What if medicine could move beyond one-virus-at-a-time defence and build something closer to broad, durable resilience?
In this episode of Ben Yeoh Chats, Ben speaks with Brian Wang, Programme Director at ARIA, about one of the most ambitious ideas in biotechnology: using the innate immune system to create a new class of preventive medicines that could protect against multiple respiratory viruses at once. At the centre of the conversation is ARIA’s Sustained Viral Resilience programme, which aims to develop “sustained innate immuno-prophylactics” or SIPs: potential medicines that could provide months of protection against a wide range of respiratory infections from a single dose.
“Your immune system is just an amazing kind of laboratory in and of itself.”
Brian explains why this matters. Modern immunology and vaccine development have focused much more heavily on the adaptive immune system, which gives highly targeted protection through antibodies and T-cells. By contrast, the innate immune system is broader, faster and potentially better suited to defending against many different viruses, but it has historically been harder to understand and harder to engineer safely. That may now be changing. Brian argues that the last 25 years have brought a quiet revolution in innate immunology, creating the scientific basis for a much more serious attempt to harness it.
“The innate immune system is the part of your immune system that’s responsible for broad-spectrum protection.”
Ben and Brian discuss why respiratory viruses are the right place to start. They are scientifically difficult, commercially relevant, and close enough to current understanding to make progress plausible. If this approach works, the implications would go well beyond seasonal colds and flu. It could fill one of the biggest gaps in pandemic preparedness: the ability to protect people early, before a bespoke vaccine or other pathogen-specific countermeasure is ready.
The conversation then widens into a broader discussion of how frontier science gets built. Brian talks about why ARIA can sometimes do what universities, startups and large pharmaceutical companies cannot: back a whole research ecosystem around a problem that is too early, too interdisciplinary and too uncertain for more conventional institutions. Rather than betting on one narrow technical path, ARIA can support multiple modalities, teams and ideas in parallel.
They also explore the promise and limits of AI in biology. Brian is optimistic, but not starry-eyed. AI can already help with design problems where there are fast experimental feedback loops, but biology remains constrained by the difficulty of generating human-relevant data, especially around safety and complex disease. That leads into a thoughtful exchange on tissue models, organs-on-chips, clinical bottlenecks and why real progress in medicine still depends on evidence, not just computation.
“We need a lot more people working on this. We need people motivated to work on this. And we need people searching in all different directions.”
In the second half, Ben and Brian step back to discuss pandemic preparedness, existential risk, medical regulation, the UK science base, and whether Britain is better positioned for frontier science than its culture of complaint often admits. Brian makes the case that preparedness remains underrated, that the UK has deep scientific talent, and that difficult but important problems often sit exactly where conventional institutions hesitate to go.
The episode closes on career advice. Brian reflects on moving from chemistry to synthetic biology, startups, pandemic work and ARIA, and argues that the best decisions in his own path came less from rigid planning than from following problems that felt genuinely important and interesting. It is a fitting ending to a conversation about working at the frontier: serious, ambitious, uncertain and deeply practical.
In this episode
Why the immune system is more complex, dynamic and underappreciated than most people realise
The difference between adaptive and innate immunity
Why innate immunity may be one of the most important underexplored frontiers in medicine
ARIA’s Sustained Viral Resilience programme and the idea behind SIPs
Why respiratory viruses are the right first target
How to think about scientific moonshots that are hard but not impossible
Why innovation often needs ecosystems, not just isolated labs or startups
The promise and limits of AI for biology
Pandemic preparedness, regulation and the UK science ecosystem
Brian Wang’s career path and advice for scientists, builders and innovators
Why this episode matters
This is a conversation about more than one programme at ARIA. It is about how science advances when a field becomes just tractable enough to move from theory to engineering. Brian’s core argument is that innate immunity may now be at that point: no longer just an interesting area of biology, but a credible target for building new medicines with broad protective effects. If that is right, the prize is large. Better defence against respiratory viruses would matter in ordinary winters, in hospitals and care homes, and in the early days of the next pandemic.
It is also a conversation about institutions. ARIA’s role, as Brian describes it, is not simply to fund individual grants but to create the conditions in which an entire field can move faster. For listeners interested in science policy, innovation, or how real breakthroughs happen, that makes this episode especially rich.
Key takeaways
Innate immunity may be one of the biggest open opportunities in medicine.
Adaptive immunity has been easier to understand and exploit, but innate immunity may be better suited to broad-spectrum protection if it can be engineered safely.
ARIA is trying to back a genuinely new category of preventive medicine.
The ambition is to build medicines that protect against multiple respiratory viruses at once for months at a time, rather than targeting one strain or one pathogen.
Respiratory viruses are the starting point, not the end point.
Brian frames them as the best-understood entry point inside a much bigger opportunity space: learning how to sculpt innate immunity across many diseases.
The right way to fund frontier science is often to back a portfolio, not a single answer.
Small teams can go deep, but ARIA’s advantage is the ability to support many approaches, modalities and institutions in parallel.
AI will help biology most where it can learn from real-world feedback.
Design tools are improving quickly, but medicine still depends on better models, better data and eventually clinical evidence.
Pandemic preparedness remains badly underrated.
Brian argues that institutional memory has faded quickly since COVID and that prevention is systematically undervalued because it is hard to price disasters that never occur.
The UK is stronger in frontier science than it often thinks.
Britain already has the talent. The harder question is how to activate it, connect it and build around it.
Good careers are often built by following important problems.
Brian’s closing advice: work on projects you find important and interesting, and let the next step emerge from that.
Summary contents, transcript and podcast links below. Listen on Apple, Spotify or wherever you listen to pods. Video above or on Youtube. Youtube.
Contents
00:00 Meet Brian Wang
00:40 What We Underappreciate About the Immune System
02:04 Could One Medicine Protect Against Many Viruses?
03:55 Innate Versus Adaptive Immunity
06:18 Why Innate Immunity Was Overlooked
10:44 How Solved Is Adaptive Immunity?
16:36 The Breakthrough Timeline in Innate Immunology
21:09 Why Start With Respiratory Viruses?
25:47 How ARIA Funds Frontier Science
29:27 Promising SIP Modalities
33:15 DNA Delivery Challenges
33:49 Non-Viral DNA Delivery
34:13 AI for Biology
35:55 Clinical Data Bottlenecks
37:21 The Safety Limits of AI
38:15 Brian’s Journey to ARIA
39:16 Pandemic Preparedness After COVID
42:38 Moonshots, Breakthroughs and Tractability
44:03 Overrated / Underrated
44:12 Pandemic Preparedness
45:54 Existential Risk
47:27 The UK as a Place for Frontier Science
48:43 London, Oxford, Cambridge and Cluster Effects 50:15 Medical Regulation
53:31 GLP-1s and Wider Biomedical Discovery
56:47 Upcoming ARIA Calls
58:30 Other ARIA Programmes
01:00:03 Choosing Between ARIA Opportunities
01:02:10 Advice for Builders
01:03:54 Closing Thoughts
Transcript (this has been transcribed by LLM AI and lightly edited, mistakes are possible)
Ben: Hey everyone. I'm super excited to be speaking to Brian Wong. Brian is a program director at Aria's Advanced Research and Invention Agency. It's the UK's mission-driven R&D funding agency. Brian is looking into innate immunity, exploring how we might better harness the body's own defense. He has worked on pandemic preparedness during COVID.
He's led R&D at a biotech, and he's co-founded a nonprofit startup working on AI driven biology and biosecurity. Brian, welcome.
Brian: Thanks, Ben. Really glad to be on.
Ben: What do you think is most misunderstood by the average person when thinking about the immune system?
Brian: Most un misunderstood. I don't know if this is.
The most misunderstood, but I would say it's something that's probably underappreciated by the average person about the immune system, which is just exactly how much is going on when you become infected or when your immune system becomes activated. And just yeah, how much is going on under the hood.
Your immune system is just an amazing kind of laboratory in and of itself. And I think of it as somewhat of an entire RD team that's just working nonstop developing antibodies against different pathogens, and different things that are going on inside your body. And yeah I think it's just an amazing kind of creation of evolution.
And yeah I think, it doesn't necessarily take all that much time studying immunology to start to get an appreciation of that. It really is just an amazing system that I, I think of it as, as, a natural selection happening in real time inside your body is to be able to select these really potent antibodies, T-cells and other kinds of immune components for whatever's needed against disease.
Ben: So you're working in this immune system space, the problem you're trying to solve. What do you think about your problem that current vaccines or antivirals or public health tools do not solve well? Why is your problem a particularly tricky and good one to work on?
Brian: Yeah. So maybe it makes sense to explain the problem that we're trying to work on here.
Aria, we have these different programs, these R&D programs that typically are around 50 million pounds, and then fund researchers and entrepreneurs to, to tackle a particular, grand challenge essentially. And the challenge that we've put out in this program, which is called Sustained Viral Resilience, is the program that I and my team lead.
It is essentially to create these new medicines called sustained innate immuno prophylactics, which you can think of as like universal vaccines. They are meant to prevent disease against many different respiratory viruses simultaneously with a single dose for at least three months or longer, which is the target that we've set out for them.
And, this would be great for providing seasonal protection against different viruses that circulate particularly over the winter season. So you think, you can think of all the different coronaviruses, the flu viruses like RSV viruses, like those that cause the common cold that it'd be great to be able to take a single shot or a single kind of intranasal dose or any kind of other route over to be able to protect you over an entire winter season.
So that this is really a. Big challenge scientifically and technically because of the enormous diversity that is represented across different viruses. A coronavirus is very different from a virus that normally causes the common cold or versus the flu or all these other viruses, the viruses that cause these respiratory infections are very different from one another.
And it's always been a real challenge for vaccines in particular to come up with a vaccine that can tackle all these different viruses simultaneously. People have been working on just a universal flu vaccine for quite some time. There's been a lot of money poured into that.
We've made some progress, but of course we don't have a universal flu vaccine yet. And so to be able to have a medicine that provides protection against more than just the flu but also these other viruses that are, that, that are much, much different than the flu is just really challenging.
So the way in which we're attempting to do this is by strengthening a part of the immune system called the innate immune system. Your immune system and it's to your question earlier, what's misunderstood about the immune system. One other thing that's underappreciated is the fact that the immune system actually contains two halves to it.
One half of it's called the adaptive immune system. And the adaptive immune system is what gets a lot of the attention from researchers, from scientists, from vaccine developers. In that it consists of antibodies and T-cells, which are really targeted kind of molecular weapons as I think of them that latch onto different pieces of a pathogen.
And then either neutralize them to prevent those pieces of the pathogen from targeting cells or detect the piece, those pieces of the pathogens on a cell surface to target that infected cell or destruction. And the adaptive immune system is essentially the part of the immune system where those vaccines end up stimulating.
The innate immune system is what we're focusing on with the program. And the innate immune system is the part of your immune system that's responsible for broad spectrum protection. So not targeted pieces of a pathogen but instead conserve pieces of pathogens that are, for example, similar across many different kinds of viruses.
And by taking advantage of the body's nature. Ability to detect those conserved pieces of pathogens if we can, if we can enhance those, if we can strengthen those, if we can boost those, then that's one particular path towards creating these new kinds of medicines that we're hoping to develop here.
So yeah we think there's many different ways to, to protect people against respiratory viruses, lots of people working on flu vaccines, other kinds of vaccines. But we're trying to take a different approach by focusing on a different part of the immune system that we think is well suited for providing more broad spectrum universal protection.
Ben: It seems to me you are trying to back what feels like a whole new category of preventative medicine, this sustained viral resilience. Why do you think so many people have missed it? And do you think there's something around this innate immunity where we don't seem to have concentrated so much? Is that 'cause it's trickier science or, vaccines have an aim at this first because they've gone for a more narrow type of viruses and things first.
So when you think about sustained viral resilience and also this way of tapping into innate immunity, what do you think you're really getting at and why do people miss this?
Brian: Yeah, I think there have been some people over the years saying, oh, we should be able to strengthen the innate immune system.
That we have the ability to boost the innate immune system, and there have been scientific efforts to do that. I think this has always been really challenging just because of a few reasons. I suppose one reason is that just the basic science of the adaptive immune system was worked out earlier than that of the innate immune system.
I think of this kind of critical moment in immunology or critical, yeah, a point in time in immunology in the early 20th century when you had Nobel prizes awarded, two different individuals. One, one for a foundational kind of discovery in adaptive immunology and one in, in innate immunology.
And at that point in time, these two sciences were on, because of those two noble prizes, you could say there was an even playing field. But then over the course of the 20th century, you had a lot more attention focused on the adaptive immune system. And I think, there's one potential reason for that, which is that the adaptive immune system is just really interesting.
It's definitely what pulled me into immunology in the first place. It's the part of your immune system which is evolving, changing, learning essentially when you are infected with a pathogen, learns, adapts and creates a very targeted kind of tool.
And I know those antibodies and T cells I was talking about earlier against those. And it's just really interesting to study those dynamics and that's what captured the attention of a lot of immunologists in the 20th century. And it was, I would say, only until the turn of the 21st century, so around the year 2000.
That the innate immune system started to, we started to uncover the mysteries of the innate immune system a little bit more. And since then, I think over the past, I would say 25 years, there's been a revolution in innate immunology. So I think one of the reasons why we haven't taken as much advantage of engineering or boosting the innate immune system previously is because we didn't really have the basic science as worked out.
And then the second point, which you hinted at, which is that the innate immune system is just harder to engineer, it's a little bit trickier to engineer than I, I would say the adaptive immune system is. And I mentioned before that the adaptive immune system generates these really targeted antibodies and T cells.
The fact that they're targeted means that there's less possibility of side effects. There's less possibility that they'll then target your own tissues and cause autoimmune problems, although, of course that does happen on occasion. But with the innate immune system, it's fundamentally a broad spectrum.
It's meant to be relatively effective against pathogens, specifically at least the parts of the innate immune system that we're trying to boost in the program. But the fact that it is non-specific by nature, makes it more difficult to harness that part of the immune system in a way that results in, yeah, broad spectrum protection against different pathogens, but also doesn't cause safety side effects as well.
So I think it's a hard scientific challenge to be able to harness the innate immune system, boost the innate immune system in the same way that we found to be able to do with the adaptive immune system. I think this is where I start to get excited about different fields that have come along.
Synthetic biology, materials, chemistry, ai all these different fields coming together to be able to enable us to, to engineer the innate immune system better.
Ben: That's great. I'll, we'll come on to syn bio and AI downstream of that. I'm really interested in your observation that Adaptive Immunology was ahead and then innate maybe around 20, 25 years ago.
We started to get better at it. I'd be interested in your view as to, if we think about Adaptive First, would you say we are. 50% solved or 60% solved. Where are we? I guess it's a little bit hard, but I could say for instance, on Alzheimer's and neuro, I think most people would agree we're only 10 or 20% solved.
Or maybe 30% for something like blood pressure or the engineering part of biology, we understand blood pressure or diabetes maybe 90% now within that. Yeah. So I'd be interested in where you would put adaptive and then where you would put innate, so the differing and then when we came to 20, 25 years ago, was it in your mind a series of mini breakthroughs, which all together, or were there any one or two key observations or papers, which have now all come about and now we've added all of these other things around?
So I'm just interested in where you think we are in the field and maybe because of where those percentages are now is the time because we've just hit a certain amount of knowledge, but I'm not sure I'd be interested in your take.
Brian: Yeah. To the first question about the adaptive immune system, how solved it is.
It depends on where you said the bar for what solved means. When I think about engineering a biological system or engineering, let's say, here the adaptive immune system the kind of ideal situation that you want to end up at in as an engineer is, you have this really complex system, but you have all the dials that you need to be able to tune it to whatever you want it to be.
So if you think of your, the state of your adaptive immune system is, as what is the state of all the B cells in my body, all the T cells in my body, all the antibodies in my bloodstream. And how can we modulate that? I would say we're very far away from being solved.
I think we have. We certainly have tools in our toolkit, very sophisticated tools. There, there's a lot of work on new kinds of vaccines. Now, for example, lots of work on engineered antibodies. Lots of work on engineered T cells like CAR T therapy. Some people might have heard of it.
Lots of sophisticated tools, but I think for those tools to get to the level where we can, fully say, we have relatively full control over, over the state of our adaptive immune system at any given point in time. I think we're pretty far away from that. I'd say maybe one one marker of when we might be at a point where we can start to say.
Yeah, we're maybe past the 50% point is when, for example we've just cured all autoimmune disease because autoimmune disease essentially is a dysfunction of it contains both innate and adaptive components, but it's really your adaptive immune system that's attack, attacking your own tissues in those diseases.
And if we can get to a point where we can say, okay, we have cures for that, that's just no longer an issue. We've been able to reset the adaptive immune system to one that's not attacking our own tissues, then that becomes something that's okay. We're on a good path there.
Ben: In terms of the tools we have, we're below 50%, but it occurred to me that there's two parts to this.
So one was. Understanding the system. I'm gonna make a really bad analogy, but it's a little bit like, oh, we can understand the map of the tube or the subway, but we don't really know how to change the train lines around. Or if we change this one train line… We can go around the circle line rather than the district line or the green or the yellow, but our understanding of the train lines has gotten better.
I can definitely see we've got targets. Some of them seem to be druggable, not druggable, and we've not got that in terms of the tools, but I'm interested as to the actual understanding of the subway and how it might work, whether that passed the threshold, even though we don't really know how to attack or change that system, subway, that understanding.
And I, I say it that way because I think even our understanding of the neurosystem of the brain system is behind our understanding of the immune system, let alone how to then, yeah. Potentially adapt the brain where we're even further behind. We don't really know how half our neuro drugs work, even when we can see that they do work.
And so that it occurred to me, actually, there were two parts to that. I dunno if you would reflect if the, if we are different for that, and then we can go on to where we are on the innate, whether we're further behind.
Brian: Yeah. I think these two things are connected in the sense that I think the best measure of how well we understand it is if we can engineer it.
I do think that I think that's famous, I think that might be a fine man quote saying something like that. But yeah, if we were to focus just on okay, how much we know about the adaptive immune system I do think we have a, we, we have a pretty good understanding of.
At least the parts list, the parts that are involved in the adaptive immune system. Again it's antibodies, B cells, T cells, these are the main players. We have a pretty good understanding of the structures of those. And yeah I would say we're at a pretty solid level there, but I think, where all the action is really in the dynamics and interplay between all the different components there.
And also, the interplay between the innate and the adaptive immune systems as well. These aren't really two separate systems. And, the dynamics it's just a really complicated system and I think you can really only understand the dynamics by perturbing the system in some way and then seeing what happens.
And that's where I think. The engineering kind of feeds back onto the science where, okay, we can try these different, for example, vaccine designs that will train the adaptive immune system and oh, if we try this certain vaccine design, that sends the adaptive immune assessment into this direction versus this other one.
Yeah. And I think that is something that we're still learning how to do. I think we're still learning how to do it. I think we were able to actually get a lot of clinical benefit from something like vaccines with relatively simple mechanisms or simple tools. Just taking pieces of a pathogen and creating vaccines out of those or just live whole pathogens.
Live attenuated pathogens. And it's just now that we're beginning to train the adaptive immune system in, in more directed manners by. Not just taking, for example, the whole parts of a pathogen or even just a whole protein of a pathogen, but actually engineering that protein in different ways to say, oh, we actually want the adaptive immune system to target this particular piece of this particular protein.
And direct it in more of a manner that we'd like. So I think, yeah, I think we're still in early days in terms of being able to tune those dynamics.
Ben: Sure. I think that seems very fair. And how far behind do you think our understanding of the innate system is then behind adaptive taking completely your account that they interact and if you're talking about, understanding in terms of ability to engineer?
We are very far behind on the ability to engineer, so that obviously puts it behind. But I'm interested if there have been enough breakthroughs in the understanding to make it ripe? So I guess, 'cause the follow on question is that this might seem a lower probability, but it is a moonshot in the sense that it's like a less than not point, 1% chance that something's happened.
We seem to have enough knowledge that actually, yeah, there's a lot we don't know, but it occurs to me that this is a tiny moonshot idea. That it's actually a reasonable probability idea, even though you might say it, it's low, but it's also increasing. However, whatever you think it is, this year is higher than last year.
And I'm thinking that next year is even higher. Yeah. Anything which caused you to think, okay, the breakthrough and how far are we behind are innate?
Brian: Yeah. I do think that we still understand less about the innate immune system than the adaptive immune system. So I don't think we're at a place where it's back to parody like it was in the early 20th century.
I think earlier in your question you asked, were there specific turning points and specific papers or big breakthroughs or a large series of small breakthroughs? I would say that I mentioned around the year 2000 as a turning point.
That was really preceded by, I would say, where people would normally point to as this prediction of at least a turning point. That came in 1989 where this big immunologist Charles Janeway Jr. Wrote this kind of piece. I think it was maybe a kind of presentation at a conference that essentially said, we have a lot of great vaccines that work, but actually we don't know very much about how they work or how well or all, at least all the different reasons why they work.
And this is at a point where we had a better understanding of the adaptive immune system, but again not very much on the innate side. And it turns out, for all these vaccines, we have extra components called adjuvant. That, that we add to them and adjuvants stimulate and that, we know now that they stimulate the innate immune system.
At the time, it was something that we just didn't really know why we had to add these adjuvants. We just said, oh, we should just be able to take a piece of a pathogen and just train the adaptive immune system and that should work by itself. But then we have to add this extra mysterious component.
And so basically Charlie Janeway predicted that this must mean the adjuvants must be stimulating extra pieces, essentially of the innate immune system that we now call pattern recognition receptors. And we didn't have any catalog of those. At the time we didn't know what those were.
And then around the year 2000, we started discovering them essentially. And now we have a whole catalog of many of these different pattern recognition receptors now. So I would say it to put this in context, if we started getting, kind of complete list of the adaptive immune system in the late 20th century or yeah, late 20th century. The parts list of the innate immune system was still being put together, somewhat from the ground up in the year 2000 and has been slowly being put together ever since.
And I would also say that the parts list is much larger and much more extensive in the innate immune system. There's a lot more players involved. And this means that the dynamics are also quite I would say more, more extensive. So I think that you, that essentially.
We are, I think we are further behind. And I think part of the reason is because there's just a lot more to know, there's a lot more to understand. But to your point about I think part of your question was, is the program essentially so much of a moonshot that it's 0.01% likely to succeed?
Or is it 10% likely to succeed or something like that? Obviously hard to know exactly what the likelihood of success is, but I would say that we specifically chose a part of the innate immune system that we understand the best, which is, I think it's its role in antiviral protection and said, okay, we can start there in terms of engineering the innate immune system.
We can start to see if we can engineer the innate immune system to provide protection against different respiratory viruses. Then we can start, building on that too, to tackle other more complicated diseases afterwards. That, that's part of the reason that, that gives me hope.
And I think we're starting to see some. Examples or some glimmers of experiments that are providing broad spectrum protection by strengthening the innate immune system. Yeah I think it's, I think it's something that, that we already see some reasons to, to think this is possible and we just need to build on those.
Ben: That took a whole cluster of thoughts and questions from me. So one cluster is I'm interested on in the, your decision making process, and I think you alluded to this in terms of how much we know, but why respiratory type viruses first and why not something like cancer where there are some immune oncology, which is more on the adaptive side, but we have got cancer vaccines as well and some thoughts about stimulatory there or even other autoimmune things.
'cause we have a product called IVIG immunoglobulins which do this a little bit of immune system boosting, although it seems to be partly adapted, partly innate, and that's a whole cluster which looks at autoimmune things. So the thinking about why within that and then the following one is 'cause what does success look like?
Because I think you're making the argument, which is true that we probably now know a lot of the tool parts of. But it's probably not a hundred percent complete because there's so many of them. And then we are far less complete in the interactions, partly because there are so many. So I'm interested in how that all clusters together.
So partly why respiratory, how many tools do we have innate and what does success therefore look like at this stage of the program?
Brian: Yeah, yeah, what I mentioned earlier in terms of the understanding of the immune system being strongest for respiratory virus or, for viruses in general.
I think that was certainly a big part of it. Maybe one additional thing I'll add here is that the programs that we have at Aria are situated within what we call opportunity spaces. So these are broader spaces that can contain multiple programs. So the opportunity space that situates this program is called Sculpting Innate Immunity.
So the broader opportunity space is engineering innate immunity in all different directions, strengthening it, dampening it for all different disease areas. And when putting together the program, we did have the, we essentially did have to pick what is the first thing to go after and what's gonna be the program that sets up other future programs in this opportunity space.
And it was the sense that, okay, even, respiratory viruses in some ways are the lower hanging fruit because of this better understanding. And if we succeed it'll set up all these others. It'll be foundational, I think, to be able to engineer the innate ME system for all these other diseases.
So that was a big part of it. But also I think we were just excited about the fact that, even if we consider it low hanging fruit, that doesn't mean it's not gonna be, utterly transformational if it is Cade. So I think, we're excited by the fact that if we can have one of these one of these medicines, these sustained innate immuno prophylactics, I know we, we abbreviate them sips one of these sips on a shelf, and we actually got one approved.
This is something that, that all of us this is, one of the most universal one of the most universal struggles I suppose that we all face as people is getting respiratory infections getting the common cold, getting the flu, whatever it is.
Just having that not be a part of the human experience anymore is just really something that would be exciting. And you kinda mentioned in my intro that I had a historical interest in pandemic preparedness as well. And yeah, that's certainly something that, that also motivates this program is we've come a long way in being able to respond to pandemics with things like mRNA vaccines, other kinds of vaccines rapidly after a pandemic emerges.
But there's still a missing gap in terms of our ability to respond to a pandemic, really in the early days before we have the ability to develop something new like an mRNA vaccine against that pathogen. It was just all of these things together, the kind of the scientific feasibility and the possibility for transformational impact across the board, across common and pandemic viruses that made us excited about choosing this too.
To then set up the ability to sculpt the innate immune system for other diseases.
Ben: That seems clear. This is a starting point within that, although I do think you need a, it's a good catchy acronym, sip. But I do wonder whether you need a better title for the long form. And this is quite a good segue into.
Maybe Arian is thinking about innovation, but I thought I would first give you my view that I do think this is really exciting. I think the likelihood that something from this then goes all the way through trials is still quite low. But just to say, normally, like at a preclinical stage, you're talking about 0.1 to 1% overall, then I would probably put it in that ballpark.
But the probability that you discover or learn something, which radically increases the probability of chance of the next program. I actually think when I looked at it as quite high, I was quite willing to be skeptical that we weren't right at the state. But actually when I looked at the state of the art, again, not as a super scientist, I thought, you know what?
It really is that, and I would probably put it as high as 70 or 80% that you're gonna make a significant difference to the next stage. That's still quite low, absolute probabilities for the next stage. But I thought that was really interesting that there's lots of bits and you are, there's. Lots of bits, which I feel is on the cusp of probably being there and actually respiratory wasn't a bad thing to go for, given that you might look at some of these other immune conditions or cancer or something like that later.
That does lead me into thinking, is Aria one of the best places to do that? What? What do you get from Arian? How should that be judged? And adjacent to that is because I'm interested. Do you think where the space you are in now, is it better being done by small teams, startups, narrow? Is it better to convince a large biopharmaceutical company to throw more resources at it?
We do seem to have covered the basic research state, but there is still more basic research to be done at university level. So in this multifactorial, how is innovation best done? Incremental versus big jumps, big teams versus small teams and Aria's place within that. How should we judge success for Aria?
Why are you there and how are you thinking about innovation overall?
Brian: Yeah. Yeah so I would say that prior to Aria I was leading a nonprofit called at the time Panoply Laboratories. Now, it's called Active Site. That, that worked on the development of these, we didn't call them SIPPS at the time, but essentially they would've been sipps.
And we were a small team, five, five people or less. And that, that had its advantages but certainly, the disadvantage is that we are only able to explore a very small part of the hypothesis space. We're only able to go in on this one potential sip design and yeah the ability at Aria to foster your entire R&D ecosystem.
That's what I think is needed for a problem of this size where the science is early enough where we don't actually know what the best way to make a sip is. The definition that I provided for a sip is it strengthens the innate immune system, or that's kinda the mechanism by which it works, but strengthens the innate immune system.
Control can, contains. There's many different ways to do that. I mentioned all the different players of the innate immune system. Each of those is a substrate for strengthening. There's all different kinds of modalities you could use: DNA, RNA, proteins, small molecules. And I think this is one of the reasons that, that kind of brought me to Aria was the ability to step back and say, we, we don't wanna just if we wanna actually have a sip, succeed and actually bring this to the world we, we need a lot more talents.
We need a lot more people working on this. We need people motivated to work on this. And we need people searching in all different directions. Crucially and I think. It is a unique advantage of being an re program director that, or of the programs generally that we fund across different institutions depending on what the pro what the problem needs.
It can be academics, it can be startups individuals as well. And just depending on the shape of the problem we can design the programs and find the individuals that will make a difference to that problem. There's a lot of flexibility essentially within the aria structure that I think makes it so that yeah that the problem of bringing a sip to, to, to reality is something that we can very much fos foster an RD ecosystem in the way that suits that best.
Ben: Yeah I agree and I think Aria is doing something somewhat unique in fostering whole. Ecosystems. Obviously you have US innovation agencies, DARPA, on energy and NIH funding and things. But there isn't something which kind of funds this earlier stage, low probability, high impact, but on the cusp.
But where it needs a, an ecosystem or a movement and it's, I think, mostly false that you get individual genius, which comes out of nowhere. They've always come out of somewhere, even if they. There one individual insight seems to have leapt up way beyond the state of the art. It always comes from where the state of the art is even going back to Feinman or Einstein within physics and certainly within biology.
So I do think that's really interesting. Maybe trying to get you to choose between your children or how you would evaluate choosing between your children. Do you have any sense at the moment whether you prefer one particular type of modality and one particular type of the tool set you, you mentioned there's a few DNA, RNA, proteins, small molecules…. Obviously there's ease of use in that. And then the different bits of where you could attack the or dampen or increase the innate system. Like you say, we've got T cells in, in all types. Or how you would judge, is there anything you think oh I wouldn't be surprised if someone chose mRNA on, something or something like that. Any thoughts?
Brian: Yeah. If I have the liberty of choosing two children I'll choose two. Go for it. The first one is this would be small molecules or a kind of a combination of small molecules and proteins potentially. But these are trained immunity vaccines or vaccines that stimulate the innate immune system in a way that provides a memory response over time.
And I, the kind of, the reason that so to take a step back into mention or a reference, an earlier comment you made about, about, about the name sustained innate immuno prophylactics or sips. So at one time we called these innate vaccines. And one of the reasons why, and obviously that's a much catchier a shorter title.
One of the reasons that we moved away from that is that actually not all of the sips that we're supporting are, could properly be regarded as vaccines in the way that they stimulate rather than, let's say, augment the innate immune system. The, I, when I think of engineering the immune system, I typically think of these, these two different categories where you can stimulate what's already there, which is what most vaccines do, or you can augment them by just adding in extraneous components.
And we're excited about both of those for sipps. And so we ended up moving towards SIPS as the main acronym. But the reason I bring that up now is because the first category you can properly regard it as a kind of a vaccine that these trained immunity vaccines, because they stimulate the innate immune system and they per and they essentially train it.
And, I give it a memory. And the reason I'm excited about this is because it has the potential to be relatively cheap and therefore more accessible to lots of people in a shorter amount of time. Similar in the ways that we think about most vaccines as being really essential and critical for public health and they can be administered to so many people at relatively low cost.
I think that could be the case for these trained immunity vaccines. And I think we're probably closer on those modality than many of the other kinds of things that we're excited about. The second child, I'd say, is on the other end of the spectrum where it's like a little bit farther away, probably more expensive or I would, or at least less technically mature at the moment.
But it is just a really exciting application of new technologies. This would be using DNA essentially as the modality. Encoding different innate immune proteins, different innate immune stimulants in DNA delivering that to the respiratory tract, the nose and or the lungs.
And then essentially your respiratory tract cells become factories for this innate immune protein or innate immune stimulant. For as long as that DNA remains expressing, which depending on the cells that are that the DNA is delivered to that could be a period of months.
For example, And yeah I think this is really exciting because I'll use the term gene therapy. And I think a lot of people associate gene therapy with high price tags and mostly treatment of rare diseases at the moment.
But I think what gene therapy is at its core is just programming yourselves to do something different in a therapeutic manner. And I think the ability to do that for the innate immune system for this purpose is something that is a little bit further off technologically. And I think delivering DNA to cells is still really challenging, especially in the respiratory tract.
But I think if we're able to, if we're able to do that, that I don't know, it is just it opens up a new kind of technological frontier that, you know, the same way that, that we're able to program cells now transiently with mRNA, if we can do that in a more durable manner with DNA. Yeah I'm just really excited about that direction as well.
Ben: They seem like both really good children. And in fact, on that latter one, I do know of a product which has actually made it all the way through where they use inactivated herpes virus in respiratory track. That, so that they've done it on the skin, but there's some early evidence that they've managed to deliver it for cystic fibrosis.
And also they've delivered interleukin two, I think for cancer. And they've definitely seen it take up in the lungs. We are not and that's phase one, but that's not it's not science fiction. So I'm saying it's like it definitely seems in the realm of possibilities.
Brian: I'm interested… and maybe sorry, just one thing I'll also add on is that even the more specific thing that I'm excited about within DNA is being able to deliver DNA without a virus. So yeah, it's obvious it makes a lot of sense to try to deliver DNA with a virus.
That's what a lot of viruses are evolved to do, is to be able to shuttle their nucleic acid into the, into cells. But there's also some, a lot of downsides that come with that. Firstly, it's often very expensive to manufacture these viruses. And secondly your body has an immune reaction to these viruses, which means that you can't often re-dose them with the same kind of viral vector over and over again.
And, for sips, that's really important. If we're thinking about something that is dosed every season you can't have a drug where your body's gonna have an immune reaction to that and prevent the efficacy of the next dose. Every time you take a dose.
Yeah so non-viral delivery of DNA is something that I think is more again it's further away. A little bit further away, but I think it is really exciting.
Ben: I'm interested in all of this. So one of the other new things which has come around has been ai, although it has been around for a long time, and obviously that's a catchall for quite a lot of complex things in our area.
'cause it's. Not just LLMs, which you think about, it's machine learning, it's computational biology, it goes into synthetic biology, or at least how we model and do all of that. So I might ask the question, do you feel optimistic around that? Is there more to go and the potential is just being there?
Or I guess critics would say it's maybe overhyped. You're still gonna have to run clinical trials, so it doesn't necessarily speed up the clinical program part, even if it may give you more at the beginning end of the funnel, make targets, which are not druggable and things like that.
So I'd be interested in where you land on AI optimism or pessimism and any particular form of what we might call AI, whether that's computational biology, machine learning, protein folding or all of it together. I'd be interested in your AI thoughts.
Brian: Yeah, I think that. AI for science, for biology, I guess specifically is gonna be most helpful for those tasks that are most easily and immediately verifiable, where you can build a loop where you have an AI generated design of, I don't know, a small molecule, a protein, you can generate binding data to a particular target.
And then you have a lot of data that you can then use to train the AI again, there's a positive feedback loop there. And as you mentioned, we already have great examples of this in protein folding and de novo antibody design is another big category now where we're able to generate antibody binders to targets pretty readily in silico.
I think all of that is amazing and it's amazing to have seen the progress over a very short period of time. I do certainly think that when it comes to especially more complex diseases that you do need that clinical feedback as well. Which means that some of the progress that we might see there, yeah it might be bottlenecked by just clinical timelines because you do need to generate data to then be able to feed into ai.
And the most relevant data is gonna be clinical data for, especially for these complex diseases. I think there's maybe some promising ways to try to bridge that gap so that we can get more relevant data earlier in the.
Development process before getting into the clinic. So if we can test more diseases in or test more drugs in, in tissue models or better, better kinds of animal models than we have historically had, for example then I think, we, then you might start to get the best of both worlds.
We can generate data quickly and it's and it's also more human relevant data. It's more, it is data that's more predictive of what's gonna happen in, in the clinic. So yeah I think there's a lot of these, a lot of momentum around these new approach methodologies or NAMS.
Essentially these non-animal models like these tissue models organs on a chip, things like that that I think are well suited for this AI age of, hopefully, these can be developed such that you can do high throughput assays, but also can be validated by, by they, they can be more predictive of what happens in, in humans.
Ben: Yeah, I agree with all of that and I think it's really exciting. I do think when I've heard some of the AI leaders who don't really know biology talk about it, though, they have not really appreciated the safety signal issues. And particularly in this area, when you're looking for rare or slightly more rare effects, which you know, could be triggered and you're not really gonna be able to model it.
Maybe someday we will get a completely computer generated animal or computer generated body where we'll feel confident enough that we understand that. But to your point, which we're talking about, we just don't know enough of the parts Yeah. To really generate that. So when they're talking about all of this, a hundred x on that part we're still very bad at safety.
In fact, we're very bad in safety overall in terms of predicting where safety might go, which is why we have to test these things empirically because we can't do that. And there isn't as yet. I see a very good, huge speed up on that part, although we have some leading indicators. That's a good segue, I think, into perhaps just your own creative or innovation process and your own journey and maybe how you are finding it at Aria. Is it as great as it looks on the outside, how is Aria going down and how does that fit into your own innovation journey and how you ended up there?
Brian: Yeah. So in terms of how I ended up here yeah, I mentioned briefly previously that I was leading a nonprofit before joining Aria. And it was certainly there was, there's a timing element of this where yeah, as I alluded to previously we ended up at a point in the nonprofit where we were like there's so many other things we'd like to explore in this space that we can't, that we can't explore.
And at that point, essentially the call for EPDs, the second cohort of EPDs, our program directors came out and it was just like, oh yes, this is the right, this is the right timing. In terms of what we hoped to accomplish with a nonprofit in the world.
And it was, it seemed like it was the perfect opportunity to take that mission that we had as a nonprofit which was a pandemic preparedness mission. And find it, find a new home for that. I think, rewinding even further than that it was certainly everything did come back to pandemic preparedness.
And this was something actually that even before this is even before COVID to 19, in 20 17, 20 18, something like that. This is towards the end of my PhD, which is in organic chemistry. Towards the end of my PhD I was thinking, how could I use this, the skillset that I had to to essentially have the most impact of my career.
And the, the kind of there, there were other other people that, that, that were thinking about this a lot. So one kind of organization or a podcast that I listened to that was particularly influential at the time was 80,000 hours. It has a, it, it's an organization that, that essentially, provides resources to help people think about having the most impact of their career. And I just remembered them having essentially three podcast episodes back to back about pandemics. And again, this is 20 17, 20 18, right? I was like, oh, huh. This is an area where developing new medicines, developing new drugs is something that organic chemists often go on to do.
This is something where that can actually be really impactful. And so I started thinking about that a lot more. And ended up then doing a postdoc in synthetic biology. Because, I realized that a lot of the ways you could have an impact for pandemics was using synthetic biology tools developing vaccines and other kinds of other kinds of biologic medicines.
And that's when COVID hit, and it was in, in 2020. So that essentially that, that was a forcing function to kinda redouble my efforts to essentially being able to see in real time and as a world was able to see in real time, how our civilization was able to handle a pandemic.
Like what was really the state of the art in terms of us being able to develop new countermeasures, new vaccines, new antibodies against a new threat. And yeah, essentially that, that kind of as much as my career directory was heading in that direction before COVID, after COVID, it just cemented that.
Yeah, I've just been thinking about that problem ever since. And that, that, led me through my postdoc at another startup that was focusing on vaccine development to the nonprofit startup I mentioned previously and then to Aria. Yeah I think one other thing I'll highlight in that kind of career trajectory is I do think that, there's kind of a parallel with how I was drawn into the immune system and to a parallel with between that and the historical trajectory that I described previously of immunologists where I was certainly drawn to the adaptive immune system first. I was drawn to developing pathogen specific vaccines and antibodies first and engineering that whole part of the immune system.
And then, they've turned more to the innate immune system to develop a kind of more broad spectrum countermeasures. Yeah, I think that that's yeah, ki how I see how I ended up at AR aria. In terms of how I've been finding it at Aria since joining.
So I've been here for about a year now. Yeah, I think it's been great. It's been a lot of fun. I think it's one of the few opportunities that you have to be able to take a vision and then find the best talent in the world to be able to work on that vision and to be able to have a real shot at making a really significant contribution to the world.
And there's a lot of flexibility to do that. This, we're, we are a government agency but we're one with a lot of flexibility and certainly the program director role is one with a lot of flexibility and autonomy. That, that's all that, yeah.
Yeah. So it is just a lot of fun to be able to think through these problems and interact with great scientists and thinkers and yeah.
Ben: It seems uniquely great to me. I think one of the interesting things, so 80,000 hours and that whole movement tends to think about three things.
So in impact whether something is over researched or under researched. And then they also tend to think about the tractability of the problem. And Aria tends to say it's on the cusp of breakthroughs. Or breakthroughs. Where there is some, there you can argue about, like we said, probability of success.
Is something really a moonshot or not a moonshot, but I actually think 80,000 hours overrates the tractability problem. Maybe that's true in a career. 'cause like in a career, maybe as an individual you maybe don't wanna necessarily spend all your time on a problem, which you think is definitely intractable.
But for a broad movement or for basic research I think the problems on the cusp of tractability is where you wanna be. You wanna, you probably wanna have. 50% of rumor biologists think like, ah, that's not that tractable. But you want at least one or two thinking no, I think we can go for that.
Yeah. Because that's where you're gonna get this breakthrough. You're still coming from a state of the art, but you are on this cusp of where something is tractable or not. I'm gonna take it as a given, the sort of impact part. And by its very nature, people think it's not tractable, it's gonna be an under-resourced area, at least within science.
So I'm very excited to see what's coming out and the program program directors that I've seen and looked at your site and all the call outs have been really exciting. Maybe we'll do a short bit of overrated, underrated, and then we can also look at other current projects or things that are looking out before we finish off.
But in terms of overrated, underrated, I guess you could say appropriately rated as well, you quick hits and why I'll start off with a somewhat easy one, I think given our conversation, but pandemic preparedness. Do you think this is an overrated or underrated thing?
Brian: Obviously coming in with a bias here given my just interest in this, but of course underrated, I would say.
I, I think despite the fact that we had a pandemic just five years ago, I think it's been big. Loss of institutional memory. I think there's not. I don't think we've learned our lessons from COVID as much as we should have. So I think there's still a lot to be done here.
I, I think part of the reason that that we're excited about this program is, we're trying to, we're trying to create medicines that have a commercial market and that don't rely on governments to act in ways that where they expect a new, another pandemic relatively, in, in a relatively short timeframe.
And yeah I think it has been unfortunate to see the lack of progress on vaccine research and some retrenchment there in the US for example. And yeah I think that there's, yeah there's a lot of work to be done there.
One, one of the things that obviously we haven't spoken very much about is the kind of nexus of AI and biology in terms of being able to potentially create engineered pandemics. This is something that's really worrying. And so I think the problems it's certainly not going away.
It's something that, that, that, that yeah. It is gonna rain a big problem for a long time. And yeah, I think there's a lot of work to be done there. And yeah, so I would say underrated.
Ben: Yeah, a relatively small amount of money would give a really good return, even if it looks more like insurance, I think I can definitely buy that argument.
Maybe that's a segue then into existential risk or bad things happening to humanity. Do you think that's an overrated risk or an underrated risk? I guess you've got a few, right? You've got things we probably can't do too much about, like meteors, but then you've got things like pandemics either manmade or natural.
You've got AI, singularity, some people talking about that, maybe the assessment of those probabilities are just far too low. So overrated or underrated area,
Brian: I would say underrated overall. I think the same for the same reason as or at least partly for the same reason as pandemic preparedness generally is underrated overall, which is it's hard to, it's hard to adequately value the prevention of something that hasn't happened.
So either that's prevention of a new pandemic that hasn't happened yet. Obviously for existential risk, we've never gone extinct as a species. So it's something that's hard for our minds to grasp. And yeah so I think we probably don't put enough resources into averting causes of existential risk.
I am also by the arguments that some of the affected, kind of parties from existential risk would be future generations. And those are people that don't have a say, don't have any ability to influence the kind of decisions we make now.
There's gonna be a systemic kind of underweighting of our yeah, of our decision making to, to avert this existential risk because some of the most impacted parties are just not able to cast their votes essentially on, on those decisions.
Ben: Sure. We're slightly underweight future persons. I can see that. Okay. Another one is the UK as a place to build frontier science or a place to just build in general?
Brian: I think. Underrated in the sense that, yeah, obviously this kind of comes back to why Aria exists in the first place, is that we think this is an underrated thing where the UK has enormous scientific talent across the spectrum.
And, for MySpace, that's innate immunologists amazing talents in the uk. We have lots of other programs in Aria as well that are taking advantage of other pockets of talent within the uk. And, essentially I think it's just it's talent that needs to be activated and that's what we're trying to do as an agency, but it's not that it's not there.
So I think yeah, un underrated overall. I think that yeah I think there's a lot of opportunities to, to create lots of, entrepreneurial ventures here in the uk.
Ben: I have to agree. I think, obviously there's great science happening in China, great science and biotechs in the US but this tends to be a little bit of complaining around Britain and we all have a slightly compliant culture within that.
But I think that completely underrates the fact that there is a lot of great stuff happening in the uk. Broadly which still puts us as world class in terms of a lot of things to do. So obviously I have a huge bias 'cause I am here, but I've spoken of my feet. What do you think about cluster or agglomeration effects?
Do you think it's underrated or overrated? So I guess here in the UK we talk about a London, Cambridge, Oxford Triangle. You've got biotech clusters in the US: a Boston cluster, south San Francisco cluster, and then other clusters for different things. Do you think we should be accelerating within clusters or do you think actually you follow the people?
I don't know: agglomeration effects, underrated, overrated or correctly rated?
Brian: I guess appropriate, yeah. Maybe appropriately rated. I think that, these are, I think, yeah I don't think it's, I don't think you can deny that these cluster effects are important in terms of, if there's just a large conglomeration of talent in a particular space then if you as an individual want to, start a new business or what, whatever it's that you wanna do then there's gonna be large returns to, to also being in that space in terms of there, there might be existing jobs there.
And also it's just the connections, the networking opportunities, the people that you'll meet just randomly. Yeah I think it's hard to put a value on that, but I think it's yeah I think there's a lot of, there's a lot of value there but I, yeah I think people understand that and in some ways it's hard to say that these cluster effects would be either under or overrated because I think people are just like showing, voting with their feet in a sense of and we see these clusters exist because people are rating them as such.
Ben: I guess the issue is they just happen, it's quite hard Yeah. To centrally plan.
Brian: Right.
Ben: Engineer them, but maybe to some extent. Okay. Last couple of two on this one. Regulation, I guess particularly in medicine. Do we have the correct amount of regulatory caution, or are we too slow or too fast?
What do you think? Our regulatory caution is about right. So is it underrated or overrated?
Brian: Yeah, that's a tough one. That's a tough one. I think I certainly have, I think sympathy for both sides of this where yeah I think there's one, one point of view where we certainly overregulate medicines because if you're a regulator your incentives are essentially to prevent harm to individuals, which means that you also are not incentivized to approve drugs that would be beneficial to individuals.
But that, or essentially you don't get you as if you're a regulatory agency, you receive a lot of pushback or you receive a lot of negative kinda reactions. If you end up approving a drug that has some downsides to a population but not approving a drug that maybe would've provided some benefit to some populations you often don't get the same.
Kind of a push back in the opposite direction. So I do see sympathy for that point of view. On the other hand, I'm also, I also don't consider myself somebody who would, abolish the FDA or abolish the MHRA or abolish, if these regulatory agencies and just say, people should just be able to choose for themselves what drugs they take what medicines they take because they should be able to just know for themselves or, just be able to tell for themselves or maybe there's this crowdsourcing effect where people, you know, where you can just understand what the efficacy is.
I do think that there's a really important role for regulation in, in that the effects of drugs are not always gonna be the most transparent to people. And you really do need these, like centralized clinical trials to be able to actually know whether a drug has been effective or not.
So I don't know where that puts me in terms of appropriately or, under, appropriately or overrated, but I essentially do take a middle of the road view here. I don't find myself really, on, on one or the other side. And I think it depends on who your reference class is, whether or not this is a under Yeah.
Ben: Yeah. And that's a really tricky question. I have to say, probably when I was younger I was a little bit more pro regulators, but as I've got older, those incentive problems I think are quite tricky. And I do think in some, in more cases than not, they could have gone, they could have gone quicker and they don't because of these agency incentive problems.
I do think there's maybe an easy win for some smaller agencies, which actually we've done here in a little bit in the uk, but I don't think, for instance, when a UK regulator looks at it and has come before or after, rather a few months after, say, a US regulator has looked at it, if you've got the FDA or the EMEA who's gone through all of the data, and I know there's slightly some slight population differences that you might have.
Although the UK and the US and UK and Europe are similar enough, I don't know whether you need to go through it all again. When actually a class of 12, 20, 50 experts have already looked at it. You get another class of 50 experts, they're not actually adding that much more value. So I do think there could be a little bit more mutual recognition, but obviously that's more of a political economy problem rather than an incentive problem.
Great. Okay. Last one on overrated, underrated, throw on a slight curve ball GLP ones for obesity and diabetes. Do you think they're gonna be an underrated or overrated class?
Brian: Do I think there's gonna, there're gonna be an underrated, overrated class, you mean some sometime in the future?
Ben: Yeah. Or even now. So you could do it now in the future. So the view from now, so you could take it either way.
Brian: Yeah. Yeah. I have to say, this is a drug class. I actually haven't followed the story all that closely in terms of the science and everything.
I'll give an intuitive answer, which is probably that there, so they obviously rated very highly right? By, by the population and by pharmaceutical companies and so forth.
It feels like the trajectory is that we just keep learning more and more about the potential diseases that are impacted by GLP ones. And I think there's probably still lots of effects that we haven't yet discovered. I think probably my guess is that if we extend g like the GLP ones to not just maybe the narrow class it might not be that narrow, but the class of drugs that are actually, GLP one receptor agonists you drugs that target, that receptor specifically, but actually to maybe a broader class of drugs that, that we start discovering because of this, GLP one revolution.
I don't know what that looks like necessarily. Maybe there's other similar receptors we wanna hit, or, or maybe. Maybe this kind of results in other drugs that are in a pharmaceutical company, libraries that were put on the shelf a long time ago, and we take a second look at those.
Essentially the ripple effects of the GLP ones I think maybe are underrated. And partly it's because we just don't know what those might look like. But yeah so I think there's probably a lot still to be learned there.
And yeah, a lot that we don't know. And yeah. So I would say underrated from that perspective. Yeah.
Ben: So I'm definitely on the side of underrated, and I guess there's two parts to my thinking. So one is, the safety concerns are definitely over flagged because we've used them in diabetics for so long.
So the actual patient number years are extraordinarily large. So fears of over that are really small, but we've now realized that actually there's a huge. Inflammatory effect of obesity or these pathways and these have an anti-inflammatory effect. So this is your point for actually, it's not just obesity, and I've been particularly persuaded, so we've seen it in addiction, sleep apnea and things like that, but there's been a recent amount of data for people who have psoriasis.
So this is why I do it adjacent. 'cause psoriasis is both immune and inflammatory. Yeah. In terms of A disease and if you add GLP one on top of your psoriasis medication, you are doubling the impact. And so you could definitely see there's this anti-inflammatory and it might even interact with the immune system.
And this is your whole point about the fact that we don't know how these different tools are, is the interaction between say, inflammation and immuno. The immune system. And they're innate and they're adaptive, but the data that we're now seeing to me seems very convincing. And so as we start to learn more of that, I think we're more likely to find more positive discoveries.
And we're not likely, I think, to find anything more in the sting in the town in terms of safety, but we shall see. Yeah. Great. Okay. Last couple of thoughts. So I'd be interested in any other projects that you are working on or current projects that you'd like to highlight or also any projects over the year.
We're now in around April, 2026, but ARIA is gonna be looking out or having calls of interest from that oh. And whether you have perhaps any other side hustles that you wanted to mention which aren't in biology, but Yeah. Any current projects or other projects that you think are really interesting that you're looking at Aria in general?
Brian: Yeah. So for me personally I'm mostly focused on getting this program off the ground. I would say that the main it's not exactly a current project, but a slightly upcoming project is I mentioned the broader opportunity space sculpting, innate immunity.
So we are going to be later in 2026 putting out a funding call for what we call opportunity seeds. So these are. These are 500,000 pound or less projects that last for typically one to two years that are first still really ambitious, out of the box interdisciplinary projects that essentially fall within the opportunity space.
But outside of the programs in the space, so for this for sculpting innate immunity, that would just mean essentially being able to engineer the innate immune system for other diseases besides respiratory viruses. So that's something that I'm excited to start learning more about, very much my background and the program is focused on respiratory viruses and in putting together the opportunity space in the first place, we essentially had this conviction that the innate immune system is.
Is really involved in lots of other diseases that I'd love to learn more about, especially as we move towards that seed call. Yeah, that's something that I'll be working on and learning more about as we start launching the program and that, that gets underway and can and can give room for more exploration of the broader opportunity space.
In terms of. Aria in general. Obviously it depends on when people are listening to this, but as of now, in April, 2026, we have a few live calls for other programs. So I'll just say generally across Aria we have a dozen or so opportunity spaces and some subset of them are live for, at any given point in time right now.
There's a really cool program called Universal Fabricators that is looking to call protein engineers to create new manufacturing processes. Essentially. Can proteins be the basis of universal fabricators? Can they create new materials that will define them? Age of materials in the same weight that we have seen, the stone, bronze, iron Ages, is there a new materials age that could be upon us by using proteins as the means of manufacturing.
So that's one that is open now. We have another program called Accelerated Adaptation. So can we engineer wild species to be more resilient to environmental changes? The pressures of climate change, for example. Can we use new tools in synthetic biology and other disciplines to actually engineer these wild species?
Instead of just relying on conservation efforts and other efforts that are important. But the kind of technological interventions might be a little bit underexplored there. So that's a new thing, that's a program as well. Who that where we have an open funding call.
I would say for the other spaces we have our website there's if you look at the kind of funding opportunities on our website, there's, there should be a place to sign up for updates. So this is aria.org.uk. And you can be kept abreast of any of those updates that happen in any of our opportunity spaces for future funding calls.
Ben: Great. So I made you choose between your children last time, or at least a couple of them. So now I'm gonna push you between your brothers and your sisters. I'll read out some, but if you weren't doing this, or maybe you could advise me, say I'm interested in something, or I'm 16 years old, so I've got two or three years to develop and then go for one.
What, what would most attract you in terms of some of the things, just to give you the breadth of scope of what Aria is doing. So you have scoped our planet. Future proofing climate and weather programmable plants, which I thought was really amazing. Engineering the ecosystem, manufacturing abundance, smarter robot bodies.
We both know, hands are really difficult for robots and things extending our perception of nature , computing mathematics for safe ai, trust everything. Collective flourishing, neural interfaces, scalable ones biogenetic engineering. So out of all of those and your brothers and sisters what would, what should I go and have a look at?
Brian: I don't know what you should be. I, so I can answer from my perspective, like what I would be doing if I wasn't if I wasn't involved in my current space. I would say that at heart I'm an engineer. I love building things and I especially love building things in biology.
I love building, engineering biological systems. I should just say molecular systems in general. So chemical and biological systems. And I think, you know, the two that would speak to me the most from that perspective would be the scalable neural interfaces and programmable plants.
I think of those three as, or, those two plus sculpting innate immunity is essentially we're all trying to use advances in synthetic biology to engineer biological systems that haven't been tractable before. The brain, the innate immune system and plants.
Yeah, certainly those two are the ones that call to me.
Ben: I have to say, this is really far away from any of my domains, although I guess I know quite a lot about sustainability and climate to some degree, but the programmable plants just seem to me like, oh my God, that seems so amazing.
And science fiction, but actually not. We do, we've got a lot of the building blocks. We haven't managed to put them together, particularly with the tricky things. But, and I guess there is a crossover with syn bio as well, to some, to, to some degree as well. So there could be a lot there.
Great. That's a segue into our last question, which maybe does that is do you have any advice for listeners, maybe there are young scientists or a policymaker or innovator or a builder or someone who's just interested or maybe they're thinking mid-career uni, they're at university or they've been an academic or they're in a startup and something else.
What would you advise if you wanna get involved in an innovation ecosystem or in your overall journey? Any general advice that you have for listeners.
Brian: I think my general advice would be, career advice would be if I reflect back on my career so far which, hasn't been the longest career necessarily, but I think what's worked well for me is actually not not planning very far ahead, and also not feeling like I have to hit a certain publication metric or I have to impress certain people or, I've always just worked on projects that I thought were important and interesting.
And I think along the way this has led me to meet interesting people and find new connections. And every time I've had a shift in my career, whether that's from PhD to postdoc or postdoc to startup or startup to aria. Most of these have not been pre-planned in advance in the sense that it is not a career trajectory I would've ever expected to go on earlier.
And I think if, yeah, if you work on important, interesting problems you'll meet interesting people that will lead you down a path. And yeah hopefully that path is one that you yourself will enjoy because it's something that you just naturally, organically came to rather than something that you're trying to fit yourself into based on some kinda preconception of how your life should play out.
Yeah, I think maybe that's just me trying to rationalize away my faults of not planning very well, but that at least that, think back that's that's what I would say.
Ben: Great. That sounds like great advice. Work on interesting, meaningful problems.
And on that note, Brian, thank you very much.
Brian: Thanks, Ben. It was great to be here.