# Drew Endy (Stanford University) - A Synthetic Biology Dream [Entire Talk]

## Метаданные

- **Канал:** Stanford eCorner
- **YouTube:** https://www.youtube.com/watch?v=PROX8gg7pSc
- **Источник:** https://ekstraktznaniy.ru/video/28427

## Транскрипт

### Segment 1 (00:00 - 05:00) []

(upbeat music) - Welcome everybody to the Entrepreneurial Thought Leader Seminar at Stanford University, the seminar for aspiring entrepreneurs at Stanford. ETL is brought to you by STVP, the Stanford Technology Ventures Program and BASES, the Business Association of Stanford Entrepreneurial Students. I'm Ravi Balani, a lecturer in the Management Science and Engineering Department, and a director of Alchemist and Accelerator for enterprise startups. Today we are thrilled continuing the tradition of the Stanford centennial. Every one of our speakers is connected to Stanford and Stanford Engineering. We're thrilled today to have Drew Endy, associate professor of bioengineering at Stanford as our keynote. How many people have heard of Drew Endy before today? Okay, so for the majority of you, it's gonna be our pleasure to introduce you to a force of nature that we are thrilled to showcase on synthetic bio and entrepreneurship. Drew has been instrumental in shaping how we think about designing biological systems in very analogous ways to how we think about engineering software or hardware or machines. Before Stanford, Drew was an assistant professor at MIT, where he was instrumental in bringing the bioengineering degree to MIT as he also did at Stanford. He has his PhD from Dartmouth and bachelor's and master's degrees in environmental engineering from Lehigh University, and he's generally regarded as a one of the leading pioneers in synthetic biology. Esquire named him one of the 75 most influential people of the 21st century because of his work on synthetic biology. And while his achievements are too long to list, I wanna highlight a few. In 2013, Drew had a team of researchers that created the biological equivalent of the transistor. So think about it was dubbed a transcriptor, but think about the invention as the final of three components necessary to build a fully functional biocomputing with data storage, information transmission, and a basic system of logic. While at MIT, along with other academic leaders, Drew worked on the engineering of standardized biological components, devices, and parts that was collectively known as bio bricks. But the reason why we have Drew here today at the Entrepreneurial Thought Leaders seminar is because Drew is more than just a scientist. He's also really an entrepreneur and a visionary entrepreneur who's co-founded several groundbreaking organizations, including the Bio Bricks Foundation, which champions open and ethical innovation in biology. And his work has laid the foundation for countless startups that aim to solve global challenges from medicine to sustainability using biology as a technology platform. And he's also co-founded companies to commercialize synthetic bio. To give us a peek into the current intersection of entrepreneurship and synthetic biology and where biology's headed, we're thrilled to invite Drew to the Nvidia Auditorium for ETL. Please join me in welcoming Drew Endy. (crowd claps) - If you look at the covered arcade in the main quad, you can see these stamps hiding out in the corners. Says, "George Goodman's Artificial Stone 1890". In 2025, we think the big deal is artificial intelligence, but in the late 1800s the big deal is artificial stone. This little stamp changed my life because it taught me that when we wanna make stone that has the properties we like, we grind up natural stone and we remake it to make artificial stone or synthetic stone that has the properties we want. Could you imagine making a mature oak tree in 72 hours? You think of that as something that takes 72 years or aboard to grow. But what if you could grind up a tree and remake a tree? Like little things just by seeing change your mind? Here's something else I saw a couple, many years ago now, a decade ago, there was a news story in Stanford Daily, "Hey, we just put up a solar farm and it's providing half of the campus's electricity. " And when I saw this story, I also was walking across campus and there was a meeting happening at the Hoover that had a security perimeter around it, and there were armed guards with AR-15s. And at MIT, Caltech, Berkeley, like I'd never seen a meeting on campus with an armed security perimeter. So I said, "What's that. " See and scratch, this tool I use. And so I'd looked up the meeting, it was the Global Energy Forum. It was a meeting talking about energy production. Why does it need a security perimeter? Because the meeting about power, political power causing people to behave in certain ways, having to do with energy. Now, why would that be? I don't know. I'm just scratching. I'm scratching. You see what I mean? I'm like trying to figure out what's going on. And what I came across was some analysis about photovoltaic solar panels.

### Segment 2 (05:00 - 10:00) [5:00]

Here's a paper, and it's asking the following question, "How much energy does it take to make a solar panel? And how much energy does the solar panel generate? What's the return on energy? " Now, as a consumer, if I buy solar panels, I wanna know how much does it cost me and how much does the electricity worth and what's my return on investment, right? Like everybody's familiar with ROI, but from a nerd perspective, nerd nation physics, right? How much joules to make and install the panel? And how much energy, how much joules do I get back? And according to this paper, sometime about 10 years ago, the return on energy for photovoltaics went above one. And maybe it's averaging about 20. That means a solar panel in our climate and latitude generates as much energy as needed to make it in about a year. And for the remaining 19 years of operation, it's just generating more energy. That's never been true before in the history of human civilization, that we have a renewable, sustainable electricity generation platform that works. So what? See and scratch, see and scratch. Well, geez, we had a wind empire centuries ago outta Europe with the coal empire of the British, we have the fossil petroleum or gas empire of today. There's a fourth energy empire coming. It's based on new modes of energy generation. Oh, that's why there's a security perimeter on the meeting across campus. What could you do if you're an electricity generation abundant civilization? Of course we've got problems with transmission and storage, but just think, stretch your mind. If we could make energy, right, what could you do with it? It turns out you could imagine things like, I wanna run a fresh water cycle for the whole earth. Fresh water's already solar panel, evaporation off the ocean and rain and snow. But imagine it never rained or snowed anywhere on earth again. Like how much energy would it take to do reverse osmosis and pumping to an average elevation of a thousand meters for the whole planet, a synthetic fresh water cycle? When I run that math, it's about 20 terawatts of energy, which is an interesting number because that's as much energy as we run on as a civilization. So if you double our primary energy supply, worst case scenario, you could run a fresh water system. This is just napkin math, back of the envelope trying to make sense of the world. I'm doing this all the time to figure out what's going on and where I wanna be. The other thing I do is I map this into my sense of reality. I have what I call a reality strategy. I'm operating on a hundred watts of energy right now. So are you, right? All of our human bodies on this planet are running on a terawatt of metabolic energy right now, right? So that's joules. Like in order to exist, we need energy, joules, and then we're made of stuff. We need atoms, right? And then there's information or bits, right? So I'm thinking about operating in a three dimensional space. I think of as joules, bits, and atoms, energy, data, stuff, right? What I love about biology, I don't start out as a bioengineer. What I love about biology is biology itself operates at the intersection of joules, bits and atoms, right? Computer science, love, computer science. And that's really just joules and bits, two dimensional field, right? But bioengineering is three dimensional in my world. Okay. So let me give you a little bit of a primer on synthetic biology and let's just do the heart of it, which is DNA synthesis, right? What if I could make DNA from scratch? synthesize DNA? Now, this turns out to be a chemistry that was invented in the 1970s and perfected in the 1980s and first brought to market back in the 1980s. It's continued to come to market. I'll talk about that in a little bit, but let me just give you the gist of it. Think of these bottles as bottles of ink, you know, like for a printer, but the bottles are not red, green, and blue. The bottles are the basis of DNA. A on the right. T, second from the right. G, second from the left and T. oh, excuse me, A-T-G-C, in that order. You hook these bottles up to a machine, you dissolve the chemicals and whatever information comes into your synthesizer, it dispenses the chemicals in that order, and you build a polymer of DNA from scratch. Remember joules, bits and atoms? This machine lets you go from bits to atoms for DNA, it's a one dimensional printer. String of DNA is a 1D object. But the cool thing about DNA is it encodes MRA, which encodes proteins, which are 3D objects. So I have a 1D printer that goes bits to atoms for the code of life that lets me do three dimensional construction by growth. I think DNA synthesis is the most important technology of this century, easily, because it's the bits to atoms conduit for life. In 2003, a younger and even more naive version of myself was leading a study for the United States government. The US government has an agency called DARPA, the Defense Advanced Research Projects Agency. And I was in charge of a study on synthetic biology, and we spent 18 months with the best scientists

### Segment 3 (10:00 - 15:00) [10:00]

and engineers that we could find to figure out how do we get better at bioengineering. That was our charge. And in October of that year, I was briefing the Director of DARPA on what our findings were. And in the middle of this slide, you can see what we were trying to get at in the top middle, this is how we thought people did bioengineering back then. It's like, "Oh, you know, I want a glowing plant. Let's say I want a bioengineer plant to emit light. How do I do that? I have no idea. It's a bespoke artistic process. I work through it. I make something like, hopefully it works. Eventually, it's a research project. " That's what the top right workflow's showing. We decided that we could advance how we engineer biology to make a more mature engineering like workflow based on composition and abstraction and programmability. And that's what we outlined down in the bottom. The people who were helping with this is the late Lynn Conway, along with her colleague Carver Mead, who helped invent VLSI electronics in the 1970s coming outta Xerox PARC. And Lynn was a great member of this study group. You see our first recommendation in the middle there on the left, DNA synthesis. "Hey, let's get better at building DNA so that you can design DNA and I'll build it for you. " And we decouple and desegregate workflow, be a massive improvement. You're the architect, I'm the general contractor, but for biology. I didn't get halfway through my pitch. A good pitch on the top floor of DARPA would result in a hundred million dollars program getting funded, and I'd be the program manager. A failed pitch would be no funding. I did worse than that. There was some public funding already deployed to get better at building DNA in the United States, but because of biosecurity concerns that better DNA synthesis would let people have an easier time building viruses to cause harm, all public funding for building DNA in the United States got cut to zero. Strike one. That turned out to be okay. Samir Kaul, now the managing partner at Coastal Ventures, then at Flagship in Boston. And Noubar Afeyan, founder of Flagship Ventures, Chair of the Board of Moderna. They organized private capital to try and get better at building DNA. And we helped start a first company called Codon Devices. When I first started teaching, that DNA printer that has four keys on the keyboard, like piano has 88 right? DNA printer has four keys on the keyboard. A-T-C-G, pressing one key on the DNA printer keyboard 20 years ago was $4 a letter, right? With this company we spent about a hundred million dollars and we got the price down to about a dollar a letter. And then we went out business. It was a really hard business, and we're having problems with operations and all sorts of challenges. There's many ways a company can fail, but we moved the needle on, in my view, the most important technology of the century, building DNA from four bucks to a buck. It was so frustrating that company failed that the very same afternoon in the boardroom where we wound down Codon, four of us started the next company without leaving the room. And that was called Gen9 with Joe Jacobson and the late Franco Serena and George Church of MIT and Harvard and BU. And with Gen9 in competition with others from, you know, up until 2017 when this got acquired, we got the price of building DNA from about a dollar a letter to about 10 cents a letter. We were heading towards 5 cents a letter. Tough business because the market is wanting you to get your price down, down, down. Which means your volume, how much DNA you're building for people has to go up, up proportionally, just to get the same revenue, right? So your investors aren't happy, but you're doing 10 times as much work if you drop your price. It's wild, wildly tricky business. Since Gen9 was acquired in 2017, the price of building genes hasn't moved, right? People think progress is inevitable. It's like, oh, not my experience. Like somebody has to figure out how to make it work. I'm really excited in DNA and gene construction, there's an innovation coming out probably in the next a hundred days or so that'll move the needle on this. Again, not my stuff, but I'll let those people bring it to you. There's another thing that happened when I came back from Washington DC having failed, right, to pitch this program. The government didn't really wanna work with us. It's like wild. But you know, who wanted to work with us? The teenagers, the students, the undergrads matriculating here in MIT. This is my lab back in 2006. The students are from the future. They could understand that getting better at engineering biology is gonna be important. They wanted to get to it. So this is a little team, a great team that worked the summer of '26, 2006. And they decided that they didn't like the smell of E. coli.

### Segment 4 (15:00 - 20:00) [15:00]

Has anybody here ever smelled E. coli? Take a guess. Like fecal bouquet, right? So they did a project where they figured out what causes that fecal bouquet. It's a chemical called indol. They knocked out a gene to disrupt indol biosynthesis. So now you have an E. Coli that's a neutral palate. And then they added in biosynthesis of methyl salicylate and isoamyl acetate which is chemistry speak for wintergreen, and banana. And so the bacteria cultures of E. coli, which normally smell like something else when they're growing are minty fresh. And when the cultures are fixed in stationary phase, they smell like bananas. And they called their project "Eau d'coli". It turns out that the fragrance and flavors businesses way back then, about 30 billion a year, right? It's bigger, bigger market now. Much more interesting to me was the idea that you could take the microbes that live on your skin and have programmable bacteria on your skin that make perfumes, that are living perfumes, right? That might be responsive to the environment or your body physiology. So with that positive experience from the next generation of leaders and entrepreneurs, Randy Redberg, Tom Knight and I on the right there, decided that we should try and make this something more systemic. And so that's become this thing called the iGEM, the International Genetically Engineered Machines competition. This is something that happens every year in Paris at the convention center. It's happening next week. The team from Stanford is shown here, and they'll be competing with 400, 500 teams from around the world. Students, this is like, a software programming competition or a robotics competition, if you're familiar with First Robotics. But this is for genetic engineering. And so what started as 16 students who believed in the future and of bioengineering back in 2003, has become about 5,000 students a year. The question on my mind is, how come it's so tiny? Why is it only 5,000 people a year? Why isn't it 500,000 people a year? That's the number I think it should be if we were advancing bioengineering at the same level of software programming. And the answer for why it's so tiny is it's still expensive. The tool set's immature. You know, there's just a lot of improvements, a lot of opportunities, a lot of opportunities for entrepreneurs. The number of companies coming outta this, I can't keep up, right? Like one of my favorite projects from last year, a winning project from last year was from Germany. And the students were working with dandelions It was a special form of dandelions that make a significant amount of latex, but I dunno if you've ever seen a dandelion, try to pull dandelion outta the ground, the stem breaks off and the roots hold tight. So they wanted to reprogram the morphology of the dandelion root so it's more like a carrot. So you could farm latex outta dandelions to get sustainable rubber manufacturing. Like imagine 500 projects like that rolling through this thing. You can find it all online at this website. So just wanna emphasize that if you're interested in what entrepreneurship or ideation looks like in my world of biosynthesis, check out this website iGEM, or talk to the people who are on the Stanford team. Scratch and sniff, reality strategy, joules, bits and atoms. Let me get to another thing. I found myself being pulled into work that was bigger than me, bigger than I would ever accomplish by myself. Like how do I make biology easy to engineer? That's more than any one person could do. And it's an amorphous dynamic puzzle that'll consume a lifetime. I started out as an academic, and what I learned as an academic is academics and universities have a superpower, which is they enable idiosyncratic innovators. Like Stanford is really good at this. It's also the weakness of Stanford. Everybody hears an idiosyncratic innovator. Like how do you coordinate stuff? How do you get things better organized so that they're, you know, like if you wanted, like I need to actually get a big thing done. Very hard to do in academia. The thing I learned about government was it has a superpower of convening and promulgation, can bring people together, can promulgate or it's a bully pulpit. But it's inefficient. It's inefficient on purpose. Like, DOGE is wild to me because anybody who understands political theory does not want an efficient government 'cause it risks oppression in a hobbesian sense, but it's also scared, which is why, you know, I was failing and then I had this experience with the dot com sector, right? And obviously, you know, the superpower of the dot com sector is you can organize people with money and the way our society operates, that's the easiest way to organize people. "Hey, I'll pay you. " Right? And the weakness of for-profit is you have to eventually make money, right? It's a constraint on what you can do. And it turns out there's one other way of organizing people, which is the for-profit, the public benefit charity, excuse me, right? And the superpower of the charities. You can organize people with a dream. The weakness is you gotta beg for money. Gotta figure out this. Now, I didn't understand this when I was your age. It took me until I was in my thirties to recognize that I could break out of the quadrant I was in, the bottom left

### Segment 5 (20:00 - 25:00) [20:00]

and navigate into some of the other quadrants. And by the way, academia's got the best passport to going into the other quadrants and coming and going. It's like super privileged passport. But when you look at the superpowers and weaknesses of these quadrants, they compliment one another. You see what I mean? And so if you're trying to do something that's bigger than you or bigger than one organization, you wanna have a strategy that helps you say, "What do I need these other quadrants, these other ways of organizing people to do for me? " Right? Lemme give you strike two. In 2011, 2012, I was organizing this thing that brought the British and the Americans and the Chinese together to develop a trilateral roadmap for emerging biotechnology. The British, the Chinese, and the US. Here's the delegation from Beijing and Shanghai. London. I was leading the delegation from the US. We knocked this outta the park. We just ran the same playbook that I've been running in 2003 for DARPA. But we ran it across these three countries. Hey, "What should we do to advance bio engineering? " We went to Beijing, to Shanghai. Here's what the Ministry of Science and Technology in Beijing had to say about their reflections of our trilateral roadmap. This is in June of 2012. They came to DC and presented, briefed back the work that we had done together. Well gosh, we gotta do all these things by 2022, get better at building genomes, work on nitrogen fixation, all these things biology could do to help us with food security and so on. And by 2032, we're gonna have full parts libraries like you would have in electronics and software like GitHub, but for DNA that's coming. And look at the bottom bullet there if you can see it. By 2032, we're gonna have learned how to construct life from scratch. Alright? It's a pretty good roadmap. This event in DC was strike two for me because it's a chair of the US delegation. We were surprised three days before the event when the entire US government delegation pulled outta the meeting. Unsubscribed. So the Ministry of Science and Technology showed up, but nobody from the National Science Foundation or you name it, showed up, right? It wasn't to do with US-China competition, it was to do with the domestic concern around fear of GMO foods. A cultural concern. Strike two. My whole field had a little ice age that ran from 2012 to 2020. You could not talk about synthetic biology easily within the US government. It's submarined. It only came back because of synthetic RNA vaccines and the pandemic. And so I was like, "Oh yeah, maybe building stuff with biology is kind of important. " Meanwhile, let's see if we get this video to work. This is a 45 second clip from the leadership of the Beijing Genomics Institute in Shenzhen, BGI. BGI is the world's powerhouse for sequencing DNA. But this interview you'll hear from Chantal who runs synthetic biology for BGI, she's like, "How'd they get going? " - If you change over the time that you've been back in China? - Hi everyone. I'm Chantal from BGI. So as you know, as John mentioned, BGI is famous for sequencing and I think like not many people knowing BGI is also dedicated, you know, developing the synthesis technology here. Because basically I think back in 2010, we have this chance, I think there's one time, Drew Endy, he paid a visit here, you know, at BGI and he gave a seminar and talk about, you know, introduce the concept of symbio and what's going on there in US. So, you know, after the seminar we start to, you know, have some discussion with one of the founder of BGI, Professor Huanming Yang. And then, you know, Drew raised the question here, like, "You know, for BGI, you guys like sequence a lot of different genomes from different, you know, from the environment, from different conditions. And that's the, you know, the natural resource for synthetic biology. You have so many different, you know, like, you know, data, you can actually, why not doing synthetic biology? " So back then, you know, because I was trained with major in bio, you know, bioengineering in my bachelor degree. - Chantal and her colleagues have been crushing it. Not only do they have the world's best factory for reading DNA, they've got the most recent papers published on getting better at writing DNA. Atoms to bits, bits to atoms for the stuff of life. Really impressive work. Meanwhile, I'm stuck in the United States of America. What do I find myself doing over last year? Well, I'm testifying before the government, US China Economic and Security Review Commission.

### Segment 6 (25:00 - 30:00) [25:00]

How did we get in this position? Or this summer before the Committee on Space Science and Technology in the House of Representatives. This is the committee that oversees the National Science Foundation, the Department of Energy Labs, NIST, the Standards Institute, and NASA. You know, op-eds in the Boston Globe. We gotta get to work. We're just at risk of becoming irrelevant on a competition basis. You think the stuff with Taiwan semiconductor and supply chains and chips is a big deal. Like, oh man, it is a multi-dimensional worse situation if you care about this type of stuff, in my world, in bio land. In the last year, we went zero to one on a team called Bio Strategy and Leadership with the help of Condi Rice. And so this was meant as an attempt to entrepreneur in a different direction at this interface between dot com, dot edu, and dot gov to help our government figure out what is biology as a strategic domain and how do we do something about it. Because if you go back in time, 10 years, or even this year, I'm usually like the only bio person in a room with decision makers and leaders. There's usually, if I'm not in that room or somebody, there's no other people in the room. We're just not thinking about biology as a strategic domain. Next tool, pace layers. This comes from Stewart Brand, class of 1960, Stanford University and Stewart's got this beautiful tool. I use it as often as I can. It's called pace layers. It's not a law of physics, it's just a heuristic device. Stewart says, "A healthy civilizations operates across six layers. " Nature, culture, governance, infrastructure, commerce, fashion, right? And it's called pace layers 'cause the pace of change accelerates as you go up higher. Fashion is fleeting. You wanna change the uniforms of the cops or the sheriff department, no problem. Just change the outfits. You wanna change the culture of policing? Much harder thing to do, longer time to change a culture. I like this tool because it lets me take a complicated topic and spread it out and find opportunities for entrepreneurship. So for example, think about the pandemic, the SARS-CoV-2 pandemic. Where's it in the pace layers? Well, coronaviruses are in nature to start, you know, we have an infrastructure for public health that's running at the edge. There's not a lot of surplus capacity. I've got a culture of freedom, so don't tell me what to do. My ability to govern what's going on is hit or miss sometimes. Is wearing a mask cool or not? Is it fashionable? Right? So see how you can take something that's not, especially when something's not working and like spread it out and go, why is this happening? And where might there be opportunities? Could you find an entrepreneurial opportunity from the pandemic? Sure, but here's what I bet you haven't thought of. Where did SARS-CoV-2 come from? We don't know. How's that an opportunity? What if I created a new type of business called a bio audit? We have financial audits because I don't trust you with money and nobody trusts me with money. So we audit, but what if we had bio audits as a private sector opportunity for managing the distrust we increasingly have in a world where people can program biology? So I'm not gonna trust you. You shouldn't trust me. Right? It's like, huh. Now will PricewaterhouseCoopers start a bio audit offering? Nope. But could somebody start that up and sell it to them? Yep. Right? So happy to talk about things like that more. But this pace layer tool is ridiculously powerful. Let me give you some examples as I'm navigating all this stuff. "Capitalism and Freedom" published in 1962 is an extraordinarily important book from Milton Friedman. The text I've highlighted is from his preface written 40 years after he writes the book in 2002 and he's privileged to reflect on his writings 40 years later. And look at what he says. "The one major defect in my book seems to be an inadequate treatment of political freedom. " Why was I deployed to China to help them accelerate emerging biotechnology in Beijing and Shanghai and Changzhou? Because the cultural framework and political framework I was inherited, right, was operating a strategy called "free markets will guarantee free people. " That turns out to not be a hundred percent correct. And Milton could see that in 2002. But because this is in the preface to his book and all the older people in positions of power bought the original edition and didn't read the 2002 version. Like, oops, right? So it's like where is this? This is at this culture governance layer, right? Or here's one I bet you haven't seen, check this one out. I'm so excited to share this slide with you. Stanford Historical Society winner, 1990. Here's a find. An article called "The End to Capitalism: Leland Stanford's Forgotten Vision".

### Segment 7 (30:00 - 35:00) [30:00]

Now what should we make of this? We'll just read the article. "In the last decade of his life, having experienced the heights of entrepreneurship and capital", literally Stanford's founding entrepreneur, he's like, "Huh, maybe there's some puzzles or problems. There's things we could do better. " And he rejects Marxism. State ownership and the means of production, but gets very excited about what he calls worker cooperatives. So I have a for-profit company, but the ownership of the company is among the workers. At times, Southwest Airlines I think did a reasonable job with this. There's some Spanish firms that are very well known for this. I'd love to talk to Mr. Stanford, right? Not gonna happen, but really interesting thinking here. And then look at the bottom highlighted section. Crash and burn. Becomes a US Senator, tries to work on legislation to advance worker cooperatives. Can't get bills outta committee, tries to found Stanford on the cooperative principle. Nope, right? It's like we've forgotten. I'm not prescribing this, but I'm just trying to surface examples from Friedman and Stanford that when you're navigating in the pace layers, a lot of times we think about the commercial layer or the infrastructure layer, but there's deep power and opportunity for disruption in entrepreneurship in the governance and culture layer, right? Like 400 years ago there was, a very entrepreneurial philosopher who came up with words like, "I think therefore I am", right? And underneath that is everybody's capable of reason. And because of that we get liberal democracy and like, whoa. And so things are ripe for entrepreneurship in these lower layers. It's just gotta find the sweet spot and it takes longer. Anyway, if you wanna see this current form of entrepreneurship, we have a website, victory. stanford. edu and you can see what we're doing. Couple more things. Time travel. This is one of my favorite tools. It's like, I like it more than pace layers. Here's some papers from 1974, the top left paper says, "Hey, we could hook up computers with packet switching networks. " And the right paper is an article from Stewart's magazine on the basic programming language. And if you read this article, it says, "Before, BASIC computers were for math majors and after, BASIC computers are fun. " Tens of thousands of little computers running BASIC are being made and sold right? Now if we were good at being entrepreneurs in 1974 and our job was to imagine the future of computing, what would we conclude from these two points of evidence? And it's an easy question 'cause we know what played out. But just to walk you through it, we'd conclude that there's gonna be computers all over the place. They're gonna be used for cat videos and other fun things in addition to serious stuff. And they'd be connected by a network that doesn't care what the data is going between the computers. We'd have no reason to know that the name of the video conferencing software is Zoom or the music streaming service is Spotify. That's arbitrary detail. But we get the big bones, the principle components of the computing feature right? And if we understood those dimensions of opportunity, wow, would we be much better prepared to be entrepreneurs? 'Cause we'd know where the future was going and how to fill that in as we wished. Does that make sense as an approach? So what I do as my method today is I collect postcards not from 1974, but from 2025 to try and figure out what's going on in my world and what are these dimensions of strategic opportunity. Here they are. I might be right, I might be wrong, but it's what I do for a living. So I'm probably better than random. Top left. I grew bioengineered tomatoes in my garden on campus last year. They've got blueberry stuff in it, so they're antioxidants in them. So I'm not supposed to get cancer as likely, right? Or I have a bioluminescent petunia I bought online from a website called light. bio. It glows in the dark. I gave it to my kids. It's a nightlight they water, right? I'm ordering GMOs to my house on campus. This is not coming outta my lab, I just buy it as a consumer, right? We already talked about DNA synthesis 'cause you know, you could use a brewing process not to make medicine, but explosives for missiles, right? Or of course we know about AlphaFold and AI and the Nobel Prize for protein structure top right. But this incredible work coming outta Stanford right now, Sam King and Brian Hie lab is training large language models, not on English, but on DNA sequences from nature. And now you prompt that LLM for DNA and it emits a DNA sequence and they're getting things coming out of these bio LLMS that are viable. Most recently a little bacterial virus got emitted by a bio LLM. Bottom right is some work from my lab where, you know, we're building cells from scratch. We're trying to make an operating system for life at the cellular scale like Unix, but for biology so that programming biology is actually easier and doesn't involve postdocs and labs in the future, right? So, I take all these postcards and it's like, well I'm gonna get a bionet in the future. We're gonna design the DNA in one place and download the biology somewhere else. Download and grow. Anything we can learn to encode in DNA can be grown. It's a general purpose technology. It's not just food and medicine, right? I think of biotechnology as being in a VAT somewhere

### Segment 8 (35:00 - 40:00) [35:00]

or a field over there. No, no, in the future biotechnology is gonna be on us. It's gonna be those programmable skin creams. It's gonna be inside us. You can buy probiotics off Amazon that are bioengineered to prevent hangovers, apparently, I've never tried it. It's gonna be all around us like that. That's my dresser in my bedroom with a bioengineered petunia. So it's like pervasive biotechnology. You know in a strand of DNA that's 135 letters long, you can encode, what is it like 10 to the 70th combinations, maybe a little bit more? That means if you make that strand of DAA little bit, you can code more combinations. That number 10 to 70th, 10 to 80th is about the same as I understand it, the number of atoms in the universe. In other words, the possibilities of biology are actually beyond astronomical. As amazing as natural biodiversity is on our planet right now, we will never see all the things biology can be. The only way to see that is to use these computational tools to search that combinatory space and print the stuff we wanna see what it is. This is wild. Oh yeah, my kids came home from school in third grade. They said GMOs are evil 'cause that's what they've been taught in Palo Alto public school. But then I gave them bioluminescent petunias and they went in the bathroom and turned out the lights and their retinas dark adapted when their cousins were visiting and they came outta the bathroom, like, "This is cool", right? So in the future, biotechs would be cool. Anyway. I might be right, I might be wrong. These are what I think of as the dimensions of strategic opportunities for the biotic future. What might that mean? Well if 50 years ago in Menlo Park, there was a revolution in the personal computer. The revolution was not in the physics of the transistor. The revolution was in the word personal. Who could compute where for what purpose? It changed the terms and conditions of computing. The PC by Apple. What if somebody made a company called Banana? And what Banana delivered was the PB? The personal biomaker, enabling, download and grow, connecting the superpower of the internet, moving information around with the superpower biology, which is growing with local atoms and energy. Leaves grow on trees. They don't come from a factory and you tape them to the branches, right? If I was younger, I'd do Banana, right? I'm gonna do something. I'll tell you what I'm doing in a minute. But like I'm doing something to make Banana easier. I know I'm going a little bit long, but I'm gonna do this. Okay, How many days we got? This is the number of days until 2050. You think 2050 is an impossibly long way from now. It's less than 9,000 days. Earlier this year it was over 9,000 days. But here's the countdown. By the time most of you are in your forties it's gonna be 2050. What do you want to be true in 2050? Not just for yourselves but for the world. We're on the clock. Not only what do you want to be true, but what do you want 2050 to feel like? I want you to tell me, we're gonna try this out loud in 20 seconds. I want you to shout out loud what you want 2050 to feel like, okay? It's gonna be a little awkward, but we're gonna do it. Just one word. (crowd chattering) Let's hear it. What do you wanna feel like? (crowd chattering) - Insurance, live forever. - Ah ha. Did anybody say multinational corporation? (crowd laughing) Interesting. Feel the future. Okay. I hope you all know of this speech. This speech was not called "I have a plan" or "I have a pitch deck" or "I have an investor or a term sheet". This was a speech we know as "I Have a Dream" which is important because dreams are tools we use to organize ourselves. I use to organize myself. Very quickly. There are two big types of dreams. They're both valid. One you know of is the nightmare. When Vice President Gore struck a warning about climate change, he made a narrative choice to frame it using the language of a nightmare, inconvenient truth, a global warning, a conflagration. It's a very powerful way to get attention and organize people. But you run up a credit card bill when you do this because you will not get sufficient collective action till enough people believe the nightmare's real. Easier to launch, harder to land.

### Segment 9 (40:00 - 45:00) [40:00]

You could say this rhetoric in a way strangely has increased the likelihood of a climate crisis. The language of like, "Wow, there's so much carbon in the atmosphere. What's our climate opportunity? Can we get the climate awesome? " Anybody talking that way? Oh, that's a different type of narrative structure. That's a narrative of positive, aspirational dream. Like Martin Luther King's dream, right? It's much harder to implement, it's riskier, but if you can pull it off, you can get collective action in advance of reality and co-laboring towards something. So a lot more to say on this, but I just wanna drop a placeholder. Dreams are tools. Choose your dream's narrative structure wisely. It matters a lot. Here's my dream. As a long ago civil engineer who loves suspension bridges. Here's a suspension bridge grown with biology from the roots of a rubber tree in east northeast India. It fixes carbon over time. It gets stronger over time. It's passed down from one generation to the next. It eats water. He's a lot of water. I'm not worried about water. Turns out, as you know, right, the physics of flourishing are pretty good on this planet. We got over a hundred terawatts of energies harvesting through photosynthesis. All that energy goes into biology and makes stuff where the biology is right? We connect this up to the opportunities that I laid out. Those six dimensions of opportunity? We can enable 10 billion homo sapiens to have a good life where they are for themselves. They're gonna have to do the work without trashing the rest of the planet. Like the napkin math on flourishing in a physical sense is really good. The politics of plenty are not worked out at all, right? Like nobody's cracked that puzzle. The entrepreneurship between these two things needed is off the charts. We're gonna start a new organization that's modeled after Xerox PARC but it's gonna be a charity and we're gonna try and unlock some of these foundational technologies that open up those dimensions of opportunity. We're gonna give 'em away, right? So that's the last entrepreneurial thing I'll do with my career between now and as long as I have. Maybe a decade, if I'm lucky. First time I'm talking about this publicly. So don't ask me too many questions. Here's my last slide. I hope you take from my story, something that's not about me, but a set of tools you can use for yourselves with whatever entrepreneurial future you have. Here they are. See and scratch. Just pay attention and don't ignore strange things like figure out why it's happening. If you wanna organize people know you have options. Sure it can be the for-profit corporation that is strengths and weaknesses, but there's three other quadrants. Go for it, right? Pace layers. Take a complicated puzzle, spread it out, figure out where the opportunities are. Travel through time. If you had gone back in time in 1970 and 1980, would you have called the entrepreneurial opportunities correctly? You can practice 'cause you have the track record, right? You don't have to just figure it out in the current moment. That's really hard. Learn from the history of this. Everybody's so much like trying to plan the future or explain the future, right? Much better to feel the future, right? Like pull that out when you're feeling like somebody's future's on me and I'm not getting what I want. You know, like what's the future I want? Feeling the future is an extraordinary, powerful tool. And then lastly, dreams is tools. Thanks so much for your patience. (crowd applauding) - That was super inspiring. Drew, I know you, you've been talking. I wanna see if we can squeeze in some questions in the few minutes that we have. I'm gonna call up Mahathi to come up to get primed to be the first person to ask the question. We're gonna go to this mic over there. And then we also have a cold call tradition in this class. And I'm gonna be cold calling whoever's in D102, which I think is that row. If you have a 102 in that row, you're on deck. Is anybody there? Okay. Otherwise it's you. So you'll be on deck as number two. If anybody else has any other questions, you can start to line up behind this mic and we'll try to get through as many as we can. Mahathi Thank you so much for your talk, Dr. Endy. My question for you is a bit about how you've championed open source biology research in the past. In your journey working towards more collaborative biology research, what sacrifices did you have to make and is there anything you would like to do differently? Looking back at that? - Yeah, thanks for your question. The reason I'm so in favor of open source technology, especially biotechnology, is it's a generative opportunity. So how many poems could be written? Well, an infinite number of poems. How many programs could be written? An infinite number. How many bioengineering applications we're gonna need? A infinite number. And so for that to come true, we need to have free to use languages and open technology. And so my niche is to make that happen sooner rather than later. I don't feel like I've given up very much

### Segment 10 (45:00 - 47:00) [45:00]

because I've been able to navigate with the supportive institutions. Here's something you might, here's something I bet you don't know. If you read Stanford's patent policy, paragraph four says, "If the inventors would like to put their invention in the public domain, they're free to do so. " We're one of two universities in the United States that allows for that to happen. And so when we do entrepreneurship and translation from the university, yes, you could do a patent and licensing, but you could also give things away for everybody to benefit from. And the rule of thumb from Silicon Valley is if you wanna start a company, have a patent. But whole sector, give it away. Right? So I've been blessed enough here to be able to experiment and push open forward. Yeah. - That's fantastic. Thank you. Thank you for the great question. Next question and go yeah, try to go next to the mic if you can. Yeah. Thank you. Audience Member Hi Professor Endy, thank you for speaking with us today. I had a question about, you mentioned how when you had that DARPA presentation, there were concerns about biosecurity that kind of flattened it. So I guess my question for you is, in the time since then, how have you engaged with the discourse around biosecurity and how, you know, the implications of synthetic biology can have, you know, pretty scary ideas. So like how have you interacted with that? - I continue to work on the puzzle over the last 20 years. The short version of the answer though is earlier this month, just week before last, we published a major report on biosecurity. You can find it at our website, victory. stanford. edu. The title of the report is "Biosecurity, Really? " And it's our view on how to secure biology. The good news is we believe we can secure biology, but it's gonna take work and we have to admit in our opinion that these capacities are gonna proliferate. So you have to price in that people are gonna be able to make dangerous things if they wanted. People are gonna make new dangerous things that they wanted and so we just have to deal with that. So, but please take a look at the report. If you have any questions about it, shoot me an note. - Gotcha. Thank you very much. - Thank you. - With that gang, I have to draw this session of ETL to a close. I know there's other questions you can come up after class for a few moments. Actually, you might not have access, but we'll try. Everybody join me in thanking Dr. Andrew Endy. (crowd applauds) (bright music)