IN THIS EPISODE: Journalist Derek Thompson and economist Eli Dourado investigate the bottlenecks standing in the way of the invention vs. the diffusion of ideas. They discuss whether new ideas are getting harder to find, how to get these new ideas to scale, and how a crisis can spur effective implementation.
“Metascience 101” is a nine-episode set of interviews that doubles as a crash course in the debates, issues, and ideas driving the modern metascience movement. We investigate why building a genuine “science of science” matters, and how research in metascience is translating into real-world policy changes.
Episode Transcript
(Note: Episode transcripts have been lightly edited for clarity)
Caleb Watney: Welcome back. This is the Metascience 101 podcast series. Today, Derek Thompson sits down with Eli Dourado to investigate the bottlenecks standing in the way of the invention versus the diffusion of ideas. Derek and Eli discuss whether new ideas are getting harder to find, how to get these ideas to scale, and how a crisis can spur effective implementation. Since we recorded this episode, Eli Dourado has started a new position as Chief Economist at the Abundance Institute.
Derek Thompson: Hi everyone. I'm Derek Thompson. I'm a staff writer at The Atlantic and the host of the Plain English podcast with the Ringer Podcast Network. I'm also working on a book about the future of progress in America and why America can't build stuff with the New York Times writer, Ezra Klein.
What's the real reason for the great stagnation? Why has it become so hard for America to build what we invent? I'm very honored to have the perfect guest to answer that question. Today's guest is Eli Dourado. Hello.
Eli Dourado: Hey Derek. Great to see you.
Derek Thompson: Good to see you as well. Why don't you give your own brief bio?
Eli Dourado: Sure. I'm Eli Dourado. I am a senior research fellow at the Center for Growth and Opportunity at Utah State University. I'm an economist by training, but I work on trying to get economic growth actually going. This takes me into a lot of spaces, especially physical world technology and how to get that going.
Before this, I was the first policy hire at a supersonic airplane company. So I've done it in the private sector as well.
Derek Thompson: There is this very famous idea in the study of science, technology, and progress in America, which is that ideas are getting harder to find. This dates back to a famous paper, co-authored by Nicholas Bloom at Stanford, that showed that it's just harder in recent years to have scientific breakthroughs in areas like pharmaceuticals.
You and I have gone back and forth about this quite a bit on why ideas are getting harder to find. One popular explanation is sometimes called the knowledge burden.
For example, the field of genetics was broken open by a monk, Greg Mendel, who was basically looking at peas in his backyard. Through that study he put together the idea of dominant and recessive genes. Today, if you want to make a breakthrough in genetics, you can't just grow some peas in your backyard and invent the field. You have to get hundreds of people together to do these big GWAS studies —Genome Wide Association Studies — to figure out some tiny detail in some polygenic disease like schizophrenia. In fields like genetics, it's getting harder to push forward.
The knowledge burden says that the smarter we get, the harder it is to push forward in the field. You come at this from the opposite end. You think that there are cultural reasons why we are making it harder for ourselves to come up with breakthroughs in all of these scientific fields.
Lay out your theory of why ideas are getting harder to find.
Eli Dourado: Nick Bloom is a good economist. I don't want to trash his paper too hard, but I think the root of what's going on is that economists are looking in the wrong place to explain the great stagnation. There is too high a degree of abstraction and maybe an unnuanced understanding of one of the core basic models of economic growth, the Solow model.
The Solow model says that economic output is a function of labor, capital, and a third term called “A”, which stands for total factor productivity. Obviously, not an abbreviation. If you were taught the Solow model in college by a professor who's not trying to be terribly nuanced, you'll come away with the idea that “A” really stands for ideas. It represents all the recipes that we have for combining labor and capital into output.
If you observe that we've had a slowdown in economic growth over the last half century – which is true – and you know this is not caused by labor and capital shortages because we can measure those. So, we know it is not caused by that.
Then, the obvious conclusion is that we have a deficiency in the growth rate of “A.” So it must be the case that we're facing an ideas slowdown. Then we can measure the spending in R&D, and we know that's not going down. If anything, that has gone up.
Therefore, it must take more R&D spending to get more ideas. That's what's causing the growth slowdown. This is the lamp post that economists are searching for the keys by. It’s the initial place that you would look.
But I think that the real explanation for what's going on here is that “A” is not just pure ideas that we know — as in, idea recipes that we know for combining labor and capital. Instead, it is all the ways that we do, in fact, combine labor and capital. But there are other reasons that we might not combine them – we might not use certain recipes even if we know them.
Some of those reasons include cultural opposition, legal opposition, legal barriers and so on. I think that’s the right place to look. We should be thinking about all the different ways that we have trouble instantiating ideas in the real world.
Derek Thompson: This is really the meat of what we want to talk about today. The word I use for what you’re describing is implementation. For a long time, I thought that progress really meant invention. All of my favorite books about the history of scientific and technological progress celebrate moments of invention. They celebrate Edison, they celebrate the Wright brothers, they celebrate Edward Jenner and the smallpox vaccine story in 1796.
But in an article for The Atlantic, at the end of 2022, I started to think hard about the question of progress, and I looked at it through the story of the smallpox vaccine. I thought about that magical, golden day when Edward Jenner stuck a lancet into a young boy and inoculated him from smallpox, maybe the first smallpox vaccination in the history of the world.
At that moment, in a world of one billion people, only one had been inoculated. Is that really progress? Is it really progress when 99.9999% of the world has not benefited from the invention of what is essentially a prototype? No, it's not. I began to think that maybe the story of progress that matters isn't the story of invention, which is of course important, but the story of implementation.
How do you take an idea from one to one billion? This thesis I called “arguing against the eureka theory of progress.” Yes, invention is of course important. Going from zero to one in an idea matters, but implementation — from the one to one billion — is the journey of that idea to the rest of the world.
That might be the more important story of progress. Back to you, Eli, as we’re circling the same idea here. Why do you think the U.S., which is still rather good at invention, has gotten worse at implementation?
Eli Dourado: We don't do transformational building anymore, in the world. Let’s look at what Robert Gordon identified as the five great inventions: electricity, the internal combustion engine, communications technologies, indoor plumbing, including urban sanitation, and chemistry including pharmaceuticals and materials.
A lot of those are inherently physical; they involve transforming the world. Fundamentally, the problem is that we've become unwilling to bear the short term costs that this entails. We call America the land of the free and think that people can do whatever they want. That’s true, as long as you're willing to abide by a few simple constraints: nobody can be inconvenienced, nobody can get hurt, and no jobs can be lost. Within those parameters, you can do whatever you want, which turns out to be not very much.
What if we invented the automobile today? This is one of Robert Gordon's five great inventions that he says drove economic growth in the middle of the 20th century. Today, we would go to regulators and the public. We’d say, we've got this great new thing. It will provide trillions of dollars of economic value, but it's also going to generate a fair bit of pollution. It's going to kill 40,000 people per year in the U.S. We're also going to have to take a bunch of land by eminent domain to build highways. It's going to put horse and buggy makers out of work.
Thinking realistically about what would happen today, people would say, “Get out of here,” and would not let these things happen today. You'd face many more obstacles than they did a hundred years ago in the implementation of the automobile idea. Not in the invention of the automobile, of course, but in rolling out all the infrastructure that we would need for it. Ultimately, ideas are getting harder to use, and that's the binding constraint.
Derek Thompson: One hypothetical that you could make is to imagine that the automobile were prescription medicine. Would we accept a prescription medicine that had all sorts of benefits, but also, using the very real example of the automobile in America, killed 36,000 people a year? That’s a lot of deaths, and reasonable people can say the status quo of cars in America is unacceptable. We hear this not only from the Ralph Naders of the world, but also from Silicon Valley, when they say that one really good reason to accept self-driving technology is that people are freaking terrible drivers. They kill tens of thousands of people a year. That's why we should be more accepting of AVs.
We could probably do hours and hours on alternate histories of the car in America vis-à-vis Europe, for instance, but let’s get into more detail on this turn in implementation. You would agree this turn dates to the 1960s and 1970s, when the U.S. had a raft of laws and legal decisions that made it harder to build stuff in America. Those laws, regulations, and surge of localism were a response to very real problems.
From the 1950s and 1960s, we did build highways over minority neighborhoods that just had no ability to have input. We did poison the air and the water of America. We did build without any kind of 21st century ethic about environmental and minority considerations. You're nodding as I'm saying this. I don't want our listeners thinking that we're about to have a debate about whether or not the spoliation of the Earth is fine.
How do you think about balancing the need to build in the 21st century with the fact that the last time we built very fast we created all of this havoc?
Eli Dourado: Environmental regulation that actually protects the environment in a narrowly tailored but effective way is an unalloyed good. One of the ways that we enjoy our greater wealth today is that we have better environmental quality. Research on air pollution shows over and over again how damaging it is.
The way that we have actually addressed environmental regulation, however, is through a lot of procedural laws that require community engagement and create a lot of veto points for anyone to use.
A lot of times that isn't underprivileged people speaking up and advocating for themselves. Often it's extremely privileged people who can hire a lawyer, who can use this veto power to block projects that personally inconvenience them.
It’s completely valid to say that we want safety, that we want good environmental outcomes, and biodiversity, and that we want to spend some of our wealth on these things in a way that creates social justice.
I’m a hundred percent on board with that. We're going to have a much better chance of getting all those things if we are wealthier, because when we are wealthier, we can afford to spend more on those considerations. When societies are at subsistence level, they spend zero on most of those considerations.
As they get wealthier, they start to spend more on them. As we get even wealthier, we will spend more and more on them. However, the laws that actually passed were highly procedural. The one I've spent the most time with is a law called NEPA, the National Environmental Policy Act. The original statute was actually written in a pretty inoffensive way.
It says that if we're going to take major federal actions that have a significant effect on the environment, then we’re going to at least state what those effects are. We're going to write them down so that anybody can see what the effects are. Like a look-before-you-leap kind of good governance law.
However, NEPA was implemented through executive orders, regulations, and court decisions such that it became highly procedural. Now you basically have to do a substantive environmental review, even if the action you’re taking doesn't have a significant environmental impact. That's actually where most of the harm of it comes from.
Then this process also now requires public input, which wasn't in the original text of the law. And that opens the door to lawsuits after the fact. The agency decision to approve or not approve a project, or to move forward or not move forward, gets put under a microscope in a way that gives anybody a pretext to sue and to try to block a project. Over and over again in some cases. There've been all kinds of projects, including ones that are good for the environment, that have been effectively blocked by lawsuits that seek to weaponize NEPA.
That’s a major part of the turn.
Derek Thompson: I buy the broad outlines of that story. After the 1950s and 1960s where we did build highways and did allow polluting factories to truly wreck havoc across the country, Congress and the courts gave the people a microphone. A microphone that they could use to have their voices heard, to block the kind of projects that were demolishing neighborhoods and turning rivers green with the spill off from textile mills in New Hampshire.
Today very often what's happening is that higher income homeowners, who are against local energy and housing projects, are using the microphone to block projects that would, in fact, help the country in the bigger picture. These are projects that would help the country decarbonize and thereby help poor people who more often tend to be victims of environmental pollution.
It would help to build local housing projects that would relieve housing inflation, which would be good for the middle class. But the people who've grabbed this microphone often use it in a way that is orthogonal or antithetical even to how the most ethical and progressive reformers of the 1960s might have imagined.
Let’s talk a bit about how regulations in science, including in pharmaceuticals, might be blocking the translation of new ideas to new products. In my essay in The Atlantic, I talk about the legacy of Operation Warp Speed, which as I see it is an absolutely fantastically ironic policy program. I say ironic because it’s one of the most successful government programs of the last few decades, and yet it has also been politically orphaned. Democrats don't seem to want to talk about it because it gives Trump a lot of credit. Republicans don't want to talk about it because it created the vaccine that half of their non-seniors did not take and think is a Bill Gates conspiracy product.
But it was extraordinarily successful at breaking land speed records for the development and distribution of vaccines. One way that Operation Warp Speed went from invention to implementation wasn't just by spending more money. It was also by creating this glide path through “whole of government” urgency from approving the vaccine, accelerating the clinical trials, and then making it as easy as possible to build and map the supply chains that would get that vaccine into hundreds of millions of arms in a matter of months.
Let's pause here before we think about some implications of Operation Warp speed. Why don't you, Eli, dilate a little bit about what you think the most important accomplishments and deserved legacy of Operation Warp Speed are?
Eli Dourado: What I love most about it is that mRNA technology was completely untested in humans before. We took something off the shelf that we thought worked because it had been used in animal vaccines.
It had been used in veterinary vaccines, and we understood the theory behind it and we knew it would work. But it had never been done in humans before. If this were business as usual, we would've been very slow to adopt it. mRNA vaccines would've gotten extra scrutiny.
We took something that we were fairly sure was going to work but hadn't been done before, and we did it. There are so many things like that in the world where it just hasn’t been done before, but we have good reasons to think it will work. But people and companies are just too risk averse and have to pay the billions of dollars in clinical trials to try something novel.
With the vaccine, however, we just went for it. I don't even want to say it was that big a risk because we kind of knew it would work, but we did something that we ordinarily wouldn't have done, which is base a vaccine on what some people would call experimental technology.
Derek Thompson: I wonder whether a regrettable feature of the success of Operation Warp Speed is that it's further evidence that America needs catastrophes to fast forward progress.
So you could say Operation Warp Speed was a wonderful idea, but we never would've gotten that pace of progress without a global pandemic. You could say the same for all sorts of technologies like the U.S. advanced airplane technology after World War I, and in World War II we had the Manhattan Project for nuclear bombs.
But you know, on a less controversial scale, we have radar, penicillin manufacturing. The Internet and GPS were obviously developed during the Cold War. Clearly, the Apollo Project never would've landed a man on the Moon if Sputnik didn't exist. The crises are focusing mechanisms. I wonder whether one meta question, of this podcast about meta science, is the degree to which advocates need to make a stronger case that there are crises that require a new, brave approach to the way that we do science and technology in America.
Eli Dourado: I agree. Statistics clearly show that the biggest period of productivity growth was World War II. That was the only time we truly had an all of society mobilization to just get stuff done. Crises jolt our complacency. During the crisis you put your complacency aside and you're willing to do unusual, unnatural things to get things done. It works the other way around too, which is that if you're complacent for too long, then the odds of a crisis hitting you then go up.
It’s like the Don't Look Up phenomenon. If we ignore problems and are not proactive about them, then that's when they become catastrophic. In terms of pandemics versus other diseases, we approved things rapidly during the pandemic because it was an emergency.
But I think about all the people who have terminal illnesses and other, serious illnesses. It's an emergency for them, also. We should be pulling out all the stops a lot more often to get treatments to those people and more broadly to try to get more problems solved.
Derek Thompson: A crisis is a focusing mechanism, but it is up to us to decide what counts as a crisis. As I wrote in the piece in The Atlantic, we could announce an Operation Warp Speed for heart disease tomorrow. On the very solid grounds that it is the leading cause of death in America. The leading cause of death in America does seem like a national crisis.
We could announce a full emergency review of federal and local permitting rules for clean energy construction under, again, the very firm rationale that climate change is also a crisis. We could do the same for national zoning laws by announcing that there's a housing crisis, since we spent the 2010s building the fewest number of houses per capita of any decade on record.
Sometimes defining a crisis is a collective subjective definition, but sometimes it's a political determination, and you need political bravery to make that determination.
In writing this piece, one of the most interesting conversations I had with anyone about Operation Warp Speed was with Heidi Williams. We talked about what an Operation Warp Speed for cancer research would look like. She told me on the one hand it would involve spending more money on cancer research but also experimenting with the way that we do research on cancer medication. That’s been a recurring theme of this podcast series.
One way that we could reform trials, Heidi told me, is that we could reform the way that the FDA uses what are called short term proxies for deciding whether or not a cancer medication is going to prevent cancer. She alerted me to this absolutely fascinating piece of information, which is that, between 1971 when the War on Cancer was announced and 2015, only six drugs were approved to prevent any cancer. That is way fewer than the number of drugs that were approved to treat recurrent or metastatic cancer.
One of the reasons why is that it's really hard to do research on whether a drug is going to prevent a cancer decades out. By the time you have evidence that your anti-liver cancer medication is keeping the 30 year old from turning 70 and getting liver cancer, well that's 40 years later. By that time, maybe the patent has run out.
Heidi said that with some diseases, say heart disease treatments and beta blockers, we look at patients' cholesterol levels in the short term rather than wait for the full mortality results of the heart disease treatments. We could similarly establish short-term proxies for approving drugs that prevent cancers if we did the research to figure out what those short term proxies are.
But it seems like we could save tens of thousands of lives or extend hundreds of thousands of lives by decades, if we figured out some way for the FDA to approve cancer prevention therapies without waiting 50 years to see if the therapy actually prevents cancer in 50 years. That's just one idea to accelerate the development of life-saving medication without spending a hundred billion dollars of extra money on research.
That was a long windup, but to throw it back to you, Eli, do you have other ideas for ways that we could create this glide path from the lab to the pharmacy, the same way that we did for the covid-19 vaccine or for other necessary medications?
Eli Dourado: Science is like other industries. We've talked about all the dysfunction that we have in clean energy deployment where we have to get a lot of buy-in from a lot of people. Science is kind of the same way.
There are institutional review boards approving or not approving, or asking a lot of questions about experiments and so on, especially on humans. That is another form of community engagement that is creating a veto point.
We need to figure out why clinical trials have gotten so expensive. Some data that I've seen says they've gone up 50x in cost per subject, and I don't know if I have an answer there. Some of the increases in costs are pretty organic and reasonable. We're going after rarer diseases now, so recruiting is harder, et cetera, but I don't think that accounts for the full amount. Getting the clinical trials cost down is almost the whole ballgame.
We're saving a life for every $3,000 to $4,000 that we spend on drugs. It’s very, very high ROI, in general, in pharmaceuticals. It’s ironic because the part of the medical system that people complain about is paying for prescription drugs. But there is a high ROI because you don't have humans in the loop.
You can imagine that you have an ailment, and you can either treat it through surgery or a doctor gives you a pill. For the surgery, you have to pay for all the equipment for the hospital, the time of the surgeons, and the time of the nurses and the anesthesiologists. The pill is so much better because you get humans out of the loop. That needs to be the goal.
With regard to surrogate markers like you're talking about, the FDA has done some of that, some for cancer already. They had a bad experience with a surrogate endpoint for Alzheimer's. They approved an Alzheimer's drug a couple years ago based on some markers. But the theory of what causes Alzheimer's was a bad one. They got burned by that experience, so I'm worried they're going to want to take a step back from that and start requiring more.
More generally on what you were saying about the problem of things taking so long that they are off-patent. We need to rethink market exclusivity for medications. Right now you have an exclusive period based on your patent filing. But what if the market exclusivity were based on who bears the cost of the clinical trials, instead of who has the patent? So if a chemical is off-patent and you prove that it’s safe and effective for a certain purpose in a certain population, you should maybe get market exclusivity for that.
Or maybe we should just unlink it. Frankly, maybe we should get rid of patents entirely because drugs are the only place where they seem to have value. Figuring out why clinical trials are so expensive is number one. Then delinking the patent from the market exclusivity. You need something to reward the company for going through the cost. But it might not have to be the patent exclusivity period.
Derek Thompson: Let’s say the White House calls you tomorrow and says, “Eli, we think that the most important bottleneck to coming up with a truly brilliant generation of medications to extend the lives of Americans is the out-of-control cost growth of clinical trials. We want you to help us solve this. We want a Manhattan Project for reducing the cost of clinical trials.”
Where might you start? Where might you start to unlock that bottleneck just a little bit? Or start your investigation into what are the most important components of this cost inflation crisis?
Eli Dourado: Some of this probably has something to do with medical records, in terms of patient recruitment. Everybody's been calling for compatible electronic medical records for a long time. We still don't have them.
That would be part of it. Not getting so hung up on privacy all the time in medicine would also be valuable. That might make it easier to recruit patients. After that, then you actually need to understand at a much more tactical level why the trials are so expensive.
What happens is that you usually use a consultant to run your clinical trial. Those consultants are very buddy-buddy with the FDA. They have a long history in the pharma industry. If you're a super scrappy biotech startup and you do a clinical trial, it will still proceed at the pace of the legacy industry.
You can't do it according to your own culture. You're doing it to the least common denominator culture. Figuring out how to solve the way those are run with their lack of urgency is the right thing. A lot of very tactical breakthroughs are needed.
The other thing to think about is: do we need to prove effectiveness in drugs, or is it enough to prove safety? So right now, since 1962, I believe, the FDA requires both safety and effectiveness to be proven in clinical trials, whereas before that it was just safety. Yet once a drug is approved for effectiveness for one condition, doctors can prescribe it off label for any other condition that they want. We give doctors complete freedom to decide what drugs are effective for.
That system of off-label prescribing is extremely valuable. We use it all the time, and doctors would be up in arms, and patients would be up in arms rightly if we took it away. This raises the point that having an effectiveness requirement initially doesn't seem valuable, and it just adds another layer of clinical trial. It’s another obstacle.
I would want to look at whether cutting that part out, at least initially, to see if that increases the rate of drug throughput.
Derek Thompson: The only thought I had while you were talking was that we've begun to have international comparisons of infrastructure costs. So for example, you can look up online the cost per mile of building a subway in New York City, Los Angeles, Madrid, Moscow, wherever else.
It'd be interesting to have that kind of international cost comparison for the clinical trials that are being done within those countries.
It's possible that different countries might have different standards and some might have gotten to a more Goldilocks position than the U.S. in terms of balancing a certain amount of privacy, the patient's health, and a care for effectiveness beyond some level of zero.
I would like a little bit of care for effectiveness, even if it’s a bit less strict than we currently have. Some kind of international comparison might be a useful data point in this investigation.
Eli Dourado: Unfortunately, the FDA right now is very selective about where the clinical trials are done and what the rules are for the clinical trials. They've rejected some international trial data, just because they don't trust it. I agree we could be creating a little bit more international competition.
Without reducing the quality of the trials, some jurisdictional competition in how recruitment could be done or other factors would be pretty valuable. But right now the U.S. is basically the major market for the world, because Europeans have price controls on drugs.
No drug manufacturer is going to recover their costs on the European market. They're going to recover their costs if they can get to the American market. So often nobody really cares about drugs unless they're approved in the U.S.
Derek Thompson: Eli Dourado, thank you very, very much.
Eli Dourado: Great talking to you, Derek, as always.
Caleb Watney: Thanks for joining us for this penultimate episode for this Metascience 101 podcast series. For our final episode in this series, we’ll talk about different career paths and how you can get involved in metascience research.
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