Monday, June 29, 2020

Out of the Crisis #11: Jeremy Howard on the power of masks, health policy, and data science in medicine

Jeremy Howard has had tremendous impact on the world of AI entrepreneurship., the company he co-founded with Rachel Thomas and Sylvain Gugger  is working to "radically democratize" deep learning by making it accessible to people beyond the tech world through courses, software and other methods. Enlitic builds machine learning-based software for radiologists that produces more accurate and faster assessments.

Data science is the foundation of all of these enterprises. It's also what led Jeremy to sound the alarm about the value and effectiveness of wearing masks when the pandemic arrived in the U.S. The "drip drip drip" of data he was seeing from countries that were hit first told him what was coming, and he made it his mission to start a campaign for masks -- Masks4All. His goals are two-fold: to get the American public to understand how crucial mask-wearing is not just for individual protection but for the protection of everyone around us; and to lobby for policy change that would make wearing them the law.
He was joined in his efforts immediately, as he told me, by dedicated and talented "self-selected people" who connected him with media outlets, politicians and more. An article he wrote for the Washington Post, published on March 28th, when America was still reeling from the exponential growth and the CDC was telling the public not to wear masks, was the first real call to arms for masks. It was followed a month later by a piece he collaborated on with Zeynep Tufekci and Trisha Greenhalgh, explaining that the real reason to wear a mask is to protect others, rather than ourselves. It detailed modeling that shows that "if 80 percent of people wear masks that are 60 percent effective, easily achievable with cloth...that’s enough to halt the spread of the disease."

Jeremy and I sat down to talk about the creation and growth of Masks4All, what it was like to sit at the center of health policy debates, statistics, and many other things. In the time since our conversation, data and science have shown again and again that wearing masks is an incredibly effective, low-cost and simple way to prevent viral spread. The difference in caseloads between counties and states that have done it and those that have not is stark. Models show that using them can make a huge impact on what lies ahead, too.

You can listen to our conversation on Apple, Google, or wherever you like to download podcasts.


A full transcript follows the show resources below.


Highlights from the show:

  • Jeremy on his background in AI, data science, and his education (2:17)
  • Jeremy on starting at McKinsey at age 18 (4:30)
  • On how his ability to look at the data early on affected his quarantine setup (6:57)
  • On the collaborative efforts among strangers to fight COVID (7:37)
  • What Jeremy was working on when the pandemic hit (10:44)
  • How masks came into his life and how he founded #Masks4All (14:23)
  • On the moment when we were all told not to wear masks and how that changed (18:05)
  • On the reasoning for not wearing masks and the science going on behind the scenes to prove they were effective  (21:33)
  • On how health policy is made and communicated (25:58)
  • The class, youtube video and article that became the first U.S. call to action on masks (28:10)
  • Petr Ludwig and nearly 100% mask usage in the Czechia (32:30)
  • Wearing masks as an act of resistance in Czechia (35:35)
  • Jeremy on people are taking matters and health into their own hands to make change (37:35)
  • The sudden availability of experts as volunteers (42:43)
  • Jeremy's TV appearances on the mask issue and what surprised him as policy changes occurred (44:31) 
  • Credentials: why they matter and why they shouldn't (52:22)
  • Jeremy's public persuasion campaign to get people to contact officials about masks (53:47)
  • Using Resistbot to get the message across (55:27)
  • The number of states that had mask laws when Jeremy started, and what happened next (58:13)
  • States that have mask laws (59:35)
  • The issue of masks vs. the virus intruding on rights (1:01:49)
  • Conversations with policy makers (1:02:54)
  • Measuring the progress of #masks4all (1:04:32)
  • The effects of doing things in minutes versus doing them in weeks (1:07:46)
  • Asymmetric upsides and downsides of the pandemic (1:09:19)
  • The history of masks in the 1918 flu pandemic (1:10:14)
  • The misguidedness of doing nothing until you can do something perfectly (1:13:40)
  • Jeremy's advice for what people can do -- the drive train approach (1:15:12)
  • What Jeremy hopes we take into the future from this experience and where we go from here (1:20:29)


Show-related resources:

Transcript for Out of the Crisis #11: Jeremy Howard

Eric Ries: This is Out of The Crisis. I am Eric Ries. If you go outside, you need to wear a mask. You know that, right? But how do you know that? Think about how quickly we as a society have gone from thinking that masks were something that were pretty strange to where in public to understanding, not yet completely, that they are a necessity. It's not a coincidence. It didn't happen by itself. People had to make a change. Some of them were politicians and leaders, scientists, public health officials, but some were just citizens who realized that something new was needed. I normally start by saying something about where we are in this crisis, however, my guest for this conversation is so concise and clear about the data and what we all need to do that I'm just going to let him summarize it.

Jeremy Howard is not a medical doctor. He's not a lobbyist. He's not a politician. He is a data scientist. This data scientist is the reason that many of our cities and states are telling us all to wear a mask outside right now. Jeremy never thought of himself as an activist, and he certainly didn't expect to be part of the reason that many cities are flattening the curve as we speak. But he is leading the #Masks4All movement. #Masks4All is advocating for everyone to wear a mask to stop the spread of COVID-19. That may sound like common sense today, but it was only a few weeks ago that this was a very radical proposition. This is a citizen-driven movement that has led whole states, countries, and public health agencies to revise their guidance on masks.

Jeremy and I talked about why he is such a big believer in masks and what the data says about why masks are important. I've learned a lot from him about how to use data responsibly, and about how we can be more evidence driven in our decisions as a society, as policymakers, and as individuals. Here's my conversation with Jeremy Howard.

Jeremy Howard: I'm Jeremy Howard, a research scientist at the University of San Francisco. I chair a medical data research lab called WAMRI, and probably best known as the co-founder of, although increasingly finding myself known, surprisingly enough to me, as the co-founder of this thing called #Masks4All.

Eric Ries: Jeremy, thanks so much for taking time to talk to me, just give us a little bit of a sense of your background before the crisis hit.

Jeremy Howard: Sure. It's a bit of a weird background. I'm mainly known as an AI guy nowadays, since I'm the co-founder of, which is a reasonably well-known research lab that also does teaching possibly the most popular AI deep learning course in the world.

Eric Ries: It's really good.

Jeremy Howard: Thanks. And we have a software library called fast AI, which is the most popular layer that sits on top of PyTorch for deep learning. Before that I founded a company called Enlitic, which was the first company to focus on deep learning and medicine. You can see why I'm known as an AI guy. Before that I was an equal partner in Kaggle, which is a popular data science competition community. But before that I did a range of different things. I spent 10 years creating and running an insurance pricing company, 10 years creating and running a popular email provider called Fastmail, and almost 10 years as a very boring corporate strategy management consultant at McKinsey.

Eric Ries: It's a very eclectic set of work experiences. What was your early life educational background like?

Jeremy Howard: Not much really. I started at McKinsey when I was 18. Although in theory I have a Bachelor of Arts, I didn't actually go to any lectures, I only went to the exams. It was a bit of a stressful time because I didn't go to any lectures so at the end of the term, I'd go to the teachers and say, "Hi, I was actually in your course. Did you have any assignments? Could I do it by tomorrow? Because I know it's late, but you know..." They always said yes, somehow.

Eric Ries: Very kind of them. How did you get into AI originally?

Jeremy Howard: Well, I was always super interested in what people now call data science. That's been the common theme throughout my career. The reason I was able to get into McKinsey at 18 was because I use this data driven approach. McKinsey called me an analytical specialist, which at the time I thought I was the only one, but I found there was two others around the world. We found each other. So I was always doing linear programming and operations research stuff, and regression models and whatever to try to solve corporate strategy problems.

Eric Ries: How did you even have the idea at 18 to take that to McKinsey?

Jeremy Howard: Too much fiddling around with Lotus123, I guess. There was actually a teacher who taught us... I think we had one class about spreadsheets in high school and I was just like, "Wait, this replaces nearly everything we've learned in math and science." So I just got to do nothing but this. So I did spreadsheets and then the guy that lived across the road from me was like, "I'm a management consultant, do you know what that is?" I was like, "I have no idea." And he told me. And I was like, "Okay, I want to do that too." So he said, "Okay, well you can look at all this human resources data for this mine in Ghana. You could probably use your spreadsheet to like crunch it."

And I did and he was thrilled. And then this thing called Microsoft Access came out, which I learned was this thing called a database. And that was like a spreadsheet on steroids. And so I started doing that with this management consulting guy. So it was all like, I don't know, something I should have been doing in high school, but instead I was doing this I suppose.

Eric Ries: Oh my goodness. I can really relate. I have similar stories about computer programming from my early days.

Jeremy Howard: I mean, I was never much of a programmer. It was all like...

Eric Ries: No, I know. That ability as a young person to get adults in the grownup world to take you seriously-

Jeremy Howard: Well it was so much easier then because none of them knew how to do this stuff. So by the time I got to McKinsey, they thought I was some magician, which is good because the rest of them used interviews and expertise and knowledge, which I didn't have any of those things. So data was my fallback.

Eric Ries: I feel like this is like foreshadowing for things that are going to happen later. That's pretty awesome. These are dark times and it's been very stressful for all of us. First of all, how are you? How's your family? What's your quarantine set up like?

Jeremy Howard: Sure. So we looked at the data a few months ago and realized this is going to be bad. We weren't sure how bad. So working on the precautionary principle, we assumed it could be really bad. So we left San Francisco a long time before the lockdown happened, went somewhere remote, but reasonably close to a good hospital. And we've been hanging out there since.

It's been okay, we've got a four year old child and she's just... It's amazing how adaptable she is. She spends more time on zoom each day than I do just hanging out with her friends and they somehow keep themselves amused.

Eric Ries: I'm very familiar.

Jeremy Howard: Yeah. It's been interesting because some of our family are healthcare workers. Some of them have got sick, but then they got better. So there was like scary moments. So plenty of dark bits, but also this weird discovery that you can create incredibly close connections with people that I've never met before and build a global community of people who want nothing more than to help save lives. And that's been remarkable. I've discovered this... I've never had such a collaborative period in my life, but by far, and I say this as somebody who's done a lot of collaborations, so there's been interesting highs and lows like that.

Eric Ries: I had so many similar experiences and I was just, someone was asking me something about one of my collaborators on one of these projects. And they asked me about his background before the crisis. And I realized, I knew absolutely nothing about him.

Jeremy Howard: Yeah.

Eric Ries: I couldn't answer even the first question. I said, listen, we're bonded for life. I would do anything for this person, but I actually don't really know them. We've never met.

Jeremy Howard: Yeah. Well, I mean, same with you, right?

Eric Ries: Yeah.

Jeremy Howard: I vaguely knew who you were because I was at Singularity University overlapping when you did some stuff there, but I don't think we ever bumped into each other and I know some of your work, but then I was introduced to you for reasons, totally unrelated to any of that. And we've been helping each other out or mainly you helping me out, which is an example of this.

Eric Ries: Well, I hope it's been helpful and certainly you've been helping me and so many of us through your work on #Masks4All so I think we all owe you a debt of gratitude for that.

Jeremy Howard: Well, it's boring and horrible as all hell, so I'll take it.

Eric Ries: Yeah, exactly. I don't think this the kind of work that anyone does for fun. Do you have a favorite quarantine tip?

Jeremy Howard: It's possible to live on a life of a diet of nearly entirely carbs that come out of your freezer and not fall apart. It's very different to the diet I used to have of like fresh fruit shopping every day, but it seems to be working okay. I've also discovered that I don't actually need my home Olympic lifting gym as much as I needed. I've discovered much more about the ability to use body weight exercises to keep myself from getting too flabby.

Eric Ries: I think we've all had that learning. That's great. Yeah. Yeah. Appreciate you sharing. All right. So where were you? Do you have a moment that you recall when the severity or the reality of the pandemic first occurred to you or became manifest to you?

Jeremy Howard: No. I mean, for me it was a drip, drip, drip of data. I think as soon as we saw community transmission, strong signs of asymptomatic transmission during, I don't know, January, then into February and happening around the world, it seemed like there was a pretty high chance this is going to be a very serious global pandemic.

Eric Ries: What were you doing at the time? How were you spending your time between fast AI and, and that year university commitments?

Jeremy Howard: Well, they're kind of one and the same. fast.AI and my university is just amazingly great. They're super flexible and helpful. So really everything I do in fast.AI is connected to the university and vice versa. So my focus has been on taking our research software and courses to the next level. I really felt like we had gotten to the point where we had a really good way of doing and teaching deep learning. And so we decided to take 18 months off, pretty much teaching and doing anything else and focus on making our software as good as it could be. So we rewrote it from scratch. We wrote a whole new kind of development environment for writing it from scratch.

And we decided to write a book about it. And we wrote a whole new kind of publishing system for writing the book. So it's kind of like being this really cool eighteen months of working with my colleague and we were coming to the end of that process. So the book was kind of through the middle of the year and recording the course started a few weeks ago. So it was really getting to a very exciting part of, I guess, the last five years or four or five years of my life building up to this moment of the first half of this year.

Eric Ries: And then life throws you a wrench into those plans?

Jeremy Howard: Yeah, a little bit. I mean, we've actually finished the book. And so, hopefully it won't be too late. People have already pre-ordered it, lots of people. And the software already works great. It still needs some documentation cleanup and I'm still teaching the course, which has actually been super weird to spend time every week in the middle of all this stuff that's going on.

Eric Ries: Yeah. But to be clear, I think it's important for people to understand, you're not an epidemiologist and you were not working on masks or quarantine and pandemic related topics, I mean, even as recently as a few months ago.

Jeremy Howard: Oh God, I would never choose to work on masks if I didn't have to. Good Lord, no. I could think of nothing worse. Yeah, no, absolutely. I do a lot of medical work, particularly, because as I mentioned, I was the founder of this company called Enlitic, which was the first company to focus on deep learning and medicine, but my focus is more on medical imaging. We do a lot of work... We work with Stanford and Harvard and UCSF and a bunch of academic medical hospitals to help them bring modern techniques to their projects.

So like one of the really cool things we did was to work with the Salk Institute, which is arguably, the top life biology lab in the world. And we worked with their core microscopy team and built a new algorithm with them that we co-published, that basically allowed them to get orders of magnitude higher resolution from their existing equipment, allowing them to map the connectome of a brain and how it changes over time in ways that have never been done before.

So that was the work I was doing. And it was a lot, lot, lot more interesting than masks.

Eric Ries: So how did masks come into your life and how did you wind up founding this group?

Jeremy Howard: Well, one of the things I care a lot about is how we understand data as evidence. And it drives me crazy to see how most medical research has treated it as this binary decision with randomized controlled trials and P values. And it's like, "Oh, this is statistically significant or it isn't." So one of my long running rants has been about how we should gather all the evidence we have to try and make a best guess as to the distribution of possible outcomes based on possible upsides and possible risks and costs and make an overall assessment of that totality of evidence and impacts. So I was teaching that in this course, because it's not just a deep learning course that covers a lot of machine learning and data science topics like evidence and probabilistic reasoning.

So I wanted a case study and one of the things we talk about a lot in the course is ethics. And we particularly talk about the idea that a data scientist should have a responsibility to not just analyze data, but to do something with it, to stand behind their results, to talk to the people who can use them. So I wanted to get something current and relevant to policy. So I noticed from stories on social media, I guess, that countries that were using masks a lot, seem to be getting better outcomes than countries that didn't at like hundreds of times better, which is exactly the evidence which a lot of medical folks tend to ignore because it's so imperfect.

Eric Ries: What kind of evidence were you looking at?

Jeremy Howard: I mean, just the data like Taiwan, Hong Kong, Mongolia, right next to China, a lot of trade, a lot of social back and forth, Chinese New Year, yet they're in double figures, numbers of deaths. I think it's four or five in Hong Kong. They've kept their economies open. Restaurants are still doing business, compared to nowadays in places like London and New York, you're getting thousands and thousands of deaths every week. And even at that time, it was very, very obvious that the trajectory in these countries was extraordinarily different.

Eric Ries: I think for a lot of people listening, they'll think to themselves, "Wait a minute, I was on social media at the same time as you were. I don't recall seeing this data or understanding it." So just talk a little bit more about what you actually... How that data came into your awareness. What did you actually see? And then what was it about that data that prompted you to want to take action versus viewing it more as an academic curiosity?

Jeremy Howard: Yeah, well when I say social media, for me, that means Twitter and I'm very careful about my use of Twitter. I use the API to find interesting topics and accounts and kind of go out from there to find a range of perspectives. That might be interesting. So my Twitter feed is fairly carefully curated. And I'd say at this point it wasn't, I was determined I was going to make a big deal of this masks thing. It was more, as I said, I was just like, "Oh, I wanted to teach a lesson." And I thought, I'd just explore a little bit for a few hours to see if this would make for a good lesson.

And so really, what happened was I was just shocked by what I found that the quality of the evidence was still a little sketchy, but the apparent size of the impact was astonishing like many orders of magnitude in terms of human life and hundreds of billions of dollars of potential economic impact. And I thought, "Wow, this is really surprising that I just don't hear anybody talking about it." While I was doing this, there was an article that came out in the New York Times from Zeynep Tufekci, basically saying, "Hey, you guys telling us that masks don't work was kind of a dumb thing to do." She's a professor of sociology. So that was-

Eric Ries: We'll put a link to some of her writing in the show notes. It's astonishing how Zeynep is always first to so many of these ideas.

Jeremy Howard: Yeah, yeah. She didn't go as far as saying we should all be wearing them, but she was like, "You should at least not be lying to people as a matter of health policy."

Eric Ries: Explain a little bit about the state of thinking at that time. I remember that there was a strong statement from, I think from the CDC saying don't wear masks. And also explain that we're talking about masks for the general public. We're not talking about N95 masks or the masks for nurses. Just say a little bit about what was the controversy at that time.

Jeremy Howard: People just used the word mask. They didn't just really distinguish the idea that there were multiple types. The surgeon general got out on Twitter as I was doing this research and said, "Masks don't help. So don't use them and let the healthcare workers use them." So he was kind of the one who made the most direct and clearly wrong statement. The CDC and who were just more like highly misleading. The WHO still has a policy of saying, "You should only use a mask if you're sick or you're with somebody who's sick." But of course we have no idea who is sick. So it's kind of--that's weird. Other health bodies like the American and European disease control centers generally had variants of the WHO, which were very different to Taiwan that invested massively... Well, their SMEs basically invested massively to get to a point where they could create 10 million masks.

I think it was 10 million a day for 30 million people in Hong Kong, where about 90% of shops require a mask to go inside. Mongolia, which I think had a law about requiring them. The interesting thing for me, I'm very interested in... I've got an implicit bias in racism and stuff like that. And to me, the idea that these countries that have fairly recent experience and expertise with respiratory pandemics were being ignored when it came to policy. And I kind of thought, "Well, I wonder if that's because they don't look like us." People assume that they're somehow different. And so it's one of these kind of systematic bias issues that I'm very interested in digging into to see whether the data actually tells us something different to what our biased intuition suggests.

Eric Ries: So what was the reasoning for not wearing masks, especially given the data that you were seeing... I don't know if you want to do a rant on statistics.

Jeremy Howard: I mean, I wouldn't exactly call it like that. That's certainly like a lack of probabilistic approach. So there's this thing called evidence based medicine, which drives me crazy. And I do plan to write something about this with folks that are experts on this. Evidence based medicine is this kind of very binary thing where you do a randomized controlled trial and you find out if the P value is less than 0.05 and if it is, you say it's significant and then you recommend it. And this is actually totally out of line with the guidelines of the American Statistical Association. They have seven guidelines around this, which clearly say don't be using P values and stuff as the basis for your policy decisions. Because a P value tells you nothing about whether a relationship doesn't exist. It also tells you nothing about if it does exist, how important it is, like it doesn't actually matter.
So the... And the WHO is very, very, very into this approach. So I've spoken to lots and lots of advisors to the WHO and they're all feeling kind of crazy about this. Because they're all saying, this so much looks like maybe the most important tool we have. It's possibly as important or more important than distancing and it's certainly a hell of a lot cheaper. And the WHO saying well effectively when we're not going to recommend it in the absence of a randomized controlled trial. And here's the thing, it's actually impossible to run one.

So what would a randomized controlled trial for the impact of masks on community transmission look like? Well it would have to be at a community level, otherwise you can't tell the impact on community transmission. So it'd have to pick a hundred cities and then say to fifty of them--and that hundred cities will have to be representative of the population you cared about. And then you have to pick fifty of them and say, "Nobody in these cities is allowed to wear masks." Then the other fifty you'd have to say, "Okay, everybody in these has to wear masks." And that would never get past an Ethics Review Board because you can't... We have such a strong Prior that masks work, that telling large groups of people not to use them would be very likely to lead to a massive amount of deaths.

Eric Ries: So it's interesting. It sounds like there are these theses out there, where the Prior is strong enough that you think it's a good idea that you can't run a trial without it. But the evidence is not strong enough, according to the P values that you can actually endorse it as the policy.

Jeremy Howard: Well, you can't even get a P value.

Eric Ries: You can't. It's unstudiable and therefore not recommendable.

Jeremy Howard: Right. It's studyable using observational techniques. So what I did for this lesson was I tried to show a range of techniques that data scientists can use to gather evidence in the absence of a randomized controlled trial. So we can do things like say, "Okay, how was this transmitted?" And it turns out it's nearly entirely transmitted through droplets. Seems like mainly when we speak, maybe also when we breathe. And it's like, "Okay, let's just look physically at... Do those droplets get stopped by a piece of cloth?" And so I actually came across... Somebody actually reached out to me and said, "Hey, I've been doing a kind of a secret study of this in a laser chamber." And it'd have to be secret because publishing this stuff at that stage was basically a career ending move. So all the scientists I spoke to were not able to go on the record about their work. So I knew about a lot of science that was being done in secret. And they-

Eric Ries: It’s antithetical to the scientific reader

Jeremy Howard: In theory, it should be. Yeah, but the problem is when you do a piece of work that suggests that the leading health policy bodies are saying the wrong thing, it does tend to undermine the credibility of the big health policy bodies. And that's a huge problem, because we need to, people need to take vaccinations seriously and take condoms seriously. So there's a lot of historical reasons why we protect these health policy bodies. And so the fact that they've messed up so badly with masks is not just telling people because they're not wearing masks, but it's also undermining the credibility of a system that we really need people to trust.

Eric Ries: Yeah. I don't know if you're familiar with the book, Good Calories, Bad calories by Gary Taubes, but he's a science reporter who looked into why so much of the nutritional research went astray over the past few decades. And this issue comes up again and again and again, as people discovered contrary findings but suppress them because they didn't want to undermine the public health authorities. Because they lacked that information we're giving people the wrong advice.

Jeremy Howard: Right. Well, I mean, one of the things we can certainly talk about is how much I've learned about how health policy is done. It'd be nice to imagine it was this kind of science- based thing and what the WHO says is based on what scientists say. But unfortunately there's this huge disconnect and the policy in false politics. And so once a health body says something, they have a tendency, particularly in the WHO's case to kind of stick with it, even as new information comes along, for far too long.

And they also tend to communicate in ways that are really unhelpful to the public. So for example, they still have this GIF up on their site, this picture saying "COVID-19, or the particles, is not airborne." Which is strictly speaking, true if you use a really kind of wacky definition of airborne, that doesn't mean borne through the air, but means reaches a certain droplet size, which hangs around for a certain amount of time and potentially go through vents to other floors of a building and so forth. But it's absolutely true for sure that nearly all transmission seems to be borne through the air.

Eric Ries: Right.

Jeremy Howard: So policy bodies communicate in weird ways and they make decisions in weird ways and there's this huge disconnect between kind of science and policy. Which means that for me to get the policy changed here, I actually had to become an advocate and a campaigner. It wasn't enough to just find these scientists that were doing good research and to help kind of publicize them and create our own research and so forth. That's just not enough to move the dial on policy.

Eric Ries: Let's go back to having this realization, that masks were going to be an important part of the public health solution. You're a university professor, I think the caricature of a university professor is maybe you would write a paper about it or teach a class about it. Or maybe if you're feeling really adventurous, tweet about it or something. But you wound up doing something different. Why?

Jeremy Howard: Well, I mean, I was a caricature professor, I taught a class about it. So I said, like, "Hey look, gang..." So I've got about a thousand people in this class today that I teach each week. And I said, "Okay, let's start looking at this evidence based kind of data analysis. So we're doing masks this week. And here's what happens when we look at the population based epidemiological evidence. And here's what we look at when we look at the physical evidence. And here's what we look at when we look at kind of efficacy studies. And overall, we can put all this together and we can estimate the economic value of a mask as being something like $5,000 per person per mask, blah, blah, blah."

And so I don't know, that was like 10, 15 minutes of class. And so my students were like, "You've got to tell other people this. Don't just tell us." Because normally we don't make our material public for a few months. So I was like, "Okay." So I extracted that little bit and put it online.

Eric Ries: Do you remember when this was?

Jeremy Howard: About four weeks ago I guess.

Eric Ries: So this would be mid March basically?

Jeremy Howard: So I can tell you the date, 24th of March.

Eric Ries: So you taught this class on March 24th?

Jeremy Howard: Yes and uploaded the video to YouTube on the 25th. And then on the 26, much to my surprise, an editor from the Washington Post emails me and says, "Hey, Dr. Howard, can you write an article about this?" And I was like, "Well, A, I'm not Doctor." People keep assuming this, is just like, I'm just a data scientist. "And B what do you mean an article?" And he was like, "Well, this actually seems like something that's important." And at this point we had actually, my co-founder and wife, Rachel Thomas and I, had actually, couple of weeks earlier written an article on our blog saying like, "COVID-19 is actually kind of going to be a big deal. Please take it seriously." So we'd already kind of done a little deep data science dive into that and much to our surprise, like a million people read it, even though we just put it up on our blog.

Eric Ries: Yeah, I remember that. It was a time when there was very little information that the popular... That was with high quality that members of the public could consume.

Jeremy Howard: Yeah. Yeah. A lot of... We heard from a lot of hospital administrators and people running companies and stuff saying, that was the reason they started taking it seriously and they started canceling their events. And so that was cool.

Eric Ries: We'll include a link to that article in the notes.

Jeremy Howard: Cool.

Eric Ries: So you can... I want people to be able to see how fast, how far we've come in such a short time in terms of our understanding of this pandemic.

Jeremy Howard: Yeah, it's ancient history now.

Eric Ries: Right.

Jeremy Howard: But again, I was tired of this thing of like, "Hey, we're data scientists. This is what the data says. This... That it's going to be hard for us to act rationally because our kind of gut is not used to dealing with exponentials." So I guess when this editor reached out, I was like, "Okay, I guess I know that our writing can make a difference. So, all right, I'll give it a go." So I wrote an op-ed and I'm lucky enough to have some fantastic friends, particularly folks that I've met through the World Economic Forum, who I reached out to, who write op-eds all the time. And they made my op-ed way, way better. And yeah, I sent it in and thanks to them, it turned out great. And apparently over a million people read this thing in the Washington Post, which, the title that I think they picked, I don't... Can't remember who picked, it was, "Simple DIY masks could help flatten the curve. We should all wear them in public." And then the subtitle was, "Got a T-shirt? You could make a mask at home." So that's still the message.

And I think that was the first time in the English speaking world, that there was a clear call to action, saying we should wear masks. But it absolutely was not the first time in the West. In fact, largely I was plagiarizing from a guy called Petr Ludwig who had already done all this in the Czech Republic. And so even when I did the video for my class, a lot of it was basically me saying, "Okay, this guy called Petr Ludwig, looked at this and then he said this. And then he looked at this and then he said this. And then this is what happened because he started this astonishing campaign in the Czech Republic, which was the first country in the West to get to basically about a hundred percent mask usage, weeks and weeks ahead of anybody else. And it was all thanks to his great science communication.

So every time I wondered, like, "Okay, now that I've decided this is important, what should I do next?" It was always like, "Well, can you try to do whatever Petr did?"

Eric Ries: What was Petr's background? And how did you know him?

Jeremy Howard: I didn't know him. As you know, part of the research was like, I kind of thought, there's not much point advocating for masks because nobody's going to wear them in the West. Everybody knows that only Asian people wear masks so why bother? And I actually came across this story that like, again on Twitter, it's like, "Oh actually that's not true. Everybody in the Czech Republic is wearing masks." And I looked into why, and I found this video in Czech from this guy, Petr with subtitles. And it was very, yeah... It was really nicely done. And then one of the people in the Czech Republic had been kind enough to write a Google Doc, basically describing the story that they watched as people saw this video. And they got really into the idea of wearing masks and within three days, the whole country had masks, within three days with no government support. They put up these things they called mask trees on street corners where people would make masks and go and hang them up on the mask tree. And celebrities would have songs and videos about masks and people in fashion would create fashionable masks. And so I...For my Washington Post story, I really wanted to anchor it with a specific example of this. So I reached out to some folks I found on social media who had to close up their bar in Prague and because of social distancing. And two days later they reopened it as a mask making factory. And when I say factory, what I mean is, they went around to their neighbors and asked if anybody had sewing machines and borrowed as many as they could. And within a week they were making 400 masks a day and had a full time driver, nine full time staff and they did the whole thing actually for free. They gave them all away.

So in my Washington Post piece, I was able to have a paragraph describing this story. I was chatting to the people actually from the bar via Twitter DM and they sent me photos and they told me all their names and they described exactly what happened. And so I kind of found myself immersed in the world of the Czech Republic. And they all wanted me to tell this story because they were also proud of what their country had done. And for them, a lot of it was this kind of weird anti-government thing. A lot of them seemed to hate their government and they were annoyed that the government wasn't doing anything. They felt lied to about masks after Petr's video. And so part of it was like, "Well, damn it, this is something we can do ourselves. We don't have to wait--."

Eric Ries: Almost like an act of resistance.

Jeremy Howard: "Yeah. We don't have to wait for the government. If they're not going to do anything, we're going to do it ourselves." So they were super proud that they had kind of, as a grassroots movement had made this happen. And it actually forced their government to change. A week later, the government turned around and started requiring masks in public.

Eric Ries: How many times in this pandemic have we seen this story of civic society rising up and leading the people who are supposed to be the leaders?

Jeremy Howard:I know it's amazing.

Eric Ries: It's been a remarkable thing to see over and over again.

Jeremy Howard: It really has and the deeper I get into kind of policy and I'm now been talking with leaders in Europe and England and Africa and America. The more I find myself talking to random people who... So I'm spending a lot of time working with a musician in England at the moment, who has turned out to be one of the key influencers in their ability to make masks happen in England. Yeah. I mean, people are just seeing that stuff needs to get done and they're seeing it's not getting done. And so they're finding ways to do it. And then that puts the pressure on when the public is saying, "Well, we're doing it anyway." Then I think governments have to respond.

Eric Ries: How does it feel to be in the middle of all that activity? I think people from the outside who haven't seen what you and I have seen up close would expect this to all be chaos and a kind of anti-intellectual mob. If you just say random people will be in charge of things.

Jeremy Howard: Because these are kind of self selected people, they're just super caring and super passionate and doers rather than talkers. Because we don't have companies organizing what we're meant to do or KPIs  to meet or whatever. So, one of the great things that happened early on was somebody reached out to me and said like, "Well, I know this Republican Senator who I think might be interested and do you want me to connect you?" And I was like, "Sure." Five minutes later, he's like, "Okay, Senator, you should talk to this guy, Jeremy, he's got this view about masks." And I sent him a couple of paragraphs, 20 minutes later, the Senator emails me back and he's like, "This is great. I'm going to do a video about this." By the next day, he had a video on Twitter of him wearing a mask.

And so this guy who helped me connect and I talked, and we had never met before. And we thought, "Well, this could be really bad if this becomes a partisan issue." So he helped me reach out to a Democratic Senator and so I spoke to his team. I didn't speak directly to the Senator in this case. And I think one or two days later, we had a Democrat Senator doing the same thing in public, showing a picture wearing a mask, telling other people to wear a mask.

And so within another three or four days, I was briefing ten Senate offices on a big conference call on the whole thing. And briefing senators who we're talking to Donald Trump that day and briefing senators who were talking to the lead policymakers in the CDC. They were super interested, they were super helpful. Watching Democrats and Republicans, their offices and the senators, just emailing each other, chatting, working together, figuring out the messaging. Figuring out, like, "Oh, we don't know... How do we get the CDC to change their tune without making them look bad?" Thinking how do we... What are the scientific issues they need to understand? How do we explain them best? That was, it was great.

Eric Ries: So here's a part of the story I don't even know. Because I remember when the Washington Post article came out, I remember there being a lot of excitement among some folks in the tech community, that there was this new idea that could make a big difference and that maybe the official authorities weren't getting it. And the next thing I know there's a masks for all organization, and you're just having impact after impact after impact, as the dominoes start to fall. What took it from an idea that you were just talking to some people about to an actual thing?

Jeremy Howard: I mean it's still not an actual thing, that's the thing. People keep emailing me and saying, "Can I join your organization?" And always like, "Look, it's just a bunch of random people doing random things." I don't like... I'm kind of the face of it in the English speaking world, but obviously Petr is kind of the very much the face of it in Europe.

Eric Ries: Well, you have a domain name in a website. So that's different than just having---

Jeremy Howard: Yeah, we have a domain and a website.

Eric Ries: Where'd that come from?

Jeremy Howard: I went and I went and registered a domain name and then a super helpful guy called Cam Woodsum and I connected, I think, through-

Eric Ries: Yeah, shout-out to Cam.

Jeremy Howard: I think through Meesha Shalem who you probably know. So Meesha is a great kind of connector in the kind of tech policy community and I've known him for a long time. He's a good friend. And I reached out to him and said, like, "I need help." And I think some of the WhatsApp groups that you and I are on Eric, I kind of begged for help. And so, yeah, got connected with Cam who put the whole website together with really minimal supervision. Because I don't really have any supervision to give, I was just like, "I don't know, look at my Twitter feed. That's what I say. And here's my media appearances. Here's the website that I... The domain name I have, tell me where to point the A records.

So he basically made that happen. And so that... And at the same time, that was happening within a day of my Washington Post article coming out. I was getting calls from Good Morning America and Nightline and Jory Reed's team and CNNs team saying, like, "Come and tell this story on TV. So I reached out to a friend who knows everybody and everything, he used to report to Obama when he was in the White House and said, like, " Do you know anybody who can help?" And he hooked me up with some volunteer PR people. Yeah, when I say volunteer, it sounds like they’re some kind of interns or something like that. It's some of the top PR people in the world...

Eric Ries: Well that... And that's a remarkable thing many of us have experienced. That some of the most talented people in the world are all of a sudden available on a part time volunteer basis that would never have been even conceivable a few months ago.

Jeremy Howard: Exactly. No, no. Exactly, absolutely. So I was like, "Could you help with this?" So they helped kind of deal with the logistics of all the inbound. And then when there was new news, I would pass it along and they'd send it off to the bookers. And then I started getting, particularly through the World Economic Forum community, I asked for help and people were like, "Oh, I know this top team at one of the world's top advertising companies. Do you want me to connect you for that?" And yeah, nobody's really got enough work to do so and they all want to do useful things. So people have been super, super helpful. It's always hard to know exactly which bits are our impact and what would have happened anyway, but it's been cool to see, I don't know, for example, The Mayor of London yesterday or the day before wrote something, open letter in The Times saying, "Hey, we want to require everybody-"

Saying, "Hey, we want to require everybody to wear masks, come on, UK government, change your policy," and he only tagged two people. One was me, and the other was a soccer player, Gary Lineker. And I was kind of like, "Okay." Otherwise, I wouldn't have known that my campaigning and neck and stuff made a difference, but when I saw he had done that, I kind of thought, "Oh, that's nice that he is saying that made a difference."

Eric Ries: What are some other things that have surprised you? I feel like I want to pick up the story kind of going back to the moment you wrote the op-ed. You went on TV for the first time, and then you started to see these policy changes happen. Tell us some of those stories. It must have been surreal to be on those calls-

Jeremy Howard: Yeah.

Eric Ries: And to see things translate into action so quickly.

Jeremy Howard: I mean, luckily, I was kind of in the right place to do this because I used to do a lot of TV in Australia. I was kind of, for the main morning news show, I was kind of the go-to IT guy if they wanted to talk about the latest Internet Explorer security problem, or election hacking or whatever. So I was kind of happy, I'm no expert, but I was happy enough to go on TV. So when Good Morning America were the first call and say, "Can you come on tomorrow morning?" I didn't totally embarrass myself, which is good.

Eric Ries: What had you been doing in Australia, by the way, that you had experience with--?

Jeremy Howard: So that was mainly around my companies Fastmail, the email company, and Optimal Decisions, the insurance pricing company, but particularly Fastmail, which was a pretty popular email service, or still is a pretty popular email service. So because it was Australian born, they were happy to have a local Aussie kind of face of IT. They'd always ask me about random stuff that had nothing to do with email, but that's fine.

Eric Ries: So you were accustomed to doing that kind of a kind of TV?

Jeremy Howard: Yeah. Somewhat, yeah. Yeah, so like the way the media works is kind of things pop in and out of the news cycle very quickly. So there was a basically continuous media bookings in the US for a few days. And one of the best ones was I was on, I think it was CNN, as a group, as a part of it. As well as the host, there was also Ashish Jha, who is a Harvard... I think he kind of runs their health policy group or something. And it was really cool because I always feel very like I don't belong in all of these conversations because I'm not a medical doctor or I'm not an epidemiologist or whatever. And there's always a lot of skepticism about whether somebody without the appropriate credentials can have any idea what they're talking about. So being able to be on a big national show like that with an extremely respected person was super helpful.

And actually, that's one of the main things I've tried to do, is to surround myself with people who are far more respectable than me. So one of the things I started finding was we had made a certain amount of progress with policymakers and I had managed to get in touch with kind of people on the inside who were able to tell me like, "Okay, this person's been briefed and that person's been briefed, and this is the conversation that happened, but this person over here isn't convinced yet," that it started becoming a view that the science wasn't clear enough, was causing policy to not move.

So at that point, I decided to try to fill that gap. And I hate writing scientific papers so, so much, but I thought, "This is what has to happen." And I thought, "It has to be respectable, so it needs people's names who are not me." So I reached out to a bunch of people who had been helpful and ended up writing a paper with 19 coauthors, of which the other 18 are extremely respectable people, unlike me, very well known Stanford and UCLA professors and founders of South African public health initiatives and stuff like that.

And that was great, publishing a... It was just a literature review basically, looking at 84 references to say like, "Well, what's the evidence around mask wearing? Do people actually do it? Does it actually block the droplets? What's the efficacy look like? What's the modeled outcomes look like?" Stuff like that.

So that was super helpful. And then that helped me get in touch with this absolutely brilliant Oxford professor called Trisha Greenhalgh, who I think she's the editor of the Oxford evidence-based team for COVID-19. She certainly produces a lot of their content. And she, luckily enough, had just written a letter in the British Medical Journal, not just a letter, I think a paper, describing that people should be wearing masks, even if there isn't enough evidence, because of the precautionary principle, which all countries in the UN I think have signed up to, which is basically, "Hey, if there's something that could save a lot of lives, you should do it, even if you're not a hundred percent sure it's going to work."

And so her and I ended up writing a joint article. It ended up just being on our blog, on Fast AI, but basically describing our kind of joint view. And she's she's super well-respected. And so once that happened, she suddenly started getting lots and lots of calls from the UK press, who have continued to be the slowest, just about, in the world at getting behind every scientific kind of development with COVID-19.

Eric Ries: Yeah, yeah, we'll save the editorializing for a different day, but boy...

Jeremy Howard: Yeah. So one of the things I definitely noticed is people listen a lot more to credentials than to science or data. So one of the main kind of advocacy approaches I've found effective is to find thoughtful open-minded people, convince them, or find people who are already convinced, and then work with them so that then we've got their credentials behind it, which I think maybe for most people even is more convincing than data or science.

Eric Ries: That paper that you wrote strikes me that that's kind of like a full circle moment, taking you all the way back to your very original insight. And in fact, one of the first things you said to me about your personal response to the quarantine principle... Sorry. And one of the first things you said to me about your personal response to the pandemic was that you made personal decisions on the basis of the precautionary principle, that you were looking at this data with your class and looking at it probabilistically, instead of using this more traditional view of data.

Jeremy Howard: Yeah.

Eric Ries: And despite you not having the credential of being the supposed expert in the virology or the epidemiology of this, had this insight that kind of carried you through the whole time. And the paper was like the official world catching up to the insight that you had had privately almost a month earlier.

Jeremy Howard: Yeah. I was kind of pulling it all together. I mean, data scientists like me are not really experts at anything, but what we can do is pull together data from other experts. It could be like raw epidemiological data or data that's shown in tables of studies. So although I was the lead author on that paper, my main job was to kind of try and find all the literature I could. And frankly, a lot of that was a community effort. Folks on Twitter helped find all this literature. And I kind of tried to find interesting-looking tidbits here and there, which I then passed off to the other 18 authors and they were able to say like, "Oh yes, that's correct. That is a helpful thing to know for this modeling perspective, and here's how it integrates with the other pieces." So yeah, I was kind of like a curator and kind of an organizer, I guess.

Eric Ries: I've noticed this phenomenon in a bunch of the efforts that I've seen, that you're describing, that there's people who have the supposed authority to speak to the public who have the credentials. And oftentimes, when they're speaking, if you go behind the scenes, you see there's actually a civilian or a programmer, or some unqualified person who actually did the analysis and got the data and helped them figure out what to say. And I think people assume that people who would have those credentials would have figured those things out on their own. So what does it mean that we've had to kind of do this credential laundering to get the message out?

Jeremy Howard: Right. It depends a bit on the jurisdiction, but like particularly in Britain, I find that the people who were the talking heads are a very, very, very long way away from the analysis that they're talking about. It's somewhat true in the US, at least in the tech sector. There's more people who are actually hands-on who actually do the work.

But yeah, it does mean that I often find myself debating people on TV who I know perfectly well are just parodying what their teams have told them. And so they're not going to change their mind because they don't actually directly have the knowledge or ability to make their own assessment.

Eric Ries: Yeah, they were just given the talking points.

Jeremy Howard: Yeah. So what I've been doing a lot is to try to find the scientific advisors behind the scenes and talk with them so that I know that then that will get passed up and hopefully get turned into new policy.

Eric Ries: Talk about the public persuasion campaign that you ran to get people to contact their officials and push for masks as public policy.

Jeremy Howard: Look, here's the thing about masks, right? Masks are only somewhat okay at protecting the wearer, but they're really, really, really good at blocking stuff coming out from somebody who's infected. And so what that-

Eric Ries: So if you wear a mask, it's not for yourself, it's for the people around you?

Jeremy Howard: Yeah, exactly. But screw the people around me, I want to be safe, so that means I want everybody around me wearing a mask. I don't want to go to the shops and find people around me not wearing masks because I'm unsafe. So how the hell do I get the people around me to wear masks? To do that, we probably need laws or massive kind of celebrity-driven campaigns. So those are the two things I've been working on.

The other reason we need laws, much more importantly, is that if everybody wears masks, then they're keeping their droplets to themselves, which means the reproduction rate, R, decreases, which means that the virus stops transmitting as quickly, which hopefully means, well, A, less people die, and B, we can start to end the lockdown. So there's like basic public policy reasons that everybody needs to wear a mask, just like everybody needs to be vaccinated. It's the same basic public policy decision here. It's not just for you, but for the community you're a part of.

So yeah, so I kind of thought, "Okay, well let's try and do these two things." So I reached out to some folks around kind of advertising to try to build some celebrity-driven messaging campaigns. And then yeah, I was introduced to this thing called Resistbot for trying to help move the needle on policy. For whatever reason, policy is still heavily driven by people who get letters. Letters to senators actually get read, and then the contents of them get told to the senators.

Eric Ries: It's a remarkable thing.

Jeremy Howard: Yeah, it's super weird. And sometimes they have to be faxed, and sometimes they have to be emailed, and sometimes they have to be delivered physically or whatever. So Resistbot is this cool thing where they figured out those details and all you have to do is send a text message and it'll take you through the process of getting that letter or fax or whatever out for you.

And so, the Resist guy I worked with on this, Jason, he was amazing. He basically said, "Well, what's your campaign?"

Eric Ries: And Jason, just for those that don't know, was a long time civic tech entrepreneur. And we'll have a link to the Masks For All campaign on Resistbot in the show notes.

Jeremy Howard: Yeah. So he basically said, "All right, write a letter and then I'll set up the SMS so it gets sent to all these governors every time somebody sends a text message." So that was kind of terrifying. So I was like, "I don't know anything about writing letters to governors." So I reached out around again for help from some of these amazing people who've been so useful, wrote a letter, got some help drafting it, which basically said, "Hey, I want to be safe in my community, and that means you have to make sure everybody wears a mask, and so please enact an executive order to make that happen."

And then it was great because I was on Joy Reid, MSNBC. And one of the things I found very helpful, which I've learned with media, is to talk to the segment producer beforehand and just be totally direct. So I actually said, "I want to speak to the segment producer beforehand." And I said to her, "Look, I want to use Joy's segment to pitch this campaign. And so I want you to have this chyron ready to put on the screen when I say it." And so I was actually able to say, "Okay, text MASKSFORALL to 50409, and this will send it to your governor, and this is going to help make sure that you're safe." And within minutes, Jason said there were thousands of letters.

Eric Ries: Thousands. Oh, the data was unbelievable.

Jeremy Howard: Yeah. It actually turned out I had a mutual acquaintance with Joy, and Joy told our mutual acquaintance, and she was like, "After this segment aired, I was like flooded with emails saying like, 'This is amazing. This is so great. Why aren't you doing more of this?'"

And so that segment was super helpful to kick this thing off. And since that time, it's taken a while, but you're seeing a lot of governors on board now.

Eric Ries: Yeah. At the time that you started the campaign, how many states had mandatory masks?

Jeremy Howard: Zero. Zero states. Zero cities.

Eric Ries: No one had done it yet?

Jeremy Howard: Yeah. But it wasn't just the Resistbot thing. I also tried really hard to find kind of insiders. So there's a lot of kind of highly connected business people who were friends with governors or whatever. And so one of the things I did was I actually made a video, a private YouTube video, where I said, "Governor, we need you to enact an executive order requiring masks for these reasons." So I kind of like personally-

Eric Ries: Yeah.

Jeremy Howard: I didn't say the name because I wanted multiple people to have it, but I tried to make it sound personal as possible. So this was like my lowest view YouTube video ever. It had like 16 views, but basically it's gone out to like--

Eric Ries: But they're all governors?

Jeremy Howard: Yeah, governors. And so then I've been kind of talking to the people who are talking to the governors to say like, "Has he watched the video yet? What did he say?"

Eric Ries: I hope you make the video public at some point because it was powerful to see, I thought. It was very direct and very... I bet governors don't get a lot of messages like that.

Jeremy Howard: I don't know. I have no idea because I have no idea what I'm doing, but it seemed to work at the time. And certainly, some of the governance that I sent it to have enacted these things, and hopefully that was something that they found useful in that decision.

Eric Ries: Where are we in the adoption of masks for all here in the US? Do you have a sense of kind of where we are and where we still need to go?

Jeremy Howard: It's still early. Like the public perception's still not there yet. It's certainly well ahead of where it is in the UK or Australia, for instance. I mean the southern hemisphere is going to be in so much trouble because people in the southern hemisphere think they've done a good job of controlling this thing, when actually, all they've done is lived in a warmer climate. UK is basically not, like I said, we've got the London mayor very much on board, but not much happening elsewhere yet. Hopefully that'll change.

Eric Ries: Yeah. How many states have done it so far?

Jeremy Howard: Obviously the Bay area communities have done it.

Eric Ries: Yeah, we're very fortunate here.

Jeremy Howard: LA was actually the first. And actually, one of the scientists I was working closely with was very much in the ear of the LA mayor's office to make that happen.

Eric Ries: Yeah. And we in San Francisco don't like LA to be first, so we got to be more on the ball for the next thing.

Jeremy Howard: Well, this was one of the things in my pitch to governors, was like, "Hey, who's going to be the first?"

Eric Ries: Yeah.

Jeremy Howard: Like you'll literally be remembered by history as being the first. But yeah, this is the thing that I guess I hadn't realized either, people don't really realize, is these policies that get enacted is only because a whole lot of lobbying that gets done, basically people like me deciding to care a whole lot and figuring out how to convince the right people.

So yeah, so now we've got New York, New Jersey, Maryland, Pennsylvania, Connecticut, Rhode Island, Hawaii, Puerto Rico, LA, Miami, Washington, San Antonio, Dallas County, San Francisco. Massachusetts is rapidly moving as well.

Eric Ries: Yeah. All those localities have something in common. I'll leave it to the listeners to make an exercise in figuring that out.
Jeremy Howard: Right. What is that?

Eric Ries: Well, I don't want to get into the politics of it, but-

Jeremy Howard: But if you're saying politics, I hope you're not suggesting that they're all Democrat, because they're not. So Hogan is Maryland, and he's actually been a bit of a star here because he did this fantastic interview where he talked about rights. And he was like, "Hey, if you're worried this is intruding on your rights, then let me tell you this. If I go out and your virus comes into me because you're not wearing a mask, you have very much intruded on my rights."

Eric Ries: That's exactly right. That's exactly right. And that is a key argument.

Jeremy Howard: Yeah.

Eric Ries: Yeah, we're lucky to have him making it.

Jeremy Howard: So I don't think this is as partisan... It's not that partisan. I mean, it became a bit difficult when Trump said he wasn't personally going to wear a mask, but at the same time he said he's fine with the idea. And he talked about like wearing a scarf or whatever, and to be fair, although it's not a great role model, he actually doesn't have to because everybody around him gets tested first.

Eric Ries: Right.

Jeremy Howard: So there is actually one person in the country who, you could argue, doesn't have to wear a mask.

Eric Ries: I want to hear some more stories about like the actual conversations you have with policymakers, or you must have had some of those moments that felt surreal, where you're talking to someone and you're like, "Why am I the person talking to this person about this topic?" Do you have any stories like that you can tell?

Jeremy Howard: I've never talked to a US politician before. And so when I was first talking to this Republican senator thinking like, well, A, "Why am I talking to you? I'm just some random data scientist." And it's also like, "Why am I talking to you," because my politics are not at all aligned with his. And it was kind of like, yeah, this feeling of how did this happen? Like a few days ago, I really didn't think about masks at all, and suddenly, here I am briefing a senator who's going to be talking to Donald Trump. It was a really weird feeling.

And one of the interesting things was how, yeah, how very unpartisan this kind of whole thing turned out to be. I've been getting so much help from people who have diametrically opposed political views to mine. And we just don't talk about that. We just help each other out because we're all clearly just trying to save lives and save the economy. And so it's been cool to see how people are happy to put their politics aside to respond to a pandemic.

Eric Ries: How do you know that we're making progress towards masks for all?

Jeremy Howard: It's pretty easy to measure progress in terms of policy change. So the CDC now says you should wear a mask, many parts of the country in the US now require a mask. Countries like Indonesia and Israel and the Czech Republic and Slovenia and Mongolia and Singapore require masks. And the vast majority of countries that require masks have only done so since the campaign. Again, no one was talking about it before.

Like Singapore is an interesting example. That's a country that did everything right, testing and tracing, quarantine, but they didn't do masks. They actually had a campaign recommending people only use masks if they're showing symptoms. And because they did all the other stuff right, they didn't have a terrible outbreak, but their R was getting above two. And recently, things have been getting super concerning. And so then a week ago, they changed and they went from officially recommending, "Don't use a mask," to immediately requiring using a mask at all times, including in the workplace.

So looking around the world, we just see the recommendations and the laws changing. And for a lot of those, I've directly been involved in the conversations with the government leaders or their advisors as those things are happening. In every case, there's always scientists and advisors behind the scenes-

Jeremy Howard: Scientists and advises behind the scenes. It's not politicians just deciding to do these things on their own.

Eric Ries: How do you know that you're having an impact? That these things wouldn't have happened anyway, on their own?

Jeremy Howard: These things might well have happened on their own. One would like to think that eventually people must realize that covering your face with a piece of cloth will stop bits of saliva coming out. It's not rocket science. I guess the question with these things is always, how long will it take? I'm concerned that it might have taken all the way up until the next winter when we'll probably have some kind of second outbreak or maybe it would have, I don't know. There was just no sign of it happening. Perhaps it would have gradually grown out of the Czech Republic, very successful campaign anyway. We certainly saw from the Czech Republic that it moved to Austria and Slovenia within weeks. So maybe it would have gradually come from there. But I don't know. I've personally been on so many calls with policymakers and emails with their advisors working directly to make these things happen. So how long would it have taken otherwise? I don't know. But every day counts with this stuff. So it certainly seems to have been helpful.

Eric Ries: That topic has come up a lot in my conversations with people who are either on the sidelines or getting involved in the fight is for a lot of the folks that I know that said it doesn't seem like this is my job, or why am I doing this? The thing that ultimately has been decisive for a number of them is even if all I do is accelerate the right thing happening by a few days in an exponential situation that could mean thousands of lives. So we're all obligated to do what we can. Even if we don't bend the curve of the long run, even if the impact is ... We don't know what it could be, but on the possibility that we could even accelerate the right things happening by a few days, we're called to act.

Jeremy Howard: Yeah, exactly. It's been cool to see how there's certain people in the world who do things in minutes rather than weeks. I think that's been one of the challenges for huge slow moving organizations like the World Health Organization that just don't tend to work at that kind of speed. Or the UK government.

Eric Ries: Listen, you're talking to someone who's been trying to pitch people an organizational transformation for speed and agility as an organizational capability for years.

Jeremy Howard: Yeah.

Eric Ries: To see people talk about it as unnecessary during the good times, and now lament its absence in the bad times, without making the connection that these are choices, there not an inevitability.

Jeremy Howard: Yeah. I mean a pandemic, you look at the difference between places that locked down two weeks earlier versus two weeks later and it's terrifying to look at or look at the difference between the countries that have mask mandates and those that don't.

Eric Ries: We knew that from the 1918 pandemic that even in the US the cities that locked down sooner had dramatically different economic and health outcomes. So we didn't study that history and act on it, it's heartbreaking.

Jeremy Howard: Yeah. It's also this misunderstanding of asymmetric upsides versus downsides.

Eric Ries: Explain what you mean by that.

Jeremy Howard: So people who demand gold standard evidence to do anything, like masks for example. When the thing has almost no cost, the potential upside is huge. So in that situation you should demand gold standard evidence not to do the thing. But this is just an approach, which is very alien to certain professions.

Eric Ries: Have you seen the historical threads about the anti mask leagues and the protest in 1918?

Jeremy Howard: Yeah, that was one of the things I studied in my research.

Eric Ries: Yeah. Talk a little about that history, especially as it relates to masks, and then what you think we should learn from that history as we go forward into this crisis.

Jeremy Howard: Sure. So the 1918 pandemic had a lot of overlaps with this one. It was a respiratory infection like COVID-19, but in that case it was the flu. I think actually we are going to be wanting to study it a whole lot, because it teaches us a lot about how people respond. So in places like San Francisco, people thought as summer came, "Oh, wow we're past it. So we did all this hard work of distancing and doing things outside and wearing masks and that's over, it's behind us. Thank God." So when things started flaring up again the next winter, there was a lot of anger when it was suggested that those hard things should be done again. So for example, the anti mask league appeared as that second winter started coming along with people demanding, "We shouldn't be required to wear masks again." Because they were the law.

They weren't good masks by the way, they were gauze masks, which obviously are not great for source control and things can go through them. I don't know why they used gauze, but there you go. Nowadays we use cotton or paper towels, which works much better. So 2,000 people got together in what we would today call a super spreader event without masks. We don't know exactly what the transmission rate was from that, but it;s pretty likely it was big. There was also war bonds, big ceremony parade in St. Louis I think it was. 250,000 people turned out and it basically turned into this huge statewide massacre. We're seeing similar things here. The fact that Mardi Gras went ahead in Louisiana, despite really as the pandemic was kicking off and now it's been so badly hit.

Yeah. I mean responding quickly and appropriately based on the huge risk versus the limited upside, it's hard to do and people are still not always doing it. But I think places like the Bay Area and LA examples of doing this pretty well. I would have liked to have seen things happen even a little bit earlier. But on the whole they've done a pretty good job and the hospital systems not being overwhelmed. In fact, UCSF healthcare workers are flying off to New York to help that's how well that's been handled.

Eric Ries: I mean, we're very, very, very fortunate and very grateful to the leaders who stepped up and did do the right thing. As you say, maybe not as early as we would have liked.

Jeremy Howard: We're still waiting for Gavin Newsome, I don't know, as a governor, he actually ordered hundreds of millions of masks. I get the impression he's waiting for them to arrive, which is crazy for me because we already have the ability to put a handkerchief over your face. So I don't know why, as a governor, he's taking so long on this important public health measure.

Eric Ries: Yeah. There's some backstory to that, to the masks in China. The whole thing has been just another completely surreal topic maybe for another time.

Jeremy Howard: Well it is one of the interesting stories here is that one of the things we keep facing is jurisdictions that don't act because they don't have the perfect masks yet and they don't have the perfect messaging campaign yet about donning and doffing them and the perfect understanding yet of how to clean them. I find it really weird this idea that we should do nothing at all until we can do everything perfectly. But it's a super common response, which I find really infuriating.

Eric Ries: It's an artifact of 20th century management thinking, not to digress or too much, but the logic of masks production and the economics of that organizational design really reward planning in advance, high efficiency, single action, measure twice, cut once and cut against speed. If you're dealing with a problem where that's a good toolkit, maybe that's okay, but it's especially bad in conditions of extreme uncertainty.

Jeremy Howard: Yeah. Careful you might get me started, I was a management consultant doing that stuff in the 90s. So yeah, I know exactly what you mean. I was not fond of it then and I'm still not fond of it now.

Eric Ries: Yeah. Boy, is change needed here and needed more than ever. So maybe let me switch gears for a moment and ask you if you have advice. There's probably somebody listening to this podcast who's still on the sidelines of this fight or has had an insight, has seen some data like you've seen and has been radicalized by it, or it's just feeling frustrated and they're not sure if they can make a difference. They're not sure what to do. What advice would you give them?

Jeremy Howard: Yeah, the same advice that I give entrepreneurs. As an AI academic who spent years as an entrepreneur, I have a lot of people asking for advice about AI product insight they have. What should they do? In both cases, I think the answer is give it your absolute best shot. Don't piss around, right? So if you think you have an insight, an idea, a product, an app or whatever, that can genuinely help people then work the hell out of it. Write it up as carefully as you can, find everybody you can who could intelligently critique it, get people to pick holes in it, make it as compelling as possible, do things in public.

If you are hearing back from people that ...if people just don't seem interested, don't blame the people. If you're not getting people interested, it's because you're not interesting enough. So, why not? Are you wrong? Are you pitching it the wrong way? I often find, one of the things I talked to my students the most about is tenacity. The biggest difference I find between people who were successful entrepreneurs and successful researchers versus not is whether they stick with things until they finish it. So it's the same here. If you've got something, then stick with it. I can't tell you how many doctors I dealt with, particularly a few weeks ago with this campaign telling me normal people could never learn to use masks properly. "They'll just touch them too much. Oh, it's just going to make them less careful about social distancing, blah, blah, blah." Just have to keep sticking with it anyway.

Eric Ries: So what would it look like to apply what you've called the drive train approach to pandemic interventions?

Jeremy Howard: So the drive train approach was something I came up with when I built this company called Optimal Decisions Group. Which is a particularly boring and not societally great company, which was all about helping insurers to make more money by setting their prices better. So insurers basically set their prices by looking at how, say car insurance, how risky are you? How about how likely are you to crash? How much is that going to cost if you do? Then try to figure out like, "All right, let's make sure we charge more than that so we make a profit." That actually doesn't tell the whole picture because maybe I'm in a hurry. So you could charge me much more. So if you only charge me like 10% more than my risk, then you're leaving a lot of money on the table.

So I developed this thing called the drive train approach, where you build a bunch of models, including in this case, an elasticity model, how likely would I be to accept a particular price and a predictive model of risk and combine them all together into a simulation that says like, "Oh, if you've charged this amount of money, here's what your eventual market share would be. Here's what your risk would be and so forth." Then you can optimize that. So the drive train approach for pandemic response would be, "Okay, what are all of the things we could estimate about how likely are people to socially distance yet? We don't know, let's make our best guess if you are wearing a mask, if you're not, what data do we have, let's try to figure out as best as we can, what it might be."

"What's the probability that you're going to remove it when you're speaking?" So he built all these different models. I think it just chuck it into a spreadsheet or whatever, or do a simple probabilistic programming model that then says, "Okay, so if we have a mask, here's the estimated number of lives lost per month. The estimated value of the economy per month. How long until we might be able to win the lockdown?" Versus if we don't require masks that's the thing I'd love to see people doing, but literally most official evidence-based policies for health care don't actually include the cost of the intervention at all. Which is why we can have something that doesn't have a randomized controlled trial, like a lockdown. And the cost is huge, does happen. That something like masks, which may be just as effective, this be something you can do in conjunction with social distancing rather than instead of. Has almost no cost, but doesn't happen. So from a basic common sense perspective, or from this drive train approach perspective, it makes no sense at all.

Eric Ries: What do you hope people will take away from this experience? What do you hope? If you could pick one thing that we as a society will take into the new normal, after the pandemic passes, what would it be?

Jeremy Howard: Main thing is I hope is that we keep our lives. So I want to see less lives lost. I hope we can keep our economy. Then assuming we find a way to make these things happen, it would be great to see ... Some of the different ways we're seeing to do things where maybe we don't have to travel as much. Maybe we don't need as many certifications, maybe it's okay for doctors to practice across state lines. In a pandemic I guess we start to realize which laws are actually getting in the way more than they're helping. So maybe some of those things can be maintained beyond this as well.

Eric Ries: Where do you think we go from here? How do we get out of the crisis?

Jeremy Howard: Well, there's a lot of uncertainty, so we have to accept that. So any planning has to be aware of the possibility that herd immunity might not be possible, or it might be, or maybe it is possible. A vaccine might not be possible. Maybe it is possible. Maybe those things last for a short amount of time, maybe they last for a long amount of time. These are all things we don't know. It could be that, seems likely to me, that during warmer months things will be a lot easier. Then during winter months, it will be much harder again. It seems very likely that people during summer times will become apathetic. They'll be hubris. That will make the winter times, the first winter way, way worse. So if we're going to get out of this, we need not just one off reactionary policies, but a complete understanding of what the whole dynamic of this looks like.

I mean, we certainly need to be wearing masks in public, especially whenever we're indoors or in very close proximity to others. To not do that is to increase the reproduction rate. So that's just going to be a massacre. At the same time, we need to realize that not everybody can stay locked up forever. We have jobs for a reason. People do need to work. To not do so has a huge cost on lives. So we need to be talking about like, "Well, how do we gradually get back to life, but also know that there will be more breakouts, so how do we be sure that we know when a breakout's happening?" Then, "Do we have the systems in place to track it?" So we need good testing. We need good contact tracing. We just need to also set this expectation that for some period of time, which might be forever, might be years. It might not.

We're all going to have outbreaks from time to time, which means we all need to be testing to know when it's happening, contract tracing to know what's happening. From time to time, regions are going to have to be getting very good at various types of lockdowns to ensure that those breakouts don't turn into new pandemics.

Eric Ries: Jeremy, I wanted to thank you for all the work that you're doing here to keep all of us safe. Thank you for coming against it's the stereotype of an academic and getting into action and seemingly being everywhere at once in defense of these values and the need to save as many lives as possible. Of course, thank you for coming on and sharing in this conversation.

Jeremy Howard: Thank you.

Eric Ries: This has been Out Of The Crisis. Out Of The Crisis is produced by Ben Erlich, edited by Jacob Tender, music composed and performed by Cody Martin hosting is by Breaker. For more information on COVID-19 and ways you can help visit If you have feedback or you're working on a project related to the pandemic, please reach out to me on Twitter. I'm @E-R-I-C-R-I-E-S. Let's solve this together.

Wednesday, June 24, 2020

Out of the Crisis #10: HelixNano founder Hannu Rajaniemi on vaccines, suspending disbelief, and the power of stories

HelixNano was founded to develop cancer vaccines. When co-founders Hannu Rajaniemi and Nikolai Eroshenko realized their work was applicable to a coronavirus vaccine, too, they changed direction immediately. It only took them a week to become fully committed to this new work. Just five weeks after that they had animal data on immune responses to their first vaccine candidates. They also wrote and published a proposal for a Vaccine Manhattan Project that calls on leaders to do more than just the status quo, reminding us all that "History teaches us that combining money with determined leadership can have an extraordinary effect on scientific and human progress. We have done this before for tools of war. Now let’s do it for tools of health."

Hannu and I talked about the process of vaccine development, how the virus works, and what it will take to launch a large-scale vaccine project.

His main scientific goal, whether it's addressing cancer, SARS-CoV-2, or something else, is "to bridge this gap between all the new really exciting technologies that I could see emerging and the actual practical applications of treating patients." And like many scientists, he's been astonished and thrilled by the speed at which biotechnology is suddenly working as the field collaborates to fight the coronavirus.

Hannu and I also discussed his other line of work as a prolific and successful science fiction writer. Like entpreneurship and science, writing requires the ability to imagine another world from the one in which we all live. Suspension of disbelief has to be managed even as it's acknowledged as a necessary ingredient for moving forward. And even as Hannu is focused on what that forward motion looks like right now from week to week, he's also keeping the bigger picture in mind. As he put it, "this is such a powerful collective experience that I am very curious to see how it will change our relationship with rapid change, technological or societal, long term."

You can listen to our conversation on Apple, Google, or wherever you like to download podcasts.


In addition, the transcript of our conversation is below.

Highlights from the show:

  • Hannu on his upbringing in Finland, background in theoretical physics, and quarantine setup (3:10)
  • Hannu on how he started writing science fiction (4:52)
  • The connection between entrepreneurship and science fiction (7:18)
  • On being allowed one miracle but not two in fiction, the suspension of disbelief, and the pandemic (9:24)
  • Hannu's segue to biology and then virology (12:52)
  • What we know about COVID-19 (15:20)
  • How the SARS-CV-2 virus works (19:47)
  • Why conspiracy theories about a lab-created virus can't be true (22:52)
  • The power and complexity of the human immune system (24:47)
  • Conventional vaccines and antibodies (27:33)
  • HelixNano's origin story (33:29)
  • RNA vaccines (34:49)
  • Computer viruses and biological viruses (36:51)
  • When Hannu realized it was time to pivot to address the pandemic (38:19)
  • Virus mutations and vaccines (39:29)
  • How thinking about mutations in cancer caused Helix Nano to take action (44:47)
  • How the work accelerated immediately (49:04)
  • The vaccine testing process and timeline (51:44)
  • What it's like to watch the biotech clock cycle go into hyper-speed and collaborative mode (54:42)
  • The need for and benefits of a Vaccine Manhattan Project (57:29)
  • Reading on the Manhattan Project (1:00:28)
  • Vaccine Manhattan Project road map (1:00:50)
  • On evaluating safety with speed (1:04:26)
  • Funding and support needed in order to launch a project of this magnitude (1:06:57)
  • On the potential to build new hubs of biotech innovation--and in other industries--after this experience (1:14:23)
  • The lessons of the immune system on being adaptable (1:18:12)
  • What others can do to help support Hannu's project (1:20:12)
  • What gives Hannu hope that this kind of collaboration might actually happen (1:22:32)
  • Getting out of the crisis by being tactical now but also thinking long-term (1:25:02)

Show-related resources:

Transcript for Out of the Crisis #10, HelixNano

Eric Ries: This is Out of the Crisis. I'm Eric Ries.

Do you ever feel like we're living through a science fiction novel right now? It's not a coincidence. You're not the only one. We're living in a state where the facts are known but they are inconceivable, and so many of the solutions that we have to find require extreme acts of imagination. So I wasn't actually surprised when the person who is leading one of the most promising vaccine candidates for COVID-19 turned out also to be a science fiction author. Hannu had dedicated his life and career to science and research and before the pandemic had started a company called HelixNano to work on a vaccine for cancer. But in the face of this onslaught, he pivoted and is not developing a potentially promising MRNA vaccine for COVID-19. Hannu is one of those entrepreneurs who has put everything on hold to try to make a difference in a worldwide pandemic and we're grateful to him for that.

And I don't know if this is related to his work as a science fiction author or not, Hannu has the ability to see the big picture and so he has put together this proposal for a vaccine Manhattan Project, taking inspiration for it's name from the legendary science project that led to the creation of the Atomic Bomb. Hannu has called for mass coordination between the government and the private sector to get to a vaccine faster, not a few months faster but dramatically faster. I know for a lot of you, that will sound familiar. There's been a lot of talk about a Manhattan Project for a vaccine or doing multiple vaccine trials in parallel and that work is really important.

But Hannu has advocated for something a little bit deeper, a little bit more fundamental in how we evaluate the safety and efficacy of something like a vaccine. And if a version of his proposal were to become reality, it would have far reaching consequences, not just for our ability to reopen our economy at the end of this pandemic, but for the creation of many different kinds of therapies and vaccines in the future. Many people are talking about this. Very few have thought through the specific steps that it would take. Hannu understands the science and knows the fundamental challenge in developing a vaccine. In our conversation, he admits that what he's proposing would be incredibly expensive. But not when compared to the incredible cost of having our entire economy shuttered.

The entire Vaccine Manhattan Project could be underwritten by the cost of the economy being closed for only eight days. So it doesn't have to have that much benefit because in a pandemic, as with so many of the things we've talked about, every day matters.

Here is my conversation with Hannu Rajaniemi.

Hannu Rajaniemi: My name is Hannu Rajaniemi. I grew up in Finland. I trained as a theoretical physicist pursuing the theory of everything. Ended up writing a few science fiction novels on the way. Started a company doing data science, AI, and applied math consultancy. And then co-founded Helix Nano Technologies, or HelixNano, which I am now the CEO of. We have been for a few years working on cancer therapeutics and cancer vaccines but are now developing a COVID-19 vaccine.

Eric Ries: So these are difficult times for a lot of us. Let's start with how are you doing, how's your family? What's your quarantine setup like?

Hannu Rajaniemi: I feel very lucky and grateful, Eric. My wife and our one-year-old Vizsla dog, Neo, are holed up in Dolores Heights in San Francisco. We have a garden so we have sunlight and access to the outdoors. On the whole, I think we are very fortunate.

Eric Ries: Do you have a favorite quarantine tip or something that's helped you get through these times?

Hannu Rajaniemi: Even before the quarantine, I was working from home quite a lot. So I think my one tip is having a routine, treating working from home as if you were going to work so taking a shower, changing into different clothes, perhaps, and trying to set yourself times to either wind down or take a break rather than letting the work completely expand and take over everything.

Eric Ries: I think I got to ask, because this will be how some of our listeners know you is not as a scientist but as a science fiction author. Talk a little bit about your work in fiction before we get into this new reality we live in that almost feels like science fiction sometimes.

Hannu Rajaniemi: Absolutely. So I do agree that science fiction is perhaps unique amongst literary genres, that it really, truly deals with situations where the entire world changes. My entry to science fiction came accidentally, actually. My initial entry point to storytelling was as, I think for many of your listeners, Dungeons and Dragons. I grew up in a small town in Finland as an outsider geek, one way to make friends was to essentially dungeon master or game master role playing games. I got pretty deep into that and also did quite a lot of LARPing. And then when I moved to the UK to do my PhD, I lost touch with that crowd and was looking for some kind of creative outlet. Ended up joining a local writers group, which I was drawn to because it included people like Charlie Stross who, of course-

Eric Ries: Remarkable author.

Hannu Rajaniemi: Has become very successful and famous. And started writing short stories. Switched languages. Started writing in English because the others in the group had to be able to read them. Got eventually picked up by a literary agent, John Gerald, who I still work with who convinced me to have a go at writing a novel and I wrote one chapter and that was picked up by Simon Spanton at Gollancz  publisher in the UK.

Eric Ries: Was that The Quantum Thief?

Hannu Rajaniemi: That was the first chapter of The Quantum Thief.

Eric Ries: On my Kindle along with Invisible Planets, right?

Hannu Rajaniemi: Ah, excellent.

Eric Ries: Yeah. I don't mean to skip ahead in the story, but just to say that I'm a fan.

Hannu Rajaniemi: No, no. Thank you. Thank you, Eric. I appreciate that. Yeah. So on the basis of the chapter, Simon then offered us a three book deal, which after lots of creative struggle, became The Quantum Thief and it's two sequels, The Fractal Prince and The Causal Angel. And subsequently I've kept writing really as a side career at least in terms of the way I use my time. But certainly I've been finding more and more that being an entrepreneur and being a writer are two sides of the same coin. You are either trying to actively change the world or to, on the writing side, show other people how the world could be different. So I very much see that as a unified mission and one has been feeding to the other and vice versa.

Eric Ries: You're not the only one in my experience, that I've worked with a lot of entrepreneurs, a lot of scientists, a lot of authors, you're not the only one that feels that way. It's actually a common theme to imagine the world in a way that it is not today. That's something that entrepreneurship and science and writing all have in common, that active imagination, that visioning of an alternate state. That's a prerequisite to any action in the world. It's interesting to hear you talk about it that way.

Hannu Rajaniemi: Oh, I completely agree. I think what makes science fiction relate to that even more is that typically you are allowed one miracle. You are allowed to assume one impossible thing. And I think it's the same for startups. You get your one miracle but not two.

Eric Ries: Yeah, yeah. That's funny because one of our venture investors for LTSE calls it a two miracle company. And I can never tell if he means that as a compliment or a criticism, but just more like a fact of how difficult it is. But, yeah. I think people outside of the business would find that confusing. It sounds like almost mystical talk. And when you said you're not allowed to, it's not like are the writing police going to arrest you or the entrepreneurial police? Talk a little bit about those rules of thumb, why they're important.

Hannu Rajaniemi: That is a great question. Approaching it from the writing side, I think there are limits to the suspension of disbelief on the reader's part. So you reduce suspension of disbelief or manage it by not having a free for all situation where anything can happen. But let's say we treat it as more of a thought experiment. We change one thing and then we try to rigorously extrapolate from that what other things it affects, first order changes, second order changes, third order changes and so on. If we have one new imaginary technology or if we have a pandemic, what changes about dating? That might be a third order prediction. It's fairly easy to see what's ...

In the case of a pandemic, it's fairly easy to see what a first order prediction might be. Healthcare system is going to be overloaded. Second degree prediction might be we will rapidly find ways to create more infrastructure or for PPE. People might start wearing masks on the street. And then the third degree prediction was how do people go on dates? How do relationships change when we are all cooped up in our homes for extended periods of time? So if you then simultaneously introduce multiple changes, two miracles like you say, there's a pandemic but there's also a superhuman AI that emerges simultaneously, it might become difficult for you as a writer to maintain coherence to your world. It might be difficult for readers to maintain their suspension of disbelief.

Eric Ries: And that's such a great lead into what we're all experiencing here. Because in some ways I think a lot of us feel like all of a sudden we are living in a work of fiction because the things that are happening around us seem unbelievable. And it wouldn't have been that long if I had said, "Listen, the whole world is going to simultaneously, practically on the same day, embrace working from home. Zoom would go from 10 million to 300 million customers overnight. All the schools would be closed. Everyone would embrace homeschooling." If I listed through those second order effects, I think a normal person six months ago would have said this is not only fiction but you're violating the one miracle rule. That's 10 miracles, 20 miracles. It's preposterous. And yet, we're all living through it. And so what used to be the suspension of disbelief, I feel like a lot of us, now we're living through a suspension of belief. We can't believe what's happening.

Hannu Rajaniemi: That's right. And this is such a powerful collective experience that I am very curious to see how it will change our relationship with rapid change, technological or societal change long term.

Eric Ries: So do you mind, just give us a little bit of ... I'll get into the whole story of how you started HelixNano and the vaccine that you're working on. But if you just say a few words about your background as a scientist and then how you got into virology in particular.

Hannu Rajaniemi: Mm-hmm (affirmative), absolutely. So I will say that I am not a virologist by training. I'm not even a molecular biologist by training. My PhD was in theoretical physics, in particular string theory. And my subsequent career was in solving difficult mathematical, computational, and data science problems for industry. But about six years ago I jumped head first into the world of biology and synthetic biology in particular trying to figure out how to engineer biological systems to develop novel cancer therapeutics and I've certainly absorbed a lot directly from my co-founder Nikolai Eroshenko who came from George Church's lab at Harvard Medical School and worked on both novel DNA synthesis technologies and genome engineering tools beyond CRSPR there.

In the course of trying to figure out how to develop better cancer therapeutics, I also became reasonably familiar with immunology, how does our immune system work, how does it interact with cancer cells, and generally the underlying principles of how we develop immune responses to foreign pathogens and even things inside our own bodies. So, yeah. My perspective is that of a well informed outsider who has spent a few years thinking about this and also learning from people who are directly trained in these sort of things.

Eric Ries: Yeah. But I wanted to make clear that you're not a layperson or a civilian here. You have been in the lab in these issues for a long time. I don't think it's a coincidence that someone who has a background in science fiction, in science, in entrepreneurship would wind up taking the lead on something as important as developing a vaccine. So I wanted to start with this, with how you think about these more abstract topics before we get into what I hope you can give us a briefing on the science itself. What is known so far about the virus and what has been your experience working with it so far?

Hannu Rajaniemi: In terms of what do we know about SARS-CoV-2, which is the official name of the virus that causes COVID-19, it belongs to a broader class of viruses called now famously coronaviruses. There are many of those around, possibly thousands. There are also coronaviruses that have been or currently are in humans, which cause common colds. There are coronaviruses in other animals like felines, cats, and notably, bats, which seems to be a particularly broad reservoir of coronaviruses and other viruses. And at some point in the recent past, one of these viruses mutated, experienced a recombination event with another virus, seemingly pangolins were involved somehow, these anteater-like armored creatures that live in China. And as a result, we got this new virus which was able to infect humans and we had this first outbreak in China, in Wuhan.

Now, the virus operates on the same principle like all viruses. It essentially needs a host to replicate, in this case us. What the virus itself is, is really like a little message in a bottle. It's a little capsule made out of proteins which contains a bit of genetic code, which is actually instructions for making also the bottle and for copying itself. It delivers that message to our cells. Initially it seems like it infects the upper tract of our respiratory system and there's a period where we don't have many symptoms but are actually very infectious. So it has this period where you might not feel any symptoms and go about your life and still produce virus. So the virus then has delivered its code into your cells and is making more virus.

And then a bit later the infection moves to the lungs and that's where things then typically get worse and can get very bad and also result in death. We do not know what distinguishes really bad outcomes from mild outcomes. It certainly seems to correlate strongly with age. Most mortality that we've seen has been amongst the elderly. Obesity and heart issues and other comorbidities also seem to be factors as well as somehow being immunocompromised. But I think it's fair to say that we still don't have a complete picture of what stratifies those groups, who exactly has high risk.

Another factor that is also important is how much virus you get exposed to and that's probably why we also see a lot of severe cases amongst young healthcare workers, nurses, and doctors. In that sense, those people on the front lines are really at high risk.

Now, in terms of how old the machinery of the virus itself operates, we can go into that, but I can also pause there.

Eric Ries: Can you talk a little bit more about how the virus actually attacks our cells and what is the mechanism that it uses? Why has it proven so difficult to combat with our usual defenses that we have against other diseases?

Hannu Rajaniemi: To unpack that, let's start with how the virus works. I mentioned that the virus is like a message in a bottle. And what that bottle actually looks like, it's like a spiky ball. The name coronavirus comes from the fact that it is spiky like a crown, hence the name.

Eric Ries: You mean when you view it under a microscope?

Hannu Rajaniemi: If you look at it under a microscope. So obviously this is a very, very tiny, tiny thing that you'd definitely need a microscope to see. So the spikes that cover the surface of this spiky ball are actually called the spike proteins. And so it's multiple copies of the same protein, the spike protein. And the spike is what the virus uses to enter our cells. There is a receptor on the surface of many of our cells including lung cells, but also heart cells and other cell types called ACE-2. The virus is able to bind do this receptor with the spike. So the spike is like ... I guess you can think of it as a lock/key type situation. The spike is shaped in the right way to bind to this thing on the surface of our cells.

So that brings the virus close to the cell surface. And then there's various things that happen. There's another bit on the cell surface that actually cuts the spike, so the spike breaks and it exposes a part of the spike that flicks open like a switchblade that then penetrates the cell membrane and grabs it and pulls the virus in. And then that gets the contents of the bottle, the virus, into our cells. And in the cell many things start happening. The virus boots up it's replication machinery. It starts making copies of both the information that it contains and all the things that it needs to make more bottles to package the message into. It also has other things inside it that help to dampen down the immune response, the defenses of the cell, that might otherwise activate.

And SARS-CoV-2 seems to be extremely good at suppressing the natural intracellular immune response to what we have to viruses. So that's one of the reasons why it's so insidious.

Eric Ries: And I hate to even bring this up, but just to dispense with the conspiracy theories that have been floating around, the fact that this is so well designed, seemingly, to penetrate human cells and to have these adverse consequences, this is not evidence that it was engineered in a lab? This is nothing more than natural selection doing its work, is that right?

Hannu Rajaniemi: That is right. I don't think we have any evidence that this would be a synthetically created virus. Viruses are generally extremely clever. They have evolved through billions and billions of years of interaction with their hosts, other organisms and us, and they have certainly had time to discover every possible trick in the book and many things that we still don't understand. They are extremely well designed by evolution. In fact, I don't think we could really design a virus from scratch even if we tried.

Eric Ries: Yeah. We lack that capability still as a civilization.

Hannu Rajaniemi: Fortunately, perhaps, but ...

Eric Ries: Perhaps. We do not lack the capability to create vaccines.

Hannu Rajaniemi: Right. So we are fortunately able to give our natural immune defenses a boost, which of course, have evolved in parallel with the viruses that they fight against to deal with them.

Eric Ries: It's like a naturally occurring arms race over evolutionary time scales.

Hannu Rajaniemi: It's been an arms race of billions of years and, in fact, it's amazing that we don't all die from viruses. It's evidence that there are-

Eric Ries: That's one glass half full look at the current situation, which I think is actually pretty good.

Hannu Rajaniemi: Yes. I mean, most of us will not fortunately die from SARS-CoV-2 if we catch it. Our defense systems do actually work pretty well. And I mean, our immune systems really are an incredible piece of machinery. I think the only thing in our bodies that rivals them in complexity is the brain. And arguably they are of the same order of magnitude of complexity because what our immune systems are constantly doing is they are looking for potential signals or for pathogens both known and unknown. They have hardwired response mechanisms to certain things that look like bacteria or viruses or parasites that it can activate very quickly. So that's the so-called innate immune system.

And then we have the adaptive immune system that can actually learn. When it sees a new pathogen, it can learn to recognize that as harmful and then develop an immune response against that, that then also remains. There's also a memory mechanism through which the immune system remembers all the things it has been previously exposed against. And then when it sees again a thing it remembers, it triggers this very rapid exponential expansion of the cells that can respond to that particular pathogen.

And what's also really incredible is that our immune system doesn't attack our own cells, and that's a phenomenon that is still unclear. How do we differentiate self from non-self? But, yeah. So the immune system is very powerful. And actually we do have the tools now to help it along in the form of vaccines, which actually is a very ancient form of technology. There was a process called variolation with smallpox dating back possibly thousands, certainly hundreds of years where you take a bit of somebody's pustule, dry it, and then give it to somebody else to protect them against smallpox. This was being done already hundreds of years ago.

Eric Ries: Talk a little bit about conventional vaccines and how they work, because I think that will help establish the foundation for what's new in the research that you're conducting.

Hannu Rajaniemi: Absolutely. Okay, so what a vaccine really is, is a way to help the immune system to identify pathogens, to identify a virus. So if you think of the immune cells in our bodies as the police who are patrolling around looking for signs of bad guys, then a vaccine is like a mugshot that you show to the immune system. So you might actually be able to show the virus itself. So one form of traditional vaccines are attenuated or disabled viruses that you show to the immune system. This is what the bad guy looks like. Here's a disabled bad guy or imprisoned bad guy. Go and look for more things like them and deal with them.

Or you can show them a mugshot essentially. So here's a picture of a part of the bad guy. So the immune system might notice that the bad guy has a very prominent mustache so they will go where--

Eric Ries: Or wears a very distinctive kind of crown.

Hannu Rajaniemi: Exactly, it wears a very distinct kind of crown with very specific kinds of spikes and then goes looking for those. So for example, one class of vaccines that is being developed against SARS-CoV-2 are vaccines based around the spike protein. So you essentially show the immune system a synthetically manufactured version of the spike protein and tell the immune cells to go and find anything that looks like that and destroy it. So that is definitely one approach. But ultimately, all the different vaccine technologies we have are different ways of showing a mugshot to the immune system.

Eric Ries: And I think that's important for people to understand, that all vaccines, however they're developed, they're different from other kinds of therapies because they're actually not directly addressing the pathogen at all. It's not like an antibiotic or a cure that has some kind of biological consequence for the pathogen in your body. A vaccine fundamentally is about teaching your own immune system to do something different, to activate that almost miraculous adaptable immune response that you were talking about a moment ago. Is that right?

Hannu Rajaniemi: That's absolutely right. In fact, you can argue that vaccines are a form of biological enhancement. It is actually making our bodies better. They're able to respond to these pathogens. So to comment a little bit on the relationship between therapeutics and vaccines, so one of the things that a vaccine will get our immune system to make are antibodies. Antibodies are essentially weapons or attack dogs that particular immune cells go and deploy. So they're basically, again in the example of the spike, if you use the spike protein as a vaccine, then the immune system will generate antibodies that will target the spike protein and potentially bind to it and prevent it from binding to the ACE-2 receptor and therefore preventing it from infecting cells.

And here's another example of how we've not really invented new biotechnology but taken inspiration from nature, on the therapeutic side one of the most promising therapeutic treatments for SARS-CoV-2 are actually antibodies, synthetically made antibodies that are inspired by the molecules that our bodies naturally make to fight the virus. But in the case of vaccines, we are essentially reprogramming our immune system to make those antibodies but people are now also, companies like Regeneron and Vir Biotechnology, are developing antibodies based on the antibodies found in the serum of patients who have recovered from SARS-CoV-2 to then actually use them as therapeutics.

Eric Ries: Until just almost five minutes ago, therapeutics and vaccines were in the category of ideas that were just part of the miraculous infrastructure of our society that pretty much all of us took for granted, even to the point that they could become controversial because we like to fight about things during good times. And practically overnight, the entire world has become laser focused on therapies and vaccines because this truly is the only underlying way that we can reopen our societies and our economy. So getting this right is critically important and all of a sudden this is something that the entire world is focused on. But you're not new to this topic. You've been working in related fields now for several years. So talk a little bit about what you were doing right before the crisis and tell a story leading up to that moment when you realized that the pandemic was going to change things for you and for the whole world.

Hannu Rajaniemi: As I mentioned, my motivation to go to work in life sciences was two-fold. Part was intellectual fascination with the emerging tools of synthetic biology and the other part was personal. I lost my mom to metastatic breast cancer in 2015.

Eric Ries: I'm sorry.

Hannu Rajaniemi: Thank you. And that made it really important to me to try to bridge this gap between all the new really exciting technologies that I could see emerging and the actual practical applications of treating patients. And I found a like-minded co-founder in Nikolai, Nikolai Eroshenko, whom I mentioned before. And together we then started to figure out how could we cross this chasm of applying all the things that people in the Church lab, in other synthetic biology labs in the world were dreaming up and cancer patients. What we arrived at was really a way to essentially mimic viruses but applied to therapeutics and vaccines.

As I mentioned earlier, viruses are messages in a bottle that deliver a little bit of genetic code to our cells which then make more virus and parts of the virus. But the amazing thing about our cells is that they really are like universal 3D printers. They can make almost anything they have genetic code for. Our genomes have genetic code for 20,000 different proteins which then do everything else in our bodies. And you can actually give the cell a new bit of genetic code to make a new protein, just like SARS-CoV-2 does. And we realized that that was a really powerful way to treat cancer. You could actually instead of giving the patient a cancer drug where you really are limited to molecules you can make synthetically in the lab, what if their own cancer cells could make the drug and then that drug could be anything that you could design, any protein you could imagine with any function you could find in nature.

Eric Ries: Astonishing.

Hannu Rajaniemi: And we developed a stack of technologies to do that using a molecule called messenger RNA, which is like a more temporary version of DNA. DNA is the RAM, if you like, the permanent memory of the cell. And when a cell needs to make a new protein, it makes a temporary copy of the information it needs to an RNA molecule that then carries the message to the protein factories of the cell. And just like viruses, we realized that we could do this man in the middle attack. By putting a little bit of synthetic RNA into cells, we could get it to make any protein we want.

Eric Ries: I have to say that as a computer scientist by training, the idea that we've reached a level of sophistication now where we can interact with the human body and use these terms from computer science and from cyber security is ... It keeps coming back to feeling like science fiction to me. What a remarkable thing?

Hannu Rajaniemi: Well, in cyber security the very concept of a computer virus obviously was inspired by biological viruses.

Eric Ries: So now we're coming full circle.

Hannu Rajaniemi: Exactly.

Eric Ries: So one way of thinking about this then is almost like a synthetic virus.

Hannu Rajaniemi: Exactly.

Eric Ries: Not in the sense that it has this negative connotation of spreading, but that it can enter the cell and use the mRNA to cause new proteins the cell wouldn't normally be able to make, to be made.

Hannu Rajaniemi: That's exactly right. And in our case, we're also not making a replicating system. So this system doesn't make copies of itself, it just gets the cell to run it's genetic code. Cell makes some protein that we want it to make. The RNA gets degraded by the cell and you end up with the effect. So in that sense, it's like a drug, but a very potent genetic drug.

Eric Ries: And let me just get the founding story. Sorry, was the company called HelixNano then also?

Hannu Rajaniemi: Yes.

Eric Ries: Okay. So the company was called HelixNano. You started it, you said, five or six years ago. The focus was on cancer therapies.

Hannu Rajaniemi: Mm-hmm (affirmative).

Eric Ries: When did the pandemic come into your consciousness? When did you become aware of COVID-19 and what was coming? Was there a moment for you where it struck you that it was going to be real?

Hannu Rajaniemi: Absolutely. In the beginning of March, I would say, I started to be very worried. I had a sense of foreboding. I guess at that point it was pretty clear that things were going to get very bad. And personally I felt quite powerless and anxious because I didn't think there was that much I could do to affect things. The point where things really changed for me was I was in early March invited to give a keynote talk at the leadership retreat of a major biopharma company which also had a COVID-19 program. And that was an opportunity to learn a little bit more about the efforts around the world that people were starting.

And talking to Nikolai, we realized that there were gaps in the landscape of vaccine efforts. One problem we saw was that not many people, or indeed any of the vaccine programs, were really thinking about what happens if the virus evolves. So to go back to our mugshot metaphor, what if the virus takes the false mustache off and suddenly your immune system can't recognize it anymore?

Eric Ries: And this is why we have to have a flu vaccine every year. There's not a definitive vaccine for the flu because these mutations are very common in viruses.

Hannu Rajaniemi: Exactly. And so flu mutates much faster than SARS-CoV-2 based on the evidence we've seen, but SARS-CoV-2 does also mutate and we've already seen some variants identified where the mutations have made some functional differences. And these mutations have also been used as fingerprints to track which strains of viruses have come from which parts of the world and so on.

Eric Ries: But I do remember, and correct me if I've got this wrong, but that in 1918, in the last global pandemic that has any kind of resonance with this, it was the second strain of the virus that was more deadly.

Hannu Rajaniemi: That is correct. The second wave was more deadly. Now this is where I'm probably somewhat ignorant of the historical details here, but I'm not sure if it is clear that the strain itself was more lethal or whether it was basically worse because of some kind of immune enhancement effect. So for some viruses, if you get an exposure to a virus and if you develop antibodies that don't actually neutralize the virus, those antibodies then can make subsequent infections worse. So if your antibodies go hunting for the spike protein, in the case of SARS-CoV-2, but they don't bind to the right spot on the spike and they actually can't block it from infecting cells. Now, you've actually potentially given it a new cell type to infect because many cell types in our bodies also have receptors for antibodies or antibody tails and now you've potentially attached an antibody to the virus that allows it to get into immune cells.

So it may well be that you're right, that the second strain was more lethal, but I would have to look up whether it was due to the strain actually evolving or whether it was some kind of effect that the previous exposure to the previous strain made subsequent infection worse.

Eric Ries: One theory I had heard was that because of World War I that we created artificial selection where those who were ill were brought back from the front lines and so were more likely to survive than those who didn't and so we created this adverse selection situation where we then mingled those populations in hospitals away from the front and almost created a perfect storm of conditions that would bring evolutionary pressure to make the virus more deadly, whereas under normal circumstances a virus which is more deadly spreads more poorly.

Hannu Rajaniemi: Mm-hmm (affirmative), absolutely. Now, it is on my list to read a couple of books on the 1918 epidemic. But I think one interesting point there is that we may end up doing something similar with vaccines, that vaccines might create evolutionary pressure for the virus to evolve and so therefore this was the risk that chilled me and Nikolai in March. Even if we get successful vaccines from this first wave, they might lose efficacy over time.

Eric Ries: And this is such a critical point and I really appreciate you talking about it and having had this foresight to see this. I talk to so many people now who seem convinced that this pandemic, though bad, there's a light at the end of the tunnel. It will be over soon and that's because we'll have a vaccine. Of course, we all pray that that will be true. But there are these complications that I think those who are coming from a more scientific background seem to be much more concerned about than those in the general public. What about a mutation? What about the second wave? What about our ability to respond? So talk a little bit about how you had that insight. You said, "Oh, there's something that is missing here." Now, I think a lot of people might have said, "Okay, I had this insight. Maybe I'll write a white paper about it or I'll publish an op-ed or I'll just make a few concerned phone calls. You decided to do something a little bit more drastic than that. So talk a little bit about what action that insight prompted you to take.

Hannu Rajaniemi: That's right. So a bit more context on our cancer work that preceded this moment. We had been using this messenger RNA technology I alluded to, to develop cancer vaccines. Now, cancer vaccines work exactly the same way like other vaccines. You are trying to recruit an immune response against an unwanted type of thing in your body and with cancer vaccines, that is obviously cancer cells. It is now possible through DNA sequencing to identify mutations in a patient's tumor that are potentially visible to cancer cells and then create a vaccine against that. So the way we were using our mRNA technology in this context was that we were essentially using mRNA to program some of the patient's cells, or in our case animal model cells, to make those parts of the cancer cell as a mugshot for the immune system to recognize.

But the problem with cancer is that like viruses, it also evolves rapidly and responds to these kinds of selection pressures very quickly. So we realized that using one part of the cancer cell for the mugshot wasn't enough. Again, the false mustache type thing. What we really needed was multiple mugshots simultaneously. And that's been traditionally difficult with vaccines. Our immune cells, as wonderful as they are, don't really have a perfect memory. If you show them something with one notable feature, they will tend to mostly memorize that feature. Perhaps to use a machine learning metaphor, it's easy to over fit with vaccines.

So in the cancer context, we had been developing a strategy to avoid this overfitting to recruit a potent response against multiple targets simultaneously. And what we realized was that that could help us combat SARS-CoV-2 evolution. That if we were able to target enough parts of the virus simultaneously with a vaccine, it might not be able to evolve away. One of those parts might be like a birthmark that it couldn't just take off so easily or even if it did, it would have other things that we could identify it by. So we realized that all this cancer vaccine work that we had been doing was potentially very amenable to being adapted into a multi-antigen SARS-CoV-2 vaccine.

And we then essentially wrote up a plan how to test out this idea, shared it with a few people in our network including Sam Altman who, as it turned out, and it was of course featured on your show, was coordinating a group of companies to create a rapid COVID-19 response across different problem domains that he'd identified. And Sam decided to then back us to actually try this out and therefore we really rapidly pivoted to being fully focused on COVID-19 vaccine development.

Eric Ries: How big was the company at that time?

Hannu Rajaniemi: Six people. We've since hired one additional person, so now seven.

Eric Ries: And how long between when you first had the realization that your technology might be useful for COVID until you had gone all in on this vaccine development?

Hannu Rajaniemi: About a week.

Eric Ries: Yeah. It’s amazing how quickly this happened for everybody.

Hannu Rajaniemi: Right. I think that has been a universal phenomenon that everybody's work has been accelerated to the point where you would not have believed it possible. Just to give you an indication of where we are now, so five weeks after that initial switch we have animal data on immune responses to our first vaccine candidates.

Eric Ries: Wow. How is that possible that it was done so quickly?

Hannu Rajaniemi: A lot of it has to do with all the infrastructure we had already available around messenger RNA. As I alluded to, mRNA has this aspect of being somewhat computer code like. Any mRNA molecule is made the same way but if you change the sequence, you change the protein that it tells the cell to make. So we had this universal platform that we could adapt very quickly to a new purpose so it didn't really require any changes in hardware or lab equipment or anything like that. The only thing we really had to develop were the readout assays for looking at immune responses as opposed to checking whether we are shrinking tumors with our mRNA therapeutic or mRNA cancer vaccine.

But I think another aspect that has been driving this, which was the thing I originally got excited about when I looked at synthetic biology is really the speed of DNA synthesis. So when we want to try a new vaccine design, we are pretty much using a text editor cut and paste together the sequence we want and order the corresponding DNA from a provider like IDT or Twist or others, and typically it arrives in a few days. And then in about a day we can make mRNA from that DNA template and then that can already go into animals or cells. So I think we are quite fortunate that in this crisis we have technologies like DNA sequencing and DNA synthesis that have enabled a very rapid response, not just for us but I think for everybody working on this.

Eric Ries: Most people who have been talking to the public about the possibility of vaccines have emphasized that this is 18-24 months away at best. Can you give us a sense of what the timeline here might be for this, assuming the technology works as you imagine, for the vaccine to be developed? And then talk a little bit about what's your level of confidence or optimism about the likelihood of this approach working.

Hannu Rajaniemi: In terms of the clinical trial process, I think we are, as an individual company, in the same boat with other people developing vaccines where we do need to go through phase I, phase II, phase III clinical trials, phase I addressing safety, phase II assessing efficacy, phase III assessing both on the larger scale. If we are successful with our technology, I think we are also in that 12 to 18 month timeline. We are fairly confident that we will have a phase I ready vaccine lead candidate in six weeks approximately, and in the background we have been setting up infrastructure to manufacture enough of it for a phase I trial. We are also very open to partnering with other companies who have mRNA manufacturing capability and have relationships with some of them.

In terms of my confidence on the approach, we are seeing quite promising animal data already. We eventually generate an immune response without needing to use a boost injection, which is something that many vaccines need. And I'm also very confident in our ability to iterate. So this has really been the core of our approach in the last few years, finding a signal, finding an optimization gradient for whatever biological effect we are trying to achieve, and then driving towards that. And now with this first set of experiments, we have a really good optimization gradient. So I'm fairly confident that we will have a viable vaccine candidate in a short timeline.

Eric Ries: That's amazing. It seems like most people really underestimate how powerful it is to be able to bring information technology and computational style techniques into biology, as they did when we first brought those techniques into manufacturing and into other aspects of life or in the economy. Sam described it in his conversation as if the metabolism or the clock cycle rate of the entire biotech industry has been accelerated by this crisis and all of a sudden teams have been able to embrace, and frankly probably funders too, embrace this power of iteration and rapid testing. Can you just describe a little bit what it's been like to be on the other side of that?

Hannu Rajaniemi: No. I think that's absolutely right. There is this sense of empowerment that all these labs and companies around the world are flexing these muscles that are actually more powerful than they even thought they were. Previously they haven't had a challenge that really allows them to use their full power, if you like, but now we do. It has been really amazing. I think one thing I've been really impressed by is how our team has embraced this challenge and really leveled up in terms of how they think about these problems, for example, through doing a lot of 3D modeling of the spike protein and other viral proteins and trying to find targets so we can get the immune system to hit, working with some collaborators at Google AI and in academia to accelerate that process further.

I think one really incredible experience has been how willing people are to help. So the barriers for collaboration have gone down because everybody has this unified cause. So collaborations or experiments that it feels like before the crisis would have taken months of legal wrangling and discussions and emails and so on now happen almost instantaneously.

Eric Ries: Do you hope that will be a durable effect?

Hannu Rajaniemi: I do, I do. I'm very hopeful that it will be at least to some extent. And also more broadly that the scientific community will continue to embrace this spirit of open data sharing. Again, in pre-COVID world, many of the experimental results or SARS-CoV-2 sequences might have been sitting on somebody's hard drive until they managed to get a publication out. Now, in this crisis, obviously everybody benefits from rapid sharing of all possible information. So maybe we will actually get much closer to universal open access publications in science, which would be amazing.

Eric Ries: I have to say, it's been really heartening and inspiring to see the scientific community all over the world, across national boundaries, rally to this cause and to share data and to behave in a way that all of us in government, in private sector, in nonprofit, we could all take a lesson from what the scientific community has done here. So I thank you for being a part of that.

Hannu Rajaniemi: Thank you, Eric. I really appreciate it.

Eric Ries: I've heard you speak about the need for a vaccine Manhattan Project, obviously drawing inspiration from the secret government project that developed the Atomic Bomb. Tell me what you mean by that and what lessons you think we should be drawing for this current crisis.

Hannu Rajaniemi: Right now we are really facing a challenge that is so big that it might as well be existential. It certainly is existential for the economy and obviously for everyone who loses their life to this virus. And the original Manhattan Project was also a response to an existential challenge to outpace Germany in developing an atomic bomb. And what that required was not just existing science but new science and technology and new infrastructure, which the Manhattan Project was able to deliver on very, very rapidly. And there were a couple of strategies that were important, and one was quickly identifying all key points of technical risk and then very aggressively finding multiple solutions to those problems I parallel.

So in the case of the Manhattan Project, not just trusting that you have one way of enriching uranium, you try to develop three methods for enriching uranium. You try to develop plus one method of enriching plutonium. The same for every other aspect of the program. The bomb design, models for the explosions and so on as well as the infrastructure needed to actually deploy the solution, city size facilities for actually refining uranium and so on. And right now there are several bottlenecks to us having a vaccine and every month or every day that delays us from getting there, has an enormous cost.

Purely in cold financial terms, if you want to emphasize that aspect, if we could get a vaccine six months earlier, that would be worth 6.4 trillion dollars, not to mention all the lives we could save.

Eric Ries: Wow.

Hannu Rajaniemi: So I think it's really worth giving some thought on how we could beat that seemingly now cannon wisdom of it's going to be 12 to 18 months. And a week ago we published a proposal, a white paper, which you can find if you search for Vaccine Manhattan Project.

Eric Ries: We'll put a link in the show notes.

Hannu Rajaniemi: Great.

Eric Ries: I don't know if you have a favorite book or reading about the original Manhattan Project but it's an incredible period in history.

Hannu Rajaniemi: Oh, absolutely.

Eric Ries: We'll include some links too if you give them to us.

Hannu Rajaniemi: Absolutely. By far my favorite book, and in fact one of my favorite nonfiction books of all time, is Richard Rhode's The Making of the Atomic Bomb.

Eric Ries: Oh, remarkable book, remarkable.

Hannu Rajaniemi: It's an incredible book.

Eric Ries: Highly recommend.

Hannu Rajaniemi: But, yeah. So there's essentially two core aspects to what we proposed with the Vaccine Manhattan Project which is to first of all follow the Manhattan approach and solve every single technical problem we have with the vaccine in multiple ways in parallel including manufacturing and logistics and which parts of the virus do we target, what platform do you use to deliver this mugshot of the virus, how do we monitor the patient's immune responses? All those things we should do in multiple ways in parallel.

And the second part is how do we do this safely while doing it fast? The key bottleneck with vaccines is that you need them to be very safe. They need to be much safer than therapeutics because you're actually administering them to healthy people and in the case of SARS-CoV-2 potentially billions of healthy people. So they have to be very safe. The traditional way to evaluate vaccine safety is to observe patients, phase III clinical trial participants for a very long period of time, typically two years or sometimes more and wait if you see any potential adverse effects.

Now, obviously, it is very important to spot those kinds of things if they are going to be there. Vaccine adverse effects do tend to be very rare so you might have to wait a while to see them even in a large trial. But with our increased understanding of the immune system and the relevant biology, we do have a pretty good idea of what those adverse effects might be. For example, sometimes vaccines cause allergies. But for a while now, we've had allergen panels that allow us to detect signs of a person having an allergy. The other big problem are autoimmune diseases where the vaccine actually causes something to go wrong with the immune system's ability to distinguish between your own self versus the pathogen and goes after your own cells. And we have methods for detecting that too. There are so-called peptide arrays that can be used to detect whether you have antibodies against your own proteins.

So with all these tools, we could potentially run much faster phase III trials where we very early detect signs that a vaccine might have potential to cause some of these adverse effects. And then that might help us to prevent those adverse effects in the first place. So with a systematic upgrade in how we evaluate vaccine safety, we might end up with both faster and better vaccine clinical trials. And that's also something that would persist after the crisis. If we solved this for SARS-Cov-2, we will have solved it for any other future pandemic or vaccine applications beyond infectious diseases like cancer or any vaccine whatsoever.

Eric Ries: I know this is a controversial idea and just to make sure I understand the counter argument to it, it would be something like ... The traditional argument in favor of vaccine safety is like, "Look, there's the possibility, however rare, that after you administer a vaccine to a healthy person via freak coincidence of how our biology works, 22 months later they would have a very serious complication or side effects and if you gave such a vaccine to a billion people and 22 months later they were all sick at the same time, the cure could be worse than the disease if you weren't careful and so that's why we observe a population for 24 months to make sure that that doesn't happen. So how can we be sure that using these new early warning systems would have the same efficacy in terms of evaluating safety as the traditional way of just waiting it out?

Hannu Rajaniemi: So what we are doing right now is waiting and seeing whether we see adverse effects or not and trusting on doctors and patients to report those. What we are proposing is first of all measuring every biomarker we can possibly think of in every participating patient and being hypervigilant to any signs of adverse effects. Even more than that, considering any weird signal of auto antibodies or response to allergens as a potential red flag. If we see anything in the many things we can measure that we don't understand for a specific vaccine candidate, we can treat that as a reason enough to reject that candidate.

Eric Ries: So your view is that we now, as our scientific understanding of vaccines and how they work is now advanced to a sufficient level that it's no longer possible for there to be some kind of unanticipated side effect that we couldn't measure with one of these early studies?

Hannu Rajaniemi: It does seem unlikely. I think the space of adverse effects for vaccines is bounded. The acute effects, we can obviously see very quickly in phase I studies already. If you get some kind of anaphylactic shock from an injection. So the problems really are these long term effects, which are very rare, allergies and autoimmune diseases.

Eric Ries: So what would be required for this to happen? I don't get the sense from you that this is a proposal designed to be provocative. Is this something we could actually do?

Hannu Rajaniemi: Oh, absolutely. I think, again, thinking about the economic cost of six months, 6.4 trillion, almost any amount of resources we pour into this should be trivial. Let's say we take $10 billion, the cost of eight hours of partial US-wide economic shutdown. We create a core leadership group to manage this project. In our proposal we mention that it might be advantageous to draw some of that core leadership from organizations which have a strong track record of complex technical project management like DARPA where a lot of the institutional memory from the Manhattan Project was captured. And then we need a unified interface with the regulators to develop and evaluate some of these novel clinical trial strategies. And then a well incentivized collaboration framework where any company or academic group can jump in to contribute and be correctly incentivized.

Eric Ries: It would be one of the largest public/private partnerships in history, maybe the largest.

Hannu Rajaniemi: It would be.

Eric Ries: Who has to say yes to do this? It sounds like we need academic research labs and we would need the regulators of medical studies and biological technology in the US federal government. Who else has to say yes to this for it to happen?

Hannu Rajaniemi: I think to fund it and initiate it, there are several possibilities. It could be the federal government. It could be a coalition of some of the philanthropic agencies currently funding vaccine work. It could even be sufficiently wealthy group of individuals. But in terms of other yes's that we need, certainly you would want the FDA and the European equivalent, the EMA, to collaborate and have a strong interface with them. To their credit, they do seem to be working very hard to accelerate approval processes for both COVID-19 therapeutics and vaccines, so I don't think that's an impossible ask.

Eric Ries: The thing that this is closest to, I think, in the popular consciousness has been a few weeks ago Bill Gates, I think he was on television or was giving an interview where he talked about his willingness to finance three different manufacturing facilities simultaneously producing three different vaccine candidates just to accelerate the maufacturability of whatever the final vaccine turns out to be. Is this related to that?

Hannu Rajaniemi: And then obviously you would need the world's scientists, both academic and private, private companies to jump in on this. But based on the things we talked about before, how willing the entire scientific community has been to rise to this challenge, I think that's probably the easiest part.

Eric Ries: Yeah. I've heard that from several people now working in the field that certainly in the US, that the FDA has been to some of them surprisingly responsive, which has been great.

Hannu Rajaniemi: Absolutely. That would have to be a part of the Vaccine Manhattan Project. If we want to get to the six months timeline that we are proposing, you would absolutely need to start building multiple facilities in parallel simultaneously. Now, for a lot of the new types of vaccine technologies including messenger RNA like what we're using, also DNA, protein vaccines, a lot of those facilities could be very general purpose. So it might not have to be just a factory to make that individual vaccine but one DNA factory, one RNA factory.

Eric Ries: It's an investment, investment in capabilities that could be very valuable when the new normal returns.

Hannu Rajaniemi: Absolutely. It would be a hugely useful investment actually not just for vaccines but potentially creating bootstrapping an enormous amount of manufacturing capability for these new types of medicines that are currently very expensive to make because you don't have the scale to make them.

Eric Ries: I mean, honestly, what could be a better long term investment for our society right now?

Hannu Rajaniemi: Exactly.

Eric Ries: Or at any time.

Hannu Rajaniemi: Exactly.

Eric Ries: And have we not all learned a lesson about the importance of investing in basic research and science related to biology and immunotherapy and life extension and all of these related fields where now the leaders and the disciples in those fields, they are national heroes and we're so grateful for the years that they spent working toiling away in obscurity doing this research in spite of the fact that we don't especially value it as a society. It seems like it would be the moment for us to turn that around and say, "Not only are we going to sing songs and say the praises of these scientists and thank them, but how about also making a commensurate investment to the scale of the problem?"

Hannu Rajaniemi: Exactly. And we have been using the Manhattan Project analogy because it does really reflect a lot of the technical approaches we're proposing but another parallel would be the Apollo Mission where we all unite behind this one aspirational human goal. And the benefits of doing this could really be huge. We talked about the manufacturing benefits but really creating the capability to respond to any future pandemic to deter potential acts of bio terror. If I was a bad actor right now, I would be looking at the US response and how difficult it was and how long it took and thinking, "Hmm, the US is vulnerable to an attack of this sort."

And then there is the potential to catalyze new hubs of innovation. If we create this network of collaborators that solves this problem, that's essentially a distributed biotech Silicon Valley and who knows what innovation that we can't foresee yet would come from that.

Eric Ries: So why isn't it happening?

Hannu Rajaniemi: That is a good question. I think a lot of the mentality in the response, as rapid as it has been, has been around “ let's look at what tools we have handy that we've created for other problems and let's try to cobble something together from them to respond as quickly as we can”. And I think that's a very natural instinctive human response. And drug repurposing, of course, for example, is extremely important and valuable for the patients who need their lives saved. But I think we have to face the fact that if you really want to solve this problem once and for all, we have to build something new. We have to change our approach and our mindset. And that is always very difficult. It comes with this enormous inertia of “this is how it has been done before, these are the technologies we have right now.” But now if ever is the time to embrace that challenge and change the way we do things.

Eric Ries: If now, when? If not us, who?

Hannu Rajaniemi: Yes, right.

Eric Ries: It's so interesting you say that because we're talking about vaccines but we could be having the exact same conversation for the manufacturing of PPE. Everyone knows that I've been working on that issue and the need of people to come together to work beyond just the immediate band-aid solutions but really to build new sources of manufacturing capability, to build a more resilient supply chain. We're seeing the same thing in food where people are going hungry at the same time that we have farmers bulldozing crops and the need to invest. How long have we been talking about some of these problems, not just since the pandemic but for many years? On the education side, we have students being sent home from school to do remote learning without the tools and the technology that they need to get it done. And one problem after another. And we started this conversation with the first order effects, the second order effects, the cascade of consequences of this single change to our society.

It seems to me like across every industry, across every kind of problem, we have to move from this first phase of just emergency response to this investment phase pretty soon. And it seems like from what you're describing, the scarcest resource here is leadership.

Hannu Rajaniemi: I think that's right. And we will certainly try to do our best to draw the attention of people who could take the leadership and take as much leadership as a small company can. But, yes. I think there may be a leadership gap in this crisis and I'm not the right person to ask how to fill that longterm. But what you said, Eric, about how this problem has been propagating across all areas of society, I think really the long term opportunity beyond vaccines and other specific problems related to SARS-CoV-2, I think the challenge is really to build a more resilient society, a society with an immune system that can rapidly and intelligently respond to new threats.

This SARS-CoV-2 is not going to be the last pandemic. It's not going to be the last or the worst existential threat that we face. There are many, many other things and scarier things that will be coming and we should really be prepared for those in a way where we don't have to scramble for the very basics of the response. Now, the danger, of course, is always fighting the last war. So I think that's where we can really learn from the immune system.

Eric Ries: To be adaptable.

Hannu Rajaniemi: To be adaptable.

Eric Ries: To be adaptable. That's right. Resilience is the key word and we'll link to a recent article by one of the experts who works at LTSE named Jean Rogers who's been writing about resilience for many years. But that sensation of building civic institutions, new institutions that are resilient, that can be adaptable, that have a 21st century ethos about learning, about experimentation, about science driven policy. I think we're all called to build that new foundation for the broadly shared prosperity that will come in the recovery. I guess, I want to thank you for not waiting for someone else to do it, but to jump in and lead yourself. I think it's hard to imagine at a time when the real heroes, of course, are the nurses and the doctors who are on the front lines of this and to take nothing away from their sacrifice and their courage. The scarcest resource seems to be leadership and we need new leaders to step up. We need all of us as citizens to ask ourselves, "Hey, what can I do? Can I lead? Can I support someone who can lead? Can I help in some way?"

If there's someone right now who is listening who was inspired by your example and the story of what you're doing, what could they do to help even in small ways to advance the vision of what you have described?

Hannu Rajaniemi: To anyone listening who is inspired by this, I would ask your help to draw attention to our proposal and to others that have recently been made to a concerted centralized response to the crisis. Please share it on social media. Write to your congress person to draw attention for the need for leadership and coordination in our response to this crisis. And then think about what you can do in your immediate surroundings to help, whether it's helping quarantined neighbors get groceries, volunteering to help make PPE, donating to the people doing good work in those areas, and generally trying to find some stillness and calm, which is I think always required to take leadership in any situation whether it's in your own life or in a big crisis like this.

Eric Ries: For those that want to get involved in advocacy for this Manhattan Project, we will include instructions for what to do in the show notes.

Okay, so I want to return to our conversation about science fiction before we close, because I've been thinking about this the whole time you've been talking. There's something about this story that sounds like fiction to me. This sounds futuristic and almost impossible to believe and it struck me as you were speaking, it's not the science. I mean, what a miracle that we can use MRNA to use the body as a 3D printer to manufacture the proteins that we need for therapy. I mean, what an incredible thing? And yet, that's believable to me. We live in an age of miracles so I'm used to that. The part that sounds like science fiction is the need for a coalition of every aspect of our society, public, private, nonprofit, academic, to come together to say this is too big of a problem to use our old ways, to squabble and fight amongst each other.

I've been building coalitions from the day the pandemic hit in education, in food, in manufacturing. And I got to say, I found it pretty hard to sit there and see how people just have a very narrow view about what needs to be done. Every group wants to be in charge. There's a lot of distrust. People don't act with the urgency that an exponential pandemic requires. I mean, I hate to end on a down note, but you're a science fiction author. You're a student of human behavior. You're an entrepreneur. You're a scientist. Why do you think this can actually happen? What gives you hope that this is a realistic possibility?

Hannu Rajaniemi: Because I think that is the story we should tell about ourselves. Part of the reason why I am a writer is that I believe in the power of stories to change minds. I think the story of humanity rising together as a whole to stop a pandemic and becoming better in the process, it's the hero's journey. I think we have to be able to believe in that. One of the things I believe with the very core of my being is that positive change is possible in our lives and in society. And that's what stories always are.

I think it was G. K. Chesterton who said that fairytales don't teach you that dragons exist, they teach you that dragons can be beaten. This is a dragon that we can beat if we come together.

Eric Ries: I really hope that this is a story we can tell our children and grandchildren with pride that we worked together under the banner that you're describing to defeat this thing. And I really thank you for your work and your leadership here. I will pledge to you right now my fealty to this vision too. If there's anything I can do to help make it a reality, please reach out to me. And to anyone who's listening to this, if you can think of a way that you can help move us in this direction, this is what's needed. Get off the couch. It's time.

Hannu Rajaniemi: Thank you, Eric.

Eric Ries: Thank you. Let me ask you one question I've asked every guest, which is simply where do we go from here? How do we get out of the crisis?

Hannu Rajaniemi: It's a very difficult question. I think it has two components. One is very much tactical. We have to at each given moment identify what is the most important problem and deal with it decisively, whether it's PPE, whether it is better testing. We, even as a society, can't deal with every single challenge simultaneously. We have to prioritize. And I think the same applies to us as individuals. And the other part is maintaining a long term vision simultaneously. This is one of those things where you need to keep two contradictory things in mind simultaneously, the tactical everyday reality and then the better, more resilient world we want to build on the other side.

Eric Ries: That's so well said and so akin to the practice of entrepreneurship, the need to keep the MVP in mind while also having that long term vision. Of course, that is so near and dear to my heart with everything that I work on including the Long Term Stock Exchange. But I think we, as a society, have gotten away from that builder mentality, that laying the foundation mentality, that sow today and reap a harvest years and decades from now and this crisis has laid that bare.

Thank you again for your work and taking the time to share a little bit about what you're doing and hopefully inspire others to follow your example.

Hannu Rajaniemi: Thank you for having me.

Eric Ries: This has been Out of the Crisis. I'm Eric Ries. Out of the Crisis is produced by Ben Ehrlich, edited by Jacob Tender and Sean McGuire. Music composed and performed by Cody Martin. Hosting by Breaker. For more information on the COVID-19 crisis and ways you can help, visit

If you are working on a project related to the pandemic, please reach out to me on Twitter. I'm @ericries. Thanks for listening.