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Gregory Zuckerman on the Crazy Race to Create the COVID Vaccine
Jan 10 2022

516b4G9sl2L._SX329_BO1204203200_-199x300.jpg In the race for a COVID vaccine, how did a couple of companies who had never produced a successful vaccine make it to the finish line so quickly? Gregory Zuckerman talks about his book, A Shot to Save the World, with EconTalk's Russ Roberts about the daring, deranged, and damaged visionaries behind one of science and medicine's great success stories.

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READER COMMENTS

krishnan chittur
Jan 10 2022 at 11:43am

That was great, thanks – a triumph of human innovation indeed.

I was glad that the listeners were reminded of two key factors that made the vaccine(s) possible – one was the “packaging” (lipids/Pfizer (mentioned) and PEG/Moderna (not mentioned in the podcast) – the packaging had to be just right for the mRNA to enter cells, get into the ribosomes, have the sequence read and spike protein made – and then exported to the surface – so, it was not trivial.  Reminds me of what Matt Ridley talks about – innovation that is needed to make ideas practical – and yes, engineers and scientists have been working on packaging also for decades!

The second was that of “scale up” – making biologicals (DNA, RNA, protein) in LARGE quantities is challenging (and “eggs” were impractical).

A related story – penicillin was discovered as an amazing drug that could kill bacteria – but we had to find a way to make penicillin in large quantities.   Scale up rules were not as well known for biologicals (we had refined the art of scaling up for small molecules/e.g. crude oil distillation).  Chemical Engineers came up with novel reactors (submerged fermentation) and efficient means of separating and purifying the penicillin for use – so the discovery of penicillin found practical use for millions because scale up methods were invented/developed.

It was important to remind the world that so much of the criticism of the US health care system, how it is funded, big pharma and all that is unfair – We, the US are indeed the world’s suppliers of chemicals/medicines that help save and preserve life.  I for one, am glad we do what we do in these USA and how because of who we are we attract the best from around the world.

Hunter
Jan 10 2022 at 2:03pm

It’s not often mentioned, but another huge factor in bringing the vaccine to approval so quickly was the fact that the virus was raging at the same time as the clinical trials were being conducted.  For this reason it took much less time than usual to accumulate statistically significant differences between the vaccine group and the control group.

I feel like Greg was much too forgiving of the public health establishment.  As one example, why did the FDA take their usual three weeks to convene a board for approval of the vaccines – couldn’t they have been looking at the interim data from the studies all along?  And why should we look to Fauci as an oracle –  when it comes to policy tradeoffs he’s no more qualified than the rest of us.

Kevin Ryan
Jan 11 2022 at 2:36am

A good listen.

But again I am frustrated by the omission from the story of the non-mRNA vaccines.

Well they were mentioned at the start, but the discussion gradually transformed into the familiar one in which the casual listener could be forgiven for thinking that there would have been NO vaccines without the mRNA technology.

Don’t get me wrong. I’m perfectly prepared to believe that the mRNA vaccines are superior;  and things would have taken a different, highly likely worse, course without them.

But I don’t think we should be given the impression that the alternative to mRNA development was a world without Covid vaccines

Shalom Freedman
Jan 11 2022 at 6:08am

This was an especially interesting conversation. There is illuminating description of the way scientists work in a passionately competitive atmosphere. We are told of how they patience, persistence and resilience required in their work of discovery in part because there is so much failure in the trial-and -error world.

And there is the main story, the story of the development of the vaccines, including a historical account of the development of vaccines. We get an inside look at the companies and how they worked with speed in order to save human lives. An inspiring story and an inspiring conversation.

 

 

 

Anders
Jan 11 2022 at 7:27am

What struck me the most, and what baffles pretty much everyone I mention it to, was the factoid that the BionTech vaccine was developed in pretty much a week. For several reasons:

One is that I, even after a year of learning more than I ever thought possible about basic immunology and virology, still suffered from the delusion that vaccine development, like for most pharmaceuticals, required massive investment and safeguards to reduce the risks involved.

Another is how deadly our moral compunctions about human trials (not the right term; I mean the possibility deliberately to infect a vaccinated group and a control group rather than waiting for over six months to have less reliable data based on infection rates overall on efficiency and risk.

A third is how, when faced with an emergency, we were able to fast-track approval down to less than a year from over four, which, I understand, is unprecedented under modern regimes (true?). In fact, another podcast listed a range of pretty stark examples of deviating from standard procedure to fast track all kinds of approvals of treatments and medical equipments, such as alternative ventilation technologies.

It makes me think that, perhaps, the alarmism and hyperbole served a good purpose in the end and created momentum that can be sustained. Similarly, this might be the case for combating climate change: perhaps we need a prophet like Great to predict doom to get anything done at all? Perhaps it will even trigger a conservative, free market alternative to the Green New Deal that will feed into that Unicornish consolidation process we all imagine that separates the wheat from the chaff and creates something that is perhaps less radical, but sustainable in the long-run.

Russ Roberts
Jan 11 2022 at 8:29am

Anders,

After my conversation with Greg, I spoke with someone in the pharmaceutical industry about the speed of discovery issue (for Moderna as well). If I understood correctly, he said that the ability to very quickly create the vaccine came from how much was learned from the earlier SARS outbreak (in 2003) and MERS (2012) and the attempts to create vaccines to fight them–attempts that achieved little because they subsided relatively quickly. But the knowledge that was gained made it much easier to create the vaccine for Covid.

Alan Goldhammer
Jan 12 2022 at 5:32pm

Russ – actually more was learned from Zika vaccine development than the earlier SARS outbreaks. There is a good summary of this work in this Mayo Clinic paper.

It should also be noted that protein subunit vaccines have been around for a number of years. Egg-based vaccine production is only used for seasonal influenza vaccines (though a number of vaccine companies are working on new platforms.)

Aladdin
Jan 11 2022 at 11:16pm

Related story (from The First Shots, book mostly described the political side of things) on the delivery mechanism:

For the novavax vaccine, which uses a lipid delivery system similar to Pfizer through somewhat different as its a protein and not mRNA, the company developed this lipid and literally had no idea what to do with it. Its medical division failed, and so they literally sold it as “novasomes” which was used as low fat girl scout cookies and lotion. That is how desperate they were.

It wasn’t until the pandemic they were really able to find a use case and actually succeed.

Flower People
Jan 12 2022 at 12:43pm

As a devoted Econtalk listener, I have to say that this was one of the best episodes in a while. I love economics which is what drew me to this show initially and I am fascinated with art and culture and society which tend to be Russ’ focal points – these are the subjects I am mostly listening for. But I think the fact that Russ’ understanding of vaccines and bio-science is not much greater than his average audience member and to hear him ask a question that I was thinking in my head and deliver it in about the way I think I would have really entertained me.

If you have never heard the song “The Prize” by the indie rock band The Flaming Lips, you should give it a listen. It parallels a lot of what is discussed here, especially the early part of the conversation.

Finally, and this may be a first, I ordered the book right after listening to this episode.

Great conversation Russ, cheers!

Gregory McIsaac
Jan 12 2022 at 12:50pm

Russ Roberts said: “I would have let the price of masks rise. And I would have encouraged people to make a lot of money from masks.”

The prices of masks and other PPE did rise substantially, and eventually PPE availability increased substantially, but neither the price rise nor early statements about not needing masks prevented extended shortages in many hospitals and nursing facilities.

Fauci has been accused of deliberately telling a lie about the effectiveness of masks, but if you listen to the statement he made on 60 Minutes in early March 2020, he did not say that masks were ineffective in general. He couched his comment by referring to the conditions in the US at the time, when there were relatively few cases. He also said that if people want to wear masks, fine. He wasn’t against it.

Did he deliberately lie about the effectiveness of masks for reducing community spread? To answer that question, we would have to read his mind. Was there undisputed science showing that masks outside of hospital settings are effective at reducing transmission?  In July 2020, after masking was recommended or required, Dr. Michael Osterholm, Director of the Center for Infectious Disease Research and Policy at University of Minnesota, called for more research on the effectiveness of cloth masks:

“It is critical that not just more research, but high-quality research be conducted so that the scientific community can assess the effectiveness of cloth face coverings in reducing COVID-19 transmission.”

https://www.cidrap.umn.edu/news-perspective/2020/07/commentary-my-views-cloth-face-coverings-public-preventing-covid-19

Osterholm was concerned that the protection provided by masks was being over stated and giving people a false sense of security, which was also a concern that Fauci expressed in the 60 Minutes interview.

A more clearly incorrect statement about the effectiveness of masks was tweeted by Surgeon General Jerome Addams on February 29, 2020 in which he claimed definitively that masks “…are NOT effective in preventing the general public from catching…” coronavirus. That tweet was subsequently deleted and Addams advocated in favor of wearing masks. Was the first tweet a lie or an honest mistake?  Again, we can’t know without reading his mind or finding contradictory statements he made in private.  From the standpoint of public confidence in science or expertise, it may not much matter whether it was a mistake or a deliberate lie. But calling it a deliberate lie without proof of that, is probably more corrosive than allowing that it might have been a mistake made in the chaos and uncertainty of a dealing with a novel pandemic virus.

Alan Goldhammer
Jan 12 2022 at 5:29pm

There were numerous scientific errors by both Russ Roberts and Gregory Zuckerman that might be excused as they are non-scientists but it did prove very disappointing to me and made it one of the poorer episodes in my opinion.

One major thing that was overlooked was Moderna already had a leg up on the development of a Covid vaccine as they had already gone through the science and developed a prototype Zika virus vaccine based on mRNA.  There were a number of other companies that also had novel Zika vaccines in development but they all stopped when Zika quickly faded away.  There was a major opportunity lost in that clinical development stopped and companies lost an advantage of doing some safety and immunological studies that might have shaved a month or two off of the Covid vaccine development.

Also the role of the NIH vaccine group was not mentioned in the podcast; maybe it is in the book which I have not read.  Barney Graham’s research group did some groundbreaking work on mRNA vaccines and there was some collaboration with Moderna.

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AUDIO TRANSCRIPT
TimePodcast Episode Highlights
0:37

Intro. [Recording date: December 27, 2021.]

Russ Roberts: Today is December 27th, 2021, and my guest is Gregory Zuckerman of The Wall Street Journal. He was here on the program in June of 2014 to talk about his book, The Frackers. His latest book is A Shot to Save the World: The Inside Story of the Life-or-Death Race for a COVID-19 Vaccine, which is our topic for today. Greg, welcome back to EconTalk.

Gregory Zuckerman: Hey, Russ, great to be back.

1:02

Russ Roberts: So, this is an inside story. There's a cast of characters at the different companies and government officials. It's an amazing network of folks, some of whom end up communicating with each other at various times in the scientific process. It takes place, actually, over decades to get us where we are today, which is a wonderful moment, relative to the alternative. I'm curious about the inside story. How did you get the details that you reveal in the book about conversations and the moods? How many interviews did you have to do for this, and how did you get access to these people?

Gregory Zuckerman: That's a good question. So, early on in the crisis, I made a bet. Much like the government ended up making a bet on various vaccine companies, I decided to track a certain number of them. And, there were those that were in the lead. There were those that were most intriguing. There were those that people in the field thought had the best chance of success.

So, once I made those decisions--they didn't all work out, but most of them did--my challenge was to get inside the efforts. And some were easier than others. Generally speaking, academics are the most eager to speak. Government officials are almost as eager. Once you get through the PR [Public Relations] people, those kinds of people, you get Fauci and his team on the phone, they're very generous with their time and open. Then corporate efforts are harder and they take much more effort. And then some are even much more difficult. Usually, it's a reflection of their personality. So, the University of Oxford was a really difficult one, and partly because those that lead it are difficult people.

So, there were various degrees of difficulty, in terms of breaking inside. What I do--I'm an investigative journalist, that's what I do at the Wall Street Journal--and my task is to get people to open up and speak often when they probably--well, I wouldn't say 'shouldn't'--often, when there are incentives for them not to speak. And my job is to present an argument as to why it's in their best interest to speak. Yes, I'm talking my book, literally, but I do think this is a historic effort and it's in their interest to contribute and make sure that the record is accurate. And that's my argument often with people.

Russ Roberts: A lot of those conversations were not the participants at Moderna or BioNTech, or J&J [Johnson and Johnson] or Oxford or Novavax, or--I'm missing one--Pfizer. Those aren't people retrospectively--two, three years later, or, excuse me, a year and a half, say, later--remembering what happened. You're keeping track of them and trying to make them feel comfortable you're not going to reveal this until the book comes out?

Gregory Zuckerman: Right. So, a lot of it was real time, more so than I've ever done in my life. What I often do--I've written a number of books--I write about big successes, and I look back and describe how they occurred. And as you suggest, this one, it was more of a real-time effort. Yeah, listen, frankly, some people are eager to speak about the drama behind the scenes, their role, and it's my job to make sure it's accurate. Then, what I do is check it with others, make sure it's accurate, etc. That's part of the challenge.

4:43

Russ Roberts: So, spoiler alert: we get some vaccines out of this. But I have to say, what makes it an extraordinary book is that you start going back in history, you talk about some of the challenges, the AIDS [Acquired Immunodeficiency Syndrome] vaccine, and then you're about--we're into the 2000s, and then we're into the 2010s.

The reader knows how the story turns out. But, it doesn't look possible in 2018. Forget 2012. In 2018, the companies that we now look to as these great success stories, had--it's not like, well, they were close. They had nothing, and that's one of the things we're going to talk about. But, I thought that drama and the poignance of the book, part of it comes from the fact that even though we know how it turns out, it was certainly not a foregone conclusion.

Gregory Zuckerman: Right. That was my goal writing this thing: to present that history, and I do so because it's important to understand--it's my way of, it's a conceit to describe the immune system, describe the evolution of some of these vaccine approaches. But, I also am trying to plant a seed in the reader--or the listener, if you're listening to the audio--I want to make it clear how challenging it is to develop vaccines and how many efforts failed along the way, which makes it all the more remarkable, this achievement.

Had I started with, let's say, 2018 or 2019 and dove right into it, it would be impressive what they accomplished, but not as impressive as if you compare it with all the string of failures over the years.

Also, frankly, when I was doing the research, I kept hearing about AIDS vaccines. 'The work we did on AIDS, Greg,' and, 'What we learned from AIDS.' And I'm an outsider. I'm not a science writer: I'm an investigative reporter for the Wall Street Journal; I do different industries, mostly financial from the world of finance.

And my assumption was, going into this thing, that an AIDS vaccine--the effort was an utter failure. And, I learned along the way, how much was actually learnt and developed and applied to COVID-19, and I thought that would be important for the reader to understand as well.

Russ Roberts: I think the other thing you learned from this book--and I want to talk a little bit about this backstory and these undercurrents before we get to the main entree. I've been in academics for three-plus decades, I guess almost four now, can think of it as, yeah, four, four-plus. It's a really petty, peculiar world. And, I think it's more so in [?science?]--I've been an economist my whole professional career. These are not economists, these are not social scientists: these are hardcore chemists, biochemists, epidemiologists, scientists--and they are peculiar people.

I think we have this idea of them sitting in the--they're standing, by the way, often. They're standing in the lab, they're in their lab coat, they're staring at a beaker, they're staring at a pipette. They keep pouring over something growing in a Petri dish with a microscope. They're looking out into the distance, thinking deep thoughts.

What your book reveals is that an enormous portion of their time--and I don't think this is melodrama, I think it's real--they're incredibly stressed out because they're afraid they're going to be scooped by a rival. They're afraid they're not going to get the glory they deserve. There's an amazing amount of competitive passion in this world that I think outsiders don't appreciate.

Gregory Zuckerman: Yeah, that's exactly right. And, I know that's right, because I was an outsider and that was my presumption, as well, about these people, these individuals: they were data-oriented and focused and unemotional. And, they were anything but unemotional there. As you say: petty--they're competitive, neurotic, they're ambitious. Yeah--the level of competition was striking.

And, partly, I write this book to introduce the reader to this world and to inform them [? unclear, ~9:09?], and frankly, how breakthroughs are developed. And, I had this naive assumption that breakthroughs, scientific breakthroughs, are some brilliant individual in some basement lab, some Eureka moment.

And, the other thing that really struck me is how it's a team orientation. It's almost like a relay race, where you have groups of people running and making progress and then stumbling and falling and passing the baton to the next group. And, that struck me as well.

So, right: and thank God for the characteristics of these, and traits of these scientists, because as a writer, I went into this thinking--I was a little wary that there wouldn't be the characters that I need to write a compelling book, and I couldn't have been more surprised by what I discovered. Yes.

Russ Roberts: And it's--they're deeply vulnerable, damaged--

Gregory Zuckerman: 'Damaged' is a good word.

Russ Roberts: There's so much heartbreak for the people--you say, pass the baton? They kind of drop the baton after they fall down and someone else sees it laying there and says, 'I guess I'll run for a while with it.' It's a shockingly intense world. Again, we think of academic life as sort of not so stressful. You teach some classes, you do some research.

These people--I mean, they're not in the academic world, they're in the corporate world, most of them. They're scientists, though. And, as scientists in the corporate world, doing effectively academic work for profit, they are driven and damaged.

Gregory Zuckerman: Yeah. It's a great observation. It was one that I was struck by. And, I understand why. It's a competitive world. You spend years making incremental progress--potentially, hopefully--and then often it's a dead end. You know there's somebody out there, or more than one person out there, working on the same thing. So--you become neurotic.

And the other thing that jumped out at me--and I was naive about--is the importance of the role of money in this world. I thought, 'Okay, you get a grant. You're an academic researcher and you've got some money and you're good to go.' It's almost like a Congressman, where, yeah, you raised money, but you're thinking about the next fundraiser right away. And, you're thinking about your next grant right away. And, will this last, and can I pay for the people in my lab, and are we making enough progress? How can I show that we're making enough progress to get more money?

The rivalries build, but also the pressure builds, and they're all under remarkable amounts of pressure. It's impressive what they accomplish and how they deal with this. But, it was important for me to shed light on that world as well.

12:11

Russ Roberts: I want to add one more lesson. There will be others. But, one more lesson before we go more deeply into vaccines that I learned from the book: there's an immense amount of what I would call tinkering. I think when we think of science, we think of: You put a bunch of equations on the board and you work it out and then you test it and it works, or it doesn't work, and you go on.

A lot of this is--it's equivalent to what we talked about with Matt Ridley, when we talked about innovation. Some of the skill in this is--it's obviously luck. There's an enormous amount of luck. There's an enormous amount of trial-and-error of developing pieces that aren't really what we would normally think of as science. It's more like repairing a car or solving a problem of a repair in your basement or your backyard where you're not sure what's going to work, you don't know if it's going to work, and you try something. You're throwing a lot of things against the wall.

And I think when we think of chemistry from, say, high school or medicine, we assume it works more like a recipe. And, they're trying to figure out the recipe, and they don't have any idea about the ingredients. They have some big picture idea, but in the weeds, it's really a lot of trial and error.

Gregory Zuckerman: Yes, it is. And it's incremental advances--hope to have incremental advances. And it's going down dead ends.

And frankly, I do what I do for a living, partly because I like to turn things around. Being on a daily basis at the Wall Street Journal, I work on a piece for a week, maybe, or a few weeks, maybe a few months, hypothetically, but that's rare.

In my books, okay, I'll spend--this one, was about a year and a half-- devote, and it's all-consuming. But then it's out: I can show it to the world. These guys, they spent years. They spent literally years on an approach that may not work. On a selfish level, I learned from them: the patience, the resilience, the persistence. It's admirable.

Russ Roberts:Yeah. The part--the uncertainty about it is part of what I'm talking about. And they have a lot of passion for their approach. There are all kinds of different approaches that were tried to develop this vaccine and other medical challenges. And, people become passionate about their horse in that race. But, the truth is: Of course they are. It's theirs. They don't really have more than an intuition, it seems, about whether it's going to come across the finish line or not make it.

Gregory Zuckerman: Yeah. That's very true. And I find the distinction interesting between the leader of the lab--who has various postdocs and others working for him or her, and in some ways, it's a portfolio approach--they all describe it that way, where you have a bunch of people working for you, and if any one of them has a breakthrough and writes a good paper, that's good for you, and a few of them are going to fail. But, that younger academic has that one approach, and there's no portfolio approach there, it's just all in on something and it may not work and you may not have a paper. If you don't have a paper, you can't get a job, you can't get a job, you're stuck.

The pressures build and it goes on for years. And, yeah: I'm glad we frankly talked about this because I've done different interviews, but there haven't been any that really delved into this world. And I think it's important for people to understand. It's entertaining, it's interesting to understand this world; but it's important as well, it's an important part of science.

16:02

Russ Roberts: Yeah, it's intense, which is--well, as your subtitle says, it is life or death. It's really not just like--the joke is: academics are petty because the stakes are so small. The stakes here couldn't have been bigger. Obviously, the participants wanted to change the world and make it better. But, they wanted to change the world. They wanted to be the ones, not just--I mean, I'm sure they were happy that other people were successful, but kind of felt like they definitely wanted be there first.

Gregory Zuckerman: Yeah, it's interesting. I don't know what your impression was of the characters in my book. I think one comes away impressed, obviously, and thankful. But, I don't know: Are they people you really want to have a cup of coffee with, have a beer with? I'm not so sure. I'm not a big believer in black-and-white characters. I love, love, love the gray. And you have a lot of gray here. So, in other words, motivations.

Yeah, they want to save lives, but do they want to get rich and famous, too? Many of them, yeah. Do they have some mixed--they want the recognition of their peers. That's hugely important, maybe more important than rich and famous. So, there are all kinds of interesting mixed emotions. Frankly, they take steps, sometimes--they're so competitive sometimes. How they react to each other is not admirable. There are a few people I mention in my book, if you recall, Adrian Hill, just really difficult on his peers, difficult on others, very, very critical. These are academics that spent years getting up in meetings and ripping into each other.

And, again, there are mixed emotions. They believe their approach is going to save lives. Save lives! And they want to save lives. But they also want to be the ones to do it.

Russ Roberts: They're also just, as we all are, they're flawed human beings and their ability to subdue some of the less attractive sides of themselves, are, of course, imperfect.

I was struck by the CEO of Moderna, which one of the coolest things--very small thing, but a cool thing I learned in the book--is 'Moderna' is Modified RNA, which is just really cool for a name and it's modern, which is also cool.

But, the CEO is--Stephane, right? [Stéphane Bancel--Econlib Ed.]

Gregory Zuckerman: Stephane.

Russ Roberts: Stephane Bancel reminds the reader inevitably of Steve Jobs. Not just--I think he's got a turtle neck issue, but that's not the reason. The reason I was fascinated by that is that he has boundless optimism, most of the time, at least in public; and he's very demanding and very difficult to work with, and yet people want to work with him. Which, when Walter Isaacson's biography of Steve Jobs came out, people said, well, turns out Steve--'What'd you learn from the book?' I would ask? 'Oh, Steve Jobs is a jerk.'

Okay, that's not interesting. So, I didn't read the book for a while. That's not what the book's about. Part of the book is about Steve Jobs is a jerk, but it's more interesting that he was a difficult person. I don't want to call him 'a jerk,' that's not nice. But, he was a difficult person, for sure. But that didn't stop people from making enormous personal sacrifices to earn his respect.

And, that comes through a number of the characters in your book, where people are driven and drive their employees to work 25/8 [i.e., more than 24/7, more than 24 hours per day, 7 days per week--Econlib Ed.] for the company. And people keep doing it. Obviously, there's a leadership factor there that is--it's easy to dismiss these people as tyrants, which they have a tyrannical aspect to them, but they also change the world because they are able to lead a team to exceed what they are probably capable of, under someone else.

Gregory Zuckerman: Yeah, Russ, that's exactly right. And also, that raises the question: Do you need these types of personalities to have these remarkable breakthroughs? Yes, Stephane Bancel, it goes back to that theme of, you're not sure if you like him or not--I think. I can't speak for the readers. But, he is difficult on his underlings, has always been, he pushes them.

There were--early on at Moderna, people were collapsing at the office, in the parking lot, hitting their heads at home, being rushed in ambulances to the hospital, because he pushed them so hard and they were trying to keep up with him. And, he fired people quickly and easily. Could be very insulting. And yet, inspiring. And if you talk to people today within the company, and I do, they love the guy.

And you say to yourself, 'Well, how do you love a guy who's so hard on you?' Well, he's a great leader. He inspires. He's the one who said a few years ago--years ago--he said to people within Moderna--I write about it, obviously, all in the book--'We are going to be the ones to step up and save lives in a crisis.' And that's inspirational. And people love him.

It also, takes time, I think, as an executive to build a team that understands you and isn't insulted by those kinds of comments. And now, the people within the firm, they love him, and within the company. It took a little while. But, right: he's one of these complex characters.

Russ Roberts: He's easier to love now probably than he was before.

Gregory Zuckerman: Yes.

Russ Roberts: Obviously, there are tough bosses who bring out the best in you, and there is a certain type person who wants to have that bootcamp-like demand put on them for their own aspiration. There are other people who want to just not deal with that. Obviously, I'm not criticizing him. He's a complicated person. But that's all my point: He's a complicated person. I think some of the exterior of these people like him and Jobs and others, they bring out something in people that, as I said, others can't bring out. It's not for everybody.

Gregory Zuckerman: I think that's true. And also, I think on the outside, if I can speak for my fellow journalists, we adopt, sometimes--there's a simple narrative, especially about Stephane Bancel. And, early on, there was a lot of talk about him being a jerk. So, we all view of him as a jerk.

I don't think it's appropriate, because you need to do the research, and realize--he is the most giving friend I've ever encountered. Like, to people in his circle, he literally writes notes, like, notes of appreciation to his friends.

And, he was reaching out to friends during 2020. I had no time. I don't know about you, I was crazed and worried about the future and writing this book and keeping my job and stressed out. And he was doing--he was saving the world; and yet, he was taking time to ask friends who had lost their job, if he could help them--Zoom calls, where he was generous with his friends. So, he's a very, as you said, complicated character--which I love. I love that great character.

Russ Roberts: Yeah. It's part of the charm of the book, for sure.

23:22

Russ Roberts: Let's get down a little, let's get into the science. We're at a really extraordinary moment in medicine and biochemistry that at least two of the most successful vaccines, Moderna's and BioNTech that was developed eventually with Pfizer and produced by Pfizer, they used a radical technique that was brand new. And, was, as you suggested a minute ago, and it comes to in the book overwhelmingly, there was never a certainty that it was going to work.

There were people who believed in it; there were people who were cheerful and optimistic as the day is long, that 'Of course it's going to work.'

But, of course, we all have doubts in the privacy of our own home about those kind of stories, even when we were telling them, sometimes.

So, let's start with the way vaccines used to work. When we think about traditional vaccination--whether it's smallpox, polio--what was the idea? How did that work?

Gregory Zuckerman: Sure. So, every vaccine is an education. We're teaching the immune system to recognize and prepare for some pathogen, some illness, some virus. Traditionally, you do that by introducing a piece of that pathogen--we call it attenuated or killed. Basically, it's either a watered down with formaldehyde or killed version of a piece of the actual virus. Traditionally, the vaccines introduce the actual virus to the body. Obviously, it's not dangerous because it's either been weakened or killed, that piece of the virus.

Russ Roberts: That's in modern times, of course. In earlier times, there were folk remedies. The first "vaccines," in quotes, were, went and got yourself sick a little bit, not too much. You probably made a mistake every once in a while. Crazy idea, by the way. Horrible idea, really a radical, bizarro idea: You want to protect yourself from smallpox, give yourself some. Really?

Gregory Zuckerman: It's true. Now, you mentioned it, right, who would even think about doing that? Talk about trial and error. It took us a lot of years to figure that out, that approach. But that's the same point where we're educating the immune system. Okay, please recognize, we're going to introduce this piece of the virus, so that the next time you actually encounter the real thing, not a weakened or killed version of it, you'll be prepared and ready to fight it off.

That was always the traditional approach. Sabin, Salk, all the famous vaccinologists, the Merck famous ones, MMR [Measles, Mumps, Rubella], we all recognize.

But over time, we realized that while it's not always the best approach. Let's say with AIDS: you really don't want to introduce a piece of that kind of virus, it's so dangerous and harmful. Others as well, it's not ideal, necessarily. And also, it just takes a really long time to manufacture those kinds of vaccines: they're challenging in a lot of ways to develop.

Russ Roberts: Just to be clear, you'd think that's a bad strategy, but the reason it's a good strategy, if I understood what you said in the book correctly, is that the body needs some time. If you just introduce the smallpox as a full-blown version, your body doesn't react quickly enough. The idea of the vaccine is to prep the defense forces to be ready to recognize it more quickly, correct? Because, you've got the same ammunition to fight the smallpox when it comes in its full-blown version. It's just that you needed a practice run, right?

Gregory Zuckerman: Yes, exactly.

Russ Roberts: That's really what's going on. It's the timing, is that right?

Gregory Zuckerman: Yeah. And also, listen: frankly, some bodies are better capable than others of fighting off the actual pathogen. Even cancer, many of us encounter and fight off. But, right, not everybody is able to. It needs that education, that dry run as it were.

But, over time, we realized that there could be other approaches. And, mRNA [Messenger Ribonucleic Acid]--should I dive into mRNA? Is that approach--

Russ Roberts: Yeah, please.

Gregory Zuckerman: Yeah. So, mRNA was always the holy grail. It was the dream of scientists.

I'll just kind of take a step back, just explain what the heck that is. So, basically, messenger RNA is a molecule. We all have it inside of us, naturally. Its job is to transport the genetic messages from DNA [Deoxyribonucleic Acid] to the part of the cell where proteins are created, proteins that keep us alive.

Messenger RNA does that job. DNA can't do it itself: it relies on messenger RNA. And mRNA is very short-lived molecule. In other words, it gets chopped up by enzymes in the cell almost immediately. So, it's a very short-lived kind of molecule. And, scientists always said, 'Wait, hold on a second. Messenger RNA transports these messages, it creates proteins, every kind of protein. What if we could develop these in the lab, synthetically? Just like you have sugar, you have natural sugar, we have artificial sugar. Maybe we could create artificial mRNAs.'

Why was that the holy grail? Why was that the goal of scientists for decades? Because, if you can send a message into the body to create any protein, any specific protein, then you can turn the body into a lab of its own, a manufacturing--a factory of its own. You can create any kind of drug or vaccine within the body, naturally, quickly, efficiently.

So, in other words, you just send a message. You want a protein? Good, let's go get it. Here, I'm going to send a message to the body, through a vaccine or a drug--a therapeutics--to create any kind of protein, which again is the key for any kind of drug or vaccine.

And just as quickly as scientists got excited about that approach, that idea, they usually gave up on the idea because, 'Yeah, yeah, yeah. On paper, it makes sense: I can create a vaccine to send a message, this mRNA, to send a message to the body to create a protein and we're off to the races. But, remember that the mRNA is short-lived. It gets chopped up immediately. So, why would I base a drug or a vaccine on something, on some molecule that doesn't last?'

Also, the body has defenses against it. It's built up over the years, and time and time again, when they tried these experiments, the body fended off these mRNA, these molecules that were created in the lab. So, it was always the holy grail the goal scientists dreamed of, but then most--not all--most said, 'Yeah. Right. Forget about'--it's a little bit like, going back to that earlier book, we talked about, The Frackers, where shale--shale was this kind of rock where everyone knew it was packed with oil and gas, but, 'Don't waste your time on it. It's too deep, it's too challenging, too expensive. Forget about it.' Same kind of thing: 'Don't waste your time on mRNA,' was always the conventional wisdom.

31:00

Russ Roberts: Right. And they were right. The convention was right for a long time, but it failed over and over again. Attempts to implement it--well, first in mice, right?, and in other, before it got to humans.

But, just to clarify one thing about the strategy: The protein you're going to create with this artificial mRNA molecule is going to be a protein that's going to send a signal to the body to fight this other thing?

Gregory Zuckerman: No. Let's fast forward to this coronavirus--it's usually the hallmark characteristic protein of the virus. So, in this case, that's the spike protein. It's something that is a good education for the body's immune system.

Russ Roberts: Oh--it's just a practice run.

Gregory Zuckerman: Yeah.

Russ Roberts: It's a practice run.

Gregory Zuckerman: In this case, remember how I say it in the book how it's like Kim Kardashian's tush and Tom Brady's cleft chin: It's something that is characteristic, because it could recognize--the body's immune system sees that protein, knows right away, 'This is foreign, this is dangerous. I'm going to go attack it.' In this case, spike protein.

And, it was fascinating, all the--and I'm jumping ahead a little bit--but everybody early in 2020 kind of said, 'Yeah, let's build vaccines built around the spike protein because that's the key to this.' It's how it latches on to the body cells. It's just a key part of this virus.

And that's the case of others. With AIDS, there's a protein that has been the basis or was the basis for a lot of the vaccines as well. So, you want to introduce a protein that is key to that virus to educate the immune system.

Russ Roberts: Well, it's just--it's just a two-step maneuver. Instead of introducing the protein into the body, you introduce the mRNA into the body. The protein is the disease. You could give people a little bit of COVID, right? as a way to get their immune system to recognize it. But, what the mRNA does is introduce a little, small piece of it?

Gregory Zuckerman: It teaches the body to create it. It sends a message to the body to create that protein. And once it's created, the body recognizes it. And it is alerted that it's foreign and it's harmful and dangerous. So, sending a message to the body to create that spike protein.

And frankly, it's the mRNA approach, but it's also the J&J and AstraZeneca approach: they just do it in a different way. But, those are just--they're genetic messages to the body.

Russ Roberts: But, they're creating a little piece of the virus to tell the body to fight it. So, again, it's the same idea: you're giving yourself a little bit of it. But, so little that it's not going to hurt you. All it's going to do is knock on the door of the immune system and say, 'Hey, wake up, come get this thing.'

Gregory Zuckerman: Yeah. Well, you're not introducing a part of the--you're teaching the body to develop that protein, as opposed to introducing it.

The other approach, the third approach in COVID, is the protein sub-unit approach, which is what you're saying, where you introduce the actual protein. That's what Novavax does, GSK [GlaxoSmithKline], and [inaudible 00:34:11] are working on one. And that's a more traditional approach. You've got shingles vaccines, HPV [Human papilloma Virus], where you introduce a protein in the vaccine. As opposed to the mRNA, where you're not introducing the protein, you're teaching the body to create, to develop that protein, sending a genetic message to the body to create that protein.

Russ Roberts: Which is scary. Which is really scary. Because if you make too much, it would kill you, right?

Gregory Zuckerman: Uhh, yeah--

Russ Roberts: Isn't that the same idea, the same worry?

Gregory Zuckerman: Right, I guess, hypothetically right. But, it's not enough to harm the body.

And also, it's also important to remember that the mRNA gets chopped up. Remember I said it, momentarily, it still does. The synthetic version of it is not dangerous because it gets eliminated by the body, and that's why some people will say, 'Oh, I'm worried about mRNA, it's sticking around in my body and changing my--'. No, no: It gets chopped up. That's why--that's the irony, and that's why scientists never wanted to work with this thing in the first place because it's so short-lived.

Russ Roberts: And so, you've got to find a husk, or a shell of some kind to get it in there for just enough to survive the assault on it before it can do its work. And when it does its work, it's gone and the body learns. That's the idea of it.

Gregory Zuckerman: Right. So, there two parts, two components to these vaccines. There's the actual mRNA, the genetic message, and then it needs, as you suggest, to be encased in something. And frankly, that delivery challenge was just as important as developing the mRNA. It needs to be delivered and eventually develop these, like, lipid nanoparticles, which is like fatty products to encase and accompany the genetic message into the body.

And, that was, itself, a scientific challenge. And frankly, doesn't get enough attention, even by the world of academia, because it was done in corporations, I think.

So, when you talk to some of the people in my book--I don't want to say names--leading academics who accomplished a lot, who achieved so much and gave so much, they worked on the mRNA side of things--they're sort of dismissive. They're like, 'Yeah, yeah, then--' and 'then Moderna figured out delivery.' Well, geez, that literally took a decade.

So, it's a little dismissive, frankly, the work within the corporate labs. BioNTech also: they had to figure out how to deliver that genetic message. That, in itself was a huge challenge.

36:38

Russ Roberts: Yeah. And, that's the trial-and-error part, that's the tinkering thing--they're trying to put thicknesses and materials obviously.

Let's talk about the miraculous part of this. So, as I alluded to earlier, it's 2018, it's 2019, and it's late 2019, and there's some rumors that there's this pathogen that's coming out of China, out of the area of Wuhan.

And, I remember very vividly reading about that and thinking, 'Boy, I'm so glad'--I didn't even think I'm so glad it's far away. I didn't think that. I just thought, 'I don't need to think that, it's far away. I don't need to read about it. I don't need to know about it.'

And, these companies were ready for that, even though they had not been successful. They were aware that, were a pandemic to come along, they would be prepared to fight it in a way that most companies couldn't. Most labs couldn't.

Why did they think that? Because, here they are--some of them going on for, I think over a decade with no commercial success. They're trying to create vaccines, which is a really profitless task, generally. No large, very few large pharmaceutical companies are interested in it because there's very little money in it. The reason there's a little money in it is that it's not socially acceptable. I think this is the reason to charge large amounts of money for something that protects people from horrible disease, especially if it's en mass, like the whole population. And, so they don't put any investment in it.

These little firms are working on it, almost as an intellectual curiosity, hoping they'll find something that they'll be able to sell, some amount of. They're small, in terms of investment; and in terms of revenue, zero. Why were they so confident, given that they had virtually no product? So, that's the first question. They were sure, 'Oh yeah, our approach is going to solve it.' They had no track record. How'd they do it? Not how did they do it: Why'd they think it?

Gregory Zuckerman: Right. So, to amplify your question, not only had they never produced anything--these companies or these labs. We're talking Moderna, we're talking BioNTech, we're talking about the University of Oxford, Novavax. Not only had they never done anything: By the end of 2019, there was intense skepticism, even accusations surrounding these companies. Moderna, specifically, by 2019, end of 2019, people compared them to Theranos--especially Stéphane Bancel, that CEO we talked about. There were a lot of similarities to Elizabeth Holmes.

Russ Roberts: Elizabeth Holmes, alleged to be a fraud and a liar.

Gregory Zuckerman: Yes. Right. And Stéphane Bancel was mentioned in the same breath. Why? Because there were a lot of similarities. There was reason for the skepticism. They're both great sales people. Very, very persuasive. Stéphane Bancel had raised tens of billions of dollars for Moderna, often from what they call tourist investors. Not really biotech experts. Some were, but many weren't. Sovereign wealth funds kinds of firms, companies, kind of entities; people with a lot of money on their hands, but maybe not the best expertise.

And they had never done anything. They're big talkers. They started off as Moderna Therapeutics. They were supposed to do drugs. They were not supposed to do vaccines.

The fact that they had to pivot to vaccines raised other questions. Who the heck wants to do vaccines? It's a lot of--no one in the world, a big pharmaceutical--likes vaccines. It's an awful business. You don't make that much money, as you suggest. Just so much you can charge. It takes years and maybe the pathogen goes away. Maybe you take a vaccine once a lifetime or once a year, maybe, but usually not. Everyone wants to do drugs.

Moderna had to pivot away from drugs because mRNA was failing there. And, they were always very secretive. There was--that talk we mentioned earlier about Stéphane Bancel being a jerk as a boss, who wants to work there? There were all kinds of suspicions about Steve Jobs--I'm sorry, Steve Jobs--about Stéphane Bancel. He wore those turtle necks, so did Elizabeth Holmes. It was fascinating.

So, other companies, too, I write about: Novavax, shares were like at $3, they were running out of cash.

So, you ask, why were they so confident? Why were the scientists within these companies? Partly it goes back to that characteristic trait of the scientist, that: they have to be. By definition, it attracts researchers who believe in their efforts. And frankly, the research on my book has taught me a lesson, not to be so dismissive of those kinds of researchers. The stock at $3, and they've been working on something for a decade and guys like me, Greg Zuckerman will be like, 'Yeah, yeah, you're almost being delisted. Oh, you sure you've got some approach that you think's going to work?'

Well, maybe the lesson is, at least to be a little less skeptical. I'm not saying don't be skeptical, but a little less skeptical. The lesson here: There are researchers all over this world convinced of their approaches. Nine times out of 10, they're not going to work. But there's that tenth time, and these people were convinced of their approaches, partly just by the nature.

The other point is that they had been developing data. And, it was below the radar screen. It wasn't well publicized. It was in animal studies, early animal studies, often; but it was enough to convince them. And they were always frustrated--I'm not just talking about Moderna, I'm talking about even the J&J group, Oxford--the University of Oxford--etc.: They often developed vaccines to attack pathogens that went away: Zika and MERS [Middle East Respiratory Syndrome] and early coronavirus.

They felt, 'Hey, we actually developed a vaccine that's pretty darn effective. It's not our fault,' that these pathogens went away, they dissipated. So, within their labs, they were like, 'Hey, we created something really good.' Everybody else outside is like, 'Really? Show me some approved drug or vaccine. I'm not seeing anything here, guys.'

43:00

Russ Roberts: Yeah. A point I've made here before, and I think it's worth remembering, especially with people like me who have certain policies, ideologies, whatever you want to call them--I've decried on the program certain favors that pharma gets from government regulation, and the way that the United States has organized its healthcare system, which allows, in many situations, basically large pharmaceutical firms to put their hand in the pocket of the taxpayer without the right kind of feedback loops that normally work with customers who are paying for things.

And, I think that's a bad thing. I think it's been done badly. I don't think they're evil. I think the incentives have been set up in all kinds of complicated ways to make that worthwhile, unfortunately. We have lots of episodes on that. If you want to hear more, or haven't been a regular listener, we'll put a link up to many of those in this episode's page.

But, one of the benefits of that system is that there's an enormous number of really smart people who have been drawn into that world to tinker.

And, the world needed those folks, this time.

We got a silver lining to the rent-seeking and whatever you want to call the big pharma industrial complex that we have in the United States. It creates an enormous laboratory for innovation. I think we have too much. I think we overpay for what we get. I don't think it's as valuable as what we pay for it.

But, when this came along, there are a lot of people sitting around at labs who'd gotten Ph.D.s in biochemistry and chemistry who were happy to try out something. As you say, nine out of the 10 fail. And that's okay: you only need one to work. So, we've got this diverse portfolio, this reserve army of biochemists and innovators and startups that turned out to serve us quite well in this crisis. I'm not saying it was worth it--but I think it probably was; we'll talk about that in a little bit.

But, I think it's worth remembering that--it's just a positive, unintended consequence, I think--a positive unintended consequence of the amount of resources we poured into pharma with more mercenary intentions.

Gregory Zuckerman: So, I agree with everything you say, and I want to amplify it or add to it. I'm not going to repeat everything you say--I agree with it. But, beyond that: Listen, I'm a journalist. We're often very skeptical. I've written skeptical pieces about pharmaceutical--big pharma, little pharma, medium pharmaceutical--but also biotech, specifically. Biotech is full of sales people and exaggerators.

But, but, I do think this episode, this experience is a reminder of with those incentives, to get really rich comes backing. Billions of dollars of venture capital money, small investors, people writing checks for the hope, just the hope, that down the road, maybe someday day there'll be some payoff. And, frankly, there's no other system out there like the U.S. capitalist system, which creates those incentives. And often, it leads to bad players and bad actions, bad actors, but it also leads to these breakthroughs.

Only in America can Moderna--and I say this after talking to the executives leading these companies, who many, if not most foreign-born--they all say, and BioNTech too, they say, there's no way we could have done these breakthroughs without investors in America writing these checks for years on the hopes of someday having a home run and seeing some success.

So, it's a reminder of the benefits--there are downsides, too, of that system, but there are a lot of benefits, too.

Russ Roberts: Yeah. BioNTech is a German company, but of course, like most foreign pharmaceutical companies, a lot of their money comes, not just from U.S. investors, but from sales to U.S. customers via the rather--this crazy U.S. medical system we have that subsidizes companies out of taxpayers' pockets mostly.

Gregory Zuckerman: And, subsidizes the world's drugs, right?

Russ Roberts: Correct. Without it, we'd have a very different landscape. I think people forget that, conveniently, when they tout their own systems, which they might be better, they might be worse. Israel right now, there are many pluses and many minuses of the Israeli healthcare system relative to the United States. But, if the whole world is like Israel or Britain, we'd have fewer drugs. We'd have fewer medical devices. Maybe not a lot fewer, that's a debate. Reasonable people could disagree about it.

Anyway, let's fast forward--

Gregory Zuckerman: It's like a free-rider kind of concept.

Russ Roberts: Yeah; no, it is. Absolutely. The stupidity of the U.S. medical care system subsidizes the rest of the world.

48:12

Russ Roberts: Okay. I want to come to January 2020. So, this virus, this pandemic is starting to gather attention around the world. People are starting to get uneasy about it. People are starting to pay attention to it.

And in the first week or so of January 2020, the genetic makeup of the virus is first leaked, and then publicly put forward by Chinese scientists.

They've sequenced it and it's published. And the most incredible thing, I think in human history--you could argue this is one of the most extraordinary--little bit of hyperbole there, but it is one of the most extraordinary achievements, I think, of the human mind. First, that's an amazing thing--I don't even know what, I could say the words. But, to publish the genetic sequence, I could say those words. But, that's an enormous scientific achievement of humanity.

But they sequence the virus and they reveal the sequence--the genetics of it. And within maybe hours--certainly days, not more than days, not weeks, not months, not years--there is a proposed mRNA tool to fight it that comes out of both BioNTech and Moderna.

And, the world--I remember very vividly, 'Oh, we won't get a vaccine for years. We're going to have to live with this.' Then people said, 'I guess, if we had this incredible effort, maybe in 18 months.'

They had a vaccine in a weekend.

Now, they had to produce it. For better or for worse, they had to show that it was safe. I think we were way too cautious in putting it out. I think it costs thousands of lives; certainly ex post, it costs thousands of lives. You could have argued, it was a time to be a bit of a risk taker, given what the world was going through.

But, within a weekend, they developed the science of the vaccine.

How is that possible, given that they'd spent decades failing at other vaccines, and then that weekend's worth of work, produced a vaccine that was remarkably safe--in the case of mRNA--and remarkably effective?

Was it because it's a well known thing, the coronavirus? Why did it work so well? Should it have? Was that just good fortune?

And they knew they had it, by the way. And they developed more than one: they had a dozen different variations they could try if they wanted. A lot of it would've been fine of those dozen. What happened there?

Gregory Zuckerman: You raised a lot of interesting points. I hope I remember to address them all. I'll try my best.

Listen, we're too close to it, I think, right now to appreciate the enormity of this scientific achievement. It goes down in history as one of the greatest. Yes, you say "they" released. It was one--Dr. Zhang [Zhang Yongzhen--Econlib Ed.], I wrote about him in my book--one researcher in China risking his career, his life, maybe. He was under lots of pressure. He was torn what to do.

He shared it with a guy named Eddie Holmes, an Australian researcher--

Russ Roberts: Co-author--

Gregory Zuckerman: Colleague, yeah. He shared the genetic sequence of this virus. He didn't have to; the Chinese didn't want him to, at the time. Not going to get into the whole politics of it, but he risked so much. We have him, so much to thank. Yes, the Chinese subsequently did share the genetic sequence of the virus. But, would they have, if it hadn't been leaked already? I doubt it, or I'm skeptical, I should say. Who knows?

Russ Roberts: Well, it's important to note that at this point in the virus and still today, the Chinese government has been less than forthcoming about the origins, about the transparency to it. And certainly then, in January of 2020, they were trying to sweep it under the rug. It does seem like the last thing they wanted to do was to publish the genetic sequence.

Gregory Zuckerman: Yes. I'm not saying so to suggest that they created the virus in any way or that it even leaked, but yes, they were dragging their feet in terms of being transparent. They were not transparent about it, for sure. Just to remind the audience about January 2020--yeah, I was pretty blasé, too. I was pretty complacent. I figured, 'Yeah, don't these things peter out? Remember that earlier coronavirus, remember SARS, MERS, Zika? Yeah, they're lethal, they're threatening for a while. Maybe it kills a few people, but then it stops being threatening, it stops spreading.' And, I can get into why this one is different.

But, the researchers--to your point--the researchers within these companies were freaking out. It was such a fascinating contrast. I was literally flying--I was in Heathrow Airport and my kids were wearing masks, these makeshift masks; and people were looking at us; and I didn't wear one. I was a little self-conscious. People were, like, thinking we were spreading something.

So, most of us in the world were a little bit blasé about it. But, the people within these companies--Stephane Bancel was on vacation in January. He starts reading about this virus and he's, like, 'Guys, this is our chance. This is our opportunity to prove our approach works.' Sahin [Uğur Şahin] within BioNTech, Ugur Sahin, he reads a paper in Lancet about this new virus, and he starts going crazy. He's a cancer researcher, but he shifts gears. He's not really an infectious disease expert; but he and his wife, Ozlem Tureci [Özlem Türeci]--they're cancer researchers--and they developed this approach using mRNA. They were like, 'We're getting worried here; we're getting scared, even.'

Why? Because the key part was that there was asymptomatic spread of this virus. There was a Lancet paper that showed there was asymptomatic spread, which was the key for why the earlier pathogens--coronaviruses--didn't spread is because you could isolate people. But, when there's asymptomatic spread, you can't isolate people and we're done.

So, they were getting scared while we were all ignoring the dangers here.

To your question, okay, so: Why was it so effective? Listen, even within the labs, the executive boardrooms, etc., that these companies that I write about, they weren't sure. They were optimistic. They thought maybe they'd have a vaccine--even come November, I'm jumping ahead a little bit, but November 2020, when the data came out for both BioNTech/Pfizer's vaccine, as well as the Moderna one, they went into those meetings with the FDA [Food and Drug Administration] thinking, they'd probably get about 70%, 75% effectiveness. They were hoping for 75% effectiveness. So, even they had no idea that it would be this effective.

And as to the question of why: You know, on a relative basis, frankly, this coronavirus is not that complicated. Relative, obviously to AIDS. I mean, HIV [Human Immunodeficiency Virus] is different within each person. It commandeers the immune system; it's ever-changing. Not so with this coronavirus. Now, I'm really jumping ahead--but, even with the variants, the original vaccines are still pretty darn effective, which is surprising. They've developed new vaccines to potentially be distributed to take on, based on the sequence of these new variants, but they haven't needed to use them so far.

So, I think, to your question, part of the reason is this coronavirus is actually not all that complicated.

And, there was a fascinating contrast. In January 2020, all the people I write about in my book are freaking out and they're scared. Some of them go home and they're buying toilet paper and tissues and a third refrigerator--if you remember that individual at Moderna--when we were all complacent.

But, by April or so--or March, certainly April--when the rest of us were starting to get really just plain scared, within these companies and in the scientific labs as well, the academics, they're pretty confident. They're pretty optimistic. There's such a fascinating dichotomy where they have early data; it's not overwhelmingly persuasive, but it's pretty convincing, that, be it in animals or early humans, subsequently, that this will be effective. That these vaccine approaches, all based on the coronavirus, they have a good likelihood of success.

56:56

Russ Roberts: It comes back to, I think, to your description of the mRNA technique: They're pretty confident they could introduce that protein into the body. They weren't maybe so sure about what was going to happen next, how quickly it would respond. Whether the case would decay appropriately or get into, to start with. But, I think the key is that: that science was well understood.

The rest of it--the body itself, the shell, the case--is a little more complicated, but that part they were confident about. And then it was just a question of whether this mechanism would work the way they understood it to work. And it did.

Gregory Zuckerman: Yes. Yes. And, the key is that there was literally decades of work on these approaches that you and I weren't aware--speak for myself, I wasn't aware of. Most people weren't. Even within the world of science, people had dismissed this work for decades. But they were making progress. It was kind of like the--I don't know what the analogy is--the specialists were, like, 'Guys, we're making progress here. Believe us.' And everyone else is, like, 'Yeah, right. Tell us when you've actually had something approved here.' But, they were right, and we were wrong. The skeptics were wrong.

Russ Roberts: But, part of that--just to clarify a little detail--some of those vaccines that had failed, it was not that the underlying idea had failed: They couldn't easily replicate that protein. And here they understood it very quickly. That must have been the problem, right? I assume. The reason those earlier vaccines had been so problematic that they were stuck in Stage One [Phase I vaccine trials--Econlib Ed.], or it didn't work, or in some it made things worse, was because it was a more complicated delivery product, that protein.

Gregory Zuckerman: That was part of it. It took years to develop the delivery, yes. That mechanism, that approach, the specific chemicals, it took a while, and there were different breakthroughs along the way.

It's also the case that there were breakthroughs--other kind of structural breakthroughs. Structural biologists that I write about in my book who developed ways to stabilize this spike protein--you'll see in the book--there were a series of small breakthroughs made along the way that some people were aware of, other people weren't. In hindsight, these people may win Nobel Prizes. But back then, no one really cared that much: Ways to get the mRNA for the immune system to recognize, not to fight it off. There was a change of chemicals and it seems simple in hindsight, but it took years to achieve. So, there were small breakthroughs made along the way that most people weren't aware of.

59:39

Russ Roberts: And--again, not a spoiler--we get a vaccine. It's remarkably safe--the Moderna one and the BioNTech that Pfizer then ends up producing, correct, and distributing. And I'm alive. I've got triple--I've got a cocktail--I've got two Modernas under my skin, and I picked up a Pfizer bonus booster here in Israel. I went down to my healthcare provider and I said, 'I have two Modernas.' They say, 'Okay, we're giving you a Pfizer.' I said, 'Am I going to drop dead from a reaction, mixing a cocktail like that?'

And she said, 'No.' And while I'm waiting for them to process me and give me the shot, I'm googling frantically on my phone, 'cocktail death side effects'. I kind of trusted the system a little bit. Figured it was kind of the same. I had understood a little bit of the science. Not much at that point, not as much as after I'd read your book, but I knew it was a similar idea. So, I felt I was in the same family, even though they didn't have the same brand name.

But, it's a remarkable thing. I remember walking out of the hospital, the first time I got the shot, thinking, 'I'm Superman now. I can go everywhere.' It's not true, of course, both--in fact, I hadn't had the second one. And, even if you have two, you can still get it because it's not 100% effective. And then I got the booster, and I felt really good. And, I don't know whether it saved my life or not, right? Because, no way of knowing. But I'm pretty grateful for it.

And, the book is very moving, because here are these people who have spent sometimes decades being mocked, or laughed at, or disbelieved. They haven't just been successful, they have saved maybe millions of lives. It's very powerful--it's an extraordinary moment that you capture in those encounters between these people who are celebrating with each other, with their families. Again, it's not just, 'Oh, I'm a success'. 'I'm a success, and it's really a good thing.'

Gregory Zuckerman: Yeah. It's historic. It's remarkable. And frankly, they were aware of the consequences if they had failed, and it put pressure on them; and they realized if they could save lives, it would be millions of lives.

And--I don't know if you picked up on this at the end--but the people I talked to within companies like Moderna, they're all rich right now. Their stock has soared. But, they're also psychologically damaged. And, I was just struck by that, and shaken, almost. Because, instead of celebrating and being lauded--so, obviously, many are appreciative. But you've also got people that--there are protestors in front of Moderna accusing them of doing bad things, all kinds of various things. Frankly, there have been articles which I think are unfair, which have accused them in terms of intellectual property; other kinds of things. But, you've got anti-vaxxers.

I went to visit their plant, their manufacturing plant, during the summer of 2020. And, I kept getting lost. It was confusing. And I was like, what kind of company doesn't have signs? There were barely any signs. And later they were saying, 'Yeah, Greg, we took all those signs down because we were worried about anti-vaxxer type people.' They were also worried about people lining up and trying to get vaccines ahead of time. So, there were both sides of things. But as that reflects: Can you imagine giving of yourself, working--literally, like you said, 24/7 to try to save lives and make your company successful? Like, that motivation wrapped up together. And succeeding. And yet, people pointing the finger at you?

And also, frankly, a lot of those people feel they didn't do enough. They could have gone faster. They never--for the book, they couldn't find a partner. They tried Merck. Merck wasn't interested. BioNTech found Pfizer. Moderna found no one, and they had to work that much harder and they didn't produce as many. They had produced many shots all over around the world, but not as many as they would've liked. So they feel they could have saved more lives.

So--and they haven't had a rest. They had to prepare for these variants. You know, maybe I'm close to these people. I've written about them over the past year or so. But I feel some empathy, and then I feel appreciation, too, for their remarkable achievement.

1:04:10

Russ Roberts: The other thing we haven't talked about with the mRNA technology is really, really important, which is: Traditionally vaccines were grown--bizarrely as a non-scientist, non-vaccine person--they were grown in eggs. Which takes a while. And, the ability to ramp up billions, hundreds of millions at least, or billions of doses was another enormous factor in this near-miracle of innovation. Which couldn't have been done with the traditional vaccine as fast. And more people would have died.

But, the point you make about the pressure--you know, the idea that every day when there were delays in, say, the clinical trials or every day meant more people were going to die. The names that are here, we don't need to name them here on EconTalk--they're in your book--these are people like the two you mentioned from BioNTech, say their names again.

Gregory Zuckerman: Ugur Sahin and Ozlem Tureci are the couple who run the company.

Russ Roberts: They were Turkish immigrants to Germany who created the technology for BioNTech, which became Pfizer's vaccine. We have Stephane Bancel, Hoge [Stephen Hoge], other heroes who worked for Moderna. There's 20 other names. There's an honor role. And then there's the person at Merck who is--I think, is it Hellerman [Maurice Hilleman--Econlib Ed.]?

Gregory Zuckerman: Hilleman is the--yes, I'm sorry, Merck, yes, exactly. He's the vaccinologist. One of, maybe the most impressive in history--

Russ Roberts: And it's a tragedy to--not a tragedy--but it's a shame to me that he's not a hero. He is a hero. He's just not a known hero--

Gregory Zuckerman: Yes. Salk and Sabin, everyone knows.

Russ Roberts: Everybody knows them and God bless them. I'm grateful for them. It's fantastic.

But, here are all these people who've done these unbelievable things under incredible pressure.

And--I mentioned this before, I'm just going to say it again, because I think it's important. Here's the sentence that's just going to come out of my mouth: The FDA delayed approval of various test kits, that I think was a terrible mistake. We have episode with Paul Romer on that, from long, long ago. He was an early champion of more testing, and I think he was right. It's a tragedy that wasn't done.

They had to go through the standard process that every drug--they did speed it up, I'm sure. But, I said "they," and I said the FDA, and I said, the government--I could have. Who are those people? Why is it that we don't know the names of the panelists on the FDA? Maybe we do know the names. But it's interesting to me that journalists don't hold those people accountable. Maybe it's too hard. Maybe we shouldn't judge them. But I think it's remarkable that we know the people who succeeded and failed in these vaccines, in the scientific community, but in the regulatory community, there's not so much accountability, and I think that's a shame.

Gregory Zuckerman: So, I'm not an expert on the test kits. Everything I understand is what you're saying, and we messed that up, and there may be fault there. I'm going to--

Russ Roberts: No, Greg, not 'we'. Not you, not me--

Gregory Zuckerman: The FDA.

Russ Roberts: Somebody. A person, an actual person made that call. And even right now, there are certain treatments for COVID and other things--there's a lot of conspiracy theories out there; this is not one of them--but the FDA tends--people at the FDA, whatever their names are, tend to drag their feet out of fear of being blamed if it doesn't turn out right. And, I understand that as a human impulse. It's not a good thing. I think we need a little more accountability. Sorry, go ahead.

Gregory Zuckerman: So, ,I'm going to make a counter-argument and it's not one I've put a ton of research into, so I may be wrong, like much of what I say are. But, I would argue that the FDA needed to be cautious. In hindsight, it would've been nice had they not been so cautious. Clearly. I agree. But, at the time, it wasn't obvious that these were going to be so effective, A. And B, can you imagine if there was some unforeseen death or something along the way? We already have, I don't know, 30% of the U.S. populace that's vaccine hesitant or worse, and there's already misinformation. I give speeches and there's always someone in the audience, or more than one pointing a finger at me, and angry. It's disturbing.

Russ Roberts: Fair enough.

Gregory Zuckerman: So, the counter argument is that even if the signs suggested they could go faster, even if there was a 10% chance of something bad happening, an unforeseen event, what that would've done to confidence? I mean, think back: in 2020, you had Biden raising questions about the vaccines. You had Trump trying to rush the vaccines.

Russ Roberts: Incredibly optimistic. One of the times he turned out to be right. Do you give Operation Warp Speed, the government-- Trump, whatever you want to call it--decision to guarantee some sales to these companies, was it important?

Gregory Zuckerman: I give Operation Warp Speed a ton of credit. I think it gets more credit than it should, than it deserves in some circles and less credit than it deserves in other circles. Operation Warp Speed, we made a brilliant decision of--they had a portfolio approach. They made a bid on six different vaccines. Two mRNA ones, they both worked. Two adenovirus ones, the J&J and the AstraZeneca worked, both worked as well. AstraZeneca, we don't need; the Oxford one we don't need in the United States and elsewhere, but it worked. And then two protein-subunit approaches: Novavax, which looks really good right now as we speak, and I think it'll be very helpful elsewhere in the world. And then another one which isn't there yet, we don't really need it. But, five out of six is pretty darn good.

And they wrote huge, big checks, and it's really, really important for people to understand that. Why was it so fast? Why was it in 330 days from the sequence to an authorized vaccine? Which is just a joke; it's crazy how fast it was.

Well, the key was obviously the years of research that went into these approaches that I write about, but it was also the fact that they could do things for the first time ever simultaneously: develop, test, and manufacture these vaccines. That never was done before. And why were they able to? Why would you manufacture a vaccine before it's approved? It's not in anyone's interest; it's billions of dollars.

Well, because there was money available. And that was from Wall Street. We have to give Wall Street credit and we have to give Operation Warp Speed credit, because they wrote these big checks and they said, 'Don't worry about the consequences. Here we go. We're going to buy these vaccines ahead of time, and here's the money you need.'

It was crucial money. It's just that they were also--I write about it sometimes in the book--where there were times when it's a bureaucracy like any other. It did slow the process down sometimes. Moderna was in the lead as of, like, summer of 2020; and then it had to slow its process due to Warp Speed because there were certain requests that some people at Warp Speed wanted them to do. In the end, it was just a waste of time. But, what are you going to do? It set them back two weeks and that did cost lives; but Operation Warp Speed, we need to be very appreciative of that, too.

Russ Roberts: To be clear, you know, I'm not a particularly fan of government subsidies to healthcare--as should be clear--but it's to offset the fact that it's going to be an enormous political pressure to nationalize anything that's discovered. There still is pressure on it and to not allow these companies to profit. If that's there, what Operation Warp Speed did for me is to offset that fear and create the opportunity for investment.

Gregory Zuckerman: That's true.

1:12:09

Russ Roberts: Let me say one more thing about the FDA, to be clear. I take your point about the mood, and the fear, and the anxiety about side effects, and there have been some side effects. And people have reacted--in fact, I think they've overreacted to it, given the risk of the virus. The only point I would make is that I think the rules ex-ante is always different than ex post. Ex post we were very lucky, we could call it; or, the science was great: The side effects were small. I don't want to say they were overly cautious because it turns out they were safe. They might not have been safe, and they couldn't know that in advance. They might have known something about it. But, again, a lot of that would've come from inside claims and who knows if they were true.

I just think when hundreds of thousands of people--and the death count in the United States will tragically start to approach a million soon; we're at, I think 800,000-plus right now or 720,000--I think there are times when you want to change your risk assessment and take some chances that you wouldn't take in a different situation.

Now, in a democracy, maybe that's too hard to do; maybe the public won't[?] react negatively to that side issue, which you're welcome to comment on--is that I think the public health community, especially within the government, has been incredibly destructive of people's ability to make intelligent decisions because of the conflicting signals that they've given and the fact that they have, as far as I can tell, misled people about the situation, in the name of, quote, "their own good".

I think it's interesting to think about what our norm should be as a democracy for how we communicate these risks to a free people. And, we didn't get this right. I can't even say that without literally laughing out loud. It's tragic. It's dark. It's not funny. It's tragic and I'm not optimistic that we'll do better in the future. What are your thoughts?

Gregory Zuckerman: Well, I agree with what you're saying. There are tons of mistakes made. I am more sympathetic to those who had to make these decisions in real time--

Russ Roberts: It's brutal. I agree.

Gregory Zuckerman: Yeah. And listen, let's talk about Fauci, for example. Obviously he's lauded in some circles and vilified in others. He made mistakes, early mistakes. He's made mistakes along the way. He, when you talk about misleading, he misled the public. He said that masks aren't effective.

Now, who wants a public official misleading people? I feel he's been unfairly criticized because, at the time, he was worried that the health system would be overwhelmed. And if he said, 'Everyone go get a mask,' he knew that we had to prepare for this thing, and there weren't enough masks. The healthcare workers--the essential healthcare workers--unlike Greg Zuckerman, sitting in his basement in New Jersey, suburban New Jersey, who would've gotten right on Amazon and ordered some masks--I would have been competing with essential workers.

So, I understand that instinct, that impulse. And I'm not saying--I don't want to judge.

Also, frankly, we have to give Fauci and others credit for betting on mRNA. They made a bet. They got mRNA years ago, and were working with Moderna, advancing the science. And I would argue that BioNTech, in some ways, are fast followers, and they didn't develop a lot of stuff. They did on their own, but they were reading some of the papers that Moderna wrote, and that's my instinct, anyway. We have to give Fauci and company credit as well as criticism.

Russ Roberts: Okay.

The only thing I'll say is--and I accept your point that it's easy to be a sideline, Monday-morning quarterback, critic of--ex-post, everybody makes mistakes.

I think, regardless of his character, his personal responsibility, I think it's an incredible mistake and tragedy when a person representing authority deliberately tells something that isn't true. I understand the motivation. I would have found a different way. I would have let the price of masks rise. And I would have encouraged people to make a lot of money from masks.

But, that's me. And it might have had its own negative consequences. Instead, we said, 'If you raise your price for masks, we were going to arrest you, and we're going to treat you as a price gouger.'

As a result, we had to tell people that masks--because then there was going to be a shortage--so we had to tell people that masks didn't work. Someone had to say that, not 'we.' Anthony Fauci and others had to say it. With the result that the faith people had in the scientific community got degraded.

And, I think that's part of the problem we're in today.

But, I take your point. I don't think it's an easy--it's not easy to sit in that chair. It's easy to sit in this chair either in your basement, in New Jersey or in my office or in your shalem[?peaceful place, home?] in Jerusalem.

1:17:28

Russ Roberts: Well, let's close on this: Do you have any idea--have you heard any number; I don't remember them in your book--how many lives were saved? What if we had no vaccine? What if this disease had just spread the way--I mean, we could have responded in different ways if we hadn't had the vaccine. We could have locked down more, quarantined more, spent more money. Who knows? There's a thousand ways to think about this, of course. But, I do feel like it has saved many, many lives.

Gregory Zuckerman: Yeah. There's a study I cite early, I think in the introduction of my book: it's a Yale study. And I think at the time--it was as of the summer of 2020, late summer, I think. And it was close to a million lives, I think. And, obviously it's more today.

And also, it's important to remember--and I don't know if it went into it, I didn't dig into how they came up with these figures--it's also important to remember that what we did with these vaccines was stabilized the healthcare system. And, as a result, we had other kinds of illnesses and diseases that could be treated. As a result, people were saved.

So, it's hard to get an exact figure. And you ask about what would've happened had we let this thing go--like, with the flu and obviously other pandemics. Yeah, we would have maybe achieved herd immunity earlier, but it would have overwhelmed the healthcare system, is my understanding from talking to people who worked in it; and then that obviously would've been just devastating.

So, for everybody who says, 'Yeah, well, it's not that much worse than the flu,' there's the death and there's other kinds of diseases. But there's also the issue of long COVID--which, I don't think it's enough focus, and, you know, I guess it's anecdotal. Here I am, a journalist doing the whole talking-to-a-cabby kind of thing. But, I know people that are suffering from long COVID; and it's nothing you wish on anyone. A foggy brain and lethargy lasting over a year, and pain sometimes. That's been prevented as well--so, in addition to the death and the hospitalization.

Russ Roberts: Well, I have to add that--it's not just--we don't just care about life and death. I've said it many times on the program. The ability to--again, I'm, joking about feeling like Superman. That feeling passed very quickly after my first dose. But it did feel for about half an hour. And that's because: I went inside a building without fear. That's what I really mean by I felt like Superman.

There was a period, in the early days of the pandemic, I go to the grocery and I'm anxious the whole time. I'm wiping down the handle of my cart. I'm wearing, you know, artificial gloves and I'm pushing the cart. I'm upset when the cashier picks up one of my items. There were some crazy, crazy moments in the early days of the pandemic.

And they still persist. I don't judge anyone. We all have our own weird neuroses about this, and fear and paranoia and things we'll do that other people won't do and vice versa. And we look at the other person and go, 'Well, that's crazy.' But, then you realize that I do that crazy thing, too.

And, I'm grateful that I'm able to sit in an office with my colleagues without a mask on, sitting--I don't huddle with them and whisper into their ear, but I do sit face-to-face without a mask. I'm not sure how much masks work with Omicron, and certainly I'm not sure about the kind of masks that I'm wearing, and people around me are wearing these paper masks. And I think there is some theater or placebo effect working there to fool us.

But, my point is that the vaccine has allowed some normalcy in life that is worth an enormous amount. It's not just that I haven't died from COVID. I've gotten to enjoy my family. I've gotten to enjoy my friends. And I've gotten to enjoy my colleagues. And, I don't think--it's hard to put a value on that, but it's very high.

Gregory Zuckerman: Yeah. And, as you know from reading the book, what jumped out at me is just how lucky and fortunate we are and how appreciative we need to be that this virus emerged in late 2019, and not late 2016, or 2017, maybe. We weren't ready then. So, I talked to scientists; I talked to these researchers. They say it might have been years before a vaccine could be introduced. Not 330 days. So, can you imagine, as appreciative as we are that a vaccine was developed so quickly, we need to be appreciative just how lucky we are that this virus emerged when it did.

Russ Roberts: My guest today has been Greg Zuckerman. His book is A Shot to Save the World. Greg, thanks for being part of EconTalk.

Gregory Zuckerman: Great to be here, Russ.


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