When the CEO of Walmart explained why his company was partnering with a U.S. global AIDS program, he didn't mention humanitarian concerns. He said Walmart couldn’t make its ten-year growth projections without a healthy, economically growing Africa—because a sick continent disrupted supply chains and eliminated future customers.

I’m joined this week by Ambassador Mark Dybul, one of the architects of the President's Emergency Plan for AIDS Relief, who argues that America has forgotten the core insight of the Marshall Plan: supporting other countries’ economic growth creates markets for American businesses, not competition for American workers.

We talk about drug development, too—why many drugs don’t work in women and people of color, how buying HIV drugs for Africa led to improved treatments for Americans, whether the FDA was wrong to reject MDMA for PTSD, and the changes that could cut drug development expenses by orders of magnitude while producing treatments that actually work for everyone, supporting American geopolitical dominance, and defusing geopolitical instabilities that will “make pandemics looks like child’s play”.

Quotes

Timestamps

1:40 - Introduction
2:20 - PEPFAR’s systemic legacy
6:48 - Why we make drugs that don’t work
10:18 - PEPFAR’s legacy in the private sector
12:38 - Covid lessons we failed to learn
16:33 - MDMA for PTSD: Was the FDA wrong?
23:35 - The President: “I want it to be big.”
26:22 - A Marshall Plan for the 21st Century
29:00 - US companies don’t understand Africa
37:02 - Global-first drug development
45:45 - What has Covid changed?
50:22 - Global-health investment is stuck in the past
52:23 - Immunotherapy and the Future of Medicine
58:03 - What’s holding back change?
1:01:47 - The Way Forward

Transcript

Introduction (1:40)

Ross:
Welcome to Development & Research, where we talk about doing things differently to develop drugs and stop disease. I’m here with Mark Dybul, the architect of the greatest public health program of the 21st century. Welcome.

Mark Dybul:
Nice to see you again, Ross. I was one of the architects.

Ross:
Okay, one of the architects. Well, it’s not bragging if I say it.

Mark Dybul:
(laughs)

Ross:
Your work has been on the AIDS pandemic—which for a while was the pandemic before we got another one, in the same way that World War I was the war before we got a second one.

And so if you were briefing yourself in 2002 [about the state of HIV research], what is the executive summary of that briefing? "Mark, here’s how the last 23 years have gone…"

PEPFAR’s systemic legacy (2:20)

Mark Dybul:
There’s an important difference between HIV and other diseases because [for HIV] you actually have to build an entire infrastructure to deliver daily therapy and daily prevention for someone’s entire life. [Ross: Perhaps not daily any more! More on that with Jacob Trefethen and Saloni Dattani on the Hard Drugs podcast. Granted, even an annual booster would require enough sustained infrastructure to make Mark’s point.]

So it’s not a vaccine campaign. It’s not a short course of anti-tuberculosis or anti-malarial drugs. It’s actually for life, which means you need a supply chain. You need a massive human resource system. You need logistics… You need everything. And then you need ongoing research and development to have better and better products.

And that [research and development] is the revolutionary part of… You’d think that the greatest legacy of the President’s Emergency Plan for AIDS Relief (PEPFAR)—which is the program you mentioned—and of the Global Fund to Fight AIDS, TB and Malaria, is the fight against those diseases. But it’s actually the infrastructure that was built out down to the community level, and the focus on the countries rather than individual programs that were run out of Washington or London or wherever.

[Health programs] became national because you can’t fight a pandemic that was HIV without—for those who don’t know, a third of adults were infected in many countries. Two-thirds of pregnant women in some districts in Botswana were infected, which means they and all their kids were going to die.

Two-thirds of women of reproductive age—and HIV, unlike most diseases which killed kids and adults, was mostly attacking 18 to 25, 30-year-olds, which is the heart of the reproductive and productive part of society. So it was absolutely devastating, and fighting that was essential to keeping countries from collapsing—and it was also a building of systems that were absolutely necessary for following on after that.

And so, during COVID, [many African national health systems] were ready to respond down to the community level—they just had no support to do it. Had they actually received support, the Delta wave could easily have been prevented, along with the massive deaths that occurred because of it. It is entirely possible that we could have prevented the follow-on waves of new variants—which were entirely predictable coming from Africa, because there are so many young healthy people allowing the virus to bounce all over.

So I think the lesson, looking back, is to focus on things that are systemic, focus on things that the countries can do [themselves], support them to build their systems, and then allow them to run them. And we haven’t quite done that. We shifted away from that [at some point].

Ross:
I want to cut in here with a scientific—or medical—question.

Was it clear to you—or to anyone—at the outset that HIV was a fight where we could turn the tide without a vaccine?

Mark Dybul:
Yes. You could turn the tide because treatment is effectively a vaccine if you can reach enough people. And we knew that we would continue our development.

Ross:
Right. Many people today don’t understand that people whose HIV is controlled are generally not infectious—even to their sexual partners—

Mark Dybul:
—correct, which is why treatment is effectively a vaccine, because if you treat enough people, you bring their viral load down and disrupt transmission [of the virus].

[Ross: Early on in my public-health career, I attended a workshop on what it would take to develop a cure—not just a treatment—for HIV infection. I was shocked to hear that one of the most-repeated asks from the patient community is rapid tests of their viral load—because they quite literally wanted to know if today was a safe day to have sex with their HIV-negative partner. Uninformed as I was at the time, I hadn’t realized that there was such a thing as a safe day, in that situation.]

We now also have pre-exposure prophylaxis and a long-acting product—three of them, actually—that can be given every three months. [Ross: Pre-exposure prophylaxis is a treatment that you take before you might be exposed to a disease, where the goal of the medicine is to stop you from getting the disease in the first place. Vaccines are a type of this, but the specific way that they work—by creating an immune memory that’s stored for later—is just one of the many ways you might try to get someone’s body ahead of a disease.] And now we have the ability to actually move towards eliminating this pandemic. We knew that technology would continue to evolve, so long as we had the systems in place to do that.

I would also say that bureaucracy is more complicated than I thought back then. I often half-joke, and it’s only half-joking, that if I knew then what I know now about the US government bureaucracy and bureaucracies in other countries, I’m not sure I would have thought PEPFAR was possible. Everyone said it wasn’t possible. But actually, it showed that if you have big ideas, you trust people, you support them, you can achieve almost anything. But we didn’t evolve as much as we needed to evolve.

Ross:
“We”—here—meaning the government?

Mark Dybul:
The world. We didn’t evolve the way we should have.

Development has not moved—not just health, but development—has not moved the way it should have or could have over the last 20 years. We stopped innovating. We just got stuck in our usual patterns and we haven’t innovated enough.

Why we make drugs that don’t work (6:48)

Ross:
There’s one model of drug development that has become very standard for developing high-priced cancer therapies for patients in the US, where these things are studied in the developed world, with the developed world in mind. And the developers might as well forget that there are places outside the US and Europe.

Mark Dybul:
Well, let’s bring it back to self-interest on that point.

First of all, it’s not just specialized cancer drugs that only get studied in wealthy countries. And let’s be clear, here, it’s 50 to 60-year-old White men who get studied. We have very little diversity in our pools of research.

What we’ve found, even in our own countries, is that those products, whether it’s antihypertensives or diabetic products, don’t work in women and don’t work in people of color—because they have a different genetic makeup. So we’re actually paying for a lot of drugs that don’t work in huge parts of the population, so they stay sick. Which is terrible from a human perspective, but it also means that we’re wasting money on drugs because we studied them the wrong way.

And it’s also for low-income countries. So chloroquine, the old drug we used to use for malaria, wasn’t studied in Africa—it was studied in Europe. Shocking, it doesn’t work particularly well [in Africa]! So we have to change the whole model—

Ross:
It doesn’t work because of the landscape of other local diseases, or—?

Mark Dybul:
—in all probability, it’s a whole mix of factors that include environment and also genes. We do have genetic differences that lead to different responses to different [drug] products. We have environmental conditions that lead to responses to different products.

So people at Harvard have actually studied antidiabetics and antihypertensives in African Americans in the United States. They come from a different diverse genetic pool. Their environment is different, their social environment is different, and the drugs we give them don’t work for diabetes and hypertension because of that mix of factors. Now, if they were part of clinical trials, we would actually have different answers. That’s where we can get to with precision medicine if we actually expand the pool.

So if we actually supported countries to move from academic research, which is happening in many places in Africa—and Asia is no different—if we supported them to expand from their academic research to be able to conduct clinical trials to meet global standards—though we also need to shift a lot of those standards—we could actually have a very diverse genetic pool that would be relevant for the world.

We could also do the studies much faster, with less cost, which could lead to lower-priced products. And the faster you get to market, the better it is for the companies—they make more money—but it’s also better for the people who will have access to products that might actually work for them rather than not working for them.

So it’s not just philanthropic or "Let’s help Africa", it actually is good for us. It’s good for our own production, it’s good for our own access to therapies, if we change the system and support other people. This is not a zero-sum game. This is actually a win-win for everyone.

PEPFAR’s legacy in the private sector (10:18)

Ross:
I want to drill in on what PEPFAR has done to the landscape of commercial development in HIV drugs—and what that’s done for infectious disease more broadly. I mean, the US government buys billions of dollars of anti-retrovirals a year?

Mark Dybul:
A billion.

Ross:
And if the US was buying a billion dollars of airplane flaps a year, that would be an enormous industry. We wouldn’t think about it as charity and it would change the face of that industry.

What has a billion dollars a year changed about drug development?

Mark Dybul:
There are many things that it has changed—one of which is, US-based pharmaceutical companies have developed global networks for global distribution. Now, it’s never at the same price, but they still make a profit. Andrew Witty—who’s one of my heroes—always said, "It’s the area under the curve. I can sell 100 things for a dollar or one thing for $100 and I still am making money." So because of these networks, you are able to have global production and distribution, and that drives a reduction in price.

That was not true in 2002. You know, some might argue, "Well, that took away from US business." It didn’t take away from US business—it added to their bottom line! And that allowed them to invest in other products that then allowed us to have long-acting drugs that could eliminate HIV in the United States and eliminate HIV in Europe, as well as everywhere else. [Ross: I swear this is the last time I’ll plug the Hard Drugs episode on lenacapavir, which explains exactly what is going on with the long-lasting drugs, chemically speaking.]

Ross:
Would we have seen those things coming to market now if the US government hadn’t been a billion-dollar buyer of—

Mark Dybul:
—No, absolutely not.

The big innovation in HIV to begin with was going from 15 pills a day, to one pill twice a day, to one pill once a day. And not only did you have one pill once a day, you had a far more effective, less toxic one pill once a day. They’re longer-lasting molecules and also less toxic—you can have a greater efficacy without damaging other parts of our bodies which—

You know, every drug is a chemotherapy. Every drug has some impact on our cells—which is why moving to immunotherapy is so important, and HIV is driving that along with cancer as well.

But we were able to get to three-in-one [HIV cocktail treatment]. Now, it was actually several companies that had the drugs that needed to go into that pill. And the CEO of Gilead told me, "If it weren’t for PEPFAR, we never would have had that product."

It would have been three pills at best. He said, their boards would never have allowed the company to play with another pharmaceutical company to put those pills together for the US market. But as long as it was for a global market, he could convince them to do it—and then they could bring it back to the United States.

It revolutionized how Americans were treated. We would not be in the position we are in now on HIV in the United States or Europe were it not for PEPFAR—the former CEO of Gilead told me that directly. Innovation was occurring because of the new different type of market that occurred, which then improved the health of people in the United States—and led to massive profits for US pharmaceutical companies.

Covid lessons we failed to learn (12:38)

Ross:
So do you see the shadow of that in how the response to the COVID pandemic played out?

Mark Dybul:
I think that Warp Speed was a great example of what can happen when we all work together and achieve something extraordinary—based on a technology that many people thought was not useful. Drew Weissman, who is a co-Nobel laureate, was my first lab supervisor at NIH, and he struggled for years to get people to pay attention to mRNA as a possible vaccine—and then it wound up working very well for COVID.

But Warp Speed—the Trump administration initiative—allowed for pharmaceutical companies to come together with research institutions like the NIH and with producers to put together a system that allowed “warp-speed” production and clearance through regulatory authorities. Why do we have to wait for a crisis for that? It’s totally unnecessary; our systems are antiquated.

It’s rather extraordinary to me that in the area that should be the most innovative and creative in the world—research and development; by definition you’re talking about innovation—is sclerotic. We are still doing things the way we did them 75 years ago, where we could be moving much faster; Warp Speed demonstrated that to us.

We could be moving much faster to produce products, to study them in a more effective and efficient way, to approve them in a more effective and efficient way—which is good for our own companies, but also good for access for people in our own country and around the world. That also improves our position in the world from a financial perspective, as well as from a humanitarian perspective.

Ross:
I mean—we are the people who are exporting the world’s medicine.

Mark Dybul:
Correct—if we do it right. And it doesn’t matter if we produce all of it at home; the benefits come at home.

Ross:
Can you say more about that?

Mark Dybul:
We saw, with HIV—companies in the United States realized that they could produce a lot in the United States, but for lower-income markets where the revenue they could get for each product, had to be lower—the supply chain became global, that global supply allowed for global access, which was good for us—

Ross:
—because the learning curve improves those products, and we bring those improved products home.

Mark Dybul:
Yes. But the whole system needs to change—and then our whole [economic] development system needs to change.

There are so many systems in research and development, including global access—which is the end of research; you don’t do research and development just to have research and development. You do research and development to sell things. That means a global market, because you make a lot more if you sell around the world than if you just sell in the United States or Europe.

Now China’s gotten into this game. For a long time, China only produced products for itself, but now, they’re moving to a global marketplace. India has been doing this for quite a while. And the US is just behind.

We need to accelerate our efforts in research and development, and we need to bring new technology into our research and development—which is beginning, but really at a much slower pace than it should. Other [countries] are moving much faster. [Ross: In episode 3, we talked about the staggering rise of Chinese biopharma in the last five years.]

MDMA for PTSD: Was the FDA wrong? (16:33)

Mark Dybul:
A great example—at least to me—is the FDA not approving MDMA for post-traumatic stress, including in our own military. I’m hoping that’s revisited—

Ross:
So this is an interesting one because I have the other opinion here.

My understanding from the trial is that there wasn’t much question about efficacy on the numbers—and also that it was clear that the trial was effectively unblinded. Did the FDA make the wrong call on—I mean, the standard is blinded trials, and they went in with a trial that was effectively unblinded.

Should we be having a broader conversation about how to do trials in general, or was this the test case that the world should have turned on?

Mark Dybul:
I wouldn’t say it’s just the issue of blinded versus unblinded—but let’s stick with that. The way we do trials is absurd. I mean, randomized controlled trials have a place but they don’t have a place for all things to be studied.

Ross:
You mean, they are not the only way that we’re going to learn things about these products—

Mark Dybul:
—and the price of our products is directly related to that, because it takes years and years and years… In fact, the size of Phase III trials—the trials that allow you to get to regulatory approval—have grown in size over the past 10 years. Most people would be shocked—there’s one being done on a tuberculosis drug that’s almost a half a billion dollars. Hundreds of millions of dollars to do the last phase of the trial, let alone the beginning of them. We don’t need to be doing these!

Ross:
And where do those costs come from?

Mark Dybul:
You’re adding so many people, and then it takes so long to do the trials because we’re still enrolling every one of those patients from a few hospitals (laughs) in the United States and Europe—instead of around the world—which leads to products that are too expensive, because it took too long to get them to market, and that don’t work in a lot of people because we didn’t study them in a diverse enough pool.

Ross:
I mean, there are trials that struggle to recruit patients with diseases that millions of people around the world have—

Mark Dybul:
—exactly correct—

Ross:
—and that’s because you went to exactly the wrong place and did all of your study there.

Mark Dybul:
What’s understandable is that you have to meet a certain standard for the trial in order for the data to be meaningful. But that can be done much better with technology that exists today, and it can be much faster. We don’t need to be doing the trials the way we’re doing them in this massive, randomized, controlled way.

There are some things you do need to do [a full RCT] for—but what is the problem with an open-label trial that shows a 77% efficacy in converting people who are literally suicidal to being healthy in a couple of months?

So the MDMA issue was partially the trial design, but it was also just the politics. You know, we’re letting psychedelics into the marketplace. People were upset about that. And then you get conservative regulatory agencies that get nervous about that.

There is an issue that needs to be studied, which is what is the rate of people who then become addicted to a psychedelic product—and then you could have pathways that could be problematic for society. Well, you can study that after this trial. And they did look at it within the trial, but that’s very simple. All you have to do is after the study is done and approved, you follow people for five years to see what happens. And if you have to, you withdraw the approval.

[Ross: My feelings on the Lykos trial aside, I wholeheartedly agree with Mark that the FDA could stand to handle more things with allow-monitor-and-withdraw-if-necessary follow-up. You could worry about companies just trying for a cash grab before their product is withdrawn, or slow-walking the follow-up; my preferred policy for that is to make them disgorge all their profits from the withdrawn drug, which cuts off the incentive for a quick grab, forces them to think critically about the odds on the front end, and removes the advantage to postponing a failure.]

Ross:
Whereas, if they have to study it for another five years before they can begin selling it, that leaves many of these drugs—

Mark Dybul:
—dead in the water from a commercial perspective. And then we don’t ever get access to them because no one can afford it.

Mark Dybul:
One of the things every investor will say when a new biotech company—or any new innovative product—is coming out there is, “How are you going to get access to a global marketplace?” That’s why biotechs have to sell to a large pharmaceutical company who have that access. If we change the system, the innovation would lead to improvement in our health dramatically.

This is very true in immunotherapy—which is the future. There is no reason if we changed what we do, that within 10 years, that we couldn’t be done with chemotherapy for cancer, chemotherapy for most drugs, where our own immune system would be able to manage the vast majority of disease. And the more we learn, the more we understand the immune system is very important for diabetes, for hypertension, for neurological diseases.

If we actually changed the way we did things, from beginning to end—and where we did things, from beginning to end—we could have a much healthier, lower cost health system than we have today.

Ross:
But—I can finish your sentence—we’re not going to understand what makes the stuff work or not work by looking at a narrow slice of people in American hospitals.

Mark Dybul:
We can’t! Everywhere in the world is very genetically diverse. But the people we study are not genetically diverse because of the way we do the studies. And so we don’t understand how our drugs.

The system does not encourage innovation at the most rapid pace. And innovation is happening in other places much faster. The pharmaceutical industry is very slow to adopt artificial intelligence right now; others are not.

Two-thirds of young people in the world, which is where technology tends to emerge, are in low and middle income countries. If we support them, our companies can do very well by partnering with and engaging with the young people around the world. You don’t need five PhDs and 30 NIH grants anymore to design the next generation of a vaccine or next generation of immunotherapy. You need access to the internet and good AI and technology, and we can blow the doors off of all of this stuff.

But we are living in a world—in our research and development approach, and especially how we do clinical trials and how we do regulatory—that is in a chokehold for getting new products to market and allowing that innovation to take hold. That all needs fundamental reform.

The President: “I want it to be big.” (23:35)

Mark Dybul:
Then we also need to reform our [economic] development systems. We have evolved since 20 years ago when I began, where, if you asked anyone in development, "What are you doing for education, nutrition, health?" the answer would be, "We’re spending X amount of money." That was the answer. But President [George W.] Bush said “Don’t. I want to do something big on this topic and I want it to be big."

The first initiative that Tony [Fauci] and I introduced was mother-and child-transmission reduction. We thought that was great—there was a time when a single pill administered around the time of birth reduced the transmission [of HIV] from mother to children by 50%.

Which is saving a lot of kids’ lives.

Ross:
And so how much did you spend on it?

Mark Dybul:
Well, the proposal was $500 million over five years. The president adopted it, but then he turned and said, "This is a nice start. I want to do something big."

That led to antiretroviral therapy, which has saved 25 million lives around the world and lifted up GDPs of countries—which has been proven—and which lifted up our status in Africa. Many countries in Africa have a higher opinion of the United States than Americans have of the United States because of these types of programs.

And diplomatically, we’re in a geopolitical fight right now, and these things matter. So there was a shift, and now everyone talks about results and, "What are you doing and how are you achieving things?", which was largely driven by [the President’s] vision—

Ross:
—throughout the government?

Mark Dybul:
Throughout the US government and globally. It had a global impact on how organizations operated. Not just in healthcare, in all of development. We shifted from "How much money are you spending?" to "What results are you achieving? How are you supporting countries?" But it stalled. It stalled, and now in some ways we’re going back to the old models.

We’re going back, not so much about "How much money are you spending?", but more on "We’re going to run the programs. We’re going to control the programs," and we do not involve the private sector—which was a part of the original vision. In the end, we focus on narrow things—HIV, malaria, TB, education, economic growth, and agriculture are hugely important, but they’re all in these individual pieces. First of all, that leads to chaos in the countries, but secondly, doesn’t lead to development. It doesn’t lead to overall development and ultimately economic growth is going to be the engine of all development, if it’s equitable.

A Marshall Plan for the 21st Century (26:22)

Mark Dybul:
We need development plans. We need the private sector at the table. We need to remake how we do development. Most organizations were created 70 years ago, 80 years ago. The bureaucracies have become bloated. Everything’s overlapping, competitive. We need a total remake of the way we do things, and I think there’s an opportunity for that.

The founding of all this grew out of Bretton Woods, which was a meeting that was held in a town called Bretton Woods at the Mount Washington Hotel, after World War II, that led to the creation of the World Bank, the International Monetary Fund, and the US Marshall Plan as a bilateral program to rebuild Europe.

Ross:
The plan was, “We’re just going to send money to them until we achieve success”?

Mark Dybul:
But the success was rebuilding their economies. It was philanthropic in a sense—and a huge humanitarian thing to rebuild the economies of Europe—but it also was, as Adam Smith would say, ‘enlightened self-interest’ because we needed their economies for our economy to grow. And it was those investments that led to the markets that gave us the ability to become the greatest economy in the world.

That same type of approach, that remaking of institutions for the 21st century—which is going to be necessary—with a 21st-century approach of development, economic growth, not just in individual parts, but supporting countries.

And that’s what these other countries want. They don’t want to be on all these handouts. I have been saying for 15 years, we should never use the word ‘aid’ again. We should never use the word ‘assist’ or ‘help’.

What we are is partners with those countries to support their economic growth and development—like the Marshall Plan—which will then allow us to have access to markets, just like the Marshall Plan did. Our companies will thrive and learn things that we can bring back home to improve our own health, our own wellbeing, our own economies, our own technology.

Our own technology could be growing in leaps and bounds if we would partner with these young kids in Africa who are dynamic and hungry and will come up with things that we can then use for our own advancement in technology. It is an opportunity to transform in a way that we have [thus far] failed to do.

US companies don’t understand Africa (29:00)

Ross:
Shifting frames but staying on this question of partnerships, when multinational corporations want to set up partnerships with African governments, to bring pieces of their development there for enlightened self-interest, or other broader opportunities—what are the models that actually work? What models don’t work? What models look like they work but are actually rotten through?

Mark Dybul:
So, we are further behind than China. In part that’s because sometimes you need development agencies to be first-loss investors to de-risk programs and draw in companies. But we’re also behind in our own companies’ understanding of Africa. A lot of people still see Africa as a single country. And while they are moving towards a continental union, like the European Union, in fits and starts, it’s going to take a long time [to get there].

It’s a 1.3-billion-person market, but most companies don’t see beyond the news of this war or that war, or this disaster or that disaster, they don’t see the opportunity that’s there. Some do. Jamie Dimon just went to Africa to open three new offices.

So there are places you can go that will lead to smart investments, economic growth and development. But our companies haven’t quite done that, and I think our government could do a better job at using our development infrastructure for that rather than the way we’ve been using it.

Mark Dybul:
We need to soften the ground and focus on the private sector. The private sector in development is always an afterthought rather than front and center. How do we have economic growth and development, which is the only way development’s going to occur. You can’t just do an HIV program. (laughs) You can’t just do a malaria program. You can’t just do an education program. They all have to come together for economic growth and development.

Rob Mosbacher, who ran OPIC (which was the private-sector arm of the US government) suggested this 20 years ago, but we couldn’t get anywhere because the bureaucracy wouldn’t let us. We still don’t start with the private sector. We don’t start with, “How does investment occur?” We don't start the way the Marshall Plan started. We don’t start with, “How does economic growth and development occur and how do we support it?”

Health and education are fundamental. You need a healthy, educated population to work, to create and ultimately, to buy. Singapore, Korea, Norway, Japan—that’s how they started to rebuild their economies; they invested heavily in health and education. The US used to do that too, a long time ago. We’re falling behind now because we don’t.

We don’t begin with the question, “How do we grow the economies?” and then fit everything into that. We start with, well, let’s do this program or that program. If we remade all of that—which we have the opportunity to do, I think, and that is the exciting moment today—both in global institutions, but also in how the US operates, we could succeed. China is way ahead of us on this because they don’t have the bureaucratic challenges we have. They just go do it.

Ross:
You mean, they’re better at preparing a country that they’re partnering with to be a trading partner? With Belt and Road, they were doing investments and that was raising their profile, but they were specifically investing in things that would let their ships sail into the port and trade.

Mark Dybul:
And the reality is we can win this because the way they do it is they bring their own employees— which doesn’t lead to jobs locally. They bring mostly loans, not actual investment, so the countries get saddled with debt that they have to repay. We could actually do it smarter and better. But right now, we’re just getting our butts kicked because we’re not even playing the game.

When I was in the administration—because PEPFAR was so important to President Bush—I was privileged to be in meetings with heads of state. They didn’t want to work with China; they wanted to work with us! But we couldn’t offer them what they needed, which was someone to support their economic growth and development as a comprehensive approach.

Ross:
Did you see that develop over the time that you were running PEPFAR? Did those meetings with those heads of states start in a very different place than they were five years later?

Mark Dybul:
Yes, because China got much more engaged in those five years.

Ross:
So it used to be the US or nothing, and then China came onto the board?

Mark Dybul:
—and the World Bank and other international finance institutions. Even the African-zone institutions—the African Development Bank, the Export-Import Bank—are not quite where they need to be to be supporting these efforts. But it did evolve because China got more active.

We’re also not paying attention to the fact that Russia, United Arab Emirates and others are getting in the game. Soon we are really going to be out of the game—and we’re seeing it in the political shifts and, how countries who aligned themselves almost entirely with the United States, now are realigning to relate to Russia and China very differently than they used to be.

So we are falling behind in every respect. We are losing the economic opportunity. We are losing the diplomatic opportunity and the geopolitical opportunity. If we redo everything and we do it correctly, we can use the PEPFAR model—which redid everything—and use that as the cutting edge to start again, to redo the Bretton Woods agreements for the modern era.

Ross:
Exciting. And I do think that there’s energy in the moment to be rethinking how we do things. I think the question is what is going to come out of when we break things down and build them back up?

Mark Dybul:
The building back up is the important part. The breaking, you know, you can do pretty quickly. The building is harder.

But I think it’s really important to emphasize that this isn’t just what we... It’s what the leaders of the countries have been saying they want for 15, 20 years. They’ve been saying for so long, “We want partners for economic growth and development. We love these plans and they’re part of it. We need a healthy population. We need an educated population. We need better agriculture.” What Rwanda is doing with agriculture right now is mind-blowing with technology.

That technology comes from the United States, and President Kagame sees that. But we haven’t put all the pieces together because our development system is fragmented—

Ross:
—and it’s stuck in this mode of, “We’re doing charity.”

Mark Dybul:
And for years, for decades I’ve been saying, stop— Africans, just like the Brazilians before and the Mexicans before—two countries that have grown from dependency status and gotten themselves out of it—hate the US government development system, because they are treated like children. Because it’s aid. They don’t want aid. They want a partner. And they want to grow from having a partner that supports their economic growth and development holistically to a partner that becomes their technological and trading partner. Moving from ‘aid’ to ‘trade’ is where we need to be going.

And there are ways to do this just in the health sector—we don’t focus enough on revenue-generating health activity, like clinical trials. Nigeria alone estimates [that a clinical-trials industry] could create a half a million jobs—good jobs—and $3.8 billion in revenue in five to seven years. That’s revenue generation. That’s not dependency. Those are the things we need to be supporting.

Global-first drug development (37:02)

Ross:
So talk me through this. If you ran a pharma company sitting on a treatment for influenza that takes mortality from—it’s 1% if my grandmother gets symptomatic influenza—to zero. It solves that problem. It’s a problem that Americans have. You’re going at this with this global first mindset, looking at the whole game board—what are you going to do differently? Differently than the replacement CEO is going to do to take this product from here to—

Mark Dybul:
—well, we have a couple of challenges, and I don’t want to stick with just pharmaceutical companies, but let’s stick with health for a second.

I actually have some empathy for a CEO of a pharma company. First of all, their shelf life is two years. And the incentive system is entirely built on, “What is my share price the next quarter?”

So you’re not focused on, “In 10 years, what happens?” and “What will my company look like?”, because you’re focused on your two years and your payouts.

Ross:
Meanwhile, the research is going to happen seven years from now—or six if I make the right choices—

Mark Dybul:
—and if you have to make these decisions today—and you do have to make them today—there is no established clinical trials capacity outside of South Africa in Africa. I’ll stick with Africa because I know it well, but in Asia, Latin America we still have similar issues, even though we have fairly advanced economies in a number of places. Outside of South Africa, though, there’s very little clinical trial capacity. You can’t do a clinical trial in these places.

Ross:
What’s going on there? Why is the first-best hospital in Kigali, Kinshasa, Addis Ababa—why are these not places where you can do a clinical trial to the level of what you’d see in Johannesburg?

Mark Dybul:
It takes resources to get there. We’ve done some of the work. Some of the work I’ve done to support a few countries to make an investment case—because that’s what these are: these are investment cases based on, what do we need to invest to get to that $3.8 billion [a year of domestic revenue]? It turns out to be a couple hundred million dollars—pretty good return on investment!

That industry also brings jobs, and we really—from a geopolitical perspective—we really need to be focused on jobs for young people in low and middle income countries, where 75% of their population is under the age of 35. Most of them don’t have jobs. Unemployment in young men in particular is 50, 60, 70%. I know our national security people worry about this—

[Ross: I’ll cut in to remind you that when a former Assistant Secretary of State says “I know our national security people worry about this…”, well, I give that more weight than when I hear it from your average bear.]

—it is a recipe for global instability that will damage the United States in ways make pandemics look like child’s play.

So, we should be focused on that economic growth, similar to what we did for Europe. It would have been absolute chaos in Europe had the Marshall Plan and the World Bank not supported their economic growth [after World War II]. We should be doing the same thing for the same reasons, but in a different [geographic] place now, because that’s where the young people are and that’s where the innovation can come from and that’s where the opportunity is

But it takes investment to reach clinical trials capacity, because you have to have data collected in a certain way. You have to have trained staff, though the vast majority of them are not medical. The vast majority are project managers, data managers, data analysts, monitors; these are completely portable within the economy, so they don’t have to just be doing health.

Ross:
This is not about hospital beds or special equipment. This is about having people to do office work, [white-collar] work.

Mark Dybul:
There is some need for hardware. For example, there are very few places that have MRI and CT scan capabilities. If you’re going to do an oncology or neurologic study, you need that capacity. If you’re going to study infectious diseases, you don’t. But that’s not a global market—at least for many of them—even though they need those products, and so we should be supporting their research and development.

People like Drew Weissman are doing this—they’re transferring their technology to investigators in low and middle income countries to develop their own vaccines for dengue and things that are in their countries, which also affect us globally too. One of them could be the next pandemic.

So this is all smart—for us—for a whole variety of reasons, but it does take some investment in some hardware, diagnostics, data, data systems… It’s hardware, and it’s ‘software’: people. The investment is not huge (relative to the output). The diagnostic center—with MRI, CT scans—can get a scan down to under $100 in these resource-limited settings. [Ross: …where labor is cheap.] If you run a business case on that the return is massive. Absolutely massive.

Now, a lot of people can’t afford that, and a lot of national health systems can’t afford that, but there are plenty of wealthy people in those countries that can afford it. Instead of flying to India or China to get those done, they’d get them done locally for $100; they’ll pay for that. And the national health systems, some of them send people to South Africa or India to get treated for cancer because they don’t have the [domestic] capacity. You now start saving all of that money.

So the investment case is extraordinary, but it takes someone to invest which gets back to—we do not bring in the investment pieces, the opportunity, the first loss-pieces into our development infrastructure that would create all of that. And that’s just for health—it’s the same for agriculture, same for education, same for business development.

On the African side, the reality is the regulatory environment is not great. The governance environment needs work; work needs to be done there too. But there are places—again, Africa is not a country—there are places you can get started on all this, show the model, and then everyone will drive it forward. Just like with PEPFAR—we started with 14 countries, we didn’t start with 100 countries, and we showed the model that could then drive that.

Ross:
Are there good models in how corporate partnerships are working that we should start from and expand? Or is that coming at things from the wrong end?

Mark Dybul:
There are some, but not many, and they’re all limited.

There was a group of African and US CEOs that would meet regularly to look for business opportunities, but it never really took off. 

Ross:
What about biotech parks?

Mark Dybul:
We have biotech parks that are being created now in Africa, but they’re not biotech parks like our biotech parks. And there are groups like Wellcome Trust, the Gates Foundation, and others that really could be investing there. There are huge foundations, like the MasterCard Foundation—people don’t know about this $55 billion foundation that’s going to grow to $100 billion entirely focused on Africa.

Ross:
They’re focused on training—

Mark Dybul:
—which is great, but you have to have a job to train someone for. So the investments have to be put together. It’s really just putting the pieces together by bringing everyone together. 

We tend to go through these fits and starts of creativity and new models, and then we forget them because the bureaucracy sucks it all back in. I don’t know of any great models for how this gets done. Maybe Jamie Dimon will be the one to figure it out.

But if we actually focused on that, and by bringing the pieces together, by restructuring both our global institutions but also our [national] institutions, and putting the private sector and economic growth at the center—which a lot of people in development don’t want to do. I just came from a meeting, everyone’s like, "How do we hold governments accountable for delivering... It’s the responsibility of the government to provide health. It’s the responsibility of…” Yeah, but they don’t have the money to do it!

If you talk about the private sector and economic growth and development—in the development world—you’re anathema. “This is humanitarian, only humanitarian.” No, it’s not. It’s not humanitarian—going back to the Marshall Plan—because economic growth and development in the rest of the world is pretty good for us. That's not ‘globalization’ and it’s not shifting jobs from the United States. It’s actually promoting our own economy.

What has Covid changed? (45:45)

Ross:
What has Covid changed about that in healthcare—in health and pharma—in terms of national attitudes?

Mark Dybul:
(sighs) It’s rather unfortunate. There was a tremendous health infrastructure, and—unlike in the United States—what the Africans built goes down to the community, literally down to villages. Now, it’s not always the best there and it’s not digitized yet, but they have really remarkable systems and national data systems because of development [programs].

Ross:
When that gets down to people—”My child has a fever.” “I’ve got a lump on my arm.”—that’s a level where someone in an African village might have better access to healthcare than the US because they have that primary care.

Mark Dybul:
They have access to identification. They might not have access to the care that goes with it.

Ross:
Sure.

Mark Dybul:
But you could build that—and that’s also where you’d want to do a clinical trial. If you’re enrolling for Covid, you don’t want to be in a tertiary care hospital—

Ross:
People have done that! People have done those trials!

Mark Dybul:
Exactly. But [the community-care level] is where you want to be. It’s where you want to be for diabetes and hypertension; you don’t want to be at a university hospital—which is where we do all our clinical studies.

[At a university hospital,] you can’t enroll quickly. It costs a fortune because your base costs are so much higher. And your enrollment takes forever because you have a limited pool and a lot of people drop out because they don’t go to the hospital all the time—

Ross:
—and the people you get are pretty weird [Ross: read: pretty sick], because the people who end up in the hospital are not—

Mark Dybul:
—the people who get identified in the community and taken care of.

So the way they built the system actually allows for a revolution in a way that we can’t do in the United States yet, because we’re not down to those types of—

Ross:
—because we just don’t deliver healthcare except in the high-cost sites.

Mark Dybul:
Well, we do deliver healthcare—you know, we all go to our primary care doctors and everything else—but we don’t have the research infrastructure that’s down to those [clinics] yet. We could build those fairly quickly, which would be good for all of us.

But what’s changed with Covid is that many countries realized that they have to be self-sufficient. That they can’t, in the next pandemic, wait for someone to provide them with a vaccine.

Ross:
Because they didn’t.

Mark Dybul:
Because they didn’t. Or a diagnostic.

As an example, South Africa fielded 25,000 community healthcare workers to fan out to test people for Covid. Twenty-five thousand. That’s more than we had in the entire United States. Sierra Leone had 9,000 because they’d just gone through an Ebola pandemic. [Ross: Sierra Leone has a population of 8.5 million. Mark’s claim here—which I have no particular reason to doubt—is that one in a thousand Leoneans were ready to pivot from Ebola straight into Covid response.] They were ready to do the same—but they didn’t have any test kits.

Ross:
We had some trouble with test kits in the US too. [Ross: For those of you who have forgotten, the FDA swung into action in January of 2020—to ban anyone but the CDC from offering a diagnostic test for Covid. And then the CDC messed up their first test design.]

Mark Dybul:
Yeah, we did. But those could have been overcome easily because any university—every university in the United States and in Africa developed a genetic test. It’s not that hard. But—

Ross:
—it was a regulatory issue.

Mark Dybul:
It was a regulatory issue. We wouldn’t let anyone use them.

That’s led to some very healthy things, but also dangerous things, in my view. So we’re focused on manufacturing—which I understand is political, that they now have to have manufacturing locally—but it’s not sustainable if you don’t have a market. And you have to have a constant market. And not just for vaccines that are going to sit on a shelf.

That’s part of what Drew Weissman and others are doing to trying to get—Dengue vaccines and other vaccines, because something has to—

Ross:
—something for which there is going to be constant demand, where we can build the foundations of the engine on those things.

Mark Dybul:
But then you have to build the rest of the ecosystem so that you have end-to-end research and development.

Here I go back to clinical trials—not because I’m wed to clinical trials; I haven’t done a clinical trial myself in 25, 30 years…though I used to do them—resources are available when there are billions and billions of dollars in studies that can’t be done because there aren’t enough people in the current [clinical] sites that we’re using. A little investment in those clinical trials then yields to economic growth and development. And those resources can then be used to build the rest of the health system, which is where that $3.8 billion—in Nigeria alone—would come.

Having been trained—and being a professor—at a university in the United States, that’s how a lot of our universities grew. University systems grew by doing clinical trials because there’s money that comes in that you can’t draw in otherwise. It’s the same with these diagnostic centers—there are ways to invest in health that lead to economic growth, development, and revenue generation, so we can get out of this aid-dependency approach, which these countries don’t want and which is bad for us.

Global-health investment is stuck in the past (50:22)

Ross:
Do you see a distinction, then, in the sorts of programs that are building towards developing medical products for the African market and developing medical products in Africa and African partnerships for the American, high-income-country market?

Mark Dybul:
Not yet. Again, I think there are some efforts occurring. Drew’s working on it; he’s been doing it actually for 20 years in Malaysia and Botswana, but it’s not at scale, because he’s interested in RNA. But it can’t be manufacturing-only, and that’s the insight that Drew has. You have to start with the discovery, but then you need the clinical trial, then you need the regulatory approach, and then you need global access. And all those pieces have to be done together. You can't just have one piece of an ecosystem. It will not be sustainable.

And so you have to look at, where can you invest now—that will be revenue-generating so you’re not just constantly dumping money in—that will feed the whole system? That’s why I focus on clinical trials, diagnostic centers, and things like that—because [pharma companies] have a backlog of clinical trials that can’t be done that are costing them a fortune, that have huge overruns because they can’t enroll enough people—

Ross:
—because [patient] recruitment sucks.

Mark Dybul:
And because you’re all stuck in the same... Take an oncology trial. You’re all competing for the same 30 university hospitals for the same 20 people (laughs) with that disease, especially as we get to rare diseases.

Now, I think the FDA has done a good job on rare diseases, providing a lot of exceptions, but why are those exceptions only for rare diseases? We should have that type of approach, that kind of energetic approach for everything. We did with HIV, but—

Ross:
—why are these exceptions and not revolutions in how we do things?

Immunotherapy and the Future of Medicine (52:23)

Mark Dybul:
Especially as we move into immunotherapy and getting rid of—

Ross:
—what makes that different? What’s going to make immunotherapy different?

Mark Dybul:
Immunotherapy—let’s take something simple like cancer.

Ross:
…sure.

Mark Dybul:
Okay, cancer’s not simple.

Ross:
Normally we treat it with a chemotherapy, a small-molecule poison.

Mark Dybul:
So it does kill the cancer, but it kills a lot of other things, which is why people get so sick. But how do you get cancer? You get cancer because your own immune system fails. It’s a failure of your own immune system. Why do we get sick from diseases? Why do some people die from an infectious disease? Because your immune system failed. And so a vaccine, for example, is designed to boost your immune system so it can manage the disease.

There are so many immunotherapies out there that within 10 years, we will be—we should be looking back and saying, “Chemotherapy was barbaric,” the same way we look back at bloodletting now. It’s what we have, and so maybe it’s not barbaric because it saves a lot of people’s lives, but it’s not a really smart way to attack cancer, because you’re attacking everything else.

We do that because the cancer lives in our own cells, so you have to kill your own cells. Bacteria are really easy—they’re these big things that float around outside of our cells.

Ross:
They have different biology than us; we can target that biology and kill them.

Mark Dybul:
It’s really easy—you kill them, they die, and you don’t kill much else. But once something’s in your cells like cancer or HIV or other viruses, you have to kill the cells—which are our own cells—and that leads to all these side effects.

If we can stimulate the immune system either preventively—and I think we will see preventive cancer vaccines that’ll be very effective, or just like we have pre-exposure prophylaxis [for HIV]—but also if you can boost the immune system to see the cancer or HIV or something else in a new way that allows your own immune system to attack the cells and eliminate the bad cells but not the good cells, then you have a fundamentally different approach.

[Ross: One thing that I have gathered from talking to vaccine developers is that, just because your body naturally learns to recognize the very end of the spike protein of a Covid viron, that doesn’t mean that that’s the best thing to base your adaptive immune memory on.

In this particular case, the outermost end of the spike protein is one of the easier things to mutate, and so immune memory—whether from vaccine or from exposure—only lasts until the virus mutates enough that the spike end is unrecognizable. And you’ll form the same spike-centered immune memory if you get protein on a nanoparticle, a dummy virus, or printed in your own cells using mRNA.

But if you picked a functional part of the virus envelope that isn’t the first thing your adaptive immune system will recognize, but is particularly hard to mutate (say, because it has multiple systems that depend on it), you could get much a more durable immune memory than you would get even from multiple bouts of natural infection.

To my knowledge there isn’t anyone currently trying this approach—but I’d love to hear that I’m wrong about that!]

Ross:
And that’s going to happen more specifically, with fewer side-effects than killing these things chemically?

Mark Dybul:
Right now, a lot of people are focused on CAR-T—which is a great in-between—but CAR-T has a lot of side effects and you have to really damage the immune system because you’re replacing [a part of] it.

There are other approaches that are being developed, whether it’s allogeneic dendritic vaccines, other dendritic vaccines, other ways to stimulate natural killer cells, or stimulating of the immune system—which is failing—to see your disease in a new way so that it can attack and control it. There are nanoparticles, and…

There are many approaches to immunotherapy out there, but our system is going to strangle them because it costs too much money to develop them.

Ross:
It’s not like the revenue potential isn’t there. You’re talking about revolutionizing how we treat cancer. The revenue is—

Mark Dybul:
—the revenue’s there if it works. A lot of great ideas don’t, in the end, work.

You have to understand that and be willing to take those risks—but you can’t support that if it costs $500 million or $1 billion, or now almost $1.5 billion, on average, to fully develop a drug to product. You can’t do that and make a bunch of mistakes. You can do it if it costs a lot less.

There are ways to get early signals with different approaches to regulatory and clinical trials that would allow us—using AI—to understand whether or not something should be pursued or not and whether or not you should invest, and then redesign the clinical trial so you don’t have to spend a half a billion dollars on the Phase III clinical trial. If we did all of that, then we can actually advance a lot of different therapies rather than the approach we're taking now.

Ross:
What lets you pull those costs down so dramatically?

Mark Dybul:
Changing where we do the studies and—

Ross:
—it’s just the cost of healthcare?

Mark Dybul:
We could actually do this current absurd approach to clinical trials for a lot less money if we did it elsewhere and have the genetic diversity to actually tell us whether or not the product works. That’s one thing.

But more importantly, redesign how we do trials, how you do Phase I trials to tell you whether or not you can move to Phase II. You could use AI to test different products in different ways to predict, “Should I take this drug to trial or not?” Some companies are starting to do that.

We have to be careful, because it’s not quite there. The FDA recently did approve a product based on an AI model that worked really well in one setting, but as soon as it got to another setting, the results were a lot worse. So we have to be careful about some of these early moves, but in terms of:

• where and how we develop products, and
• what is allowed to go to Phase I trials and all the things that are necessary, and
• how you decide to move from Phase I to Phase II and how big that study needs to be, and
• whether or not you need to do a closed-label, randomized, controlled study with hundreds of thousands of people—
• or if you can do it with a small number of people in an open-label study or a cohort observational study—
• or a platform trial where you’re comparing multiple drugs against each other so you find out the best one, not just one that works—that Medicare and Medicaid are going to pay for—

There are different approaches that we can be looking at and taking. Now, regulatory authorities, both the European Medicines Agency and the FDA have signaled that they’re open to this, but they’re not moving fast enough.

What’s holding back change? (58:03)

Ross:
So what’s stopping us? Do they have applications on their desk that they’re slow-walking or that they’re throwing the book at?

Mark Dybul:
We’re not well-staffed. We don’t have a lot of people in the staff that are up-to-date on AI and those types of technological things, and there’s just fear—political fear that you’re going to make a mistake and there’s going to be a problem—which is very understandable.

Ross:
Are companies bringing them attempts at these new methods, or do we have this sort of vicious spiral where that fear is driving the industry to—

Mark Dybul:
—they are, but in the end, until you get to the trial result, all the FDA can do is provide you informal guidance. They can’t say, “We’ll do this if you do that.”

And I think the FDA is a great organization that saved a lot of lives, but there are probably things we could do to advance them. I think a lot of people on the staff would love to do that; they’re just limited in what they’re able to do, because of the whole environment.

Ross:
So here’s a question that sounds a little bit basic: Why do we care so much about what the FDA does?

When you talk about “sclerotic” regulatory systems, how is it that there’s one regulator who controls 4% of the people on this planet—Europe is larger; Africa’s four times the population—why is there this central importance of the FDA? [Ross: Previously on D&R…]

Mark Dybul:
The basic reason is not a bad reason, which is quality. Most governments—most people—don’t want to receive poor quality products, and so you need to have strong regulatory authorities. That is not inexpensive to do.

But the way we do it is outdated and takes too long.

Then you look at something like the African Medicines Agency, which is very nascent. It was supposed to be up and running already, but (shrugs) the lack of support and lots of other things… It is meant to be continental-wide—or at least regional-wide to start with—

Ross:
—as a drug regulator?

Mark Dybul:
As a drug regulator.

Ross:
That means, one approval process for 1.4 billion people?

Mark Dybul:
That’s the vision. They might start regionally—which is what they’re doing now—which would be fine, too!

Ross:
There’s a model in Europe here where you have national regulators and harmonization and cross-recognition—is that where they’re going?

Mark Dybul:
I hope they go a little bit further actually—

Ross:
—with one office, one set of procedures?

Mark Dybul:
All the countries would have to agree to that and support it, and that’s going to be challenging. And maybe there’s a system where you have a light-touch in-country that reviews—and you’ll always have to have ethics boards because ethics systems are a little bit different—but we should be able to align and reconcile all that, especially with modern technology. We shouldn’t be stuck in the old systems.

The African Medicines Agency actually has an opportunity to do something extraordinary if they get the support the way they hope to—which gets back to the African Union trying to create itself like the European Union so that you have one marketplace of billions and billions of people—which for the United States would be a tremendous [business] opportunity, if we don’t mess it up—

Ross:
—rather than going country by country, one market at a time. That’s too dense a thicket for companies to try to enter.

Mark Dybul:
The Africans have signaled that they want to do different types of approaches—platform trials, using technology, using a different regulatory model—because they’re starting new which makes it easier than if you’re recreating. I mean, we should be recreating at the same time as we support them to do it, so that we could learn from them on how to do it better as well.

The opportunity to make investments will repay us a thousandfold in every respect. It’s out there. It’s just that our current systems can’t do it.

The Way Forward (1:01:47)

Ross:
…so what’s the way forward?

Mark Dybul:
If you go back to 20 years ago when President Bush said, we gotta do something big on HIV, but we’re not going to do it the way we did it before; we’ll do it completely differently. We did, and we did it by shifting from, “How much money do you spend” to “What result are you getting?”, to providing an incentive system in-country and within the US government to function.

But we also did something which is essential if we’re going to do this as a government ourselves and internationally. Unlike the rest of the governmen—where we have 50 agencies doing everything and they have their own independent appropriation and they don’t have to listen to anyone—all the money went to one person, the coordinator in the State Department— [Ross: from 2006 until 2009, that coordinator was Mark.]

Ross:
—and that person reported to the Secretary.

Mark Dybul:
While I was there, you functionally reported to the President even though the law said it should be the Secretary. And you then distributed the money to the agencies, so the agencies all had to work together because you controlled the money that they were getting; they didn’t have an independent spigot. And that requires reform within the US government.

We actually studied the central command of the US military because prior to the ’60s, in World War II or the Korean War, the independent parts of the US military—the Army, Navy, Air Force—they wouldn’t coordinate an attack. Literally! Which is not too smart.

So a central command was created. That's the kind of thing you need—with accountability. Congress needs to change, too, because of the appropriations [process]. Say you want economic growth in the private sector to drive development—that’s not the Foreign Affairs committee; it’s Commerce. And Agriculture. It’s in different parts of the US government. They all need to be working together, which means you need to do basically what we did with PEPFAR.

You need to create someone who is accountable, who will get all of the money from all those different spigots and be accountable for economic growth and development, including the private sector. Right now, it’s spread all over the government with independent…everything.

This goes back to what Rob Mosbacher and I wanted to do 20 years ago, where we said, "Why don’t we take five countries where we have huge Millennium Challenge Corporation, huge USAID and PEPFAR programs, big OPIC (which is now the Development Finance Corporation Program) and do a development plan, support the countries and bring in the private sector.

Ross:
You want to start from the endpoint, “We’re trying to get this economic engine going—

Mark Dybul:
—that’s the goal. How do we all support that goal? That’s impossible in this bureaucracy, but that’s the kind of thing you can build; it is possible to do it. PEPFAR showed you can do it.

Now, it’s hard to change all of the US government—

Ross:
What made it possible [for PEPFAR]? Was it just that the president said, “...and now we’re doing it”?

Mark Dybul:
Yes.

When the President announced PEPFAR, there were around 70 presidential initiatives. He probably didn’t know about 67 of them.

But this one, he paid attention to and he made clear to the bureaucracy—and in very smart ways—that he was watching, and this is what he expected, and yes, this is an Assistant Secretary of State level, but you Secretaries are going to listen to what he says and your agencies are going to do what that person directs.

It was accountable, results-based… We wanted to see, every six months, what’s happening so that we could change how the money was used every six months—and we did. We shifted money from countries, we changed incentives… We worked closely with the governments; everything was national now, not little projects village by village.

Ross:
Can you talk about that [results-based approach]? Were there programs that seemed like good ideas at the time, then they hit reality and you had to trim them down?

Mark Dybul:
Yeah—trim down, or shift. Targets were set. Expectations were very clear—and small number, not a thousand. Though, when you pick those targets, you have to be very careful about how you pick them because you can set bad incentives. They have to be what I’d call ‘cascade’ incentives: to get to this—to get to antiretroviral therapy—you have to do a whole bunch of other things [first], but don’t monitor those other things, because then all the people are going to be doing is spending their time on it. Instead, monitor “Did you get to the antiretroviral therapy?”, because then the rest of that stuff has to be built.

Ross:
“How many people are we treating?”, not “How many people did you walk into your clinic?”—

Mark Dybul:
Exactly. That’s what we often do: “How many people do we reach?” Who cares how many people you reach? How many people are better? It can be the same with economic growth and development.

This has always driven me nuts in the development world—they’re like, “That’s too complicated, you can’t measure it.” You can measure it. You can’t measure growth in GDP in six months, but if you’re trying to get to growth in GDP, what can you measure in six-month intervals that should be changing? And you can [measure] that. Companies do that.

So that’s where the private sector can come in, if you’re engaging the private sector into doing all this, and the countries, and importantly, the private sector in those countries.

There are lots of very wealthy people that I know have invested in private hospitals, in private clinics, in private systems in Africa, just like we do in the United States. They make a lot of money. (laughs) Work with them and they will develop the systems that we then don’t have to pay for. But it’s still good for our businesses because we have companies working with them, too, investing in them, and we learn from them and bring things back to the United States.

So the moment right now reminds me of 20 years ago when we looked at things in a different way. And people have been saying for 15 years, whether it’s in the countries I work in—in Africa—from the heads of state down to the village level, they want something different. They don’t want aid, they don’t want dependency, they want economic growth and development.

We have models going back to the Marshall Plan and more recently, models of how we can do this. But it has to be done intentionally, with leadership, and it has to be done with global leaders and national leaders. I think the US is in a position—as it was 20 years ago—to lead, and the people in these countries are ready to come together.

But that means remaking how we do everything, because our current systems will not allow for that. It’s not just within the executive branch—it’s also how we legislate and it’s how we think and what we focus on. If we shift all of that—and we can—we can not only support countries to grow, we can then—like the Marshall Plan—build the marketplace for our economic future.

Ross:
—for our enlightened self-interests.

Mark Dybul:
I'll end with an anecdote. I worked with—I guess it’s been long enough and the CEO’s changed—the CEO of Walmart. When I was at PEPFAR, we did a lot of public-private partnerships, which was also anathema to the rest of the US government. These were partnerships like the one with Gilead that allowed triple therapy that saved so many lives and created so much money and revenue in the United States and better products for our people.

So we did a public-private partnership with Walmart, and the CEO invited me down to this big Saturday event with the CEO and the entire staff and I—

Their offices are what people say—I mean, you’re standing in the CEO’s office and it looks like it’s an IKEA college dorm. They all really do take out their own garbage. It's all true.

—and I was asking him, "Why are you doing this? I don’t understand why Walmart cares [about Africa]." Now, he had been head of emerging markets for the company before he became CEO, and he said, "You can’t see it, but I have a lot of sub-sourcing in Africa, down to sub-sub-sub-sourcing. If I don’t have a healthy population in Africa, I don’t get those goods right now."

But what he said next was even more important. He said, “I can’t make my 10-year projections for growth if I don’t have an economically growing Africa.” If we think that way about the American economy—and if we build our systems and how we act based on that—we can transform, not only the world, we can transform our own economy and be a little less worried about the fact that our population is decreasing. Because we will have the international growth that—like the Marshall Plan—fuels our own growth.

Ross:
I think that’s a great note to end on, and I think a really exciting vision that perhaps we have a moment to jump on here in the United States.

Mark Dybul:
Thanks. Good to be here with you again.

Ross:
Thanks so much, Mark.