The power of AI, from curing cancer to ballot boxes

In this special episode of Reid Riffs, Reid and Aria are joined by Pulitzer Prize–winning author, oncologist, and Manas AI cofounder Siddhartha Mukherjee for a few questions about cancer, AI, and the second edition of The Emperor of All Maladies. Reflecting back on the 15 years since its initial publication, Reid, Aria and Sid discuss how cancer prevention, early detection, and immunotherapy have fundamentally shifted while the disease continues to be a defining challenge of modern medicine. The conversation charts how AI can become a true engine of drug discovery and how Manas was built to be an AI-native biopharmaceutical company focused on developing entirely new medicines. The episode then broadens out to tackle the current cultural moment in Silicon Valley, questioning whether the Valley is entering a new Renaissance driven by more meaningful work, clearer values, and a renewed theory of human progress. The episode closes by grappling with AI’s growing persuasive power in politics and public discourse, and the responsibility to design systems that elevate truth, agency, and humanity rather than distort them.

• 0:00Speaker 00

  I am so excited because we have a special Reid Riffs today. At the top of our episode, we're welcoming a past possible guest who is an acclaimed author and company founder, Siddhartha Mukherjee. Sid, it is so great to have you on.

• 0:14Speaker 01

  Given the amazing second launch of one of my favorite books of all times, Emperor of All Maladies, Ari and I have decided to invite Siddhartha Mukherjee, who is both the author of said book and also an amazing oncology researcher and a CEO and co-founder of Manus AI, which we're doing together. We thought that since the second edition came out of this book that I first met you with, Sid, this is like my very first encounter of Sid was reading this book and going, oh, my God, this is amazing. So Sid, say a little bit about how your path into becoming an oncology researcher and then writing this Pulitzer Prize winning book.

• 0:53Speaker 02

  I started off in medical research. I went to Oxford and then became more and more interested in cancer. I was first interested in viral cancers. By viral cancers, I mean cancers caused by viruses in humans. Cervical cancer is a good example. And then became more and more interested in cancer in general, decided to get a medical degree and became an oncologist. I thought it was the most interesting problem that anyone could hope to solve. The book was a journal. It was a journal that I kept when I was training in oncology and I was a trainee. So you have to realize that I was at the bottom of the flagpole. I began the journal because a patient said to me, she was getting treated for lung cancer and she said to me, how did we get here? And I thought to myself, you know, actually

• 1:36Speaker 02

  even I don't know how we got here. I'm not sure how we got here today. Why are we using this treatment? How do we think about cancer in this way? And if I don't know, like what about the hundreds of thousands of patients and their families and loved ones who encounter cancer? How did they get there? And so that's how I started writing the book. As I said, it was a journal at first and grew and grew and grew. And then it became what my mother called the telephone directory from hell, because there were so many pages of bound in black. And so that is how the book was born.

• 2:10Speaker 01

  And so why a second edition now? And what are the updates for the book?

• 2:15Speaker 02

  Fifteen years have passed. And in those fifteen years, enormous things have changed in the landscape of cancer biology, cancer research, cancer medicine. And yet, cancer remains the meme for everything that is malignant. And yet, people use the word still to signify so much metaphorically. And so, in those fifteen years, you know, I asked myself the question, how much has changed? What has changed? And I really felt as if the book needed an update because science moves so fast. It was very interesting to write a book fifteen years ago and then realize that you have to write another book fifteen years later. People generally don't bring out completely new second editions of their of their book. But it felt very necessary. And so, that was that sort of the purpose.

• 2:59Speaker 02

  To answer your second question, what's changed? So, very broadly, I would say that we think about cancer in four areas, I would say. Number one is prevention, cancer prevention. What's changed in cancer prevention? Well, we are discovering, at last, at long last, a whole new universe of potentially carcinogenic agents that don't act in the way that we thought that carcinogens, as in cancer-causing chemicals or cancer-causing agents, usually act. In other words, they don't cause mutations in cells, but rather, they create an environment for cells to be able to divide, to form tumors, and become malignant. So, this is a whole new class, and I think we will discover many more. A great example of this, by the way, is air pollution, which we never knew.

• 3:42Speaker 02

  Another great example, which is emerging, are potentially things, new chemicals that we've invented. There's a whole debate going around whether these forever chemicals might be might be implicated. So, that's one arena. Very, very important, very exciting, new research, entirely new direction for cancer. Okay. Second is what we call early detection. Can we find cancer early? And if so, what do we do about it? So, once again, a huge difference. So, we've heard about blood tests that pick up early cancers. So, there's a whole chapter on those. We've, you know, people are going through. Full body scans, are they worth it? Are they picking up something that we didn't know before? What do we do about them?

• 4:26Speaker 02

  So there's a there's a chapter on early detection. We weren't doing that, obviously, fifteen or twenty years ago. And finally, a chapter on treatment. Major theme is immunological therapy and immunotherapy, which is curing cancers such as melanoma, skin cancers previously considered incurable, CAR T cells or T cells that have been engineered, curing cancers such as lymphomas, leukemias, myeloma, previously thought incurable. The whole book is capped off by what I call a new vision or a physiology of cancer. Like, what's what happens next? How are we reimagining cancer? Because it's all about imagination and about experimentation and of course, science and medicine.

• 5:07Speaker 00

  So Sid, I love that your book, it traces the progress against cancer and how it comes in waves. Like, there is basic biology breakthroughs, therapeutic revolutions, there's political mobilization, of course. And it's been super fun to have sort of a front row seat at everything you all are doing at Manis. Do you think the reason for Manis is that we're at sort of the forefront of the next wave of cancer research and treatment?

• 5:31Speaker 02

  So that's an excellent question, Arya. Reid, Ujwal and I co-founded Manis because we started firmly believing that information revolution, every information revolution has had enormous effect on medicine. You know, think about the basic computer revolution and its effect on how medicine was was and is practiced in terms of how we keep notes and how we can compare notes and switch notes. Think about the information revolution in digital technology, imaging and CAT scans and MRIs. It seemed as if, it doesn't seem as if, it is becoming amply true that the AI revolution, which is, among other things,

• 6:15Speaker 02

  a data revolution, among other things, a computational revolution, a learning revolution, it became amply clear that if medicine, especially cancer medicine, wasn't going to embrace it and move forward with it, that we would lose momentum. And that's how Manus AI was formed. Manus AI is an AI-native biopharmaceutical company. One of its main focuses is using AI as a device to understand how to make medicines. Not AI as a data management engine, not AI as a clinical trial engine, but using basic AI and physics and chemistry to find how one drug, a new drug, a new chemical, new chemical matter can interfere with the growth of cancer cells.

• 7:00Speaker 00

  So for the layperson who's watching this space and might not sort of have the deepest understanding of drug discovery or how that interplays with AI, and Reed, feel free to jump in on this one. Sid, what is the difference? We're seeing lots of startups claiming that they're using sort of AI plus bio to cure cancer and other diseases. Like, what makes Manus different in the way you guys are approaching this?

• 7:23Speaker 02

  Well, we are approaching it in two fundamentally different ways. One of the ways that we're different is that we're not a software company. We make medicines. The question to, one of the first questions that Reed is, as an entrepreneur, asks his fellow entrepreneurs is, what does your company do? And it's amazing that you can ask this question to many, many, many companies and not get a straight answer. But what does Manus do? Manus makes medicines. How does Manus make medicines? Manus is building a foundation model, what we call a molecular oracle, which enables us to, at an atomic level, with atomic level precision,

• 8:07Speaker 02

  understand the dynamics of a cancer target, one of those proteins that is driving the malignant growth of a cancer cell. And again, with atomic level precision, place atoms inside that target that will block the activity of that target. It's a little bit like, you know, how you might place Go pieces. In fact, we call, one of the modules, we call the molecular Go. It's a little bit like how you might place Go pieces on, in this case, a three-dimensional Go board, and figure out where the optimal pieces would land such that this protein can no longer activate all the cascades it activates in order to make a cancer cell malignant.

• 8:53Speaker 00

  And Reid, you obviously are using AI in so many different ways to attack so many different problems. What is the reason that you thought AI plus cancer would be so powerful?

• 9:04Speaker 01

  You know, building upon what Sid said is that I think the best way for AI to actually make a huge difference in medicines is to recreate the medicine discovery creation process, being AI native, starting with AI in a set of things you're doing. Now, most Silicon Valley people says, well, that means doing everything in silicon. No, you're doing a lot in silicon, but not everything. There's a lot of reasons not to do everything in silicon. And there's a set of other different kinds of things that, that, that, you know, as we make medicines will be more revelatory of. But a simple way of looking at it is, when

• 9:45Speaker 01

  you saw the current AI revolution, which ended up using scale compute and scale data in order to make predictions, for example, predictions that led to move 37 in, you know, Go, predictions that lead to, you know, being able to write an essay of an original sort with a large scale LLM, you know, predicting the next token as a, as a, as way of doing this. The question around making medicines is the prediction of which molecules might

• 10:26Speaker 01

  be the right therapeutic for a particular, you know, disease, a particular cancer. And, and that was kind of the, oh, this is, this is why I think AI could be really stunning, if done in an interesting new way. And, you know, the way that Manus came about is I had known Sid as a, as a, you know, amazing author. I'd known him as a world-class cancer researcher. I'd known him as a, as a kind of a general intellectual. I was like, wow. Oh, I have this idea about AI. I'll go chat with him. And he's like, and by the way, not only is that an amazing idea, but cancer is the right

• 11:11Speaker 01

  subject because it basically it kills all ages, you know, all races, all genders, you know, et cetera, et cetera, et cetera. And it's just like, uh, this is the thing for us to focus on. Now, there's obviously a bunch of other things that become possible abandoned diseases and a set of other, um, a set of other things that are also very important for, you know, human health and humanity. Um, but, and then the thing I learned about Sid in this amazing Sid also has a minor superpower in choosing amazing restaurants. Um, in this amazing Japanese restaurant that we were talking about, he's like, and you know, I brought drugs to market. And I was like, no, I actually didn't know that. So the other things shone so bright, I couldn't

• 11:55Speaker 01

  see the, the, the, the, the history of entrepreneurship in the, in the past. And so, um, the, uh, you know, this is what led to, and we should do Manus. And along with Ujwal Singh, um, you know, uh, we're anticipating 2026 to be a really great year.

• 12:13Speaker 00

  Sid, thank you so much for joining us. I'm so excited to read the new edition, which for everyone listening, it is out now. So please go, uh, grab a copy and also of course, follow all of Manus's work. And for those who want more from Sid, we actually did a full episode with him, uh, two years ago. So look for it in the feed and tell us what you think.

• 12:31Speaker 03

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• 13:00Speaker 00

  Loved hearing from Sid and now we are going to turn our attention to some Silicon Valley tweets that have been happening in the last few days. A few days ago, Patrick Hollis and tweeted out something about how the valley is ripe for new frameworks and I want to get your thoughts on it. So I'm going to commit to cardinal sin of reading a tweet on a podcast, but here we go, just in case anyone didn't hear it. Patrick Hollis and said that two conversations this week weekend made me think that there's a vibe shift afoot in Silicon Valley around what one should work on and what is worthwhile. Culturally, it feels like the moment is ripe for new frameworks. Davos expert morality is stale and discredited. It's also apparent that the just be super based counter enlightenment

• 13:42Speaker 00

  is not really an answer. Yes, woke went too far, but simply inverting it doesn't work. EA is no longer the automatic default for smart people and there's increasing skepticism of slot and slop machine dynamics. So overall, what is worthy and valuable feels like it's becoming more central. So I actually loved this tweet from Patrick, especially because I think a lot of people in the valley listen to him and really care what he has to say about what it is valuable to work on. So I would love to get your thoughts. Like, how did you take this tweet from Patrick?

• 14:11Speaker 01

  Well, as usual, Patrick is extremely thoughtful. I mean, one of the things that I like about Patrick is not only is he a, you know, kind of amazing and smart entrepreneur, but also thinks more systematically, you know, whether it's the acceleration of science, whether it's the pattern of entrepreneurship, whether it's kind of what's going on within, you know, kind of patterns on the internet, culture, etc. And so, you know, the fact that he is, you know, not just kind of, you know, creating straight press, but also kind of commenting on kind of what is the culture of the valley? How does that target, you know, kind of things that matter, things that matter in entrepreneurship, things that

• 14:56Speaker 01

  matter in business, things that matter in industry, things that matter in society, things that matter in humanity, things that matter to science, etc. As is ways of doing it is exactly the kind of thing that I think makes him a, you know, one of the, you know, important leaders, both in the valley and the world. And I think that the, the, the question around

• 15:16Speaker 01

  You know, kind of saying, hey, what actually really matters is building important technology that makes a big difference for industry, for society, for humanity is, is the, is the, is the thing that really matters. And I think that the, um, you know, this is obviously one of the reasons why I've been giving these speeches in Italy, you know, Bologna, Perugia, you know, for, you know, remembering what it is that was why the Renaissance actually in fact really matters, not just because it was an enormously generative period that all of a sudden we moved to an acceleration

• 15:56Speaker 01

  of science, acceleration of art, acceleration of humanism, but that we also were on what kinds of things really matter, uh, in terms of this. And that's, you know, to, to, to have this kind of popular trope about in Silicon Valley, about how Silicon Valley can be, you know, the next Renaissance, the next Florence, the next, you know, uh, Bologna, the next Perugia, you know, as, you know, part of, um, what's being created. It also should be embodying this what matters. And what matters, of course, is the elevation of humanity, is the kind of, the theory of human nature, the theory of, of, of what journey are we on? What can we become? How should we do that as a, as a part of it?

• 16:39Speaker 01

  And, you know, I think, um, you know, I think part of it, you know, the classic, you know, um, Patrick is stating this in kind of a classic Silicon Valley way, which is, you know, down with the old, the complete invention of the new. I think it's actually important to be learning things, like actually in fact, I think, um, there was a bunch of stuff that was important in the Davos Assembly, um, in terms of, you know, like, okay, what are all the voices across the world? Global South is part of what I'm doing this and being in dialogue. And I think that's, you know, while there's like the bureaucratic, you know, nonsense of that's not how the invention of new science, that's how the invention of new technology happens, but, you know, that the dialogue is important.

• 17:22Speaker 01

  And then similarly, like for example, to take EA, you know, I think EA, you know, has a bunch of challenges to it. But the notion of saying, hey, let's treat every human life as, as, as, as roughly equivalent and, and be maximizing the quality days of human life. When you kind of think about it across the globe is not something that's outmoded. That is, I think, actually still an important thing. Now, the way to think about that, the way to get there, I think, is important. And I think that there's, you know, anytime they, that something starts becoming a religious canon. And by the way, you know, similarly like the, hey, let's, let's just be bold and, and genuine

• 18:05Speaker 01

  and totally raw on the being quote unquote, super base. Those are good elements for entrepreneurs. Those are good elements for being contrarian and right. But I think that the question is, is to actually think seriously what you're doing. And, you know, my gesture overall would be a theory of humanity, a theory of human nature, a theory of how technology evolves that and being, you know, something better than the HBO show in terms of how you're articulating it. And I, that's part of the reason why I think, you know, Patrick's, you know, uh, call to arms or perhaps call to meaningful technology is such an important call.

• 18:46Speaker 00

  And do you think the, you know, sort of those ideals are right? First, don't tear down the past. Let's actually take the best parts of these, um, these waves that have come previously. But do you think the valley is heading in the right direction towards more meaningful work? And are there things you would say to entrepreneurs who are just starting out now that sort of nudge them in that right direction?

• 19:06Speaker 01

  It can be. It's one of the reasons why I'm such a strong advocate of Silicon Valley, even amongst its various absurdities. It's a little bit like you say, hey, what's the range of crypto? Well, obviously there's a lot of absurd stuff in crypto. But on the other hand, of course, you know, crypto has the amazing elements of the next generation of the, of the internet technology. In terms of identity systems, value systems, you know, banking, you know, recreation of financial systems that allows the, you know, high functioning financial systems around the entire world. And those are kind of the things that, that, that, that crypto has

• 19:49Speaker 01

  the, the, the, the trajectory to potentially create, you know, which is also like you got to get rid of the garbage, you know, minimize it, can't get fully rid of it and increase the, the amazing transformation of the world. I think it's kind of a similar thing where I think at the moment, the valley, it's, it's all obviously very focused on AI. But I think that the question about how it manifests itself is I think still in its earliest phases. And I think that the call to how do you work on this in very meaningful ways is exactly the right kinds of question that people should be asking. That's what I hope for.

• 20:26Speaker 00

  So Reid, you, you mentioned the speech that you gave in Bologna, which I was lucky enough to attend. And I think, again, you were talking about the similarities between the Renaissance and sort of Italian history and what could be and what has been in Silicon Valley. Can you say more about that?

• 20:41Speaker 01

  Bologna was the first of these Italian speeches, which was a great honor to, to, to give to the Bologna Business School and, and, and the folks there. The, you know, one of the things I was thinking about it is that the progress of humanity comes through this kind of Hegelian dialectic thesis, antithesis, synthesis, which is you start with a thought, you go to the, to the, you know, kind of the opposite, the contradiction of it. And then you try to build, as it were, the best of both worlds, the, you, the, the collection from, you know, kind of what was the original thesis that was interesting, the antithesis that, that challenged it, and then the refinement and the synthesis. And then this iteratively

• 21:24Speaker 01

  is part of how we make progress. We can make progress scientifically, we can make progress, you know, in, in society, we can make progress in governance systems and so forth. And I think that the important part of the work is to see what's good in both the thesis and the antithesis, to draw, to draw it into a synthesis when you're making progress with this. So historically, you know, part of the You know, thesis here is to say, hey, there's, you know, we're, we're, we're, we're building infrastructure that, um, you know, kind of, uh, you know, kind of rebuilds society. Or, or for example, in the case of, you know, Davos or a political discussion, it's a, we're

• 22:06Speaker 01

  having a discussion about what really matters in the world and what kinds of agreements can we get to and what kinds of questions we ask each other. The antithesis is to say, okay, well, you actually need a, a creative destruction where, you know, the, the, the, the exact patterns of this, of this industry, the exact patterns, you know, needs new technology, it needs a new, a new way of working. Um, and, um, and then that, you know, you're creating alternative technology and synthesis should be something that's along the lines of a, call it a, you know, what's our theory about how this is good for humanity overall? And this is of course, one of the reasons why at the beginning of this year, you know,

• 22:51Speaker 01

  Greg and I wrote super agency, because it's kind of a focus on, you know, not just what is great technology, but what gives people more agency? What gives them more of a, of a sense? And by the way, doesn't mean all of your previous agency is preserved, but the new agency, uh, should be, you know, kind of collective set of superpowers, which then enables our humanity in much better ways. And that's of course, what we're, what we think is the right lens for thinking about what kinds of AI we should be putting our efforts into creating.

• 23:25Speaker 00

  Well, speaking of what kinds of AI we should be creating, uh, earlier this year, you and I actually talked about how excited we were when we heard about some AI persuasion tools that was working with people who believed in conspiracy theories. So AI was, um, very effective at getting flat earthers to rethink their views, for getting people to believe in the moon landing, some of these sort of outrageous conspiracy theories. That usually, when you say like, ah, I try to convince someone with facts and it doesn't work, but actually, a chatbot can be infinitely patient and they can sort of tailor what they're saying to help these people come to, come to understand the actually facts of the case. And so that is a side where persuasion can be used for good. Recently, we saw two new studies come out in Nature and Science, and they found that even

• 24:10Speaker 00

  brief interactions with AI chatbots can meaningfully shift people's political opinions. And they found that in some cases, chatbots were about four times more persuasive than US television campaigns, and between 4% and 10% of voters in some counties and countries switched to supporting the chatbot-backed candidate after just a single conversation. And so are we entering a zone where we're gonna, instead of political ads all over the place, we're actually gonna have chatbot persuasion wars? And it might depend what chatbot you're talking to could sort of meaningfully sway who you're gonna vote for on Election Day. So should we, what should we do about this? Is this something, how should we think about it? Should there be government intervention?

• 24:54Speaker 00

  And how will this affect the political climate?

• 24:56Speaker 01

  Well, I think, not surprising, since you know me pretty well. The way that I think that we should think about the beginning of interventions is measurement and transparency. So the kind of a question around, you know, like, what are the things that, you know, should be, you know, advertised about like, okay, is this chatbot, you know, have a position? You know, so for example, if it's a, you know, if it's Grok, it should say, well, I've got all these meta-prompts about, you know, how to say that Elon is, you know, the best athlete ever and the most intelligent scientist in the world and, you know, da-da-da, because,

• 25:35Speaker 01

  you know, I've been trained to be the court jester of, of saying, you know, how amazing Elon is. And so, you know, but whatever the, the basic thing that you're doing for a chatbot, you should, you know, have your kind of principles, how it's designed, kind of what you're accountable to in it. And I think that kind of thing of, of statement about what you're Kind of design and so forth is and what your what your efforts are for it. And obviously, most of the quality chatbots will do things like saying, hey, we're we're trying to be reflective of the best of current scientific knowledge.

• 26:14Speaker 01

  We're trying to be, you know, kind of, you know, answer what you what you try, but we also try to avoid conspiracy theories and we try to do other things as as ways of doing it. And then, you know, obviously, being able to have a dialogue by which it's specific, not, in this case, ad hominem slogans, which is the most common thing like, oh, it's a woke chatbot. And you're like, it's a woke chatbot because it's, you know, kind of willing to be critical of President Trump, or it's a woke chatbot because it's not giving you a, you know, a riff on Biden, you know, etc., etc. It's like, OK, these are, these are, these are kind of silly

• 26:57Speaker 01

  arguments, but credible people make them, which is part of what makes them so absurd.

• 27:05Speaker 01

  And it's, I think that's the kind of thing that's going to be important. Now, the short answer is we're going to have lots of failure points. We're going to, you know, in this politicization of the information age where, you know, it's so badly politicized that, you know, you can't have a coherent conversation around something that's relatively scientifically understood like vaccines, that, you know, that's, oh, that's, that's, that's political information. That's, you know, and it's like, no, actually, medical studies are not political information. Doesn't mean they're always right, doesn't mean that there isn't an evolution over time, doesn't mean that, you know, for example, it's, wow, but, you know, people are saying that vaccines never have any side effects. Well, only idiots say that. It's like, that's not an argument. Anyway, so back to AI.

• 27:48Speaker 01

  We should want these things to be good foils and participants in truthful discussion. Now, part of the problem, of course, is we as human beings have to get to truthful discussion. And right now, I'm not, I'm not enormously optimistic about our, about our, you know, how well we're doing the truth discussion.

• 28:06Speaker 00

  So, Reid, if you were running a frontier model company, if you were running a chatbot, you were the CEO, would you let it answer the question, who should I vote for in the next election? Do you think that's OK?

• 28:18Speaker 01

  I think I would let it answer the question, but I think the way that I would answer the question, like, I wouldn't say, you know, vote for Sarah or vote for Bob. I would say, well, um, the theory of voting for Sarah is da, da, da, da. The theory of voting for Bob is da, da, da, da. Um, and here is what, you know, some, like, if you cared about, for example, economic prosperity, here is why tariffs are actually a terrible idea, right? And actually don't work. And, you know, and in, they say, well, but it hasn't been working, it hasn't been doing that badly so far. It's like, well, we're actually, the tariffs are decreasing the major economic boom that we're getting from the market with the AI investment

• 29:01Speaker 01

  already. Um, and so it's like, it's, it's actually decreasing what the benefit of, you know, the last 10 years of building towards AI prosperity has been. Um, and so it is actually, in fact, a, you know, is actually, in fact, a decrement, but we're, you know, it's a decrement in a wave that is, that is overall propping up economic stuff. But that's, of course, part of the reason why people say, well, you say the economy is doing better, but the, but prices are going up and, and affordability is a challenge. And yes, because the, the AI doesn't answer all of that. Um, and so whereas tariffs do create that, and that's part of the, the economic challenges that people are feeling right now.

• 29:44Speaker 00

  Makes a lot of sense. Give folks the facts, give them both sides, and they can decide what is important to them and which they want to vote for. Reid, thank you so much.

• 29:52Speaker 01

  Possible is produced by Palette Media. It's hosted by Ari Finger and me, Reid Hoffman. Our showrunner is Sean Young. Possible is produced by Tenasi Delos, Katie Sanders, Spencer Strasmore, Imo Zoo, Trent Barboza, and Tafadzwa Nirmurundwe.

• 30:07Speaker 00

  Special thanks to Surya, Yala Manchili, Sayida Sabieva, Ian Alice, Greg Beato, Parth Patil, and Ben Relis.

• 30:14Speaker 04

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