Beyond the Sequence: People, Pathogens, and Power Dynamics

The cutting edge of infectious disease control isn't just about vaccines or treatments—it's increasingly about data. Dr. Stephen Molldrem, Assistant Professor at the Institute for Bioethics and Health Humanities, takes us deep into the world of pathogen genomics and the remarkable ethical questions that emerge when we sequence disease-causing microorganisms.

What happens when genetic analysis can potentially reveal who infected whom with HIV? Why do some communities welcome these technologies while others resist them? From the controversies surrounding HIV surveillance in America to the enthusiastic adoption of TB genomics in Botswana, Dr. Molldrem reveals how the same scientific tools can take on dramatically different meanings depending on context, trust, and community involvement.

The COVID-19 pandemic accelerated the global adoption of pathogen sequencing, bringing terms like "variants" and "mutations" into everyday conversation. But this technological revolution has also revealed deep inequities—when South African scientists identified the Omicron variant and transparently shared this information, their reward was travel bans rather than support. This pattern reveals how scientific advancement doesn't happen in a vacuum but within complex social and political realities.

At the heart of Dr. Molldrem's work is a fundamental reminder: behind every genetic sequence is a person, a community, and a set of lived experiences. As one HIV advocacy slogan puts it, "We are people, not clusters." The challenge for public health isn't just implementing new technologies but doing so in ways that respect human dignity and build rather than undermine trust.

Whether you're fascinated by the science of disease tracking, concerned about health privacy, or interested in how new technologies reshape our understanding of outbreaks, this episode offers a thought-provoking journey through the socio-technical landscape of modern infectious disease control. Join us as we explore what happens when cutting-edge science meets complex human realities.

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Transcript

Speaker 2 0:09

This is a podcast about One Health the idea that the health of humans, animals, plants and the environment that we all share are intrinsically linked.

Speaker 1 0:17

Coming to you from the University of Texas Medical Branch and the Galveston National Laboratory. This is Infectious Science. Where enthusiasm for science? Is contagious.

Speaker 3 0:30

Welcome back to the Infectious Science podcast. We are excited to be back here. We have Christina and we have Camille. How are you guys doing?

Speaker 4 0:39

Doing well. We're hanging in there. Yeah, it's been a lot, it's been a big beginning of the year and we're coming to the close of our academic year, and so it's just everything's piling up, but we're getting there.

Speaker 3 0:53

Christina, since we're coming to the end of season number two of the Infectious Science Podcast, we've gained quite a few new followers. Let's do some introductions Like who are you, christina?

Speaker 4 1:05

I am Christina Rios. I am a second year medical student here at the UTMB School of Medicine. I am originally from San Antonio, texas, and I love my hometown very much. I am of Latino descent and I'm very proud of that. I'm a daughter, I'm a sister, I am an aspiring scientist and physician, and I love animals.

Speaker 3 1:34

Camille, who are you?

Speaker 5 1:37

Not as good of an intro as Christina. Yours is much better. I'm Camille Adu. I'm one of your co hosts. Thanks for listening in to Infectious Science. We appreciate all of our listeners and it's always great to hear from everyone who's been reaching out. I am coming to the end of my academic journey. I'm defending next month.

Speaker 3 1:55

So right now, as we record this it's January 31st 2025.

Speaker 5 1:58

2025. And I am very excited to defend next month. You must be so proud. I am so proud and also so stressed. But we're getting there and I'm really excited. When I am not in the lab or writing my dissertation, I'm reading a lot. I think my book count so far for the year is at 11 books, so we've restarted again.

Speaker 3 2:19

What was it last year?

Speaker 5 2:20

Oh, what did I finish out at?

Speaker 3 2:22

That is a great question. Oh, it was more than a hundred.

Speaker 5 2:24

Yeah.

Speaker 6 2:25

Let's see.

Speaker 5 2:25

What did I end up with for 2025? I'd just like to preface this by saying I think it was like January 2nd, that Camille sent Dennis and I a text that she had finished her first book of the year.

Speaker 3 2:39

That is true. Yes, last year was 127 books, and I yelled at my phone when I got the text because I wish I can finish a book in three months.

Speaker 5 2:45

Yeah, so last year I read 127 books. This year I'm hoping to do more, because I will not be spending as much time in grad school, so I'm excited to finish and start my work as a medical writer.

Speaker 4 2:55

Amazing, who are you? Yeah, dennis, you're looking very snazzy today. Reintroduce yourself, just for you guys.

Dr. Moldrum's Work in Health Ethics

Speaker 3 3:01

Hi, I'm Dennis Bent. I'm a professor of microbiology and immunology and I'm a German. I'm a man, a son, and what else did she say, christina? But I'm also very excited to talk about our guest today. So it's a great pleasure to introduce Dr Stephen Moldrum. He's an assistant professor in the Institute for Bioethics and Health Humanities and we've talked about having him on the show for quite some time because his research is really interested, and I'm really excited about this episode. Can't wait to get into it. Stephen, do you want to introduce yourself?

Speaker 6 3:40

Sure, yeah, thank you. Thank you so much for the introduction, dennis, and thanks so much for having me here on Infectious Science. I'm looking forward to the conversation we're going to have. My name is Stephen Moldrum I use he him pronouns, and, as Dennis said, I'm an assistant professor on the Institute for Bioethics and Health Humanities here at the University of Texas Medical Branch, where the Infectious Science podcast is recorded, and my research mainly exists in the field of science and technology studies, also public health ethics, and I'm an ethnographer, and so I use mainly qualitative methods and policy analysis methods, largely to study the politics of health data and also of infectious disease and the introduction of emerging technologies into infectious disease control, and I think that's what we'll mainly be talking about today, but I'll leave it there.

Speaker 6 4:31

I have a few other interests too. I mean sexual and gender minority health, mainly in regard to data practices, and I'll also say my research is mostly based in the US, but I also have done studies in global health policy, global media discourses, and also I have an ongoing project in Botswana related to tuberculosis. My PhD is in American culture the field is actually called American Studies, but Michigan has a strong identity of keeping the title American Culture and I also have a certificate of graduate studies in science, technology and society from Michigan. And I did a postdoctoral fellowship for two years at the University of California, irvine, in the Department of Anthropology, and then I came here and I've been at UTMB in the Institute for Bioethics and Health Humanities for three and a half years.

Speaker 3 5:18

Are you originally from Michigan?

Speaker 6 5:20

I am not originally from Michigan. I traveled around a lot growing up. I went to undergrad in Washington DC at the George Washington University. But yeah, lived many places growing up.

Speaker 5 5:31

Very cool. What is science and technology studies for our listeners?

Speaker 6 5:35

Yeah, science and technology studies is a field that emerged from the sociology and anthropology of science and technology in the 1970s. That was a heady time for the social sciences. There were a lot of challenges to, for example, institutional ways of knowing in the sciences from the social sciences that were really interested in using the tools of the social sciences to understand, for example, how the quote unquote hard sciences develop knowledge and then how knowledge takes on material form in society in the form of, for example, the formation of disciplines, the translation of scientific knowledge into policy, and so the field that's often talked about is this new upstart field, but it's 50 years old at this point. There are different branches of science and technology studies. Of those, I am primarily probably working in social studies of biomedicine and social studies of health and also infrastructure studies.

Speaker 6 6:34

We use the term in socio-technical a lot, so in science and technology studies, or STS as I will call it as we move along is always interested in thinking about how technology, the tools that scientists use, are co-mingled with the social and professional lives of scientists and how the operation and maintenance of things like large data infrastructures, which I think about a lot in the public health context, are always bound up with the people who are using and building and maintaining those systems and the technologies that they're using to do so. A lot of this has actually become diffused throughout the social sciences and the culture at this point, but it was a really radical notion in the 70s and 80s that you could, for example, treat the emergence and construction and use of scientific facts using the tools of like sociology and anthropology and science technology studies as many things, and I think we can continue to revisit it as we talk. Yeah.

Speaker 5 7:33

No, I think that's an excellent overview and I appreciate it as well because it's not something people tend to be like siloed in their field. So I always appreciate hearing what other people are doing and studying. So, in regards to like more specifically, what you're doing, when we first talked about this episode, we really talked about your work looking at pathogen genomics and pathogen phylogenetics, and so, before we get into that, I just wanted to quickly define them for our listeners. Pathogen genomics is the study of genetic material of microorganisms that cause disease. Pathogen phylogenetics is the study of how microorganisms evolve. It's often used in public health to track disease outbreaks and reveal transmission patterns. So, with those definitions out of the way, of course, if you have anything to add to those definitions, I want to hear it. But could you tell our listeners why pathogen genomics and pathogen phylogenetics matter, particularly right now, like in the present moment?

Understanding Science and Technology Studies

Speaker 6 8:23

Yeah, totally no. I think those are good definitions of pathogen genomics as a field. There are many things that are gathered under that signifier and pathogen phylogenetics being both like a method right that is used to track pathogen evolution but then also has specific applications in research and public health, whereas pathogen genomics isn't necessarily about pathogen evolution but can be used in, for example, tracing the emergence of in surveillance, for example, drug-resistant variants of pathogens or within an individual patient, clinical applications of genomics. To take a little bit of a step back in terms of how I got focused on studying this on studying this, my work initially was about the emergence of the application of digital infrastructures and public health programs in the United States, really starting in the period after 2009,. When there was a law passed it was called the High Tech Act. That was actually part of the 2009 American Recovery and Reinvestment Act, huge bill, spending bill that digitized the US healthcare system. And when I say I'm interested in emerging technologies and infectious disease control, it is about pathogen genomics. But the use of pathogen genomics in routine public health practice was really facilitated by this much larger phenomenon, which is the digitization of the health system in the United States and health systems generally, and this is something that really took off in the 2010s and began with the process of digitizing electronic health record systems, which was a very fascinating policy battle in the United States, but then also electronic laboratory reporting infrastructures to public health, and so what I've tried to document in my work over time is how basically this digital base has been developed that enables different forms of interoperability between the domain of clinical care and the domain of public health practice.

Speaker 6 10:18

Since pathogen genomics became an object of interest for me when I was actually studying this process in regard to changes in HIV care, surveillance and prevention during the 2010s, and so I was doing research, I did over two years of ethnographic field work in Atlanta, georgia, in the HIV safety net from 2016 to early 2019. From 2016 to early 2019. And I was studying there there were these multiple transitions happening during that time in regard to HIV and how it was managed by public health institutions. One of them was the introduction of knowledge about undetectable viral loads becoming undetectable, making one untransmissible, or U equals U in the kind of public-facing messaging, and when operationalized as a public health strategy, this is often called treatment as prevention, and so this was taking off in the period when I was doing my field work and what I was paying attention to most closely was the ways in which public health systems.

Speaker 6 11:20

Then they had a much greater incentive to monitor in real time who was virally suppressed in their jurisdictions, because there was just a real reorientation, this time in HIV care and public health, around bringing viral loads down and then in identifying. During this period in the US there were a series of programs rolled out that were focused on identifying people who had fallen out of care based on whether or not the public health department had received blood work from them. Identifying people who had fallen out of care and then reaching back out to them to bring them back into care. So this was a very new set of programs in the United States.

Speaker 4 11:58

Historically, like these, hiv surveillance systems and clinical care and prevention infrastructures were quite separate from one another, that's really interesting actually seeing how the actual clinical aspect of HIV care was translated into a public health outreach in ways that a lot of people maybe didn't know about. So that's really cool.

Pathogen Genomics in Public Health

Speaker 6 12:20

Yeah, and this is as part of this. In 2018, in all health departments, cdc began requiring the use of HIV genetic sequence data, which are generally ordered in the clinical context to monitor drug resistance, the potential emergence of drug resistance in a patient and CDC standpoint was using phylogenetic analysis to monitor the growth of emerging transmission clusters of HIV. This is what actually brought me to thinking about pathogen genomics and pathogen phylogenetics. I was initially interested in the digitization of health systems and how that facilitated different uses of data such as this, and how that facilitated different uses of data such as this.

Speaker 5 13:05

I had a question about this. So do you think this kind of reorientation has? Has it increased the people that were retaining in care? Because I know and I know this because this is just in my dissertation, we were just talking about it, so I just found the stat so the CDC says that for every 100 people living with HIV in the United States, only 54 are retained within the care system and about 66 achieve viral suppression, which is certainly, with as wealthy of a country as we are, we could do better. So do you think that it changed like how we're maintaining people in care and like the level of care that people were receiving?

Speaker 6 13:39

Yeah, so this is actually quite a fraught question. So this is sort of where I think we can think about where the science and the public health practice meet politics in this regard, because what I discovered when I was doing my research is that these programs and the reorientation of the US National HIV-AIDS Strategy so it was the first National HIV-AIDS Strategy for the United States came out in 2010. It was this big moment and it has been updated since then. But if we situate ourselves in the period of the mid-2010s, there was a great deal of optimism around technology digital technology generally to solve social problems which has really waned in recent years right this sort of what we call an STS techno-optimism right around digital technologies to solve social problems. There's a great deal more of societal skepticism of that.

Speaker 6 14:30

But if we position ourselves in the 2010s, you had a few things going on in regard to HIV, because you had the convergence of a very optimistic sort of civil society liberal progressive coalition that had coalesced around Obama. You had the digitization of the health system, being able to use data in new ways to link people to care, and then, at this time, you also had the emergence of treatment as prevention. So this was a moment of huge optimism that maybe we can use data in new ways and this new knowledge about HIV transmission to end the epidemic by bringing people into care, whether the programs have worked generally, what the evaluation papers in this space has found and this program initially it was called Data to Care and it's still called that when the technical literature and the people who do this if you want to look up these programs, that's what they'll be called, the evaluation literature has generally found that it's very expensive to conduct these investigations to bring people into care and relink them. Their effectiveness is debated but in partly because a lot of it is done using cost-benefit analyses for bringing people back into care, have been of this other process that was mixed up in HIV in this time, which was the integration, right of care, prevention and surveillance, where they really put a lot of effort in. I'm thinking about a group in Washington and Seattle, for example, to try and keep people retained in care after a successful relinkage intervention, and it was just really hard and a lot of people ended up still falling out of care, not being able to be retained, because people were having trouble remaining in care. In the United States we don't have a health care system that's designed to keep people in care. We have a very bad health care system, but also you're generally talking, these are folks who are having a hard time in other ways too, maybe with housing, food security, things like this substance use, things like this substance use. But in any case, I'm going to answer your question.

Speaker 6 16:30

But it's a long way around the barn, because what happened was there was all this optimism around moving HIV toward a treatment as prevention paradigm, and then things really changed after 2016 and into 2017. So you had HIV. Civil society was really on board with these uses of data and then there was a switch that happened sometime between 2017 and 2018, when actually that coincided with the use of molecular HIV data or HIV genetic sequence data in these programs, doing this cluster modeling. So at this time, the organized networks of people living with HIV and others in civil society there had been a switchover from the Obama to the Trump administration began to really voice a different set of concerns around privacy, concerns, confidentiality, concerns around criminalization, because, for example, hiv genetic sequence data and phylogenetic analysis can be used potentially to infer who may have infected whom in a data set. So there's a lot of concern around this and then this led to a real backlash during this period to these programs. That was led by segments of HIV civil society, which is ongoing to this day, in fact, and I've written a couple of papers tracking this controversy.

Speaker 6 17:50

And to answer your question, do I think that these programs have worked? I think that we're still at like less than 70%, certainly probably around 65%, viral suppression in this country. I would say probably not at a population level, but also even if we look at their implementation. Their evidence of effectiveness is very much debated and I always like to say, if that, if someone could walk down the street and get into care easily, there wouldn't necessarily be the need for all of these programs and advanced data uses. But that's not the healthcare system we have. So they remain an object of a lot of controversy.

Speaker 3 18:24

Yeah, Stephen. I was wondering can you give us some examples how pathogen genomics and pathogen phylogenetics is in their life or where they run into this during their life? For people that probably don't know exactly what this is, Can you give some very 30,000 feet examples?

Speaker 6 18:43

Yeah, sure. So where an everyday person might run into pathogen genomics, there might be a couple of different ways. If you're a person living with HIV and you, for example, are having problems keeping your viral load suppressed with your care provider, your care provider might order a drug resistance test for you. That is, the provider ordering an HIV genetic sequence Because HIV is a reportable condition to public health. Right, it goes to public health so that they can use it in surveillance programs and also in prevention outreach programs. The data that the lab generate will be reported back to the provider and to public health.

HIV Surveillance and Treatment Evolution

Speaker 6 19:22

In the clinical context, these data can then determine okay, this patient or this person is having trouble remaining virally suppressed because they have a kind of HIV that's resistant to this particular medication, so we're going to change their medication. The guidelines change around this with some frequency. So what providers do? It's generally in line with the guidelines, but the guidelines change a lot. They're like updated every year. So a lot of providers will order an HIV genotype test or a drug resistance test for our patient upon enrolling or re-enrolling in care. And so an everyday person who is not living with HIV.

Speaker 4 20:01

where they might run into this, it's hard to actually say Would you say it could potentially be used in, like the analysis of bacteria, let's say an antibiotic resistance when it comes down to it, used all the time.

Speaker 5 20:13

Yes. To see what antibiotic your particular infection might be susceptible to, especially if they're concerned. You have an antibiotic resistant infection, used all the time.

Speaker 6 20:21

Yes, and this is where I was going to go, which was in media coverage, is where I think people might see some of this. So if they're hearing, for example, about the emergence of antimicrobial resistant or antibiotic resistant, let's say, gonorrhea is, there are waves of media discourse about this almost every year. Cdc has been warning about the coming pan-resistant gonorrhea since the 1970s. That has its own fascinating history, but also, for example, in the H5N1, avian flu is being covered in the media a lot right now, when the news articles are basically talking about how pathogens, how bacteria or viruses, mutate and acquire new characteristics. This is pathogen genomics in use.

Speaker 4 21:07

And so yeah.

Speaker 6 21:08

So they will be framed in the media often as like the potential emergence of a super bug or a species crossover, for example. I know that's of big interest here in infectious science, but these are media discourses that happen that I think most people would be familiar with and also, I would say, linking it back to HIV the public communication of emerging HIV clusters that have been identified through phylogenetic analysis. Public health departments will often work with local media to communicate about these. One very well-known example is Scott County, indiana, in 2015, where there were several hundred new cases of HIV because of very distinct practices of needle sharing that were going on in that community. But now the health department wants to communicate about growing HIV clusters. So if you're hearing this term HIV clusters, this is probably a reference to phylogenetics being used in public health practice growing HIV clusters. So if you're hearing this term HIV clusters, this is probably a reference to phylogenetics being used in public health practice.

Speaker 3 22:08

Steven, I'm going to throw you a curve ball right. This is a One Health podcast, so are you aware of any relevance in veterinary medicine, animal medicine or environmental sciences where, like pathogen, genomics plays a role, or whether this is being discussed, or is this a purely human topic?

Speaker 6 22:29

No, so pathogen genomics are very much used in One Health. One Health is not my area, my primary area. I will be very clear in saying, however, there is one project I have waiting in the wings that I need to pursue further, which intersects a lot with One Health, with One Health meaning the whole thing human-animal environment, right, and this is the concept of a resistome. Which is this very interesting concept that essentially is a conceptual abstraction used to describe the drug resistance profile of all of the bugs that might be in a particular area and they so. The technology generally is metagenomic sequencing sequencing everything inside of a sample to see what's there. You can generate what scientists who are working in this area call a resistome profile, which will give you the resistance profile of all the bugs in that sample.

Speaker 6 23:23

What I find very interesting about this concept is that it scales in these sort of incredible ways, and so one is.

Speaker 6 23:32

For example, and when I first became aware of the concept is there was a paper about the specific resistome profiles for bacterial antimicrobial resistance among men who have sex with men who were taking PrEP for HIV, which is an HIV prophylactic medication. In the paper, they had done throat swabs and determined that gay men who were taking PrEP had a distinct resistome profile in their oropharynxes this is when I first came across this term in their oropharynxes. This is when I first came across this term. However, the term resistome is also used, for example, to describe in other papers I've seen, like an entire region where there's like maybe a lot of agriculture accounting for, like water samples from agricultural runoff, sampling from animals and maybe people there, or like a city block. So there are some papers where they would have gone around a city block, swabbing various surfaces and then sequencing it all to come up with a resistome, and so that is the closest to One Health that I think my work has gotten on. That's a project I want to pursue, but I haven't quite yet.

Speaker 3 24:37

And antimicrobial resistance is such a big topic in One Health right, because we have the overuse in human medicine, but we also have the overuse in veterinary medicine, so your resistome projects is probably extremely irrelevant and from my perspective. Also coming back to the veterinary medicine right, the phylogenetics is often used as a public health response to fight highly transmissible animal diseases. Right, like we see this now with avian influenza, where they track where did this come from this virus, what migratory bird brought this to this agricultural farm or to this, and they can trace it and they can almost like trace the history of where it came from and what farm got infected next, and so on. But I think it's way less controversial than it is in human disease. Would you agree or disagree?

Speaker 6 25:26

I would agree, but I would also say even making some of the claims that you're making there right. So, like this idea that you can use pathogen phylogenetics in the H5N1 avian influenza context to track which bird or which flock brought this strain of H5N1, and strain might be the wrong word to use but this subtype, let's say, of H5N1 to another area, you're making transmission, what are called transmission directionality inferences, when you're doing that right, and one of the things I'm interested in in pathogen phylogenetics is where making these kinds of inferences becomes acceptable and when it is problematized it's not acceptable.

Speaker 6 26:05

Yeah, that's fair, yeah, so in HIV, for example, and programs that have been rolled out in the United States. There's a lot of concern about inferring who may have infected whom and inferring directionality. Cdc says they don't do that. Activists claim if you're mapping clusters and doing investigations based on the combination of the phylogenetic data and the behavioral data, how can you not be doing that? And this is the heart of the controversy? But right, if you're talking about birds or, honestly, if you're talking about other pathogens, for example TB, in certain contexts for TB affecting humans, those directionality inferences are made and they're much less controversial. So it depends a lot by pathogen and context.

Speaker 5 26:48

And I think also depends who you're talking. To A vet, that might not be a controversial statement to say here's the farm where it originated, but to a farmer who owns that farm, who then might be responsible for everyone around them in a radius to have their flocks potentially destroyed to prevent the spread of avian flu. That might be a very sensitive topic and that definitely happens in the United States and we've certainly seen that where entire flocks have been culled and, as someone who grew up on a farm, there's strong concerns about biosecurity. But also, who is the source zero of something like that happening, because it can be devastating for that particular community. So, yeah, I think it all depends on who you're asking, on whether or not it's considered.

Speaker 3 27:26

But I think this brings back then the question of science literacy, though. Do the farmers understand why certain decisions were made based on phylogenetics or not, because often the veterinary health response is so strong and there's this response of culling instead of not what we normally do with humans, right? Do they understand what was implemented based on, maybe, right? Do they understand what was implemented based on, maybe some sequencing?

Speaker 5 27:48

Yeah, I think farmers understand what happened. But I think when you're saying there's this like line of transmission, then you always have someone who might be at fault potentially.

Speaker 6 27:57

And I think that's what's sensitive more than like.

Speaker 5 27:59

yes, certainly, people can lose their livelihoods and there's entire issues with that, and that's an interesting conversation within the ag community. But I think the idea of here's where this originated in this local area, at this farm or something that's what's more sensitive.

Speaker 6 28:11

Have there been culls of like flocks based on phylogenetic studies?

Speaker 5 28:17

Based on phylogenetic studies? I'm not sure based on phylogenetic studies, but certainly if it's found in a local area. So, like I grew up on a farm, and certainly if you had avian flu, everyone around you who has poultry, their flocks will be cold. So there's still this assignment of fall. I don't know that it's ever been down to phylogenetics. I've never gotten into it or had to deal with it. I'm like a person.

Speaker 3 28:38

I think it's just more based on epidemic. Radius. Yeah.

Speaker 5 28:42

Like location.

Media Coverage and COVID Variant Tracking

Speaker 6 28:43

To connect this back to the conversation about HIV. The fundamental question in the controversy about HIV phylogenetics there are these specific issues, right there's is directionality being inferred. Can directionality, epistemologically speaking, methodologically speaking, ever in fact be definitively inferred? That kind of thing, these questions exist, but they are specific manifestations of a deeper, underlying issue, which is the introduction of pathogen genomics and, in the HIV context, specifically pathogen phylogenetics to inform public health action for reasons other than surveillance, but to inform actual outreach to people, to link them to care. Does adding these technologies in some way fundamentally transform the work of public health and what public health agencies are doing in mapping clusters, or is it an additional tool that is in the public health toolkit that informs routine practice?

Speaker 4 29:46

And I think that's a really good segue into our next question that we have for you, dr Moldrum, which is you've written about the role of media in bringing pathogen genomics into the public eye. But, as you've previously stated, there is still a gap that persists in using this information to better the public health when it comes down to it, and also better the care for the people who do have these diseases and these infections. How would you recommend that we bridge this gap?

Speaker 6 30:15

Yeah, that's a really big question and so for me, my studies in pathogen genomics, pathogen phylogenetics, have been in three areas. Right, I've looked at HIV in the United States and the introduction of molecular HIV surveillance is what it's called in public health right Into routine practice along with using that in cluster response. I've looked at media coverage of controversies are about pathogen genomics in SARS-CoV-2, particularly some of the early controversies around claims about evolution of SARS-CoV-2 toward greater transmissibility. So for our listeners you've probably heard of things like the Delta variant and the Omicron variant and all of the Omicron sub-variants. I've written about those and the media politics of those, but also of earlier controversies even before the COVID-19 pandemic declaration and in tuberculosis in Botswana. And in global health policy following, the World Health Organization has recently recommended that all countries with capacity implement a version of sequencing called targeted next generation sequencing, targeted sequencing to identify TB, drug resistance and for use in routine surveillance. And I've thought about this technology and this technology has been my entry point to think about these issues in a number of different contexts and so I'd say that, to answer your question, each context has been extremely different. Right, for HIV, I think that the use of HIV phylogenetics and cluster detection and response methods in public health and whether or not that is going to become something that's acceptable to the community of stakeholders is something that's fundamentally unsettled.

Speaker 6 31:55

We can talk about the political economy of pathogen genomics, which is something that really interests me, which is basically what are the political and economic drivers of health departments investing in these technologies in the first place? You know what the COVID-19 pandemic did. Is it really accelerated the rate of adoption of sequencing technologies across the world? So you had large global health funders really sending sequencing machines to ministries of health around the world along with reagents around the world, along with reagents and saying sequence COVID uploaded into GIS aid and other repositories so that we can understand patterns of SARS-CoV-2 evolution globally. Huge increase in the sequencing capacity around the world, which we can talk about later in the podcast. But that's played a huge role in understanding the emergence of different variants and also the reformulation of vaccines.

Speaker 6 32:43

I'm a little less convinced that media stories about every single SARS-CoV-2 sub-variant of sub-variant are helpful.

Speaker 6 32:55

But what I also think is that and have observed and written about, is that the wide uptake and use of genomic discourses to describe the evolution of SARS-CoV-2 have been fundamental to public discourse about the COVID-19 pandemic and I think, have induced changes in how people relate to pathogens generally.

Speaker 6 33:19

I was in this really weird position at the start of the COVID-19 pandemic where I had been writing about HIV phylogenetics I've been writing about pathogen phylogenetics in the HIV context and so I knew about the technology and how it could be used and found myself fascinated by early controversies around SARS-CoV-2 and then writing about them, where scientists were having debates in public forums, for example, and forums like web forums, sometimes papers, but in those early days they were often fighting with each other online about whether or not SARS-CoV-2 was evolving to be more transmissible, and then to see this actually become like a major orienting media discourse about the pandemic itself and so like within the span of a few months. I was someone who studied something that was this sort of very obscure thing that no one really knew anything about unless they were really in the field, to something that my relatives were talking about uptake of media discourses about pathogen evolution that have been enabled by the increasing infrastructural capacity of the global health system to sequence and analyze pathogen data.

Speaker 4 34:35

Yeah, and I can imagine too, just like being able to execute a large public health response really does vary, like you're saying, on what is pertinent to the public at the time. So I can imagine it can be frustrating at times too when you have all this data and all this information on variants and viruses and bacteria and a lot of different pathogens that could be really beneficial but that it maybe seems like the public doesn't really care about too much at the time being, and so I guess the battle there is like bridging that gap between the interest and the actual data. That's there too.

Speaker 5 35:13

I do think it's interesting. I worked as a contact tracer in New York. I just graduated with my degree in infectious disease biology Again, something everyone was like why do you study this, what do you know about? And then the pandemic happened. And then suddenly everyone was calling me, and when I was a contact tracer in New York state, so we certainly collected data on what variants we were seeing in populations. But we would, of course, call people and then do contact tracing and people wanted to know what variant they had and we and it's just not something that would populate for us Like we collected on a an aggregate level but not on an individual level. We weren't like oh, like, you have Omicron or whatever, and so I think that it is interesting that people were relating to it in that way that they wanted to know, like what particular variant they had basically gotten infected with. So it was very wild.

The Politics of Pathogen Data

Speaker 4 35:59

That's really cool, and I think that it also shows how, even if you don't have a strong science background, people really are invested in their health, and I think they're becoming more and more invested in their own personal health, and so I think that this is hopefully a promising direction for pathogenomics and pathogen phylogenetics too, because if people want to know more about what's happening to them or what they're susceptible to, hopefully you guys can step in and play that role.

Speaker 6 36:23

Well, just to follow directly on something that Camille said and yeah, I totally agree, I think this is where science and technology studies is really useful, because it's like people, because there was the possibility of having public discourse about different kinds of variants, that was enabled by the underlying public health infrastructure changing. They were then able to ask you this question, but actually, infrastructurally, for you to deliver that information then was not actually possible. There were no best practices. Laboratory infrastructure was set up to receive this information but not to deliver it back to patients because it wasn't set up that way, it was only for our purposes as a public health agency.

Speaker 5 37:03

But you're right, yeah, it was not set up to basically deliver that to patients.

Speaker 6 37:07

Yes, and we have different identifications with pathogens happening at multiple different levels of the public health infrastructure as people interact with it, which is capacitated by new uses of technology that then acquire what we can think of as like a public life, right In the media ecosystem around the pathogen.

Speaker 3 37:27

So I vividly remember that time early in the pandemic or like when things were sequenced, and I think often what was discussed in the media were like the bad sides of phylogenetics, right Like where like a new variant was discovered in South Africa and it was claimed as the South African variant and flights were banned from South Africa.

Speaker 6 37:44

That was Omicron. Yes, Omicron.

Speaker 3 37:46

So do you think there's also a positive side to ramping up the sequencing capabilities, and so you were really into this or you're still into this? What were the benefits of uploading all of the data you think?

Speaker 6 38:02

Yeah, totally. These are conversations, right? We have in STS all the time, right. So we are.

Speaker 6 38:07

You want to be critical of technology, but also accounting for more than just in the full sense of critique, right? Not in the sense of just pointing out the bad, but in really understanding something in its full, rich complexity, by generating empirical accounts of how technologies are actually used, how they produce certain kinds of users, and then how they generate representations of the organism or the problem that they are intended to generate, and then how those acquire a material life, right? So we're always trying to do this in STS. And there's a phrase in technology studies I always forget the actual person who said it, but it's a truism in critical studies of technology, or something that you say in your STS-101 lectures which is that technology is neither good nor bad, nor is it neutral, right?

Speaker 6 38:57

Technology, whether it's doing good things or bad things in the world, is dependent on who's using them and why and in what contexts. And, for example, in the HIV context, phylogenetics were central in validating the undetectable equals untransmissible paradigm, because in the partner and opposites attract studies which were the name of the studies that showed this there were people who became HIV positive during those studies. These were studies designed to tell if HIV viral suppression actually was effective at preventing transmission. Several people in the studies did seroconvert. However, through phylogenetic analysis they were able to determine that it did not come from their primary partner.

Speaker 6 39:41

And so because the strains were dissimilar from each other that had gotten it from another partner. So this is an example of a positive use of phylogenetics. Like I said in regard to SARS-CoV-2, the reactions to the discovery of the Omicron variant in Botswana and South Africa closing of the borders, stopping of the flights is absolutely unconscionable right. However, tracking the emergence and spread of variants globally was very important to pandemic management and then also reformulation of vaccine. So there was a lot of media discourse around the first major reformulation of the vaccine, which was called the bivalent vaccine, and phylogenetics help and have helped for a long time, for example in flu help. Public health agencies and, like the industry partners that they work with, determine what kind of vaccine reformulations or formulas will be important to roll out that year for flu and now in the case of like SARS-CoV-2. So like it's not good, nor is it bad, I think that we have to pay attention to specific uses of the technology. Dennis.

Speaker 5 40:44

So I guess my follow-up question to that is is then, can we use it better, like for good? And so, in particular context, my question is really about like HIV surveillance, and I'm someone who works in a lab where we study HIV. We study the neuro effects of HIV, which can be myriad and really deleterious for people, and so in I don't know that a lot of people know this outside of the HIV research field, but basically the recommendation is that everyone get HIV tested like at least once in their life. Certainly, if you're in what's considered like a high risk group and that varies depending on like where you are geographically on what high risk is they recommend you get tested more often?

Speaker 5 41:21

What are your thoughts on including something like HIV testing as part of what's a normal like CBC panel as a way to help people just be informed of their health and a CBC panel? Christina can probably explain it better, but basically, if you're getting blood work done at like your annual visit or for anything, you go to the ER or something, you're getting blood work. That's what they're running. They're checking all your values just to make sure everything's looking normal. What are your thoughts on like including something like that? So it's not something you have to opt into, because I think there's a stigma to opting into it, right and so if it's just run as, like this is normal, let's just do this. Does that help destigmatize it or does that cause more problems, or is it both?

Speaker 6 41:58

This is a great question. I'm going to take it in two parts, so the first on criminalization. I hate to be the bearer of bad news, although it's important to raise awareness about this, but HIV criminalization is still a very live issue in the United States, and it varies a lot state by state. There are some states that have laws on the books that have very outdated information, such as that spit and bodily fluids that do not transmit HIV can cause HIV transmission. There are some states that HIV transmission isn't criminalized, but even allegations of, for example, non-disclosure of one's HIV status, even if it was a very low risk event, for example if condoms were used people have been criminalized. Based on this, I really recommend Trevor Hoppe's book Punishing Disease, hiv and the Criminalization of Sickness, and also Alexander McClellan's new book Criminalized Lives, which is about the experiences of people who've experienced HIV criminalization in Canada and so that.

Speaker 6 42:57

HIV criminalization is still a very live issue. Hiv decriminalization movement, hiv justice movement. That has gotten some states to reform the HIV criminalization laws to require something like malicious intent malicious intent without consent and so to make their HIV criminalization statutes very narrow. But there are other states that have very broad and sweeping HIV criminalization.

Speaker 5 43:23

I did not know that. I guess I'd only ever focused on the federal level. But that totally makes sense. That in the United States you've got to look at the state laws. Oh my gosh, that is wild to think. We are in 2025 and there's still criminalization. It was 2010 that we decriminalized giving visas to people who were coming to the United States that were HIV positive.

Speaker 6 43:41

So 2010, which is very recent remembered that it was like a. That was when the obama administration was doing a lot around hiv around that time, so that would have been right right, right also around the time of the launch of the first national hiv aid strategy in 2010, which is talk about having a non-functional health care system in this country. We did not have a national hiv aid strategy until 2010 that is insane yeah, that's been almost 30 years into the epidemic right.

Speaker 4 44:07

Wow, when we talk about criminalization of HIV. I personally don't have a lot of knowledge on this. Are we literally talking about? You can be like put in the penitentiary for things that have to do with HIV and if you are someone who's HIV positive, yes, and so this operates at a couple of different levels there are.

Speaker 6 44:27

One level is we can talk about HIV and criminalization being like populations and groups of people who tend to be criminalized tend to be more associated with HIV.

Speaker 6 44:38

So sex workers, transgender women, gay and bisexual men, people who use substances these are people who tend to be criminalized in other ways and who also tend to have higher rates of HIV. So there's that. But then there are actual specific HIV criminalization statutes, and so the Williams Institute at UCLA has really good reports about this. For example, I remember this report came out when I was doing my fieldwork in Atlanta about HIV criminalization in Georgia. It's like outside of the Atlanta metro area, 10% of people living with HIV have experienced some kind of criminalization directly related to their HIV, and so this doesn't mean that they had to have transmitted HIV to someone, but it could, for example, be that they spat on a police officer when they were being arrested and it like got added on as something like resisting arrest.

Speaker 6 45:32

Another charge, and then that would be added to their charge as a kind of enhancement. And then there is HIV criminalization, where there is alleged nondisclosure or transmission of HIV, and again this varies a lot from state to state and country to country and the HIV Justice Network is the organization that kind of globally tracks and drives conversations around HIV criminalization reform.

Speaker 6 45:55

Wow, yeah, and if you want to know more about that you can check out the website of the Williams Institute has some good reports there at UCLA, or, the Center for HIV Law and Policy maintains like a compendium of laws, like they have a profile of every state's HIV criminalization laws.

Speaker 6 46:11

I mean to connect this to the second part of your question and to bridge it, I would say, also to phylogenetics, this idea that you can use phylogenetic analysis, which is a different question than should HIV testing be part of routine blood panels when someone comes in for a primary care or ER visit? The fear that HIV phylogenetics could be used to infer, even with a degree of uncertainty, who may have infected whom in a transmission cluster was a real and remains a real source of fear, because HIV criminalization laws do remain on the books. Now I will give public health credit. Public health is very good at protecting and safeguarding data. This would be taken for granted for people who work in the public health space in any way, but the data that we're talking about, that are reported to public health as part of routine care for people living with HIV. This is done without consent, which is a longstanding practice in public health because these are routine reportable infectious diseases.

Speaker 4 47:10

Actually going to be my next question, but that does also apply to all reportable infectious diseases, not just HIV.

Speaker 5 47:16

Correct, so anything that is reportable is yes, it's just given.

Speaker 6 47:20

Correct, and this is connected to your question about testing. Hiv data in the United States have a very specific history where, since data about HIV were first being collected or aids before they identified the causative agent HIV beginning in the early 1980s, hiv data have been an object of political contestation by advocates and people living with HIV that have made them a special class of data in the public health system. Because initially, in the early years and still, but particularly, in the early years, having a positive HIV diagnosis was so likely to result in things like housing discrimination, job discrimination, there were no effective treatments, and so there were these fights. That happened at the federal level, but then also each kind of state has its own story about how this played out in each state. Because of the US system of federalism, states have a lot of say in terms of the actual data elements that they collect and how they do it, about whether or not HIV tests would be connected to people's first and last names, or if they would be connected to people's first and last names, or if they would be de-identified. If anonymous testing should even be possible, and then also this applied to HIV testing, should there have to be specific consent to receive an HIV test rather than what is called routine opt-out. And so, to give the big picture, these fights have happened at regular intervals in the 40 plus years of the HIV AIDS epidemic.

Speaker 6 48:50

But when effective treatments for HIV became available in 1996, and then more and more widely available after that, the ethical case for names based HIV reporting became stronger and stronger it was. Basically we know, if we can have a better epidemiological picture of who is acquiring HIV, who's living with HIV, who is out of care, we can then have better surveillance data more complete and accurate surveillance data and better serve people living with HIV. And the privacy concerns began to be positioned lower than the kind of public health benefit because people were living longer lives. There was a real, substantial benefit to getting people connected to care, and so this process of the transition to names-based reporting was completed in 2008. And that really forms the basis for all the programs that we've talked about that identify people living with HIV who've fallen out of care and bring them back into care.

Speaker 6 49:48

Part of those fights, which are again very live and differ a lot from state to state, is the question of routine opt-out HIV testing or opt-in HIV testing, which that means do you need a person or a patient's specific consent to order an HIV test for them, or can it just be part of a regular test panel, maybe with asking them hey, we're going to order this, do you want to opt out? I will say there has been a major move toward routine opt out for exactly the reasons that you're saying. Let's destigmatize HIV, let's expand testing, let's de-exceptionalize HIV and make it like other tests that we run. There's not 100% consensus on that, though, and there are still some advocacy organizations that would prefer opting in, and it varies a lot from state to state.

TB Research in Botswana

Speaker 6 50:37

And then also, when states implement, for example, a routine opt-out policy, oftentimes providers don't want to implement it because they're afraid of the consequences of ordering HIV tests for patients, and so this is something that you hear a lot about. Again, this makes me think about STS and how we think about infrastructures, where, for example, a health system you can think about that as an infrastructure sets a policy, puts a policy in place that they're going to implement routine opt-out HIV testing. The policy is only as good as those who are to implement it right, and so you can actually then think about what's the material life of a policy Is it implemented or not, and why? If you talk to people who are working in health systems in the US, where they're doing a lot of HIV testing, and particularly in ERs, you will probably find if they've had an initiative like this, there was some resistance to it and it's very uneven across different health systems.

Speaker 4 51:31

Interesting.

Speaker 3 51:32

So Stephen you expressed your interest in I think you called it the directionality of transmission and where you draw the line right If a transmission occurred, proven by phylogenetics, from A to B. Right Like, where do you draw the line? What is acceptable, it's not acceptable? And we spend quite a bit of time talking about HIV and how you can criminalize or you could use it in a bad way. Right, if you say this came from you or from you.

Speaker 3 52:05

So a lot of people here in the gnl work on the other end of that spectrum. Right where you want to find out the zoonotic spillover of a disease. Right, like from an animal to a human. And the directionality is like the goal. Right, like you want to find out did it come from a mink or did it come from a bat or something like that, where it's very essential. And then often we're like with our backs against the wall because it's all and something that happened in the past and we are trying to put the clues together to see what happened in the past and it's often just an inference. But I'm curious can you talk more about drawing the line right, like we have on the very strong side, the HIV transmission? You don't want to have this directionality of who transmitted to who, but then we, on the zoonotic spillover, we must find out where it came from. So when you, with your interest in transmission and the directionality of it, where would you draw the line?

Speaker 6 53:07

Yeah, I'll take your question by drawing on one of my favorite books, which is a book called the Epistemology of the Closet, by a literary theorist named Eve Sedgwick, and this is one of the foundational works in the field of queer theory, which is another field where I work. And she opens her book with several axioms or axiomatics. One of them is that people are different from each other in the same way and this is like her starting point for thinking about the diversity of human sexuality, right in that context and of human experience period, right, a very powerful, simple notion to return to all the time People are different from each other and people like different things. Right To relate this to the discussion we're having now. Pathogens are extremely different from each other. Right To relate this to the discussion we're having now. Pathogens are extremely different from each other, right. So even this term.

Speaker 6 53:52

I had the problem with the term pathogen genomics for a while, because it indicates it's a set of technologies, but it also, in a way, reduces pathogens that are very different from each other, have different transmission modalities, affect societies, people and, in the case that you brought up Dennis, animals in different ways. It reduces everything to like, oh, a genetic sequence that can be analyzed using a particular method. It has a way of flattening all of this very rich difference that actually shapes the world that we live in, and so this is what I like to remind myself of when we're thinking about the use of this technology to understand different pathogens and where this line could be drawn on something like directionality. Right, I will say I don't take a strong of a normative position, and STS is actually much less than a field like public health. Ethics isn't necessarily interested in staking out very strong normative arguments most of the time. But I will say in the HIV space there is not a consensus about when directionality can or ought not be inferred.

Speaker 6 54:54

There are proponents of using phylogenetics to infer directionality of transmission, and it's usually used with qualifying language like the putative transmitter, the putative recipient, or using the language of inference, but it will be paired with something Well, we ran our model and it was correct 998 out of a thousand times or something like that. So right. And then there are people who will say, no, you can actually never definitively know, and that's like a strong epistemological claim that actually have a colleague who's a statistician, who often calls himself the party pooper on the interdisciplinary phylogenetics team because he's always saying no, you can't definitively infer directionality. But in these other cases, in HIV, this is a highly stigmatized lifelong infection associated with criminalization and a whole other slew of health disparities that shape the lives of people who are living with and affected by HIV.

Speaker 6 55:49

But in other cases the stakes would be quite different and some of the examples that you were talking about, dennis, you would be talking about different pathogens with different stakes, and so I don't want to come down strongly on making a normative argument for or against directionality in any and all cases.

Speaker 6 56:05

But I would urge scientists who are working in this space and who are thinking about the ethical dimensions of their work and what the goals of their work are, the kind of language that they're using and the kind of inferences that they are making and the stakes for the people and the communities who lie behind that data. In a controversy over molecular HIV surveillance and cluster response one of the clarion calls from people living with HIV that has been used in advocacy but also in the editorial a group of folks wrote in the American Journal of Bioethics we are people, not clusters, which is that they were saying. The CDC says all that they're looking at are data and that, basically, this is benign information, and what people living with HIV and HIV networks have wanted to remind the public health agencies is those data that you're working with represent people.

Speaker 3 57:00

Right.

Speaker 6 57:01

And people with rich lives and experiences who might object to what you're doing. Some of them might not, but in any case, you need to do a better job, remembering that there are people behind the data and communities behind the data that you're working with, and I agree, and I think you could even argue the example that I brought.

Speaker 3 57:18

There are also people behind the animals, right, like we talked about, the farmers, right? If you say this came from farm XYZ, right, and they lose their livelihoods, or from farm X Y, z, right, and they lose their livelihoods. Or you say the zoonotic spillover might occur in the country of blah, blah, blah, and then now, all of a sudden, exports are banned from this, and I think you always have to be very cautious with your statements, absolutely.

Speaker 5 57:42

Yeah, I think it can generate a lot of fear when you talk about zoonotic spillovers, but I also think that sometimes it's important to have that information out there right, especially if I think about COVID and people's concerns about a lab leak, versus the recognition that pathogens like this do exist in animal populations and in the wild and routinely are hitting human populations that are naive to them and have never experienced them. And I think again, there's always this kind of desire, I think, by people to find who's at fault, and that can be pretty dangerous when you're talking about illness and something that has dramatically altered somebody's life.

Speaker 6 58:17

This is not an uncommon story in HIV in terms of people wanting to know who gave it to them right After a recent infection. I was just interviewing a provider the other day for a study that I'm doing, and then she is not the first provider who I've talked to, who's people who have had patients who've come to them asking interested in the technologies oh interesting, Can you tell me who gave me HIV? Or wanting just to know. This person I was interviewing was talking about actually a patient who was aware of HIV phylogenetics who was saying, oh, can you use this to tell me who? And she was like no, I can't. And not that she couldn't because she couldn't disclose the information, but more it's not possible to do so. But this is a very common kind of thing that comes up when people talk about new HIV diagnosis, just like people want to know where did it come from, how do they get it, and that's not often the most productive conversation to be having.

Speaker 6 59:11

The productive conversation to be having is remaining in care, but also all of the community infrastructures and support systems that exist for people living with HIV at the community level. Focus on that rather than on the assignation of blame is, I think, one of the kind of enduring messages that the HIV justice movement repeats over and over. Whenever you assign blame for, I think, the transmission of a pathogen, you're moving in a bad direction.

Speaker 5 59:37

I totally agree, but I think we do see it on a large level. Like I can think about the rhetoric that surrounded COVID, there was definitely blame assigned on where it came from right and that was a major part of public discourse that did not do good things. Yeah, I mean look at the Omicron variant example right.

Speaker 6 59:53

I mean you had the EU and the United States shutting borders from Southern Africa because that is where the variant had been identified, but then a few days later we found it was already circulating in Europe and the United States, completely unproductive, harmful to economies and also punishing African countries that had done exactly what Global North funders and scientific agencies have asked them to do, which was to invest in sequencing infrastructures, then being punished for investing in science and sharing the data as they were asked to. That's a great example of where assignation of blame was occurring during the COVID-19 pandemic in ways that were hugely unproductive and harmful to human health and trust within the global health system and all sorts of things, all sorts of problems from that.

Speaker 5 1:00:38

Yeah, yeah, absolutely Okay. Could you talk to us a bit about your work on TB and how that is related to this public discourse around pathogen genomics, because I can think about what I've seen in the news. A lot with TB is certainly this sort of rise of, like multi-drug resistance with TB and that there's much more of this fear that we may get to a point where there are some TB cases we can no longer treat.

Speaker 6 1:01:05

Yeah, there's a wonderful book by Bharat Venkat called At the Limits of Cure. It's an absolutely beautiful book and he's a science and technology studies scholar and an anthropologist and he uses methods from anthropology and history, which his book is a history of tuberculosis in India, but it's organized around the idea of the looming potential future where antibiotics no longer work to control TB and India's path-breaking attempts at TB elimination since the advent of effective antibiotics that can cure TB. It's a book I recommend to everybody who is thinking about this topic, although it came out like two or three years ago, so my work on TB actually began when I was a postdoctoral fellow at the University of California, irvine, and so that's four or five years ago at this point and it has been focused on the views of stakeholders in TB and health system stakeholders in Botswana, including TB survivors in Botswana, which is a Southern African country just north of South Africa with one of the highest HIV prevalence rates in the world but actually a very strong healthcare system. Botswana has much higher rates of retention in HIV care, for example, than the United States and it's an upper middle income country with a very strong healthcare system relatively, and so I got linked up with a group that does TB whole genome sequence phylogenetic studies in Botswana, mapping transmission dynamics and the potential emergence of drug resistance in the capital city of Haberoni, and I wanted to work with these folks to understand if stakeholders in the country supported the uses of the technology, and this was in 2021. We began collaborating.

Speaker 6 1:02:51

We received NIH funding to do a study where we interviewed 30 people and did four deliberative dialogues, basically asking people in Botswana who either worked in the healthcare system or were in civil society or were people who had survived TB about what they thought about the technology, and so we made a video series that we've published. You can watch it if you'd like. We have a publication in PLOS Global Public Health that told the story of a family that experienced TB diagnoses and contact tracing investigations that were informed by uses of TB phylogenetics, and so one of the interesting findings from a lot of this research is that, for example, two cases in the same household that would be assumed to be in-household transmission are oftentimes actually unlinked pairs. Genomics has upended our understanding of the context in which TB is transmitted, but the husband had drug-susceptible TB and his wife, in this fictional story that we created using animation software, actually ended up having a multi-drug-resistant TB and had to go into a longer period of isolation. And it told these people's story and it told the story of the ministers at the Ministry of Health who debated should we publish these data about, for example, transmission hotspots?

Speaker 6 1:04:10

And I was going into this research coming from the American context. Okay, I had not done much work in global health and I was coming from being actively studying this very intense controversy around molecular HIV surveillance and cluster response, where the stakeholders in the US were reacting against HIV sequencing very strongly and there was an active controversy. We in Botswana. I didn't know what we would find. I expected that there might have been a lot of skepticism about TB genomics and TB phylogenetics among stakeholders in the country, but actually what we found is that people wanted it. People wanted it to be implemented yesterday, right Like universally across our sample, and that was somewhat surprising to me.

Speaker 6 1:04:54

I went on to learn more about Botswana and the history of post-colonial development of the state there and the strong healthcare system and it became less surprising to me.

Speaker 6 1:05:04

But what was interesting is we were able to demonstrate through that study that people in Botswana really wanted TB sequencing in order to identify drug-resistant TB there, but then also for secondary uses to improve surveillance and research in the country. And as we were analyzing and publishing that data, some of which we're still working on publishing, the WHO in 2023 recommended the implementation of sequencing for TB drug resistance diagnosis in any country that had capacity to do it, and so that led to a follow-on study that we're doing now where we're actually developing implementation strategies for sequencing. So it's been cool to go from developing and understanding whether people would support it to actually now developing strategies to assist with the implementation. And again, the benefit of the technology in the context of TB is really to identify drug resistance. So culturing TB samples to identify if there's drug resistance this is a process that can take weeks or months. That's like the gold standard of phenotypic drug sensitivity testing. Targeted sequencing can potentially identify drug resistance much faster in order to inform treatment.

Speaker 3 1:06:14

If you compare this to HIV, is there the same blame game with TB? Are there questions like who gave me this multi-resistant TB, or is this less the case compared to HIV?

Speaker 6 1:06:25

What we found is that it's less the case.

Speaker 6 1:06:27

There are still some of the same ethical concerns, but again, in Botswana people tend to trust the state a lot more than in the US, just generally, and so the idea that the ministry will safeguard the data and will use it well was very much part of what our participants said.

Speaker 6 1:06:44

But people did also want engagement about the technology and how it would be used, so wanted listening sessions, wanted ministry to engage the media if this were to move forward and to stay informed. The blame game and kind of skepticism about the value of the technology really did not manifest. And something that came up a lot we were talking about the economic impacts of a district being labeled as having, let's say, a high rate of MDR, multidrug-resistant TB. There were concerns that that could harm businesses in that area, and so participants had recommendations about how the ministry could maybe mitigate or any harms that could come from that, maybe just use the data internally rather than publishing it, and they wanted to be engaged about these issues. But it never manifested stop, no, this shouldn't be implemented, whereas in the US there's a much broader spread of people, including people who are in social movements, who really just have called for a moratorium on uses of phylogenetics in the HIV context. There's actually an active call for a moratorium from some networks of people living with HIV.

HIV Criminalization and Public Trust

Speaker 3 1:07:50

Why do you think there's the difference that you outlined between Botswana and the US?

Speaker 6 1:07:55

I think you can connect this to an earlier discussion we were having about our healthcare system in the US. I think that you could look at the rates of HIV viral suppression in the United States, which are below 70% I think below 65% the lowest of any high-income country. People have good reason not to trust the healthcare system here. Hiv is a highly stigmatized disease that remains associated with many social inequities. People living with HIV are not treated well in this society, and the healthcare system doesn't treat people well here, and so this leads to diminished trust in state institutions and the healthcare system doesn't treat people well here, and so this leads to diminished trust in state institutions.

Speaker 6 1:08:32

And what's interesting is that, by the way that TB is handled by public health in the United States, we're a very low morbidity country in the US, to use the language of public health when it comes to TB right, and so when there is a case of TB, particularly DR drug-resistant TB, public health really, really, really makes that a priority. In the United States it has been since the 1990s, quite effectively using a molecular surveillance system developed for TB to map transmission patterns and to contact people and get them into treatment. But I would say things like transmission inferences, are used much more liberally and less problematically in a particular way, where there really is no analogous social movement for other pathogens. There are networks of people who are TB survivors or affected by TB, but they have nowhere near the political clout of the HIV social movement, and so I think that we also have to look again at the political economy of these diseases and why certain practices are problematized for some and not others.

Speaker 3 1:09:56

I feel like we opened so many doors. We asked so many good questions. I feel like there needs to be at least three follow-up episodes to this. I know I'm going to go back to this episode. I'm going to listen to it multiple times because I got me thinking on a lot of different subjects that I've not really thought about previously. What do you think, Christina?

Speaker 4 1:10:16

I completely agree and it just has me turning a bunch of questions over in my head that if I asked right now, this would be like a four hour podcast.

Speaker 3 1:10:24

So, stephen, you have to come back.

Speaker 6 1:10:26

It would be my pleasure and thank you so much for having me, and it's been great to see infectious science really come into its own these last couple of years. Thanks for the great work that you're doing here at the GNL, where we are right now in this beautiful recording studio in the Galveston.

Speaker 5 1:10:43

It's much larger than a closet. It was actually a closet. Oh, it's much larger than a closet, it was actually a closet.

Speaker 3 1:10:49

What was the name of the book that you recommended with the axioms and the closets? I recommended four books.

Speaker 6 1:10:56

Okay. So one of them is by the sociologist Trevor Hoppe called Punishing Disease, hiv and the Criminalization of Sickness, which is a great book that is about the history and effects of HIV criminalization the conversion of what he calls sickness into badness in the United States. Alexander McClellan's new book, which just came out last year he's a Canadian criminologist and a collaborator of mine called Criminalized Lives the experience of people who have experienced HIV criminalization in Canada. I didn't get the title perfectly right, but the first is Criminalized Lives. That's the name of the book I also recommended, yeah, eve Sedgwick's Epistemology of the Closet in a kind of sideways way, that's our book here in the closet right.

Speaker 6 1:11:37

Yeah, here in the closet Epistemology of the Closet yeah and then finally, venkats At the Limits of Cure, which is about the history of TB in India.

Speaker 3 1:11:46

It's such a beautiful title, we'll put that in the show notes. Yeah for sure, cool All right.

Speaker 4 1:11:50

Thank you so much for just taking the time out of your schedule to come here. We know you're a very busy man, so just thank you so much and hopefully we can link up again and discuss these topics a little bit deeper.

Speaker 5 1:12:04

And thanks everyone for tuning into this episode of Infectious Science bit deeper and thanks everyone for tuning into this episode of Infectious Science.

Speaker 1 1:12:13

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Speaker 2 1:12:19

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Speaker 1 1:12:32

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Book Recommendations and Closing

Speaker 2 1:12:37

So we'll see you next time for a new episode, and in the meantime, stay happy stay healthy, stay interested you.