Developing Faster, Simpler Tools To Treat Tuberculosis

FLORA LICHTMAN: This is Science Friday. I’m Flora Lichtman. We’re continuing our conversation about tuberculosis, the deadliest infectious disease in the world. This bacterium kills more than a million people every year, but scientifically, it’s also just a fascinating bug. It can hide in the body and evade antibiotics.

So here to nerd out on the science of TB is Dr. Mireille Kamariza, who’s dedicated her career to getting to know this deadly bacterium and figuring out new tools to suss it out. Mireille is a chemical biologist at the University of California, Los Angeles, and a cofounder of OliLux Biosciences, a company that makes tools for rapid TB detection and treatment for low-resource areas. Mireille, welcome to Science Friday.

MIREILLE KAMARIZA: Thank you for having me.

FLORA LICHTMAN: Let’s start with a little bit about you. How did you find your way to TB research?

MIREILLE KAMARIZA: Oh, God. How many hours do we have?

[LAUGHTER]

FLORA LICHTMAN: I’m here for all of it.

MIREILLE KAMARIZA: Yes, well, the very beginning, I was born in this tiny little country in eastern central Africa called Burundi. It’s a landlocked, small country that has roughly 10 million people. And during the time I was born, it was plagued by civil war at a time. And in the midst of it, I would notice people getting sick and not getting better. And this particular disease, tuberculosis, the name we have for it in Burundi is almost a synonym with a taboo event. You don’t want to say that somebody has TB. You want to say they have the flu, they have a cold, under the weather, not diagnosed with tuberculosis. And that has always pricked my curiosity as to why that could be the case.

FLORA LICHTMAN: Would you just tell me a little bit more about that? John Green talked a lot about the meaning that we make around illness. In Burundi, what’s that narrative around TB?

MIREILLE KAMARIZA: As sad as this is going to sound, TB has this connotation that it’s a disease of the dirty and the poor, which couldn’t be further from the truth, right? You could be walking into a high-end grocery store and catch tuberculosis. If someone sneezes in the bus, everybody will say, oh my God, TB! [LAUGHS]

FLORA LICHTMAN: Really?

MIREILLE KAMARIZA: Yes because it’s transmissible, right? So TB is just like COVID-19. If you were speaking in a room and there were people who are in the vicinity, they could inhale those aerosol droplets, and they could get tuberculosis. And in some places in the world, like Burundi, being diagnosed with tuberculosis could be a life sentence, if not a life-long sentence. People, first, they don’t want to be diagnosed with it, so they won’t even get the test, but also they don’t want to talk about it. They don’t want to tell people. They don’t want to get quarantined.

So that’s sort of where my motivation came in. And fast forward a lot of years. I moved to the US.

FLORA LICHTMAN: Wait, before you fast forward– before you fast forward, how did you end up in the US? You’re now at UCLA. What was that journey like?

MIREILLE KAMARIZA: It was a journey of ups and downs and almost uncharted roads, so to speak. For those people who don’t know, in the early ’90s, Burundi was going through upheaval. So people have heard of the genocide in Rwanda. That’s our neighboring country. So, essentially, what was happening in Rwanda was also happening in Burundi. So there was chaos, instability, and along the way when I was a young teenager, my family and I, we moved to the US as refugees. So that’s how I ended up arriving on the shores of sunny San Diego when I was 17 speaking not a word of English and absolutely clueless of what this new land had to offer to me.

FLORA LICHTMAN: How did you get to science?

MIREILLE KAMARIZA: A very good question. I think, fundamentally, the reason why I got into science was because I had a language problem, funny enough. I arrived here. I didn’t speak a word of English. I couldn’t communicate properly. But when I took that first chemistry class, I really didn’t need to know English to do well in that class. I understood the language of molecules. I understood hydrogen. I understood how a hydrogen bonds with an oxygen. You don’t need to speak French, Arabic, or Kirundi to be able to do error pushing. And I think that gave me a sense of comfort and security during a time of transition.

And I wanted to do more in that area, but I just simply didn’t know what else I could do. I just wanted to have a skill set and then find a job that pays me well enough to pay the rent until I met mentors and instructors along the way that opened my mind to the possibility that you could be a scientist. I didn’t know anyone who comes from Burundi and becomes a scientist.

FLORA LICHTMAN: How did you find your way back to TB, or when did you find your way back to it?

MIREILLE KAMARIZA: By luck, almost. So I started at community college. I took all these science courses, did really well in them, and I transferred to UC, San Diego, where I was majoring in chemistry. And long story short, I settled with pursuing a PhD at Berkeley. I learned about this soon to be famous scientist who’s a chemist. Her name is Carolyn Bertozzi. And now she was the 2022 chemistry Nobel laureate. But back then, this is 2012. She was well known in the world of chemistry but not much more beyond that.

So during my research, I learned that she had done a lot of work in fundamental chemistry, but there was a footnote that also highlighted that she had an interest in tuberculosis. And I was like, huh. How does a chemist, fundamental organic chemist, connect the dots to an infectious disease that matters to me and the people in Burundi and sub-Saharan Africa in general? So that piqued my interest, and so that’s how I ended up joining the Berkeley molecular biology department, hoping to work with her.

FLORA LICHTMAN: And what is it about this pathogen that interests you? Of course it’s connected to people’s health and the lives of people you knew, but are there things about this bug that sort of interests you from a nerdy, sciencey perspective?

MIREILLE KAMARIZA: Absolutely. Just bringing it out from a big-picture perspective, when I landed in the us in San Diego, I realized tuberculosis is not a huge problem here. It’s not similar to how it is in Burundi. You don’t walk around the streets and hear about people who are sick, and hospitals are not filled with people with tuberculosis. So this is a curable disease. This is a disease that we can eradicate or at least significantly reduce.

And my first question was, why is it controlled here but not there? I wanted to learn as much as I could about this bug to understand how that could feed into the state of global health. And it turns out that this bug has a really special armor, I would call. And unlike other bacteria– your E. coli, salmonella that everybody hears about– this mycobacterium tuberculosis– this is the pathogen that causes TB– has this ability to quickly adapt to treatment, can recognize, can see the drug. It has a special armor. So I noticed that these cells, what’s really interesting about them is that they have this really thick armor that can block out treatment. That’s why a lot of people don’t respond.

So, for instance, just to give you a context here, someone who is diagnosed with tuberculosis has to take roughly 16 pills a day for six months to get better.

FLORA LICHTMAN: 16 pills a day for six months. Wow.

MIREILLE KAMARIZA: For six months, and that is if they have what we call a drug-susceptible tuberculosis. So that means we think that this pathogen will respond to drug. So if it’s a drug-resistant version, you take these pills plus additional pills for two years to try to clear these cells, and that’s because they have this special armor that’s around the cell that protects it against attack from drugs. And so that became my obsession, honestly. When I learned about this, I was like, OK, how can we break this down? How can we find it? How can we see it? And sort of the–

FLORA LICHTMAN: How can we use chemistry to fight it?

MIREILLE KAMARIZA: Exactly. Exactly. So along the way, along the journey of trying to find ways to break down this armor, we first needed to see it. We needed to understand its superpower. How does it work? Is it made of iron? How does it function?

I leveraged the chemistry that Carolyn and her team have developed over the years to be able to add little colors, little lights on top of the armor so that we can have a visual of the whole shape and how it’s made and composed and how it changes over time, particularly in the context of drugs or not drugs.

FLORA LICHTMAN: You’re tagging it with fluorescence?

MIREILLE KAMARIZA: That’s correct. We made fluorescent dye that can only turn on– so it can only glow green in the presence of this armor. So if TB has this armor, you will see it.

And what was really useful and attractive for clinicians in the field was how easy it was to use this probe to find the armor. So if you can find the armor, if you know the composition of the armor, say, from a patient sample, then you know how to properly destroy it, to get through the cell.

FLORA LICHTMAN: You can use this to figure out which antibiotics to use?

MIREILLE KAMARIZA: That’s correct.

FLORA LICHTMAN: So you’re not taking four drugs. You’re just taking the one you need. Is that what that means?

MIREILLE KAMARIZA: That’s correct. So we can use this probe to identify what therapy works best for this pathogen.

FLORA LICHTMAN: Is it expensive, the probe?

MIREILLE KAMARIZA: It’s not. It’s so simple to make, and it’s super stable at ambient temperature, which is important at the point of care, right? So we’re thinking, how could this be used for surveillance purposes in a place like India? It’s incredibly crowded, and not everybody can go to the hospital to get detected, to get diagnosed. But maybe you can have community health workers going out in the villages, going out in the schools and swabbing places and seeing what kind of tuberculosis is spreading around, is getting transmitted in the environment.

FLORA LICHTMAN: And what problem is this solving? Because, of course, in the US and in other Western countries, we have diagnostics that work really great. Why did you need to make this, or why is this helpful to have this tool?

MIREILLE KAMARIZA: This is a fantastic question. In places where there is high prevalence of tuberculosis, there tends to be limited resources. So there’s no electricity, not a lot of trained personnel or high-end tech equipment to do sort of the standard diagnostics we can do here in the US. So having a cheaply manufactured, easily available, highly stable reagent that can tell you not just that you have tuberculosis and the pathogen in your sample but also whether the kind of tuberculosis has responds or not to the treatment is completely priceless. There is nothing like that right now on the market that can do that. I’ve dedicated my career to try to bring this tool, and many others like it, to point-of-care settings to save some lives.

FLORA LICHTMAN: This is Science Friday from WNYC Studios. If you’re just joining us, I’m speaking with Dr. Mireille Kamariza about the current state of testing and treating tuberculosis. Because your diagnostic can tell you which antibiotics to use, does it help with this problem of drug-resistant TB?

MIREILLE KAMARIZA: It helps identify the drug resistance early, and, hopefully, it helps doctors administer the correct drug early enough to tackle drug resistance.

I want to be careful here. This is just a diagnostic technology. There is also a public-health infrastructure problem in the world of TB, and it’s not sufficient to have a good test. You also need to have good infrastructure so that that information is passed down quickly enough to get to the patient.

FLORA LICHTMAN: I mean, on that note, we’ve been covering how the US has been withdrawing from global health efforts under the Trump administration– the dismantling of USAID, leaving the World Health Organization. From your point of view, what does that mean for TB?

MIREILLE KAMARIZA: It’s devastating. The consequences and ramifications of this could be felt for years from now, right? I have colleagues, international colleagues, who we have collaborations and collaborative projects that we don’t know what’s happening next. They’re funded by the agency, and their salaries, their ongoing patient recruitment to do diagnostic tests, and we are just in limbo. What’s next?

The question is the future. I’m particularly affected by what happens with the NIH. And so there, everybody is paying attention to what could affect our work if you’re federally funded. And so there’s just a lot of uncertainty and fear around the actual clinical ramification of the political landscape we find ourselves in.

FLORA LICHTMAN: Yeah, what it means for people’s health–

MIREILLE KAMARIZA: That’s correct.

FLORA LICHTMAN: –and the spread of this disease.

MIREILLE KAMARIZA: Yes.

FLORA LICHTMAN: Yeah. One thing I really appreciate about your work, Marielle, is that it feels, of course, so connected to people and to your own life story. That isn’t always the case in science. I don’t know that it always has to be the case in science. But I wanted your thoughts on that.

MIREILLE KAMARIZA: That’s an interesting question. When I was at Berkeley, when I was in graduate school, I was surprised by how little or how few opportunities scientists had to be in the field and connect with the people that we’re working towards helping. And I like to believe that it is my connection and my background in Burundi that sort of drove me to making the connection between tagging this armor and its potential clinical impact, and I think more of that would help scientists.

I also think improving science communication, explaining what we do to regular folks, and showcasing what we do would help us in the long run and even give us more ideas and better ideas on how to help people.

FLORA LICHTMAN: Thank you, Mireille.

MIREILLE KAMARIZA: Thank you.

FLORA LICHTMAN: Dr. Mireille Kamariza, assistant professor in the department of bioengineering at the University of California, Los Angeles.

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