Amy Proal | Rethinking chronic disease

‍Allison (0:55):
Hi everyone, welcome to Foresight’s Existential Hope podcast. I’m so delighted to be here with Amy Proal.

Amy, I think we first met online during COVID when we had this standing Zoom room twice a day — one for US time zones, one for Europe — where people could join and discuss what was actually happening as the pandemic was kicking off. We invited people with different lenses to share as it evolved, and that was the first time I really got to know you and your work. You were such an illuminating voice — trying to bring light into the dark during that time.

Later, as Foresight’s work expanded into the biotech space, we found that many of your insights connected deeply with our focus on aging and longevity. So I’m really delighted to have you here on the Existential Hope podcast — where we try to explore ideas that might build more resilient, healthy futures for humanity.

Thank you so much for joining us. Maybe start us off by telling those who might not know your work — what do you do at PolyBio, and how did you come to do it? I understand you had a pretty unique journey.

Amy (2:09):
Sure. So yes, I’m a microbiologist, which means that I’m just a huge nerd when it comes to understanding how different infections — bacterial, viral, or parasitic — can drive different forms of chronic disease. There are many mechanisms by which that can happen.

What I do now is lead a nonprofit research organization I co-founded called the PolyBio Research Foundation. What we do is bring groups together — people at different academic sites or even in different companies — and pull them into collaborative research projects to study and innovate around how infections contribute to a range of chronic disease processes.

As for what got me there: I was a pre-med student doing very well, and then I got an infection — and I did not do well afterward. This was at the end of my college years. I got really sick, and when I went to the student health center — well, it’s a typical story that millions of people share in what we now call infection-associated chronic disease.

I asked why I still had symptoms after the infection, and not only did no one have any answers or diagnostic tests to even know what infection I had — which is pretty sad, and something we’re now trying to fix — but they didn’t even believe me.

Amy (3:41):
It was ridiculous. I was sent to a psychiatrist, who tried to analyze other factors. The system was so clearly broken to me — even early on, when I first felt sick.

To skip the long version, I eventually started doing some experimental treatments: antibiotics, antivirals, and supplements to support immune function — things I basically designed on my own.

Allison (4:09):
How did you go about that? I guess this was before the time of ChatGPT and such — were you just out there on the internet, in forums and subreddits?

Amy (4:15):
Very much that! There were people online who would share thoughts, and they treated common symptoms. But what I really did was go back to the scientific literature.

In the 1950s and 60s, some research groups did incredible work on infections — especially bacteria — and what they’re capable of doing. Picture your classic lab: a scientist in a white coat with a microscope, isolating bacteria in petri dishes, looking at what they could do.

They documented truly fascinating phenomena — for example, a bacterium could lose its cell wall in a way that made it practically invisible to the immune system. It could remain in an animal’s or human’s body in a chronic state, completely different from what it did during an acute infection.

They also showed that normal tests don’t pick this up at all.

Amy (5:25):
That resonated with me, because I realized that normal tests weren’t picking up what I might have either. Those papers — some of which I still revisit — have beautiful microscopy images and solid techniques.

They helped me understand the capacity of many organisms to change their behavior, manipulate our immune systems, and even alter human gene function to persist in our bodies. Reading that literature inspired me to understand how persistent infections might work — and gave me ideas for what I could try myself.

Allison (6:08):
Why do you think this knowledge has stayed so under the surface?

Amy (6:13):
It’s a really good question. One key factor is that even though those earlier researchers were on the right track, the theory of autoimmunity got in the way.

That theory gained momentum in the 1970s because it’s simpler and less messy. Instead of saying, “These chronic diseases might be driven by many infections hiding in tissue — messy, complex, hard to find, variable from person to person,” it says: “What if the immune system just screws up? What if it’s mistakenly attacking the body?”

That’s a much easier story to tell.

If you believe that, then you can develop immunosuppressive treatments — drugs that knock down parts of the immune system. These can make people feel better, at least temporarily, by reducing inflammation or immune activity. But they don’t address the root cause.

When the immune system can’t fire or identify what’s actually there, people might feel palliatively better for a while — but the infection isn’t gone.

Amy (7:52):
So immunosuppressive drugs — like Humira, for example — became a huge business. They’re used for many chronic conditions. They’re also very expensive — around $30,000 per year, sometimes more.

And here’s the sad truth: because these drugs don’t target root causes, patients often need more over time — higher doses or additional drugs.

So you get this market dynamic where there’s no real incentive to stop and say, “Wait, let’s find the infection driving this.” Instead, the system just keeps people on these drugs for life.

In my view, the dominance of the autoimmunity model really blocked the study of persistent infection across chronic disease.

Allison (9:11):
So you started looking for an alternative path — what did you uncover?

Amy (9:18):
In my case, I think there were some tick-borne infections — for example, Babesia, a parasite carried by ticks. Treating that bacterial infection helped me a lot. But as part of that process, I became interested in many other kinds of infections and what they might be doing chronically.

Allison (9:44):
Wow. So it started with one thing, and when you pulled on that thread, you uncovered a much bigger ecosystem of causes. Can you share what you discovered through that research and personal digging?

Amy (10:01):
Yes. As I started realizing that infections might play a role in many people’s conditions, I found the biggest issue in studying or diagnosing them is where they hide.

Let’s say you get an infection that stays in your body — in your tissues or nerves. That’s very hard to study because most of our medical tests look only at blood.

Doctors draw blood, run tests, and hope that whatever’s causing the problem is circulating in that vial. But persistent infections — bacteria, viruses, or parasites — don’t want to hang out in the bloodstream. If they did, they’d be easily recognized by immune cells.

So instead, they hide in tissues — in your nerves, your central nervous system, even your brain or spinal cord.

That’s a huge challenge, because you can’t find them with simple blood tests. To study them properly, you need infrastructure — labs that can analyze what’s happening in tissues.

Amy (11:26):
That’s why we created PolyBio in 2018. We wanted to help research groups build the infrastructure to do this kind of work.

We started setting up tissue-collection studies. There are a few ways to do this: you can get tissue via biopsy procedures, or you can collect samples that would otherwise be discarded during surgeries.

For example, women with endometriosis — which we study as having infectious components — often undergo surgery to remove painful lesions. Usually, surgeons just throw that tissue away.

So I contacted surgeons and said, “Please don’t throw it out. We’ll send you tubes with preservation solution. Just put the tissue in there instead.”

Now we’re working with surgeons who operate on various parts of the body — even some who handle central nervous system surgeries. We’re getting tissue types that have never been analyzed from living humans before.

One study I’m especially excited about involves collecting tissue from the vagus nerve, which connects the body and brain. It’s responsible for some of the most important signaling between them.

These samples come from people who, sadly, experience trauma and pass away in hospitals. As soon as that happens, surgeons can collect and preserve parts of the vagus nerve. We’re now running the first-ever study characterizing the microbes — viruses, bacteria, and others — that might actually be living in that nerve.

Amy (14:50):
So we’ve set up a whole pipeline of different tissue-collection studies that allow us to see what’s really happening. It’s fascinating, because in many cases, we simply don’t know if viruses or bacteria are present in these tissues.

That’s the foundation of what we’re doing at PolyBio. Sometimes we even joke that our slogan is “The issue is in the tissue” — and it’s true. That’s where we focus most of our time.

Allison (16:25):
How many different tissue samples do you have now?

Amy (16:31):
Good question. I think we counted recently — at least twelve or thirteen distinct tissue types, many rarely studied, and that number keeps growing.

Allison (16:40):
Once you got going on this, did you face any institutional resistance? Is it easy to call someone and say, “Hey, don’t throw that tissue in the trash — send it to us”? Why hasn’t that been done before?

Amy (16:58):
That’s a great question. There are definitely hurdles. Part of it is how hard it is to gain permission to get those samples. You have to go through ethics review committees — the IRBs at universities or hospitals — and they need to make sure you’re not doing something unsafe. Of course that’s good. But because we’re often asking to collect a new kind of tissue, the review process can take almost a year. It’s painful.

So you have to be very patient and persistent. You also have to find the right surgeons — people who care about the research. It takes extra time for them to put the tissue in the tube, label it, store it properly. Sometimes we even need to make sure dry ice or special storage is available.

Academia isn’t structured to encourage that kind of innovation. Most researchers work step-by-step to get NIH grants. You specialize early — maybe you study T cells, then T cell receptors, then one subtype of receptor. You get a small grant for that, produce a paper, and then apply for the next grant to go one step further.

If you go too far outside that narrow path, reviewers say no. It’s a very conservative system. So when you call someone and say, “Hey, what about collecting tissue for persistent infection research?” — it just doesn’t fit into their world.

That’s why, to really move, you often need non-government funding.

Allison (19:59):
Right — even just the logistics sound familiar. I had a similar experience recently when I gave birth and wanted to bank the umbilical cord. You have to research private companies, order a kit, bring it to the hospital, remind every new nurse or doctor what to do, make sure it gets picked up — there are so many hand-offs.

I can see how, in surgeries, valuable tissue could just get thrown away. The pipeline isn’t designed for preservation.

Amy (20:56):
Exactly! You just described my daily life — saying, “Wait, what if we collect that?” Then you go through hoops and loops: this person needs that permission, that person needs another person’s permission, and it takes forever.

In some cases, we’ve had to build the infrastructure almost from scratch — systems that make sense and are agile. That’s part of what we do.

Allison (21:51):
So once you have these tissue banks, what happens? Suppose you uncover a cause that’s different from the one medicine traditionally assumes — what does that mean for patients?

Amy (22:03):
Right now, our main goal is to get the data out — publish the scientific papers. We’re not yet giving patients direct access to their data. But that’s the next step.

We’re starting to pivot toward taking discoveries — say, finding a virus in Alzheimer’s brain tissue — and asking: how do we translate that into actual diagnostic tests or clinical tools?

Let’s say we know an infection is in someone’s tissue. What can we do with more accessible fluids like blood or saliva to detect it? We’re now scouting for teams that have innovative diagnostic platforms — things that can pick up tiny traces of viral material.

Some groups use microfluidics to isolate extracellular vesicles in blood that might contain one or two pieces of a virus hiding deep in tissue. If you have the right tech, you can extract that signal.

But these technologies are scattered across different labs, so we work to unite them — designing studies, for example in long COVID, where we collect both tissue and blood, then compare which diagnostic tests best reflect the infection in tissue.

That’s the process of validating new diagnostics.

Allison (25:42):
Can you talk more about long COVID — and maybe also how this connects to aging? Once you start looking at infections, everything seems interlinked.

Amy (25:53):
Yes. Before long COVID, we focused a lot on infection and Alzheimer’s disease, which shaped how we think.

One of the lowest-hanging fruits in medicine right now is understanding how infections drive Alzheimer’s. There’s data showing that different viruses — especially herpes viruses — can be found in Alzheimer’s brains.

My mentor, Rob Moir at Harvard, made a discovery that I think is one of the most important in neuroscience. Around 2018 he published in Neuron, showing that the amyloid plaque in the Alzheimer’s brain acts as an antimicrobial peptide — part of the innate immune system that responds to infection.

In their experiments — both in brain organoids and in mice — they dropped herpes viruses, like human herpes virus 6, into the models and saw amyloid plaque form around the virus, as if to trap it.

That means the plaque is forming in response to infection.

It’s a complete paradigm shift. It places infection at the heart of the Alzheimer’s process.

Amy (28:22):
For decades, Alzheimer’s research has assumed the plaque itself is bad — remove it, and you fix the disease. Billions have been spent on that idea, but if you look at the data, Alzheimer’s cases are still rising.

When you test amyloid-clearing drugs, they fail again and again. The few that got approved offer only minimal improvement.

But if you instead ask, “What if the plaque forms for a reason? What if infections seed it?” — then removing plaque without addressing infection won’t help.

That’s the paradigm shift.

Allison (31:25):
Could you, then, prevent the plaque from forming simply by preventing infections in the first place?

Amy (31:31):
Exactly — though it’s tricky. You can’t avoid every infection, but we could intervene earlier.

For instance, a recent study by Ben Readhead’s group at Arizona State showed that cytomegalovirus — another herpes virus that persists for life once you have it — seems to start in the gut, then travel up the vagus nerve into the brain, where it seeds plaque.

So if we could either prevent infection or treat it before it reaches the brain, we could stop the disease process altogether.

And honestly, we underestimate the simple tools we already have. People hear “infection prevention” and think only of vaccines — but there’s more.

Amy (33:08):
Take respiratory viruses — COVID, flu, RSV, enteroviruses. We inhale them. Simply cleaning indoor air could massively reduce transmission.

HEPA filtration today is incredibly effective. Add far-UVC light, which safely kills viruses in the air, and you can dramatically lower infection rates.

We filter our water but not our air. It makes no sense.

If we layered these technologies — strong HEPA plus UVC — we could cut infection risk drastically.

It’s madness we don’t do it already.

Allison (34:00):
I noticed that at the conference where we last saw each other — the DIA conference in the Bay Area — they had filters everywhere.

Amy (34:06):
Exactly. For gatherings, especially large ones, it’s becoming more common to use filtration. We do that for many of our Foresight events too. If you’re putting a lot of people in one space, it seems irresponsible not to at least think about air quality.

And it’s really not that expensive. That’s what frustrates me most.

Allison (34:24):
Right — and both UVC and air filtration came up in several of the subcultures we move in after COVID, and even in some government circles. But has much actually happened on a national scale? Who are the useful players in this space, especially thinking ahead to the next pandemic?

Amy (34:41):
That’s a great question. Right now, unfortunately, the public isn’t even demanding clean indoor air, and that’s where it has to start.

There are even unfair situations — I’m pretty sure the White House and government buildings do have great UVC systems now, cleaning their air with taxpayer money. But the average school doesn’t have anything.

It’s just not equitable.

I know people in the Department of Defense who told me that since it’s so hard to modify their workspaces, they’ve resorted to surrounding themselves with plants — which might help a little! But it’s not enough.

Some wealthy people have installed air-cleaning systems in their homes, but for most people, it’s out of reach.

We need coordinated government and public action. There was a recent meeting at the UN where several countries pledged to improve indoor air, which is encouraging. But to make real progress, we need bottom-up demand too — the average person has to want it.

Amy (36:05):
The challenge is that the pandemic burned everyone out. COVID mandates, heavy vaccine focus, polarization — people were exhausted. Now, when you bring up viruses again, even if it’s about something practical like clean air that requires no behavior change, people just don’t want to hear it.

We need to acknowledge that COVID wasn’t handled perfectly. Many things about that period weren’t ideal. But that shouldn’t make us give up on controlling viruses altogether.

The COVID response can have been messy and it can still be true that we need to manage airborne viruses better. Those two things can coexist.

We still have to care about viruses — getting them out of the air, understanding their role in diseases like Alzheimer’s, and controlling them in our bodies.

Allison (40:28):
That’s really useful context. But if we zoom out — from an existential-hope perspective — your information can sound scary at first. It might make people reluctant to be in public spaces. How can we frame it more hopefully?

If we focused more on root causes — infections, prevention, real cures — what kind of future could that create?

Amy (41:26):
Exactly. People do often tell me I scare them by talking about infections in chronic disease and aging. But what’s far scarier is what’s happening now: an epidemic of chronic illness.

The incidence of most chronic conditions is climbing, kids are getting sicker at younger ages, and people are relying on multiple prescriptions just to get through life.

That’s what really frightens me. We are not on the right track.

The models we’re using — the assumptions about what causes disease, and the band-aid treatments — just aren’t working.

So it’s actually hopeful to look at infections as root causes, because then at least we have a new problem we can solve.

And the truth is, we haven’t even begun to use the straightforward tools we already have to tackle infection in chronic disease.

For example, there was a Taiwanese national study that looked at people who’d been prescribed anti-herpes antivirals like Valtrex for cold sores. They found that those people had a ten-times lower risk of developing Alzheimer’s than those who hadn’t taken the drugs.

That’s incredible — and it makes perfect sense if herpes viruses can seed Alzheimer’s pathology.

Allison (44:11):
That’s extraordinary — and it’s a generic, inexpensive drug.

Amy (44:16):
Exactly. If we took this seriously at a global level, the world would look totally different.

First, there are existing drugs like those antivirals that hardly anyone uses preventively. You could rotate in an antiviral like that as part of a health-span protocol and probably lower Alzheimer’s risk significantly.

Second, new therapies are emerging that support the immune system instead of suppressing it.

For example, ImmunityBio’s BioShield activates T cells and natural-killer cells — key parts of the immune system that fight infection. There are several other companies exploring similar approaches.

We could be developing immunotherapies that strengthen our defenses instead of shutting them down.

Right now, many people — even young ones — start life on immunosuppressive or purely palliative medications. That’s crazy. Imagine if, instead, we proactively supported immune health — giving people periodic immune-boosting treatments to keep T cells and NK cells active.

That alone could prevent countless infections and their downstream effects.

We need to stop thinking of the immune system as our enemy. Most of the time, it’s our greatest ally. We should help it help us, not silence it. That simple shift in mindset would go a very long way.

Allison (46:43):
I love that. And of course, diagnostics are part of getting there — we have to be able to see what’s going on before we can treat it. That’s a lot of what you’re doing at PolyBio.

But if this were scaled up across society — if we could actually create that mindset shift and infrastructure — what would need to happen?

Amy (47:09):
At this point, we really need government to get behind it. Private funders can do a lot — and they’re crucial for breaking new ground — but public funding is still the backbone of science.

Right now, it’s extremely hard to get a grant to study the role of persistent infection in chronic disease. It’s even harder to get funding to test proactive immunotherapies.

Take Alzheimer’s research. The NIH grant panels in that field developed what’s been described as a small “cabal” — a group of reviewers who would routinely reject any proposal that positioned infection at the heart of Alzheimer’s.

Why? Because it threatened existing pharmaceutical pipelines and entrenched research programs.

We have to stop that. We can’t let a handful of people block new thinking on infectious causes.

This is an urgent situation — there are massive numbers of infections out there, we’ve just gone through a global pandemic, and if we want to solve these problems, we have to fund people who can actually look at infections for what they are.

So the first step is opening this area up — making infection research a priority and not something impossible to fund.

Allison (49:21):
Do you see any signs of hope that it’s changing?

Amy (49:27):
Yes, I do. More people now recognize that what we’re doing for chronic disease isn’t working. There’s more acknowledgment that we need new solutions.

I’m also encouraged by the technological progress — the new diagnostic tools for identifying pathogens that are finally being developed. If we can integrate those into mainstream research, we’ll have the foundation we need to move forward.

So yes — I’m hopeful. The first step is always admitting that what we’re doing doesn’t work. From there, we can build something better.

Allison (50:44):
Acknowledging what’s not working is at least a step toward the positive direction. We have one more minute — is there anything you wish I’d asked?

Amy (50:55):
No, I think that’s a great start.

Allison (51:01):
How can people learn more about your work?

Amy (51:04):
Just go to polybio.org — you can find all our projects there, and I occasionally post podcasts or talks as well.

Allison (51:10):
Thank you so much, Amy. Your message may be hard to hear at first, but it opens up a much richer way of addressing root causes — not just of chronic diseases, but even of aging itself.

You’ve left us with real hope that with the right approach, we can build healthier systems for humanity’s long-term future.

Amy (51:36):
Thank you so much.