going great, and it is a journey because the world that we live in right now is the world where um bits, AI bits, meet real-world atoms. And I think people often underappreciate just how much complexity exists at that interface. And the fact that when you move out of the realm of the world where all of this data is being generated by the minds of 8 billion people, images,
2:04text, and so on on the web, code that you can generate and test immediately, and so on. And you have to exist in a world where data generation and verification that what you're doing is actually working, you're working at the pace of the physical world. You're no longer working at the speed of light. And so, I think there is a I have a great admiration to all of the companies that are building world models where they are actually modeling the physical world with all of
2:34its complexity. That's the world where we live in, except we have an even one layer extra of complexity, which is the world that we're intervening is is the world of the human body. So, the the company that I'm building right now is a company that does AI for making medicines. And the fund- fundamental technology at its root is a causal AI model of human biology. So, you can make a prediction of what will happen if you perform an intervention in the
3:03real world, the real world being the real world body of individual patients, like all of us, what will happen in an experiment that has never been performed. So, you don't get to perform the experiment. The perform- The experiment is at the end of the journey when it's called a clinical trial, and you actually put a drug in a person, and you get to see what the experiment is up. How do you make that prediction about that counterfactual world that has never happened with data that isn't actually doing that experiment. And so,
3:32what we've had to do in the last 8 years, and that's why it took 8 years, is to collect a unique of-its-kind data set that combines observational data from millions of people with a causal underpinning in human genetics, and combine that with causal data in experimental systems that we can generate and perturb at the scales of tens of billions, soon to be hundreds of billions of cells, and bring that
4:00together to the point that we can make accurate predictions in what we call the virtual human, which is a first of its kind, we believe, AI model for human causal biology, making causal predictions in the real world of human beings. And so, making data takes a long time, making data at the quality and uh and reliability that an AI model doesn't get hung up on artifacts and batch effects and all of the many things that can make an experimental system go
4:29wrong. And then taking that data, collating it, curating it, and training that AI model is what we've been doing for years, not to mention making molecules against that and doing all the preclinical studies that regulators legitimately require before they will let you put a brand new molecule into a human being. And so, that's what we've been up to, and we'd be excited to tell you about some of our first programs.
4:49Yeah. So, uh I also want to correct I just looked it up. It was 200 million people, not 150 people. Um la- for Corsair, all right, last month you published "Drug Discovery Has No Magic Wands."
5:02Can you explain why that's relevant to our audience? And um you spent close to 30 years at the intersection of AI and biology. Why write that now? Did you have some epiphany? Uh are you being paid off to represent some like uh lobbyist group?
5:20That would be nice, actually, if someone were to pay me to write. No, um I write in my own free time. So, I think that there's a lot of um enthusiasm and excitement about the role that AI can play in the physical world, and specifically the role that AI can play in human health. And I think that is a not unreasonable thing, and we all would love for AI to do something that helps make the world better, um as opposed to, you know, all the predictions of doom and gloom. and I think there is and that
5:49has caused a lot of predictions that are aspirationally correct, but on timelines that I think are unrealistic. So, when you say something like AI is going to cure all disease in 5 to 10 years, I, you know, I like to think back on Eric Topol's response. Eric Topol is an incredible physician-scientist and and one of the smartest people I know, and he says, "If you list the number of diseases that we have quote cured outside of infectious diseases." And
6:18underneath he has an empty box. We have not yet cured a disease other than infectious diseases and a few um and a few pediatric cancers. Um it's it's hard to cure anything. You can slow disease. You can treat disease.
6:31So, saying we'll cure all disease in 5 to 10 years is, you know, uh I think it's it's a bit optimistic. I think directionally that's what we'd love to do, but I think we also need to understand what is feasible and what it will take to get there. And so, one of the main messages that I uh make in that article is uh we are now better positioned due to the incredible advancements of technologies like AlphaFold, which originated in, you know, in the company
7:00that owns this campus, to make better molecules, far better molecules, far faster, far easier than we've been able to make. Unfortunately, in most diseases we have no idea what to make molecules towards.
7:13We do not understand the biology. It is not a chemistry problem. It is a biology problem. And the amount of data that we've been able to acquire for understanding human biology is a de minimus fraction of what we need, and the more so as you get towards the diseases that are much more intrinsically human like anything in neuro neurodegeneration neuro psych. You can't collect that from animal models.
7:37You can't collect that from cells. You need to collect that from humans, and that becomes a much more complicated problem. So, I just wanted to create a sense of reality while also maintaining a sense of the incredible importance and aspiration of this problem that we're trying to solve.
7:53Great. So, there's a number in that essay that just got my attention. The count of novel targets entering development fell from about 100 a year uh in 2015 to 30 in 2024.
8:09During the exact decade when AI-driven molecular design got dramatically better.
8:14What what is that number telling us? Is should that be a warning? Should that should that be telling us to do things differently? Is there an opportunity there?
8:24It's an incredible number. It's a depressing number and and I and also one that to your point prevention a few years ago or I think people were maybe less risk off than they are right now. I think that there has What does that mean risk off?
8:39Risk off means um technical term or It it it's a it's a term of art. No, it's a term of art. Um it's an investor term of art especially in the biotech industry where it refers to people being unwilling to take biological risks. So, 10 years ago, I think there was maybe more openness to exploring novel targets and as the statistics of our industry which remain a dismal dismal 10% success
9:07rate for a novel mechanism that goes into the clinic, um people are like, "Why do I want to take that risk? I'd much rather go after a target that, you know, my fellow pharma bro has de-risked for me and I'm going to be second to the clinic and I'm just or third or fourth or 17th." And by the way, there's 37 programs have over 50 37 targets that were 50 programs against them which is a shockingly high number. I mean, you can make the argument that maybe it wasn't the first statin that was the best.
9:36Maybe it was the sixth or seventh statin that was best. But what are you going to get from the 30th? I mean, not very much. Certainly patients are not going to get very much. But we have this incredible, what's called target crowding, another term of art, um of people like not wanting to take biological risk, not wanting to explore novel biology. Now, let me add another stat that you didn't cite, but I think is equally important. The number the fraction of diseases that have any FDA-approved therapeutic, depending on how you define the denominator, any
10:06FDA-approved therapeutic ranges from shy of 10% to 22%. That means the vast majority do not have even a single FDA-approved therapeutic. That subset that do, most a lot of these drugs don't do very much. One of the programs that we're really excited about at Enceinte that we're working on is ALS. There are four approved drugs for ALS. Um how many of you are familiar with ALS?
10:30Ice Bucket Challenge. Three to five-year death sentence. Horrible horrible death. Um the drugs that are out there extend lifespan by two to three months. That's all they do. They're palliative at best.
10:44So, coming up and so this is in the subset that small subset that actually have a quote FDA-approved therapeutic, just doesn't do very much. So, that is where we should be devoting our attention. And coming back to my previous statement, it is not a chemistry question. The reason why we haven't made more drugs for ALS isn't because there is a target that we know is going to work and just nobody's been able to drug it. It's because we have no idea what to drug. And so that is the problem that I think presents an incredible opportunity for uncovering
11:13new biology that will give us all of, you know, potentially opportunity to go after disease after disease after disease and come up with drugs that actually work, that are actually, another term of art, disease-modifying.
11:29Uh you know, I I unprompted, yeah, I Uh what is the real constraint now?
11:34Compute, data, or the right data? When you say you generate data that that What what does that physically mean?
11:44People hear data and picture a server rack. What is actually going on in your in your in your shop, in your building or lab or whatever?
11:52Where you have biologists and machine learning people.
11:54It must be like convection current or they uh They talk They talk to each other all the time and it's actually an incredible source of our uh innovation, how that cross-disciplinary fertilization happens. So, to your point about the right data, most of the data that we use to train AI models right now is observational. They tell you what is What is the state of the world? It's patterns, it's correlations.
12:17Correlations are great. And if you're trying to produce a manuscript or an image, that's awesome. But if you're asking, "What would do if we did X?"
12:24That is a causal question. That is a question that involve a taking an action in the world. And if that action You use the word causal. AI is predictive, but you're saying AI is causal.
12:36I'm saying we need AI to be causal if we're going to make predictions about taking actions in the real world.
12:44Um I think it was mainstream for a while. And if you talk to any statistician or economist or epidemiologist or clinician, they will tell you that correlation and causation are very, very different things. And the place where people often go wrong is because they interpret correlation as causation and they do something where two things happen to be correlated because of some shared confounder or something, but have but acting on one has no consequence on the other. And
13:13when you're making a medicine to put in a person and undergoing what is a multi-year, often billion-plus dollar clinical trial, you better have your causality right. You better have some conviction that when you take an action that has never been taken in the world before, which is intervening in a particular way in a particular way in a human being, that that has a causal impact on that person. And so, that is a really critical gap in the data that
13:42we have available to us. And what we've done in our labs, to your point in South San Francisco, is we have a causal data factory. We take billions and billions of cells from different cell lineages, some of them are neurons, some of them are liver cells, cardiac cells, immune cells. We intervene in them by knocking down the a particular gene, amplifying a particular gene, and then seeing what happens. And when I say seeing, I mean that literally because
14:11microscopy is a significant part of our technology stack, and it's amazing what AI combined with advanced microscopy techniques can see in a human cell, especially when it's a living human cell, because we have a live cell microscopy. We also um look at what happens to other transcripts using sequencing type technologies. And we're collecting the largest causal database of human biology that has ever existed when you look at cells, and then we're combining that with data with causal
14:40data that you get from humans, and you ask how do you get to causal data from humans when we can't do experiments in humans, correctly so, until a clinical trial.
14:48quick questions. All right, let's get specific. You identified three ALS targets that you mentioned ALS that Biogen and My Scrip then nominated. Take us through one. What did the model see, and how did you know it was the real it was real rather than an artifact? And I got a lot of questions here. I don't want to do some stuff on education, so don't um Okay, I'll be fine.
15:11Oh, okay, I'll be I could, but I won't. Okay. So, we created a set of cells that replicated ALS biology by creating sort of an ALS in a cell. we put our microscopy stock on that and identified a never-before-seen disease access for ALS that showed what happens when a neuro when a motor neuron develops ALS and gradually dies. And then we deployed our cell-based screening with a causality to identify targets and when you knock them down
15:42made the unhealthy cells revert back to a healthy state. And then we took a whole bunch of different um traits that we know exist in human neurons and occur when those neurons die and we showed that those same targets revert those.
15:57So, specifically in the picture and then in the spirit of a picture is worth a thousand words, damaged neurites, those little neurites that emerge from a neuron when they're damaged in an ALS patients do not grow back in the same way that they do in a healthy individual and when you put our drug into those same neurons, they actually do grow back. And that is the fundamental functional deficit that occurs in ALS patients. So, in addition to a whole bunch of molecular reversion that we were able to to do, we are also seeing a
16:25functional reversion. So, we are so excited about this program because we believe it could be a truly disease-modifying intervention for the 97% of ALS patients that are sporadic ALS that have what's called TDP-43 pathology. And that will be if I do nothing else in my entire life, that will have been worth it.
16:445 years from now, what what does it what does your company look like your venture look like? Does it flex towards being more of a tech company uh or does it go deeper into biology and drug development? Or like 23andMe doesn't exist anymore? Or is it straddling that line um that you know, what what's the hardest part of what you're doing? I'm just I was going to say yes until you got to 23andMe or something.
17:10showing there's a risk, right?
17:12No, there is a risk, but I do think but No, I don't I don't think he I'm I position you as a leader who can pattern set a pattern that others can follow and I just wanted to where you where you want to be heading.
17:23So, I believe that more and more companies are going to be AI companies that have a strong vertical presence. I think that yes, you absolutely need these, you know, horizontal [snorts] AI plays that create those foundational AI models that provide general intelligence, but I think the world is coming more to the realization that there's an equal value and existence to verticalized companies that develop a proprietary data set, proprietary
17:51harness, specialized tools in a particular vertical and really go deep and solve a problem. And so, I think that yes, we are absolutely a technology company. We're absolutely developing cutting-edge causal AI models that do not currently exist, but at the same time we're solving a problem that matters to real people.
18:08All right, you co-founded Coursera on the belief that technology could democratize access to great teachers.
18:13Now, every student can potentially have an AI tutor. Is this the fun fulfillment of the Coursera vision or does it fundamentally change what education is and and your you know, you're frustrated by this this direction?
18:28No, I think we I mean, when we founded Coursera, one of the things that I spoke about even in my TED Talk was the Bloom two sigma and how people this stands for two sigma, two standard deviation of performance that an individual student can get when they have a personalized tutor. Um, and we tried to get some level of personalization with Coursera in the early days and you know, the technologies just wasn't there.
18:53There's only so much personalization you can get with pre-made video snippets and you know, some quizzes and such. And so, what we did was that we achieved scale, we achieved democratization. I don't think we achieved in the early incarnations of Coursera that personalized teaching experience that can give you that two standard deviations of performance that you get from a personalized tutor. And I really hope that with the technology that's available today, and hopefully, and I would expect some data collection that is really fit for purpose in education,
19:22you're able to get to that level of performance, which I think is amazing.
19:25So, you if you founded Coursera today, would you build a platform of courses or an AI teacher?
19:33And does the traditional lecture survive in AI?
19:37That's a hard one. Um I would absolutely other people to figure out cuz you're busy curing ALS and other things?
19:45And I so, I'm absolutely leaving this to other people because there's only so many hours in the day, but I believe that today I would probably start with the AI tutor. I don't know that lectures are entirely dead because there is something so inspiring about being taught by somebody who's truly gifted and inspiring teacher. And I think we've all had that experience where we walked out of a lecture hall feeling entirely transformed motivated. So, it would
20:14probably be somewhere in between and I'm hoping somebody's figuring that out.
20:18So, we're training students who may soon build systems that affect millions or billions or trillions of people.
20:25Trillions, I'm extrapolating a little bit. Um should it still be possible to graduate from MIT or Stanford or, you know, any school as an AI researcher without seriously training in ethics, history, governance, and consequences of technology? Should that be mandatory?
20:44And you know, you're in a good position to answer that cuz you you stopped everything to build Coursera as a way to give a gift to humanity. And now you're trying to figure out how to use AI to cure all diseases. And there're going to be a lot of people following your footsteps. And I do think we may miss some things and break some things. And we're going to have to build some, you know, best practices that we may not have had to even consider and in your unique position uh lead us.
21:12I think that we absolutely need to be mindful of the consequences of our actions in the world today and frankly, I think that a lot of people would benefit not just if you're a machine learning scientist, but in general from thinking about the consequences of our actions in terms of environmental impact. I mean, machine learning is very much on our minds here in this room, but there are other disciplines that have I think significant world consequences. If you're in the energy sector, you know,
21:40God knows, right? Um and I think that we should we would all benefit from having more, I would say uh giving more thought to the consequences of our actions in the world and trying to pivot more of our activities towards whatever discipline we're in, doing it not just for gain, but also for good. So, doing good while we do well at the same time.
22:04So, um I'm about to host James Landay, the amazing leader of HAI. You played a role and I think recruiting Fei-Fei Li and you were her mentor or or mentored her.
22:16Um what do you know about leading these big groups today that people may not realize and and I guess Fei-Fei's taken a leave to start something you know, I think Stanford's been in the news a little bit for being at the forefront of facilitating entrepreneurship.
22:35But I do think there's some things we need to be careful in and I think universities are are institutions now thinking about how do we strike a balance where three can be the new thousand. What do our faculty do in terms of leaving, coming back and and how fluid is that? And um I I do think we're at a moment where people are like trying to figure this out and it's not clear.
22:57I think that in general, universities should be trying to make the walls of the ivory tower more porous so that there is a greater movement of people, ideas, IP from industry into the academic world and back again or whichever way you'd like to start that circle.
23:15I think that that would make the work in academic labs more impactful and better able to impact society. One of the reasons I left Stanford was because I was struggling back in the day to have the ideas that I was coming up with in uh academia turn into products that that that industry could adopt. It's a little easier now, but I think still not as easy as it could be. And I think universities should take a deep hard look at how they operate and how they can
23:45regain the impactful position that they had 100 years ago um in a world that is so drastically different today. And so I'm thankful that I'm not a university president cuz boy do they have a lot to think about right now, but I really think there is an incredible opportunity for the more forward-thinking to to do something very different.
24:03All right. Uh say something profound or something that you know that no one else knows that you can't tell anyone.
24:12Uh but I can't tell anyone. Um No, but but we're we're around. We're with friends.
24:16[laughter] It's being live-streamed. Um Well, no, it's not being live-streamed.
24:21Uh Shh, don't tell anyone what you hear. Uh no, you you have a big brain. You've had a lot of experiences and you know where the puck is You're You're deciding where the puck is going.
24:32Um I think uh so that I'm I'm going to come back to the beginning of this conversation which may or may not be sufficiently profound for you, Don, but is what it is. I think that there is a tremendous wealth of opportunities for those of us who are willing to adopt um the uh what is it? The uh unease and uh lack of comfort, the discomfort of being outside of our own discipline. So, being
25:02at the boundary between a discipline where you feel like you're swimming like a fish in water and one where you feel like you're asking really dumb questions all the time because you don't understand the basics. I think that is really uncomfortable for people, but it's also where the greatest impact is to be had because that is a place where you can take ideas that are like very natural to you and do something that is completely transformative in the other discipline. And whether that is AI for, you know, medicine like what I'm doing
25:29or AI for agriculture, AI for government or or I can think of probably agriculture 100 There's probably a dozen or history dozen disciplines, two dozen, maybe more where AI hasn't really permeated and the impact is so huge. And do you want to do the latest twiddle on the next, you know, slight variant of a transformer model or do you want to do something that is truly impactful? I would think
25:57the latter offers a lot of opportunities. So, I would encourage people to leave your comfort zone and do a little bit of that.
26:03Great. Ladies and gentlemen, a true leader at this moment. She just doesn't wave her hands and say things. She's doing stuff. She's a practitioner and she's someone to watch and to all the people you're trying to help cure their their disease.
26:18Thank you for helping them and their loved ones and thank you for Coursera and and you know, I think we need more people who are willing to you know, take a a break from the rat race and say, you know, I'm going to do this because it needs to be done not because I'm going to get paid to do it and you're a very special individual.