Preet Bharara:

Hey folks, I have some exciting news. Stay Tuned with Preet is on the docket again.

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From CAFE and the Vox Media Podcast Network, this is Stay Tuned in Brief. I’m Preet Bharara.

In March 2022, the Biden administration announced the creation of a new government agency, the Advanced Research Projects Agency for Health, or ARPA-H. The agency is designed to drive biomedical innovation, and they have big goals like ending cancer as we know it.

He appointed Dr. Renee Wegrzyn as the first director of the agency. Before she came into this role, she was a leading scientist at Ginkgo Bioworks, where she focused on using synthetic biology to outpace infectious diseases, including COVID-19. Now, over a year has passed since the agency’s birth and with a multi-billion dollar budget, they’re trying to change the nature of scientific discovery and take big risks.

I’m excited to be joined by Dr. Wegrzyn in to talk about this exciting new chapter in US scientific research. Dr. Wegrzyn, welcome to the show.

Renee Wegrzyn:

Thank you, Preet. Please call me Renee.

Preet Bharara:

Renee. Don’t walk away, Renee, as they say.

Let’s start at the beginning. What is ARPA-H? What is DARPA on which ARPA-H is based, and why couldn’t we find better names for both?

Renee Wegrzyn:

Well, they tend to go through a metamorphosis of names. DARPA launched about 65 years ago in response to Sputnik. At the time, it was known as ARPA, and has really grown into an agency that is so well known for some of the big bets that DARPA took and the promising breakthrough technologies for national security that have resulted. For example, stealth technology, the internet are just two that certainly are a fruit of the model that DARPA has put forward.

Preet Bharara:

Wait a minute. Wait a minute. Just so we’re clear. It was DARPA and not Al Gore that spawned the internet.

Renee Wegrzyn:

Correct. The ARPA net started right there at DARPA. I’ll call back to that history a little later on when I talk about some of the things ARPA-H is up to.

Preet Bharara:

What is the mission of ARPA-H?

Renee Wegrzyn:

So as an inaugural director of ARPA-H, I was sworn in last October, and one of the first things that I had the privilege to do was to assign our mission statement together with the team. We landed on a mission statement that is accelerate better health outcomes for everyone. We think this is really a mission statement that will stand the test of time and is a nod to the catalyst function that we really are intended to bring forward here, to take some of that great innovation that might be happening in the private sector or in universities and really ramp up the pace and how we get that out into the real world to impact people’s lives, change those health outcomes.

So we’re not counting our success on the number of companies we launch or the number of papers we publish. It’s really changing the lives of everyone. And so we want to make sure that as we push out these breakthrough technologies, that we’re not doing it just for the top 1%, that this is really something that’s going to be accessible for all Americans.

Preet Bharara:

Why weren’t existing institutions or agencies like NIH and others sufficient? I mean, we made it through 200 some odd years without ARPA-H. What’s the new thing that gives it its worth?

Renee Wegrzyn:

Yeah. I think when the president really shared his vision in March of 2022 when he called on Congress to give the first funding appropriation to ARPA was a nod to this business model that allows innovation to move forward in a very non-traditional way. And I’ll be really concrete in what that means for ARPA-H.

There is very important foundational research happening at NIH and other places in the federal government, but the unique role that ARPA-H will play is that we do so in a very bottoms up approach. And what I mean by that is we actually hire people called program managers that we find out there in the real world, who have this incredible passion, demonstrated expertise and they have defined a problem in health that they want to solve. And so we hire them not only for their amazing CV, but for this very specific ultra focus problem that they want to solve. So we hire the person and the challenge. Not a single one of our dollars is linked to a specific disease or technology. It really gives us the freedom to fund the efforts where we think we can have this asymmetrical impact on advancing the state-of-the-art.

The way that we do this is also very different from the rest of the ecosystem. We empower our program managers to be sole decision makers. We don’t do study sections or decisions by committee. And by giving the program manager that capability to make those decisions, we allow that person to take on a lot of risk, a calculated risk, mitigated risk, but we can take on risk.

We have a seat at the table during the course of an effort. We don’t issue any grants. With grants, you give researchers that money and it tends to be a pretty passive process. We are not a passive agency. We’re very proactive. And so contracts, other transaction cooperative agreements, these are the funding vehicles that government can use, making sure that government has a seat at the table with the private sector or universities that develop it.

So all of those key features put together is really made magical and made urgent through some of our authorities through Congress that give our program managers a term limit, which is three years.

So every two weeks that goes by, those program managers, 1% of their time has lapsed. So they come here wanting to solve this problem with incredible urgency and are very well-resourced to do so. And there’s just not another place in government, in HHS, or the health sector that is able to move in that way.

Preet Bharara:

Yeah, it’s just so interesting because a lot of people think about government as being bureaucratic and slow moving and not innovative and certainly many government agencies fit that description, when we think of the private sector, Silicon Valley and other places as being innovative and also willing to take risks and put a lot of money into research and development. But here, as President Biden put it, the idea of your agency is to, in his words, “develop ideas so bold no one else, not even the private sector, is willing to give them a chance or to sink a lot of money into trying to solve.”

Can you give an example of the kind of thing that well-funded pharmaceutical or other life science companies would shy away from that government would embrace?

Renee Wegrzyn:

Yeah. One of the examples that I can just start to even point towards some of our programs that we’re launching. Our very first program that we launched is called Nitro. It’s a program focused on the challenge of osteoarthritis.

Preet Bharara:

Nitro, by the way, that’s a great name. Nitro is a good name.

Renee Wegrzyn:

It is. One of the fun things of being a program manager is you have freedom to name your programs and these incredible acronyms that we tend to make in the ARPAs.

The program manager behind Nitro came to the agency and said, look, “I’m a surgeon and I look at what surgeons can typically accomplish in their career, which is helping a thousand, 2000 people. That’s an incredible number of people.” He said, “If I do the math, I think if I can create a way for joints to heal themselves that we can basically reverse osteoarthritis, I can help millions of people and do so proactively and have people live their healthiest and best lives possible. That’s what I want to do.” We got excited about his vision as well, Dr. Ross Uhrich.

When he came into ARPA-H, he created a framework for what program could look like over a five-year timeframe. So from the very earliest, demonstrate that you can build and engineer these cells, the osteocytes, the chondrocytes, that can turn into bone and cartilage and even grow implants in the lab themselves. How do you test it in a preclinical model that we’re actually working with the FDA to determine what will that preclinical model be, and then eventually take it into the clinic and do so in a five-year time frame?

That is a massively aggressive schedule, that point in our mission around accelerating. Maybe this would’ve happened in the next 20, 25 years if you let industry move forward and for technology to de-risk itself, but we want to increase that pace. We want the government and Americans to be a customer of those capabilities earlier. And so it’s this incredible convening function. Bringing technologists to the table alongside FDA and other regulators who are going to need to be there at the back end of the program is some of the magic of what we’re able to do.

Importantly, in standing up that program Ross also talked with a lot of experts from the private sector to understand the market landscape, know who the key performers are, these are the people that could potentially do the work longer term, but also what are the gaps that the investor community sees that if we address them, they will be able to pick it up on the other side.

And that’s really important for us because ARPA-H funds projects more of like a transaction. We take the uncertainty out of a project, we take down the risk, and then we have to transition that out of the agency. So knowing what those downstream funders, whether they’re private sector or public sector, need to see de-risk as a really important part of every single program we launch.

Preet Bharara:

So if your agency develops the technology or device, you say you transition it out. That means you transition it out to the private sector on some occasions for them to make a profit on, and if so, how does that work and how do you select?

Renee Wegrzyn:

Yeah. There’s a lot of different ways you can transition and it depends on the maturity of the project or the product. Those may go to the federal government, that might go to the private sector. And the private sector is free to make money on projects. And as I noted, the government would be really excited to be a customer in many of these cases.

What’s important to understand is if you look at DARPA, the big D in front of DARPA stands for defense. The Department of Defense is an advanced developer, is the transition community for all of those breakthrough capabilities for national security. That doesn’t exist for health. Health and Human Services is not that for ARPA-H because we have a state level healthcare system across the United States. There’s just not an advanced manufacturer that’s going to build this. So we have to engage the private sector. And we really want there to be a commercial activity. We want to maintain dominance, honestly, globally in our ability to deliver medtech and biotech as well. So it’s really important that we’re addressing that from very, very early days in our agency.

And it’s important that we’re making it easy to work with us. It’s interesting you said most people look at the government like a bureaucracy. For us, we look at the government and that bureaucracy as a series of puzzles that we can figure out how much of this do we want to adopt and how much do we want to start processes on our own from scratch that are going to be simple, that are going to make us easy to work with so that we can really engage non-traditional partners, smaller businesses, community health centers? That is really a driving factor for what we do. And we are just so lucky that the Congress and the President have given us the authorities that we can really act nimbly and use contracting mechanisms that really make it simple.

Preet Bharara:

Yeah. I’m going to talk about cancer for a moment, the eradication of which President Biden has made a priority. He talks about the Cancer Moonshot. And he has said that it is his goal to cut cancer death rates by at least 50% over the next 25 years, turning death sentences into chronic diseases. Is that something that is within your agency?

Renee Wegrzyn:

Yes, absolutely. I did mention that not a single one of our dollars is predetermined to be aligned to a specific disease or to a specific technology, but as we have ideas that come from program managers and our open broad agency announcement, which is a place where anybody can submit an idea, we look for those best and most promising efforts where ARPA-H investment will really advance the state-of-the-art. And because of the President’s passion for Moonshot and ARPA-H being announced in a lot of that context to create an agency where you can have many, many moonshots, a lot of the initial interests that we got from the public was around cancer.

And so we were just really excited to see opportunities for us to fund efforts such as the new program that we launched, Precision Surgical Interventions, which our first proof of concept were really using for cancer pathologies. This program is imagine if you’re a surgeon and in the operating room you can look into a surgical cavity in a patient and you have brand new imaging capabilities that allow you to see the margins of a tumor and be able to in real time know when you’ve cut all of that tumor out and the surgery is done and all of that healthy tissue is protected.

It sounds simple and straightforward. We want it to be. But actually, the way it’s done today is a pathologist down the hallway in a microscope gets a slice from the surgeon. And there’s this back and forth like, “Did I get it all?” “Nope. Keep going.” You get a lot of bad outcomes and you have a lot of re-operation required. And so we really want to invest in technology for imaging, for some of the optic sets used, even the robotics that will be associated with that surgery.

That’s just one example, but you can imagine that’s really a platform tool for any surgery. Any surgery that you can do and prevent nerve damage as a side effect is going to be a wonderful kind of secondary outcome of the PSI program.

So this is the lens that we use. Even if we might have a proof of concept for a given indication and it will absolutely advance Cancer Moonshot goals, we’re looking for opportunities where ARPA-H can de-risk technologies and capabilities so that when it goes to the private sector, it’s malleable and can be used and shaped into many different commercial opportunities that we can all benefit from.

Preet Bharara:

That goal that I described Joe Biden embracing, cutting cancer death rates by 50% over the next 25 years, is that doable? Are those kinds of quantitative aspirational metrics a good idea?

Renee Wegrzyn:

I live for metrics like that, right? You want to set these pie in sky. Maybe if it’s not a moonshot, maybe it’s a Mars shot. What is that really, really ambitious goal that you have to go towards?

The truth is, when you take big bets like this, not every bet you make is going to be successful. And so you have to fail fast, know where those failures are. And that’s why we have this really active program management where the program manager have a seat at the table. And honestly, for projects not working, then they reserve the right to pivot and use those funds elsewhere. And that is something that we would do at ARPA-H.

The other is also just in the example that I gave you. Let’s say… I hope this isn’t the case… but if in the PSI program, for whatever reason the intraoperative imaging for tumors is not successful, you still might be able to have advances in the state-of-the-art for protecting healthy tissue, just as one example.

So whatever the successes are, we will be transitioning those out of the agency. But by going after those moonshots, if you hit that goal, it’s amazing. But even if you don’t, you’re often bringing the field forward five, 10 years from where it was before. And that’s really why we designed programs in the way that we do.

I think this just goes back to your earlier question: Why can’t the private sector do that? Why can’t government do it? Well, nobody else is making those moonshot bets. So we really are this unique place where you can take these very, very ambitious, very technically risky shots on goal.

Preet Bharara:

You said something very interesting a moment ago. You said you have to learn how to fail fast and pivot. Why is that important? And is that something that every company in every government agency should adopt the principle of failing fast?

Renee Wegrzyn:

I’ll take that in two parts; what is it, and then should everybody do it.

What is it is when a program manager launches a program, if we just take the side program again as an example, what the program manager is going to do… her name is Ileana Hancu… as she goes through her proposal she’s going to select several efforts. We like to think of it as friendly coopetition. They’re not exactly working together, but they are learning from each other. She may fund five or six teams at the beginning of the program, but by the time we get to the end of that program, probably only one or two teams are left. And that’s because she’s very actively managed the program. Sometimes she’s re-teamed. But you continue to invest in and advance the capabilities that look to be most promising.

And so that fail fast is each of those teams is going to have a very different solution they bring to the table. Also, very ambitious. But what are the milestones and metrics to know that you’re making progress at a pace that’s going to match an ARPA project? And so that’s some of that active program management.

And then knowing what are your failures? Are you trying to defy a lot of physics? Well, okay, you’re not going to overcome that, but maybe your challenge is, you know what? We don’t have the right technical expertise to look at this problem. That’s where ARPA-H can help. We can tap our networks. We can try to bring that expertise in to our performer teams and help them advance the state-of-the-art.

And so, working with us, we really do want to bring other stakeholders and experts to the table, including the whole community at NIH that’s able to support us. And so those are the different ways that will help those teams fail fast.

Our projects tend to be really well-resourced so that we are limiting execution risk. What I mean by that is that we have all the right equipment, we have all the right team members present so that you can really just focus on what part of that is really technically hard.

And then you ask if everybody in government should fund work like this? I really hope not. We need a place for foundational research, for workforce development. These are all really critical pieces of what the federal government does in this ecosystem, but they’re inherently not what ARPA-H does. So we really need to have all of these folks working together with all of our different business models.

I do hope our budget grows over time, though. My team will tell you, I really hold them to a very high bar. We’re moving very fast. We’re not going to miss this opportunity that the President and the country have given us to launch this agency, so we’re going to do it really well and we’re going to do it in a big way. And we want to convince folks to let us take even more moonshots for disease by growing our budget over the next years.

Preet Bharara:

What’s interesting, I had not really heard the term fail fast before, but I’ve often used the term early success. When you start something new or you have a new project, particularly one that needs congressional or bipartisan support, you want to show early success. So I guess that’s part of the principle too.

What is your budget, by the way?

Renee Wegrzyn:

We’ve received two appropriations. Our first appropriation was $1 billion, and then we received an additional 1.5 billion. So we have two and a half billion total now.

Preet Bharara:

You also said a couple of times that no dollars are allocated specifically to a particular disease. Why is that?

Renee Wegrzyn:

Well, two and a half billion dollars sounds like a lot of money, but at the end of the day, we have a $2 trillion healthcare ecosystem enterprise, and that represents a really tiny footprint. And so you really have to protect it to allow ARPA-H to have this full flexibility to look for the projects that are going to be most impactful for us.

If I just compare to the National Institutes of Health, there’s 27 institutes at NIH and each of those, like National Cancer Institute, obviously that’s where the cancer investment is happening. And so there’s a lot of federal dollars already earmarked for specific diseases. I don’t think we need to do that. We need to be able to have that flexibility.

What’s important about that is our program managers are on a term limit. They’re here for three years. They can renew for another three years if we both agree it’s a good idea, but then they have to leave. And that vacates a spot on the team to have a totally new program manager, a new problem in health that they want to solve. So looking at ARPA-H this year and the projects that we fund should look completely different from ARPA-H five years from now because we’ll have new program managers and new ideas. And to really catalyze the entire ecosystem that includes NIH and the private sector, we have to have that flexibility that we can pursue a variety of different diseases and technologies.

Preet Bharara:

Is your agency doing anything to prevent the next pandemic?

Renee Wegrzyn:

Stay tuned.

Preet Bharara:

What?

Renee Wegrzyn:

That is an area that we are pretty excited about. I think there’s a convergence of a lot of interesting capabilities, whether it’s on the AI machine learning side, but also the ability to produce medical countermeasures at scale, but also test them at scale. This is a really interesting time and convergence, and so let’s check in a little bit on what we might be doing in that area.

Preet Bharara:

Dr. Renee Wegrzyn, thanks so much for your work, and thanks so much for your time on the show.

Renee Wegrzyn:

Absolutely. Thank you. Take care.

Preet Bharara:

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Stay Tuned is presented by Cafe and the Vox Media Podcast Network. The executive producer is Tamara Sepper. The technical director is David Tatasciore. The editorial producer is Noa Azulai, and the Cafe team is Matthew Billy, David Kurlander, Jake Kaplan, Nat Weiner, Namita Shah, and Claudia Hernández. Our music is by Andrew Dost.

I’m your host, Preet Bharara. Stay tuned.