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.

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