Claire Bergstrom Johnson - Neuroscientist, Entrepreneur and Change Maker

And I was trying to get some last results together for a conference we had the next week. And I was in on a Saturday to finish this assay. And we decided, why don't, why don't we not just test for IgG, but we also, let's test for IgM and see what we find. And I remember finishing that assay on a, that test on a late Saturday evening in the lab alone. What you do, you look at this fluorescent plate. Underneath a microscope in a dark room. So, you know, that kind of sets the scene for how dramatic this can be. And as expected, not really finding much IgG at all. I did find one for the first time ever, which was super exciting. But then lo and behold, I found positivity against IgM for what I knew is the— what was the first time they basically this was identified, and it was at, if I recall correctly, 3 or 4 times higher incidence than IgG, which was pretty striking, and it was really strong.

Welcome to the Making the Most of Now podcast. Claire Bergstrom Johnson PhD PhD is a researcher at the University of Oxford where she's researching some very rare inflammatory neuropathies, nodopathies. We'll get into the detail of what exactly that is because I get lost very quickly. But alongside her scientific bench, she is a huge advocate for increasing the representation of women in science and the sciences in general. She is a travel blogger. She is an entrepreneur who supports people to kind of follow in her footsteps and get access to the kind of funding needed to do PhDs and postdocs, that kind of thing. And she has an ambition as well to set up her own biotech startup and translate the scientific knowledge she's learned, she's gathering, into something practical for patients. Um, so that's a hell of an introduction. Sorry about that, Claire. Um, probably got too much in there, but welcome to the podcast.

Um, thank you very much.

We've got a lot to delve into, um, yeah, because there's so much that you do. Um, and but I think it's probably useful— where are you now? What are you doing now? And then we'll step back and go, okay, how do you get there? And then we'll talk a little bit about What next, short term, medium term? Because one thing I forgot to mention to the listeners is Claire has recently been the recipient of 3 years' worth of funding through the Benson Fellowship of the CIDP, GBS CIDP Foundation International. And so with that and some bridging funding from Inflammatory Neuropathies UK, You've kind of, I'm guessing, got a bit of a plan for the next 3 years. So that'll be our short-term horizon, and then we can go along. But where are you now? Sorry, Claire, I've talked far too much already.

No, all good. Thank you. It saves me from people having to listen to my voice longer. I am currently in Oxford. So I'm currently in Oxford right now as a clinical research fellow, as you said, as a Benson Fellow. That fellowship officially started at the beginning of November. But as you said before, I had about 6 months bridging funding from Inflammatory Neuropathies UK, our friends there, after I finished my doctorate. We call it a DPhil at Oxford because they like to be special and call things something different.

Just to confuse the rest of the world, isn't it? It's like, what is that?

Yeah, exactly. Just to make it sound even more elitist. A PhD in clinical neurosciences. So I received that in July. Yeah, so that's what I'm doing now, starting up that research program, as you said, for the next 3 years, kind of spinning off of my doctoral work.

So that's— so the doctoral work, layman's terms please, because I still don't understand the difference between B cells, C cells, T cells, and the rest of it. What have you been studying? What have you learned?

Yeah.

And what are the next steps?

For sure. So my doctoral project was really immunology heavy. So you're right, it's in the inflammatory neuropathies, focusing specifically on something called autoimmune neuropathies, which I'll explain in a moment, but particularly on the immunology side. So we've got what are called B cells, one of the things you just mentioned, that make antibodies. We've all probably heard of antibodies at this point because of COVID usually. And so we know these are supposed to be attacking foreign invaders like viruses and bacteria and stuff, right? But often, as is the case with autoimmune diseases, like many inflammatory neuropathies, something kind of goes wrong in the body. And instead of, your B cells making antibodies that are attacking these foreign invaders. Instead, they make antibodies called autoantibodies that attack something in your own body. In this case, and in particular what I studied for my doctoral work, is a class of diseases, and it used to be diagnosed as Guillain-Barré or GBS because it presented similarly. So patients often present really acutely, severely at A&E, and they really rapidly deteriorate within kind of 4 weeks. But these patients often have to be ventilated, so their lungs will fail often. And before we kind of figured out what was going on slash what could work to treat them, because importantly, these patients, unlike most people with inflammatory neuropathies, they don't respond to front-of-the-line therapies like IVIG or steroids. And so before we kind of figured out what could be going on there, upwards of 50% of these patients would die. Actually.

Oh wow, okay. So this is, this is acute, this is acute like GBS, but all, all, all the kind of toolbox for that's used for GBS wasn't working, right?

So what has been figured out, um, you know, in particular Oxford, um, and Prof Simon Rinaldi in particular has kind of been at the forefront in the past 5 to 10 years at sort of identifying that a drug called rituximab, which is usually used for B-cell cancers, when you treat patients with this type of drug, it can actually really help them. Some people actually will go into remission with one course of treatment and not need treatment again. However, there is a huge proportion of patients that the response to rituximab, if they respond, it's pretty slow, you know, at least 3 months to see, is this even working? Working. And even then, you know, responses can be kind of incomplete. A proportion of patients will subsequently relapse. So when I kind of picked my doctoral work to do at Oxford and apply with that, that's kind of, that's what we put forward was looking into what the heck is actually going on with these B cells. Why are they doing this in the first place? And I think that kind of work particularly appealed to me because I'm never somebody who's wanted to work on research that's just contributing to slapping a band-aid on stuff. I don't know if you— do you say band-aid or plaster in New Zealand?

I— both work.

Yeah, yeah. All right, just curious, it came into my mind. Um, but I like English.

English people say plaster, don't they?

Plaster.

Yeah, yeah.

Um, in any case, just popped into my mind.

It's like, it's like the difference though between— would you say Hoover or vacuum cleaner? Vacuum. Right. Yeah.

So do you say Hoover?

Yes. Which of course, like Band-Aid, is a trade name, trademark.

Right. Yeah. But do you say garbage or rubbish?

Rubbish.

Right. Okay. Well, I've heard Australians say garbage, so I didn't know if there was a similarity there with New Zealand or not.

Well, I'm English, so—

Oh, you are. Right.

I'm a bugger's muddle.

Right.

Yeah, because I've now got the worst, probably the worst of both worlds in that I'm English, but having been here for 15 years, I'll drop into random Kiwi phrases.

So you belong everywhere and nowhere. Anyways, sorry, I'm contributing to early tangents. Anyways, as I was saying, I think this kind of work, it attracted me because it wasn't just slapping a bandaid on the problem and saying, Yeah, we don't really know what's going on, but if we throw this thing at it, it kind of works and we don't really know why, but it is instead kind of figuring out like why are B cells kind of glitching and something along the development process is going wrong where they're creating these autoantibodies. And it's this very well-characterized disease because they found this group of diseases with autoantibodies targeted against various proteins. That are at these very important junctions in the nervous system. So you have these long axons where you have these electrical currents that get sent down, and that's how you move.

Yeah.

But then for a whole bunch of very fancy physics reasons, which I probably couldn't even remember off the top of my head right now, but it's kind of like insulation for a wire. It's possible probably a lot of listeners have heard of the myelin sheath. It's kind of this fatty coating over the axon.

Yeah.

But it's not just like a uniform coating. It has these gaps in between chunks of myelin, and that actually allows the current to jump way faster than if it were just a uniform coating. And so if those particular junctions get damaged, then this action potential, this electrical current, just really can't flow very fast at all, if at all. And so this group of Sorry, go ahead.

No, no. So this is the node of Ranvier, right?

Right. Yeah. The node of Ranvier.

People, if they've listened to my, some of my conversations with people on MMN, will know that that's a, that's a key feature in MMN as well. So, yeah.

Right. Yeah. So, so we have this group of diseases and there are different autoantibodies for different types of nodopathies, but they're called nodopathies because different various proteins at the node or like what's called the paranode, which is kind of, it's getting onto the myelin sheath. On either side of the node, but it's like right there, it's flanking the node. And these proteins, various ones, multiple ones, can get attacked by autoantibodies. And over time now, since I began my doctoral work, we're getting some more evidence out, being able to really show that there is this massive damage happening at this juncture, which is what we hypothesized causing such severe disability and damage and mortality. So that's what I set out to research. I, and I guess an important feature of this too, for me to mention part of the story, there are different types of antibodies. Again, your listeners have probably heard this before. I, at one point in a talk that I did for Twist Bioscience earlier this year, I kind of just impulsively called them different flavors for a lay audience, and they seemed to really be fans of that. So sometimes I call it that. So different flavors of antibodies. With different letters. So we've got IgG, which is the most common. We've got IgM, which is like common in MMN, right? And then we've got IgA and a couple others. And in this particular group of diseases, when I started my doctoral work, at least IgG was the main type of antibody considered and found in this disease. And I mentioned this because I basically, I went and, you know, stop me if you don't want me to get into the story.

No, no, no, keep going, keep going. I have questions, but keep going and then we can come back. Yeah, sure.

So I essentially what I did during my PhD is I kind of went into the lab for 2 and a half years trying to look for these IgG antibodies. So what I was doing was I was taking patient cells, patients who have this autoimmune neuropathy, and I looked at something called panneurofasciitis autoimmune neuropathy. So this means patients who who have autoantibodies against two types of a protein called neurofascin that's at this juncture. And looking at these patients' cells, and what you have to do in order to study the antibodies that they make to begin with is you have to kind of like grow up these cells in a dish and get them to spit out these antibodies so that you can gather them up and you can characterize them and study them. And nobody had done that yet in this context. So I was doing a lot of technical methods work, basically, which is pretty thankless work. It's not usually something you can publish at the end of the day. And you're setting the foundation for everyone else who does it afterwards. So it's pretty thankless. It's important, though. And so that's what I was setting up and trying to find these IgG antibodies from some patients' cells I was growing for about 2 and a half years. And I just couldn't find any. I couldn't find any, and I was trying to figure out everything that I could do. Wasn't finding anything. We started coming up with new ideas to use kind of what we call baits, antigen baits, where you kind of like mix a patient's cells with this bait that should attach to the types of B cells you're looking for that would attack the target you're looking at to kind of enrich for them.

Yeah.

Which was a whole process in and of itself trying to develop that. Because we were looking at a hit rate of 0.2% or something or less of individual cells from patients that I would culture. And then let's see, this would have been early June of 2024, so about a year and a half ago. We asked the question, are we maybe looking for the wrong thing?

Yeah. Yeah.

Are we looking for the wrong thing? So decided to— and the funny thing is this stuff, it almost always happens like late on a Friday evening or a Saturday. It's like at the end of the week or on the weekend. And I was trying to get some last results together for a conference we had the next week. And I was in on a Saturday to finish this assay. And we decided, why don't we not just test for IgG, but we also Let's test for IgM and see what we find. And I remember finishing that assay on a, that test on a late Saturday evening in the lab alone. What you do, you look at this fluorescent plate underneath a microscope in a dark room. So, you know, that kind of sets the scene for how dramatic this can be. And as expected, not really finding much IgG at all. I did find one for the first time ever, which was super exciting. But then lo and behold, I found positivity against IgM for what I knew is what was the first time basically this was identified. And it was at, if I recall correctly, 3 or 4 times higher incidence than IgG, right? Which was pretty striking. And it was really strong. I mean, the IgG signal, when we look at this for, like, for listeners, it's, it's for, excuse me, for the most part when we do this, it's pretty qualitative. You see how strongly it glows and you've got controls to kind of compare it against to decide whether it's positive or negative. The IgG positivity I had found even at that point, it's kind of, it was not, not too strong except I think in one case, but like the IgM, it was really bright. So I remember essentially, like, I think I was on the floor of the lab because I was just like so shocked. I was so overcome by what had happened. And there was no one there to— maybe it was good no one was there to watch it. And I could just have my moment. But I remember like texting my supervisor and being like, look at this. This is interesting, right? I wasn't sure. He was like, yeah, yep. In typical British fashion.

Yeah, yeah. Understated.

Yeah, it was very understated. So I was able to present that for the first time at the Peripheral Nerve Society conference that we have, our annual conference each year in Montreal that year. And of course, it caused a huge stir and a lot of people were really interested in it because the reason why this is important, Clive, is it's very possible that there are a proportion of patients with this type of neuropathy, and part of my hypothesis is autoimmune neuropathies in general that I'm going to be looking at for my fellowship, but certainly for panneurofasciomyelopathy that I was researching for my PhD, it's possible there is a proportion of patients that are presenting with the symptoms of this disease. But when they go for diagnostic testing, which is at least in the UK and around where we are, more clinicians become aware of what this could look like. And especially if they're aware of our laboratory and testing for this, they'll send off samples. It's possible that these patients are— they're going through the typical diagnostic tests, which are looking for IgG only.

Right.

And they're not getting diagnosed with the disease right away. And so they might spend a lot more time going through testing IVIG, corticosteroids, plasma exchange, you know, a lot of very labor-intensive, sometimes very expensive, time-consuming things with these patients when you don't really have a lot of time to lose because they can deteriorate so quickly. So the idea is if we find a pattern, which I think we will, and we already just testing the sera of a series of patients with these autoimmune neuropathies, panneurofasciopathy in particular, compared to a different kind, you know, we found 18 out of 18 samples we've tested before for IgM were positive for that. Whereas for contactin-1 autoimmune neuropathy, which is just a different target in the same class of diseases, had out of 16 samples, I think about 2 or 3 hits maybe, if that.

So you're potentially developing a— you're validating that there's a— you're validating a correlation between the generation of these antibodies, IgM, and this condition. And that's how— that's therefore giving a test that can be used clinically.

Yeah, potentially. So, so it's potentially that we can diagnose a lot of these patients more quickly if we test for both IgM and IgG, because it's possible there's a proportion of these patients that we're missing, so we're not able to give them something like rituximab. As quickly as we could have otherwise and prevent irreversible damage and disability.

Okay, so if I think, so someone, acute condition, someone presents at hospital, let's say, right? And it's not always easy to even get a diagnosis of GBS initially. You know, I hear of lots of people like, no, just go home, you'll be all right, kind of, you know. So the odds are, at the— as they— at the moment, as they're doing their kind of bank of texts, but also very conscious of the time-sensitive nature of, of that kind of condition you want to treat. So they're— at the moment, presumably most people at the moment with this— these other conditions are treated as if it was a GBS patient, and they're given IVIG. And what you're saying is that you would, you've got this potential to capture it, you know, to differentiate between GBS and this condition much earlier.

Potentially, if there is in fact a proportion that are testing negative who are actually positive for antibodies against these targets, just not IgG potentially. So, it does depend on the clinician who catches it, you know, if they they might catch it and say, this— it, it sounds like a nodopathy, it looks like a nodopathy, but we're not getting the, the positive test back right now. They might go for rituximab sooner. But what would be standard protocol is usually try IVIG, try steroids, try plasma exchange, maybe, um, before you go for rituximab. And of course, you know, I realize I come from a different healthcare system than the NHS, and the NHS is more important than ever that, you know, there are standard rules for the types of treatments that you choose and that you prove something doesn't work before you go on to the next. And I believe this is certainly one of those cases. So yeah, that was really an exciting outcome of my work and it was pretty much an accident. And I think it was a really important lesson again of like Taking a step back and asking if you're looking for the wrong thing was a pretty simple question.

There's so much you could play into that because you go, how? I mean, firstly, maybe this is where we, we, we can delve into motivation in a moment, but it, it first begs the question of how do you keep, like, for 2 and a half years getting, getting no, and then and, and still keeping going. Um, yeah, but it is also, yeah, what does it, what does it take for us to then go, hang on a minute, let's, let's stand back, look at the bigger picture and go, all right, this isn't, you know, at what point do you do that reassessment to say, okay, is, is this, is it because we're looking for the wrong thing? Um, do we need to take a different tack? Um, and it, I mean, there'd probably be people out there going, my God, 2 and a half years and you didn't, you know, and I'm sure it's not like you're going, I mean, what are you thinking in that process? Because you, you're presumably thinking it's not like you're going to the lab, doing it, getting a negative result, and going, "I will do it." You must be thinking, "Why?" constantly. Why are we getting these results? Yeah.

I mean, these are really good questions that you put out there. I think as far as showing up for 2.5 years and not really getting results, I am fortunate. And that I did it. I was doing a PhD and I chose to do the PhD. And, you know, I was 2 and a half years in and I did know, you know, it happens where you can— you have a PhD and you don't really have any positive results to show for it, but you show you went through the scientific process and there's a finding. It's different, you know, when you get to like where I'm at now, where you're on a fellowship and you're back out in the working world, so to speak. And if you spend 3 years doing that and you're not writing results, you're in a lot more trouble. I mean, because of this, for example, I don't yet have a first author publication out of my work from my PhD, which, you know, in the world that we live in, in this world I live in at the moment, it is unfortunate. It's still very much publish or perish, and it did prevent me from getting the type of visa I would have liked to get for my work because all they saw is you don't have a first author publication. And part of the reason was because I I concentrated on trying to disseminate this information out in a very unofficial, I guess, way as quickly as possible to start changing the way we're already doing things in the lab over painstakingly putting a paper together on it, which is what's being done now. But in any case, it also took a great supervisor who could help me ask the question, are we looking for the wrong thing? You know, I can't take full credit for asking that question. Certainly a joint effort, but, you know, it's difficult in this line of work. You watch some people and you, you all go through the scientific process, but everyone does it a little bit differently, and that some people really want to go through the list of A through Z for all the possible ways the problem could be approached before they leave it alone, which sometimes could be a good thing because what if Z was the answer? And most people didn't stick around to the, to the 26th letter. Um, but you know, all other times, and I kind of tend to be this way because I think of my entrepreneurial way of doing things where I, I don't want to wait till things are perfect. I want to get them out there.

Yeah.

And I think that's also a way of looking at it when you work in industry like I did for a couple years before my PhD. You're not always stopping and going through every possible, every possibility, right? You have to make strategic decisions and decide when to cut bait and move on. And so, you know, it was a matter of going through that process, what felt reasonable enough before asking this question, but also testing for IgM on top of IgG is not a hard thing to do. It's not a difficult thing to add on to what we were doing. It would be another thing if it was very labor-intensive, so that also goes into the decision.

Yeah.

And it was, it was the right combination of people looking at the problem. You know, I had one of my assessors— so you have two milestones during your PhD just to make sure you're on track basically before you do your defense. And the first one is called transfer of status after you've been doing it for a little over a year. You're not expected to really have results. It's just a check-in that like you've got a plan, you are attacking the problem, et cetera. And I had, you have two assessors for these things. And I had one assessor who he, I mean, he shares an office with Simon and he's generally a nice guy, but a terrifying assessor. And, you know, asks a lot of really good questions, but I'm not gonna lie after that, I like to think of myself as a pretty mentally resilient and tough person. But after that, I quite literally, I went to the bathroom, I cried afterwards.

Yeah.

Because of, you know, the way the questioning was done, it was like an interrogation. However, you know, one thing that he came up with when we were talking about it, he said, well, I think you should just stop trying to go down this route. Just go for this thing that you don't feel like you're ready for yet, but is in your plans and see if you get an answer. And I think at first a lot of people were like, no, don't know if we're ready yet, but we decided to go that way anyways. And it was the right course of action. So I think as I'm talking about this now, you know, pulling themes out of that, continuing to talk to people about stuff and not living in the echo chamber of your own head, which I think applies to so many problems in life. Yeah, a lot of this, a lot of these, my PhD taught me to do that. You have to do that.

Yeah.

And I think I have been someone— I think a lot of high achievers are like this too, where you don't want to— you're not in the habit of asking for help, um, either because you're afraid it will make you look bad, make you look like you don't know anything, or you've learned somehow that, you know, you shouldn't share things or people might steal ideas, which is certainly the atmosphere in American academia for sure, um, which maybe we'll get into later on this depending on how much time we have. But, but yeah, just like continuing to talk to people, listen to people and have no ego about it also is an amazing example that I've had in this department at Oxford that I've been struck by from the get-go. It's never been my experience in academic research before. I've had some nightmarish experiences. I'll throw in here because I want to make sure it gets said in case we get short on time. But I When I finished my bachelor's degree and, you know, maybe we'll get into this later, but like I got all of my rejections to PhD programs and I had to figure out, okay, what do I want to do now? And I was applying to jobs and I got a laboratory technician position at Harvard in Boston.

Yeah.

And I was very excited about this opportunity. It was in Harvard's stem cell and regenerative biology department. Yeah, because I was very interested in not just looking at, um, this stuff from the, from the standpoint of what's going wrong, what's getting destroyed, but how can we understand this to start repairing it. So I was very excited to be there, and for a variety of reasons, it just ended up being an incredibly toxic environment. And I will not name names, but, um, my PI of that lab, very successful guy in that field. Yeah. He— I remember one day he called me into his office and he had seen that I had posted this position like on my LinkedIn as part of my, my experience. And I had taken a quote from their lab website to kind of describe what was being done in the lab and what I was contributing to. And I remember he accused me of not understanding it at all and just, you know, getting this job at Harvard to look important and look smart, but accused me of not knowing at all what I was doing. So I forget where I was going with that. But in any case, that, that was just one of my many interesting experiences in academia leading up to this point. And then this department at Oxford really surprised me from the get-go. You know, starting with Simon, my supervisor, who I just got so amazingly lucky with. I mean, you know him well too. He certainly is the exception in my experience, but in this department in general, there's just like very few people who have a huge ego about them. And I find that really impressive. It's incredibly difficult to find in academia, and it usually selects for those kinds of people. And it does end up being a very exclusionary environment. And to me, it becomes no wonder why we sometimes do get a lack of women at the top. That's been my experience throughout most of my academic career. I remember working in an immunology lab in MS during my bachelor's degree, and I was the only woman in the lab doing actual research. There was one other woman who was doing administrative work, but I was the only one doing research. You know, it— you did have men kind of making offhanded comments about the fact that I was the only woman there. A lot of people assume, like, once we got into the 21st century that this doesn't really happen anymore. But it's not true. So especially in immunology, I've really seen a lack of women, certainly in a lot of other biomedical fields. The demographics relative to each other have shifted to be a lot more equal. But in immunology, neuroimmunology, what I do, there's still quite a lack of women at the top. But, you know, I remember when I was working in a biotech company in Boston, the first biotech company I worked at, and the CEO, you know, he was getting a lot of questions about why there were so many women who were kind of in much lower, lower positions. Yeah, but there were no women in the C-suite at all. And this is Boston. It is filled with talented people, including a lot of really smart women. And he came at us with, well, the people just aren't there. You know, we would, we would choose them if they were there, but he tried to tell us they weren't there. The next biotech company I went to, the women were there because they were compensating them well, because they were treating them well, because they were valuing them. And I see that in my department at Oxford. And that's awesome.

It's interesting, isn't it? I think, you know, there are so many things you could unpack there around what each—

I know, I just said a lot.

You have. There's a few soapboxes there, which is cool. It's about how do you, you know, ultimately, how do you maximize our collective knowledge, brainpower, skill set? To further our understanding of ourselves, if you like, and what's going on in our own bodies, and then to translate that into actionable clinical differences and make a difference for the patient and academia. And a long, many moons ago, I did a PhD, um, in geology, so completely different, completely different, um, completely different experience to yours. Um, but this driving this, you know, this narrative of, um, it's all about, you know, funding. Funding drives everything. Funding is driven by your research assessment exercise, I think they used to call it then. Which was, you know, every few years someone goes around and they assess seemingly mainly based on how many papers you're generating and what— if it's gone into Nature, it's worth 10 points, and if it's gone into, you know, in my case, the Scottish Journal of Geology, it's worth a point, but it's not really. And And then getting a grading. No, and interestingly, not really. So, so what I experienced was people were given positions based on their research capability as opposed to their teaching capability, and they're then teaching people, but they're also then supervising people.

Yeah.

And, and, and every so often you'll find that someone, and I think it sounds like Simon's a good example where they're not only technically really, really good, but they can actually lead teams.

Yeah.

But it's quite rare.

It is quite rare. Yeah.

And the system isn't encouraging you ironically to collaborate. Yeah.

Very true.

Because you're all fighting over, you know, trying to get your rank— you up the ranking. And it's in complete contrast to the fact that, you know, you can't— however good you are, you can't think of everything. Um, and especially in my own experience was one where I was very focused and I could not see the wood for the trees. And it's, you know, coming back to, I suppose, now, which is 30-odd years on, um, the one thing I've learned the most in my journey of with, with MMN, and particularly the journey I've taken in the last 2 years of, you know, trying to ride around France and all that kind of stuff on a bike is that the biggest, you know, and I will say this, biggest super— the superpower is vulnerability and your willingness to ask for help. And, and, and not just ask for help, accept the help if it's offered. Um, not, you know, ego. We've all got our egos, whether we admit it or not. We all— and I, I will package mine up as strength and independence and resilience and, um, and not wanting to be a burden. And, and, and, and then we'll realize that that behavior is not necessarily helping. I'm pushing people away. I'm not letting them contribute and, and, and play their part. Um, so it's, it's, it's a similar journey, you know. It's Um, you're, you're in a position where you could very easily go, I'm, I'm strong, I'm independent, I know what I'm doing, I don't need anybody's help, especially as a woman in a male-dominated kind of world. Um, but that's, that's not actually going to help you or anybody else, really. I don't think so. Yeah.

I think my personal motivation for being here has made it easier, I think, for me to not have, you know, certainly like you just said, we all have our own egos. I have my own ego for sure. But I think in this domain has helped me not let my ego get as much in my own way because it, was never about me. And so I guess I could have found a more elegant way to probably get this part in earlier because as you saw, like at the INUK meeting—

Well, this is a beautiful segue, isn't it, to why do you do what you do?

Yeah. So, you know, and like you saw this presentation that I did in Manchester at this INUK patient meetup and AGM, You know, I start with this picture of this little girl in a wheelchair and talk about her and say, you know, one day when she was 7 years old, she was on the playground playing at recess and the bell rang and that means it was time to queue up and go back inside. And this little girl, instead, she fell down. And she couldn't get back up. And, you know, her parents spent a couple of weeks, months trying to figure out what was going on, going around to different doctors, trying to get a diagnosis. Meanwhile, she became emaciated, you know, at one point quadriplegic, and ended up being in hospital at Mayo Clinic in Rochester, Minnesota, and was then diagnosed with CIDP. And at that point in time at least, was told that she was the second youngest case in the world. So pediatric cases really had not been identified. And if we think that we knew— know very little about GBS and CIDP now, we certainly knew even less back in— what, that must have been in about 2002, 2003. Yeah. And so then, you know, this is when I reveal that little girl is my twin sister, my fraternal twin sister, Megan. And so she is the reason that I do what I do. And, you know, I can— I can certainly— I was even talking to somebody yesterday about kind of— it came up why I do what I do. And, you know, one feature that can happen for both GBS and CIDP is pretty extreme neuropathic pain. Not for everyone, but for her, she was very temperature sensitive to extreme temperature. And she and I grew up with what's called a Jack and Jill bathroom. I don't know if you've ever heard that term. We had our own bedrooms, but then we had connecting the sinks and then like shared a shower bathtub. And so I, yeah, I remember when I was growing up in elementary school and primary school, you know, hearing her scream, being lifted out of the bathtub. Because the cold was just so, so painful for her, which was horrible. Right. And so she had a PICC line in her arm for many years. She got weekly IVIG infusions. She then had a port put in here.

Yeah.

And probably didn't have that removed till maybe age 15. I want to say she refused— or she got weekly infusions. I would say when we were about 16 years old, maybe, went to Mayo Clinic. So that, that would have been 13, almost 14 years ago. Went to Mayo Clinic and kind of got it confirmed that the disease hadn't progressed further at all. And so she doesn't receive infusions anymore, hasn't for a very long time. And so she's kind of, I guess you could say, in the clear. Yeah. But she did lose her ability to flex her feet and she'll never get that back. And she did. You know, and this is interesting, especially for my work, too. When we were 21 years old, she was diagnosed with non-Hodgkin's lymphoma, which is a B-cell cancer.

Okay.

Which is pretty interesting. So luckily, that was like the less bad type of lymphoma, the one that has much better outcomes, especially for young people. As she does, she was a fighter and she beat that, too. And yeah, now she's a software engineer. She lives with my family, around my family back in Michigan, and just celebrated her 1-year wedding anniversary this year. So that's, that's awesome. But basically my whole thing is we're very lucky that she survived. At one point there was a ventilator on standby waiting for when her lungs might fail, and we were lucky that she made it through. But as we all know, on this podcast, not everyone is so lucky.

Yeah.

And so, yeah, Megan, Megan is my why. And I kind of want to— if I can prevent one other family in my life from having to go through what my family did and what Megan did, it's spending her childhood relearning how to walk in and out of hospitals, foot braces, surgeries. If I can prevent one other family and one other sister from having to go through that, then my life will be complete.

Which is, you know, that's— it's incredible. I mean, it's an amazing story. It's an amazing approach you've taken to take that as your motivation. I think it's, you know, It's such a— it, it explains this in, in many respects. It's this— your, your, your decision, if you like, that having discovered something that's of use, your, your desire to want to tell the world rather than, you know, through as many means as possible, rather than go, okay, I'm now going to spend 6 months getting this through the relevant editorial process to go in a scientific, you know, paper that, you know, a few— shouldn't say this— a few people might read. I mean, I think this is one of the biggest challenges. I, I talked to my neurologist about it only yesterday, actually, is how hard it is for doctors, even specialists like neurologists, to keep up with all the research, let alone patients to keep up with it. And to know what's out there. And you've got to make a noise when you've got something that is going to make a difference. And beyond, it's not just about— if you make a noise, if you, if you're, if you spend that 6 to 12 months getting the paper out, that's one thing. But there's only one, one very kind of narrow group of the kind of, let's call it the, the medical ecosystem that's going to hear that.

Yeah.

And that ecosystem is, is everybody from the patient, the potential patient, and the potential you know, those that surround the patient. It's, it's the other researchers. It's the practicing neurologists, the practicing GPs. It's all, you know, it's the ED doctors. It's the biopharmas, the pharmaceutical companies that go, oh, wow, there's something in that, right? I want to turn that into You know, let's maybe, maybe there's a way to speed up the, the, that assessment. Um, because unless you've got, if you're working on everything happening sequentially from, um, right, I'll do the research and I'll put it in a paper and then this will happen and then this will happen, it will take 10 years for something to happen. And I think, you know, you look at respect to this idea of collaboration in that things will move faster if we collaborate on them and we're doing them in parallel and people are working on different aspects of this altogether. You've only got to look at COVID vaccine, you know, something that should, should in inverted commas, take about 10 years to develop a new vaccine and get the approvals happens in what, 18 months? Why?

Right.

Why? Because everyone, frankly, cares enough, almost gives a shit. And then also you look at my wife, for a wee while, worked at the Wellcome Trust in London, who are a big funder of medical research. And when they were trying to characterize the human genome, they said, You know, we will only fund you if you all collaborate, because various companies or organizations were working on trying to describe the human genome. And, um, they made it a condition of funding that you had to share your data. Um, yeah, and it's often, so often people's willingness to hold on to, for want of a better phrase, their intellectual property. Yeah, actually gets in the way of innovation. And so, you know, by you having at the forefront of your mind always this, like, this, I want to help someone who— I want to help others avoid what happened to my sister. Means you are gonna just shout it from the rooftops.

Yeah.

Yeah.

I mean, you put it, yeah. Sorry, go ahead.

And just being in an environment that enables that is, is doubly powerful as well because like will attract like. And I think that's, people will go, that's a cool place to work. And we— I can make a difference. And I'm sure for some people, and you read this a lot about— read books about disgruntled doctors who've, who've had it, you know, there's been a load of kind of these people in recent years write their books about how horrible it is being a junior doctor. And how, and how the humanity gets sucked out of you, right? You go in for all the right reasons and then the machine puts you through 80-hour weeks and you lose, almost lose your compassion and your—

yeah, yeah.

And that's not everybody, of course, but it, it's a pretty hard—

happens to many. Yeah.

And I could imagine in the scientific side of research side, it'd be very easy to almost dehumanize you in that system. So it's very cool that you're not.

Yeah, and I think on this topic of kind of collaboration and the atmosphere sometimes, you know, I don't fault most academics for being that way because they've basically learned that if they don't look out for themselves that way, their entire career is unstable and you know, they're kicked to the doorstep next year because they didn't put out their publications. And if you get scooped, if somebody publishes the thing before you did, how much work and money is that down the drain? And again, you could be booted out the door a year from now or less. It's like, it's a very scary system to be a part of. Um, and it's incredibly stressful because it works this way. And I've also, I've had to acknowledge the fact that like, because of the way I have done this for what we're talking about and publicizing these very preliminary findings, what we found with these antibodies. And again, I think it's very exciting. So I talk about it this way. I also don't want to overstate it. We've got hypotheses, et cetera, et cetera. But I think it is potentially very exciting. And I didn't get to say before too, because if IgM is implicated in this, it also implicates a whole— or it indicates a whole other class of drugs that could be really helpful, like complement inhibitors, et cetera, for these group of patients that hasn't been looked at before, which is what I will do for part of this fellowship. But in any case, where was I going with that? Yeah, I've, I've had to acknowledge the fact that, like, I very well could get scooped. Somebody could very well publish something more thorough than I've had the time to get out right now for a variety of reasons. That will really stink if that happens, you know, for my career. But I get that this is also not only my personal motivation, but also the fact that I like do and love to do other things like my entrepreneurship and my business, which is not benchwork at all. That I think helps me a lot too. It makes the stakes feel a lot less high, which I think is really helpful for me. Not to mention the fact that I think the entrepreneurship has made me a better scientist. And vice versa.

Yeah, yeah, yeah. I mean, I think you've, you've, um, given, given the age you are— don't take this the wrong way— but it's, it, you, you've, you've got to a point in, in your thinking about, you know, how to spread risk, if you like, in, in your own career, that I've taken 30-odd years to work out, but having one job and doing what, just one thing, you know, really, really well, but at the same time being entirely reliant on the vagaries of the economics of a particular industry at a particular time is, is in some respect, in sometimes it feels very stable and supportive, until it's not.

Diversification.

And so spreading, spreading your risk, um, and, and also learning from, learn, you know, learning from different things you're doing. So, you know, you, you've, you've had this, this all enables you to do what you do so well because Okay, you did, you, you had a travel blog, so that, that's all about how do you communicate, right? How do you tell stories, which is what you end up doing as a scientist, because scientists have to tell stories.

Yeah, I agree.

Um, you're, you know, the— I'm sure helping others to, to, um, work their way through the kind of admissions processes of, of, you know, Oxford and Cambridge universities and find funding is— must have— I mean, that must be an absolute minefield, but just from a process perspective. But there's also— and I've seen a lot of what you've doing is about, okay, it's It is about, I'm paraphrasing what I took from the, what's on your website, which is, yes, sir. It's about, it's not about to use the American, you know, GPA, grade point average, right?

Yeah.

It's not necessarily, although it helps about what university you went to. It's about who you are and selling who you are and what you stand for. you know, yes, done that very well. It's about the rounded individual. Um, and, and probably if you take that approach, you will very quickly find out if that is the right team to be joining anyway. You know, is Oxford the right place for me? Because actually, if they don't want me with all my weird idiosyncrasies, then I'm not going to enjoy it anyway, even if it's going to look good on a CV, right? And maybe I'm better off—

Exactly what I tell students too, that it is a two-way street and you don't want to be somewhere anyways that's not going to appreciate all these facets of you. Do you mind if I like take a couple of minutes to kind of describe my, or, you know, this Oxford Admissions Club, what I do and like what, why I do that?

No, absolutely not. No, why not?

Yeah. So in any case, This is how you pay the bills, isn't it? To be honest, yes, yes, um, it is. So my business precisely, um, allows me to afford to be an academic researcher, which is the unfortunate truth.

So we get the little violins out for the, oh, the poor.

I honestly, it would have, it would have been a much smarter financial decision honestly for me to go back into biotech after my PhD because especially when you do your education in United States, most people, including myself, are left with a lot of debt.

Right.

Um, and so, you know, there are lots of things at play there and that's not really the main point, but anyways, I say that because you mentioned that and you're right. Um, and a lot of people, I think, don't realize that this is not just like a fun hobby. Um, it's, it does pay the bills. So in any case, when I graduated from my bachelor's degree from the University of Michigan in 2017, I decided, and it was kind of a little last minute. I had toyed with the idea of a PhD for a while back and forth, and then I decided I would go for it. And I kind of had all of these things that people told me I would need to get into a top PhD program. You know, I graduated in the top 10% of my class, magna cum laude is what we call that at the University of Michigan, you know, from the honors program. It's a good university. I had good grades. I had all these different leadership experiences and extracurriculars. I had this personal motivation. So I thought, that's good enough, I think, to get in. And I kind of didn't realize— you don't know what you don't know.

Yeah.

And so I applied to over 10 master's and PhD programs and not just, you know, like top Ivy Leagues, but also toward kind of run-of-the-mill universities, I guess, if you will. I don't want to call them that because I really don't want to sound like I'm poo-pooing them at all. And that's not it. But, you know, places where I think almost anyone around me thought I was a shoo-in. Yeah, rejected to all of them. Not even a single interview, just nothing. And I think this was devastating for me because one, it was very unexpected, and two, you know, I wanted to work on research for my twin sister's disease. But also looking back on it, I wanted to do lots of different things. It's the blessing and the curse of what you're saying, how I do all these different things. It's a blessing and a curse of being what's called the multipotentialite. I just love doing many different things, but if you're not careful, it makes you sound very unfocused and you have to know how to focus it properly. And that's been a lifelong thing I've been learning. In any case, I digress. So that was like one of a number of mistakes I made through that process, but I basically, I didn't know what I did wrong. It was devastating. I kind of, I, so I decided to get some extra work experience for a couple of years. I got fired twice.

Everybody needs that on their CV.

Yeah. So, and it was the first time I got fired from like a 3-month stint at a financial consultancy startup in Boston that just, in any case, not important, but 3 months in was let go and allowed me to like travel full time for 6, 7, 8 months. Which was amazing, and really lean into the travel blogging thing just because I, I love to travel, especially like solo female travel has been something I'm very passionate about because I grew up in a place where no one ever gets out of it really. They don't even really go travel, um, and it's not because people aren't aware or highly educated, you know, both my, my mother has a doctorate in veterinary medicine, my dad has a PhD in clinical psychology and runs his own private practice, but they didn't own passports until I was studying abroad for over a year in 2017 and came and visited me. So that's kind of the place I come from and had this kind of this inkling that I was missing something and I really wanted to find out what it was and I loved it. So anyways, that's the reason for the travel blogging thing. But, um, I decided in 2020 with everything that was going on and I was working in biotech at that time. So I was an essential worker, um, that I would try to go for PhD programs again because I decided if I want to progress in biotech, if I want to create these therapies that are going to change people's lives with peripheral neuropathies, I've got to get a PhD at the least. So I decided to do it, but I completely changed the way I did things and I stopped being scared to ask people for help. Theme. And I happened to work with somebody who got into top US PhD programs the year before. So I decided to ask her, you know, hey, do you have any tips? Could I see some of your application materials? And I actually just— it wasn't this simple, really, necessarily, but I kind of just tried to reverse engineer it. I was like, how can I use these frameworks I see in the way she's done her CV and the way she's written her personal statement and apply them to mine so I'm not reinventing the wheel where I don't need to. I tried to talk to as many academics as I knew from various things in my past to figure out stupid simple tips. For example, there's a specific time of day that you can send an email to a potential supervisor that it practically 10x's the likelihood that they actually respond to your email versus ignoring it.

Really, Claire Bergstrom Johnson PhD.

It's stuff like that that actually makes a huge, huge difference, and you just don't know that you don't know it. Yeah, is most people when they're applying the Oxbridge process in particular. So I, after, gosh, I was so scared when I tried again, I was so scared of getting rejected again. And I am lucky that I also had people around me who were like, no, you can do this, go for it. And I made this my life's mission that year. I worked and then I worked on these applications. I'm not a morning person. I got up at 6:00 AM to work on these before I went to work. I came home and that's what I did. And then I ended up getting like 7 PhD interviews in the span of 10 days, which was incredible and incredibly stressful. And then I ended up winning 2 fully funded offers to both Oxford and Cambridge. And so that's kind of my story. I turned over 10 rejections into these 2 fully funded offers and learned how this whole process worked. And I couldn't stop thinking about Wow, there's so much I never knew about how this works, and you don't know until you've done it. And as I got to Oxford and as time went on, it just kept hitting me more and more. There are so many people out there who are like me, and they've got this really deep why for why they want to go do what they want to do. And a graduate degree, especially at somewhere like Oxford and Cambridge, is going to help them make that change in the world. But they're not given the opportunity simply because they don't know when to send an email to a supervisor. That's silly. That's just silly. And so I thought, why don't I, as an experiment, I'm going to try flipping the very expensive private admissions consulting business on its head and do what I've seen a lot of people do in all kinds of other subjects and niches and do this with kind of like a self-paced DIY online course. Yeah, it's never been done before in this niche. And I decided let's try it because like people think this has to be really complicated and hard. But a lot of it doesn't have to be. It actually is simple. And so that's what I've done. I've been running the company now for over 2 years. And it, man, it has challenged me. It has changed me. It has grown me. And I've been fortunate to have a lot of success, especially early on. But I've now helped over 1,400 applicants from over 80 countries around the world. My students get 2 to 3 times more offers than the average postgraduate applicant to Oxford and Cambridge, as well as other top UK universities. And I just— my why behind that is not just Megan, but also thinking about shifting the demographics of the people who are getting into universities like this. I, I don't like that the world still works this way, but it does. We have to admit, if you've got a place like Oxford or Cambridge on your CV, it is going to at least get your foot in the door of a place that otherwise might not have even glanced twice at your CV. Yeah, think about who's getting those opportunities versus who's not right now because they didn't know when to send a frickin' email to a supervisor. So what I'm also, I'm trying to do is fundamentally shift who's getting these opportunities, who's getting to be in these rooms. And man, like, I can't even, I don't think I can even fathom how much that could be changing the representation of people doing things at the very top. In like 10 years' time. And maybe that's me overstating what I'm doing here, but I, I've been seeing it. I've been seeing my students, especially I have a lot who are from third world countries and minorities who think Oxford isn't for them.

Yeah.

And they need someone, somebody to just tell them like, look, this is my process. I didn't do it right the first time. You can fail, and you can fail again, and I talk to my students all the time about failure too, because I always say, if you're pushing yourself hard enough, if you're trying to challenge yourself and grow, you will keep failing. It will keep happening, and that's okay. We all get way more nos than yeses. I say, if you get way more nos than yeses, you're doing something right. A winner is just a failure that tried one more time.

Yeah, it's very powerful. It's interesting, the, the, um, I've, I've recently reconnected with getting kind of back to being interested in politics, which is— yeah, I don't get too political, but particularly, um, listening to a couple of, you know, UK political things and, and the, the UK has been through um, more— what was it— more prime ministers in the last 10 years than the previous, like, 30-odd. It's kind of ridiculous.

Yeah, um, 4 years ago was a bit of a circus.

Yeah, but listening to one particular podcast and talking about this, still very much in politics, a path, a pathway for a huge amount of politicians, and particular prime ministers, go through a particular university. Like, they go, they go, what in the UK is public school, so private schools, certain schools like the Etons of the world, and then they go to Oxford, and then they do a particular degree at Oxford, and then they end up in politics, and these are the ruling classes. And, and, and that's one area, but it's the same, right? If you, you know, some people believe, and this isn't— I probably shouldn't talk politics, but you hear Boris Johnson and you learn about Boris Johnson, and the sense is he— people, some people are born with the belief that they have almost like a right by birth to be in charge.

Mm-hmm.

And to be the leaders, and that is their given right. And, and, and equally to your point, so many of us are born with this idea, what comes to us quite early is that's not for us. That's what somebody else does.

Yeah.

And so it's amazing being able to um, yeah, that you're, you're not just recognizing that but actually doing something about it. And, and, you know, there's no doubt that, that what you have learned, you know, if you look at what you've probably learned in the last 3 years of both the PhD and running this business, the sum of the two is much bigger than if you just focused on one or the other. But as somebody who with ambition to kind of run our own biotech at some point, there's gonna be so much you will have taken from the entrepreneurial side of the business.

Yeah. Yeah, for sure.

That probably means we should, and it is inspiring and it's amazing to hear. They, they just, what? Yeah, it's just, The impact you must be having on a, on a generation of, you know, of young academics, driven academics, um, is really cool. It's really inspiring. What, what's next for you? So what's, what are you going to do to spend the money that's been given to you by the GBSCIDP Foundation?

Yeah.

What, what's, what, what are you, what are you hoping you'll, um, do with that? What's the, what's the next problem, um, to solve?

Sure. Yeah. So this suspicion of a pattern that I talked about earlier on from my PhD, basically a good chunk of the beginning of this fellowship is gonna be spent on looking at more patients. I, at least the cells themselves, have only looked at one of these patients. And using this technique that I talked about earlier called antigen baits, which I've been developing in parallel, which is going to be a very useful reagent for not just me, but anyone who wants to collaborate to use to much more efficiently capture these cells when we kind of like One of the ways we study them is we put them through a machine called a flow cytometer or a cell sorter that, based on different markers that different B cells along their development express, we can put them into different bins and grow them separately. So basically it gives us a snapshot of all of their B cells throughout the development process. And based on that allows me to figure out at what point are they creating these autoantibodies. Mm-hmm. So I can, I've seen this in one patient with kind of an interesting signature. His cells happen to have where, um, and I'll find simple, simple terms to put this in. When you have these IgG-producing B cells, you expect at that point when there's a B cell producing IgG, it's a pretty mature B cell. It's had a lot of time to literally, what we call it is be educated, right? You know, learn what it's supposed to react to. In this case, you know, something's gone wrong there. And when they're producing IgG, they've gone through a lot of processes of recombination and mutation. This is how you have such a diverse immune system, because there's such an amazing number of ways these things can recombine. It's actually amazing. But then it's no wonder that some things can go wrong. It's just usually that gets kicked out of the immune system when you've got a healthy functioning immune system. Those autoreactive B cells are otherwise like they're eliminated or they're inactivated, but something's going wrong that that's not happening. So it's a failure of immune tolerance and what it's called. So when you've got IgG-producing B cells, they've gone through a lot of mutation, and you can see that signature when you sequence their B cells, when you get like the DNA sequence from these. That's what we do in order to create monoclonal antibodies. So basically, we, we find this antibody, it's produced naturally in culture, we get the sequence for that, and then we can create hundreds, thousands, whatever replicates of that. So we've got the exact same antibody and we can study it and we can use it. But this particular patient I looked at, he had these IgG-producing B cells, but they actually were very— they had very few, if any, mutations, which is super curious. And I'm— this is one of the things I'll be doing in my fellowship is looking at more patients to see, are we seeing this? It has important implications for what's going on in the immune system and exactly what is going wrong. In this case, there's potentially something wrong with these centers called germinal centers throughout your body where your B cells do mature, and potentially something's going wrong here. And the details of that, for the intents and purposes of what we're talking about today, is not so much— not so important as much as to say this kind of work can potentially help us really target where specifically something is going wrong. So we don't have to have this broad broad spectrum approach of let's wipe out all of your CD20 expressing B cells, which is not a good solution. You need your CD20 expressing B cells because that's your immune system, right? Right. But instead targeting what is specifically going wrong. And that goes again back to what I said about, you know, not putting a Band-Aid on the problem but figuring out what's actually going wrong. And so that's going to be the first part of this fellowship. And then what I hope to do is to use these myelinating co-cultures that we've got in the Rinaldi Group here at Oxford, where we can have these cultures of human peripheral nerves and they need to myelinate so that we're actually recapitulating what's happening in the body. And importantly, we can get these nodes of Ranvier, which for my particular applications is of course crucial. And we can not only be able to actually observe and image what's happening when we take these problematic antibodies I've been able to isolate and then create many copies of, what happens when we throw them at those cultures? And then I can image what I suspect is a ton of damage going on, but also measuring other things like complement activation and cascades, testing different drugs that are out there and seeing Does that stop damage and allows us to like quite literally in a dish observe what could potentially happen in a human. And we always cross our fingers that we see a pattern because that's very powerful. However, all of us in inflammatory neuropathy research know that when you have something that's a group of syndromes, it's very heterogeneous. And that's a difficult problem, I think, in scientific research into the inflammatory neuropathies, we still don't have good, I think, bins to really separate out similar patients and then get enough of them that we can come up with powerful conclusions and patterns. Almost always when we have studies into inflammatory neuropathies, even specific kinds, you still get variance between patients, either how they've been treated, when they've been treated. You know, some of these things are unavoidable. You can't just like, because it might be interesting for a study later, delay treating someone for 3 months.

Yeah.

So some of these things are unavoidable, but they're still, you know, you always look at the— I feel like I always look at the clinical data from these papers and I see, well, what would you have found if you had separated out these 2 groups? Or how much does that factor affect something? And it's a unique challenge and it's a unique challenge in particular for rare diseases like this. And autoimmune neuropathies are even rarer than things like GBS and CIDP. So getting enough power for your sample size is certainly, certainly a challenge. But, you know, something I'm doing right off the bat right now, which is a lot easier than looking at people's cells, is their serum just from the blood that we collect and starting to look at longitudinally, you know, same serum samples from a patient that's been treated over time. Maybe they relapse. Relapsed, checking them for not just IgG, but also IgM, IgA even, and see how these things change over time. It's not data that we have yet. And particularly, I wonder, looking at IgM, is it going to help us predict things like chance of relapse? Do we have a proportion of patients that are seronegative? They tested negative for this nodopathy because they weren't tested for IgM, but maybe in their clinical data it says that they responded really poorly or they were a non-responder to IVIG. I wonder if this is a seronegative autoimmune neuropathy. So that's another what I'll be doing. And I think it's a low-hanging fruit, but it will, I think, rapidly give us a much more detailed picture of perhaps what's been a missing puzzle piece. At least that's what I'm hoping.

So can I try and— try and— you're frying my brain.

I'm sorry, that's all right.

But in— if I look at that from a kind of layman's terms, and what I— what we're saying is it— in— and, and my observations is it is incredibly difficult to, with ultra-rare conditions like these, to get definitive kind of diagnoses and be able to know that and I know I've heard this in people who are running trials at the moment saying actually finding the quantity of people that definitively we can hand on heart say 99.9%, that is what they have got, is really, really hard.

Yeah, it is hard.

And the other side of that coin is, of course, many, many people You know, I know lots of people who've had 1, 2, 3 different diagnoses. And, you know, that's, that would suggest that there's lots of, oh yeah, we think it's this, we think it's that, we're not 100%, but we'll treat you for this. Um, it's, it's a really, it became, I was at a rare disease world orphan drug congress in Amsterdam recently and This challenge of finding enough, enough people with definitive diagnoses that are able to be part of trials and part of research. It's difficult because it's not just about finding that they've got to be in the right place where they've access to the right doctors. They've got to have had, you know, in some instances their treatment if they're on particular treatments, they can't be on that for a trial, or this, that, and the other. Really difficult finding the number of people. Also, and so the question, and it's interesting you raise longitudinal stuff, studies, is then how do we use longitude? How do we develop the databases that follow, track people through time to get what they described as real-world evidence? So even when there's a treatment and you say, yeah, well, we're going to give approval to that, regulator says yes, it's available, it's made available. But you know that actually the, the trial has only had, let's say, for, for argument's sake and keep the math simple, there's been 100 people on the trial. And so statistically, against a trial that you might want to do for I don't know, prostate cancer, where you can probably get thousands and thousands of people and be really statistically kind of go, yeah, the results stack up statistically, particularly for things like which might be adverse reactions. You know, if an adverse reaction is a 1 in 100 people, but you've only had 100 people on the trial, are you really going to see it? Or if it's 1 in 200, you might not see it at all. And so being able to study cohorts of people over a long period of time to get at, you know, is, is, is a huge challenge. Um, it's also interesting, and I don't really under— I don't understand this at all, actually. Let's be honest, I don't understand this at all. I've heard about AI. Being used to create, like, I don't know, almost model patients. I don't know what the right word is. So that those can add to your cohort of real patients so that you can use AI to model stuff. Yeah. In the way that they talk about creating digital twins of populations.

Yeah, sure.

Okay. I'm at the furthest edge away from that, but there are biotech companies looking at this apparently, or, and how trying to address this challenge of how do we get enough people to be able to study?

Yeah.

To really understand what's going on. So long-winded, but it's It's incredibly challenging. I mean, obviously I do find it fascinating, and this is the thing that I, I couldn't believe it when Simon and Nicola, when I visited Oxford last year or earlier this year, gosh, um, just said, yeah, what I'm showing you now is we've grown human nerves. Yeah, I'm like, hang on a minute, how do you do that? And I, I will It's a fascinating insight because you hear this whole, like, people do, you know, they'll trial drugs on mice and things like that, and then they'll try them on humans. But you've got this whole stage before that, or woven into that as well. It's fascinating.

It is really, and it's amazing how much this has progressed. I think even the last 10 years, like, I remember, for example, doing stem cell research used to be a very ethically, well, for a lot of people it was ethically questionable.

Yeah.

The way you had to get stem cells. But, you know, ever since, you know, the Yamanaka paper came out, I don't remember when that was. But in any case, these factors that you can give somatic cells, so we just take skin cells off the body and give them through the variety of ingredients and factors that they need. To get the instructions to go back to a pluripotent cell or a cell that can become any type of cell in the body except a germ cell. So except an egg or sperm cell. So that question is out now. And I think there are still a lot of people who don't even realize how advanced that is. But yeah, that's not an issue anymore. Yeah, it is. It's absolutely mind-blowing. And Sometimes even us who've got our nose to the bench have to kind of like take a step back every now and then and, and say exactly what you've said. Like, we could take a skin cell and make it into any other kind. That's just wild.

It is, it is. And it's— but it, it, it's— I was thinking about this earlier. I've written down it's an exciting but challenging time. And the, the challenge comes from, you know, again, at this conference they were saying there are now recognized 13,000 rare diseases. So, and if you work, you know, it depends where you are, but 1 in 3,000 people seems to be about that kind of, you know, metric for a rare disease. So 1 in 15 people has a rare disease was one of the stats. But the thing they made, there were people going, yeah, it wasn't that long ago that we only had 8,000. And part of me goes, okay, that makes— it's incredible. It's now we're learning more about these, so we're able to categorize them more. Now, that, that in one sense is a real challenge because everybody is getting into smaller, smaller boxes. So You used to think there was you and 100,000 people with the same thing across the world, and now there's you and another 1,000. So as a patient, on the patient side, how do you advocate for that small community, or you get lost?

Yeah.

How do you, how do you make sure people do, do the research that's going to help and, um, you get the treatments, etc., etc., people are willing to spend the money on developing the treatments and governments to pay for it, etc. But the other side of it is, well, that also means that we're learning more. We're getting— we're able to get more precise. So the likelihood of finding better treatments, the cause maybe, um, is, is higher as long as you can get people studying them. Um, it's— I mean, it— a lot of people have said to me over the years that, you know, um, not much had happened in this space, inflammatory neuropathies and things like CIDP and MMN, for 20-odd years. Once IVIG was kind of identified, you know, became a an incredibly valuable treatment because you kind of got— you get this sense of, oh, thank God we found something, right?

Yeah. And is that something that works well enough?

Works well enough for most people. And, you know, there's— right, that's— that, that'll do. That is your Band-Aid. That is your, you know, right, that'll do. Um, but now people are digging into the next level. And it's ever more complicated. But the opportunities in that to get much more precise, both, I think, both in diagnosis, you know, all the way from diagnosis to, you know, so better, faster diagnosis, because if there's one thing most of us would like, it's one diagnosis that we can hang our hat on pretty quickly. And then the right treatment at the right time. So, yes, challenging but exciting.

Yes. Yep, that's a good way to put it.

And wonderful to have people like you kind of championing that and fostering, bringing people into the system and continuing to do the research because Yeah, it does need people who are driven and are willing to, you know, in some instances not go where the big bucks are, although there's equally, you know, there's again, it is a partnership. So you, you know, partnership between industry and academia and patient organizations and all of that has to work. Everybody has to work together. To be able to do this work as quickly and as efficiently as possible, I think.

Yeah, I totally agree. And so, you know, long term, if I'm to remain kind of in this academic research world, which, you know, I don't know what the future brings, but whatever I am doing in the future in this domain, really do want to be focusing on, as you've said a couple of times throughout this chat, focusing on bringing this to the next level of actionable therapies that are actually changing patients' lives. And it is tricky. You have to get enough people focusing on the problem. We've still got so much basic science to understand about what's going on here, but at least it is with real patient samples. We have real human nerves to work on. Of course, therapeutic development is time-consuming and it's painstaking. And also, like you mentioned, there is an element, you know, what do you do when you've got a rare disease? So you can't get a volume of a massive volume of people throughout the world who might need a certain therapeutic unless you get lucky and you happen to stumble stumble upon something which I kind of like hope for that immunologically would be valuable for many autoimmune diseases and not just this one in particular, because tolerance failure happens with all sorts of autoimmune diseases. Things go wrong with people's B cells. So I would hope, you know, maybe that's a happy medium, finding something that is useful in this context as well as others, because if you don't have something like that from a business standpoint, I understand. A company, a drug company especially, it's one of the riskiest things to do, right? You pour millions and millions and millions of dollars into developing this thing that might actually just fail at the end of the day.

Yeah.

So I understand from a business standpoint too, you've got to have an incentive to take it up. And if you haven't got the volume of people who need it in the first place, there's arguably not a huge incentive. And that's another challenge, isn't it, with rare diseases?

It is, yeah. But it is very interesting when you start looking at some of the trials that are happening, that the, the, the trial is designed to tackle a particular, you know, focus on a particular condition. And how often over a period of years, you start to see that they've added to the list of conditions because they're learning more and they're understanding that crossover. And of course, that suddenly generates that— a big enough population to make it financially viable. Um, yeah, yeah, it's, it's a really interesting space. I feel like that's probably— I mean, it's an exciting space, so I think it's probably a good place to leave it for this conversation. There's so much more we could have delved into, and I'm, I, you know, I'm sure Um, I think let's, let's keep, keep in touch and we can get you back on and find out how you, how you're going.

Um, yeah, for sure. Thanks for letting me get on my soapbox a couple times. I'm sure you will— you can please cut that, feel free to cut that.

No, no, you see, the point about this is— so, so the whole point is, um, I've always said this is Conversations with the MMN Community, and that's great because that means I can talk about anybody to anyone.

Yeah.

Um, because any— if I connect with somebody, then that's part of my MMN community. Um, and yeah, I mean, we could— we— I did honestly think about you could have a— you could almost have like a leadership focus on the podcast. You could have a focus about the pure science. You could have a focus about communication and particularly science communications, and that you could split this into many. So we'll see how— what people think. There's lots, lots lots to talk about, but thank you so much, Claire. That was awesome.

Oh, thank you so much. I really, really enjoyed this. So yeah, let's keep in touch.

I don't know what you all thought about that out there, but I was truly blown away by Claire, by her enthusiasm, by the drive that she has, founded in such a deep personal experience with what her sister my sister went through, but not just that her focus is on the pure science of what she's doing to better understand our immune systems and bring different treatments to those with conditions similar to MMN, but it's that entrepreneurial spirit that is helping open doors for others, you know, who potentially might not have been able at any into the kind of, um, cloisters, so to speak, of the likes of Oxford and Cambridge to do their study, to further their careers. So it is remarkable what she's achieving. It's fantastic that she's been able to secure funding through Inflammatory Neuropathies UK and more recently GBS CIDP Foundation to continue her work. And it's also great to hear that she's in a fantastic environment, a collaborative environment. I've been lucky enough to visit the labs where she works, and I can testify that it is mind-blowing what they are doing. If you're ever up there and you can reach out to them, I'm sure they would love people to learn more. I'm going to be hopefully visiting there late or early next year when I'm over in the UK for our UK leg of the Tour de M&Ms. MMN film talk, so watch this space, maybe we can catch up with Claire then. Thanks everybody for listening and probably appropriate to say wish everybody a happy Christmas, enjoy the holidays, happy New Year, and I will be back in the New Year hopefully with Dr. Ludo van der Pol talking about trials and what's involved in trials. So I look forward to chatting then.

Take care.

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