Ingrid Katz: What Would It Take to Eradicate HIV?

Transcript:

Harlan Krumholz: Welcome to Health & Veritas, I’m Harlan Krumholz.

Howard Forman: And I’m Howie Forman. We’re physicians and professors at Yale University, and we’re trying to get closer to the truth about health and healthcare. Our guest today is Dr. Ingrid Katz, but first we always check in on current for hot topics in health and healthcare. What do you have today, Harlan?

Harlan Krumholz: I thought we’d talk about Jalen Brunson. How about those Knicks?

Howard Forman: Yeah, that was an exciting game.

Harlan Krumholz: You’re a New Yorker. You’re a New Yorker.

Howard Forman: I know.

Harlan Krumholz: I thought you be over the top about this.

Howard Forman: And I still did not watch it. I’ve stopped watching sports events at night because it keeps me up. I was with my father today who specifically told me that he uses his pacemaker as an excuse not to watch the games live because it might set him off too much. He is a true diehard Knicks fan, and this was nice for him to get to see after 53 years.

Harlan Krumholz: Watching those players cry after the game, seeing the joy in New York City. I mean, I grew up in Ohio, but we watched the Knicks. We always watched the Knicks too. It was remarkable. It was just remarkable.

Howard Forman: It was exciting.

Harlan Krumholz: All right. Look, I’ve got something else I want to talk to you about this week. And it’s something that’s not a great thing. So let me start with talking about the UK Biobank. So for those of you who are listening, many of you will know about the UK Biobank, but not everyone will. So let me give you a little bit of an update about it. Beginning in about 2006, half a million people in Britain, just ordinary volunteers, agreed to be studied for the rest of their lives. They gave blood and saliva, sat for scans of their hearts and brains, let researchers link their medical records together and their medical histories, had their genomes characterized, and agreed in many cases to come back over time to be remeasured. And that entire resource, the UK Biobank, was open to scientists anywhere in the world who wanted to ask serious questions about it.

You can imagine for someone like me who’s an open science advocate, this is a dream. This is a dream because you could be in a place where you’re bright, you know how to ask questions, but you just don’t have the resources to implement a large study like this or even a small study. I mean, you don’t have the grants, you’re in a country that doesn’t give that. Anywhere you were in the world, you could leverage this dataset. And what came out of it, it’s hard to overstate. Tens of thousands of studies on how we develop heart disease, dementia, cancer, diabetes, on the way our genes interact with our lives to create disease, what we can do to reduce risk. When I want to show someone about the generosity of volunteers and scientists in the true service of science, meaning all these people worked on this so that others could write and study and produce knowledge that would benefit people throughout the world, but these people themselves wouldn’t directly receive credit. UK Biobank, of course, did, but many of these people’s names would never appear in print. It was an entirely generous thing to do. We in this country tried to do the same thing with the All of Us Program. You may remember Obama in the Precision Medicine Initiative. We never have been able to achieve anything quite close to this. I admire that all of us effort, but the UK Biobank was really the standard for what could be achieved. So earlier this year, the medical records of those half a million people, the gift they gave, turned up for sale on a Chinese e-commerce site, Alibaba. Can you imagine, pay money, and you’ll get access to this database? And it did happen several months ago, which was terrible news for all of us because it’s when people start corrupting the internet and you say the internet’s not going to be able to continue as it is because people are doing things to it that are harmful. This is the same kind of thing.

This happens, and all of a sudden the openness, the generosity, people start questioning it. I’m raising it this week because this past week the BMJ published an investigation showing that the problem’s not behind us. Three months after the Biobank insisted it had things under control, and I so admire all those people in the UK Biobank, reporters found the data still online, copied and mirrored onto servers around the world. It’s not been contained and probably it never will be because once it was up, it spread.

Howard Forman: Right.

Harlan Krumholz: So here’s where I want to be careful about. There’s an easy version of this story, which is that there were outside hackers that got in and there are thieves that stole something precious, but that’s not exactly what it is. I think of it more a little bit like Camelot. Camelot and the Round Table, they didn’t fall to invaders at the gate. It fell from the inside when people who had sworn to uphold the code broke it themselves. And that’s a little bit closer to what happened here. There were people who had legitimate access, scientists, but they were sharing passwords, and other people got it, and it began to spread. And next thing you knew, this thing was out in the open. Now, I want to make a really clear point. This is not a story about China. People could reflexively say that this is about China.

It’s not. The data surfaced there, but the archives, for example, keeping it alive are in France. It’s just that there are a lot of archives around the world that copy other data so that it’s held safely and securely. But in this case, it was data that wasn’t really available. So let me just end this by saying this doesn’t make me think we shouldn’t be doing this. Of course we should be doing this. The UK Biobank is amazing. It just means we need to be thinking of clever ways, better ways, to protect the security data while still making it open enough for anyone in the world to use. And, Howie, I’m going to end with this with an idea I have about this, which is when you have these large databases with sensitive information, what you could do is create a synthetic dataset that’s not perfect but enables you to hone the code that you’re writing in order to perfect your final run that you want to do on the data.

And so you’re working with data that aren’t real. They’re synthetic. They’re not real patients, but they resemble the real data. And when you’re done and you’ve got your code written, you can submit it to a third party who in a safe and secure environment runs it for you and gives you the output.

Howard Forman: Yeah, that makes sense.

Harlan Krumholz: But whatever our solution is, I don’t want us to quit the open science. I want us to innovate on how we can make sure the data stays safe.

Howard Forman: Yeah, it’s so important. And I think next week’s episode we have Dr. Bhramar Mukherjee, who’s worked with the UK Biobank and also has been committed to data security and data equity, but it is a topic that I personally don’t think nearly enough about. I’m sure most of our listeners don’t think enough about it. I’m always grateful that you are paying attention to this because our future depends on it.

Harlan Krumholz: Yeah. And this is what truly accelerates discovery and also improves the reproducibility of science because everyone has access to the same data. If different scientists are getting different answers, then you can come together and try to resolve it. It’s not like “I’m publishing a study, no one can touch it.” You actually don’t even know if I’ve made a mistake with the coding if I can’t share the data. If the data are out there, it just elevates science all the way around, and it makes it so that a brilliant individual in a poor community who just has access to a computer in their own mind can leverage a vast resource that took millions to create.

Howard Forman: Yeah.

Harlan Krumholz: All right. Hey, let’s get onto the interview with Ingrid. That’ll be a great interview.

Howard Forman: Dr. Ingrid Katz is a physician, researcher, and global health leader who serves as director of the Yale Institute for Global Health, professor in the Yale School of Medicine, and acting chief science officer at the U.S. Department of State, where she has held several leadership roles in global health security and diplomacy. Her work focuses on HIV, global health security, and the challenge of making care more accessible and sustainable. As part of that work, she has studied HIV treatment in South Africa, including why people may delay or refuse care and how stigma and health system challenges shape those decisions. Before joining Yale, Dr. Katz spent 16 years at Harvard Medical School, including serving as associate faculty director at the Harvard Global Health Institute. She earned her bachelor’s degree from Amherst College, a master of health science from Johns Hopkins, and her medical degree from the University of California, San Francisco.

She went on to complete her residency in internal medicine at the Brigham Women’s Hospital and then an infectious disease fellowship at Beth Israel Deaconess Medical Center. So first of all, welcome to the podcast. It’s really such a delight, and we’re so glad to have you at Yale overall. I mean, our global health leaders at Yale over the years have been some of the most extraordinary people. We’ve had Saad Omer on the podcast in the past, but a lot of your work particularly in HIV and the challenges to treating people even in an era where we presumably have a cure in many places has really informed a lot of the most practical translational work in sub-Saharan Africa in particular. I just wanted to start off, if you could summarize why is it so hard for us to... we have the drugs and we even have the affordability of many of these drugs.

What is the challenge to basically eradicating this from the planet right now?

Ingrid Katz: Well, thank you for that really kind introduction, and I’m so thrilled to be here. So I think HIV, obviously it’s a chronic disease like any chronic illness. And I think we really need to, in many ways, normalize it the way we think about treating hypertension, the same way we think about treating diabetes, that people are living with a chronic illness that will need daily treatment for the rest of their lives. The challenge we face, I believe, is much more at the person level than at the systems level, the way it used to be. And so when you go back in the time machine 20, 25 years, when there was really inequitable distribution of HIV medications globally, then we really had a systems issue. There was fundamentally inequitable supply of medications. But with PEPFAR [President's Emergency Plan for AIDS Relief] rolling out in 2003, as well as Global Fund and other big donors that were part of a bigger ecosystem of contributing to treatment, that was certainly, I would say there was a large effort to rectify that, but we still have places where we’re not touching people who need lifelong treatment.

And the problem is, when we don’t have people in care, then we have onward transmission of the virus. We know that if someone’s on HIV treatment and they’re virally suppressed, there will not be onward transmission of the virus, which means it stops right there. Not only keeps that person healthy, but they’re not going to transmit it to their sexual partners. They’re not going to transmit it to babies. And so fundamentally, if we can have people on treatment virally suppressed, then we can essentially end the HIV epidemic, but we still have millions of people around the world who are not virally suppressed, who are living with HIV, and so therefore the epidemic will continue to roll out.

Howard Forman: But I just want to follow up on that because first of all, I just want to emphasize what you’re saying. We really could eradicate this from the planet. We could get rid of it just like we got rid of smallpox at this point, but one requirement is you have to test people so that you identify them and then the other is to treat them. And a lot of your work is about both of those issues. Can you just reflect on how important it is to answer those questions? Why can’t we get people tested, and why can’t we treat them?

Ingrid Katz: Yeah, absolutely. And it seems really straightforward. I mean, this should be a no-brainer. We should just be able to test and treat, right? That’s the objective. We even have a slogan: Test and treat. So some of it, yes, is health systems in the sense that we have these very static systems all over the world where people have to come in and get care to... they have to stand in long lines. They have to see healthcare providers, will often take a full day. To get tested often comes with a decent amount of stigma. They may run into someone they know. They’re standing in a line. Many health systems still separate people in rooms where half the room, you know, “if you are living with HIV, go stand on that side of the room.” I mean, it’s highly stigmatizing. I understand it’s often done in situations where they’re triaging large numbers of people, and they are clearly understaffed.

There’s also, I think, points of what we call these “pain points” when people come even at the place where they’re meeting the security guard out in front, where they’re thinking to themselves, “I’m not sure I want to go in there through that line and meet all these people who may judge me.” And so we’ve certainly increased access to things like self-testing and other ways that you can reach care through what we call differentiated service delivery models or DSD models, which I do think meet people where they are. So you could do a home test. If you are living with HIV, you could ideally go to a pharmacy where they could prescribe antiretroviral therapy for you. That’s the best-case scenario when someone’s healthy and they can start treatment right away. Or they could go to a free clinic that’s close by, but too often that is not possible.

We have highly static systems with mobile people, so they’re not meeting each other. Sometimes the mobility relates to the need to move for seeking employment or they’re escaping violence or some other reason that people are on the move. Or perhaps they’re just mobile within their community and they’re moving around from place to place and a clinic might work at a certain time and then they have to move and they’re uprooted and they have to go find somewhere else. Static systems don’t meet mobile people. And then of course you have highly dense systems where people are triaged and wait in long queues. That also doesn’t work for people, for many people. So at the end of the day what happens is we end up having this tiered system where only a small percentage of people can navigate these spaces to get the care that they need.

Now, over time we have managed, and I want to commend all the people in the community who’ve worked on this, we have managed to reach in our program at PEPFAR, we have 20 million people in care. I mean, that’s a phenomenal number, right? So it’s not to say that we haven’t done, and this program hasn’t done a tremendous job with accessing care for people. However, we still have far too many people who are living with HIV who are not getting the care they need.

Harlan Krumholz: I think it’s a really interesting point. I love the way you’re phrasing it because too often everyone’s too ready to blame people, the patients themselves for not following directions or not doing what we tell them. But the truth is, the systems make it very difficult. And I mean, it’s true in this country too. I mean, why are all our clinics open during the day when the people who... We have so many hourly workers who cannot say, “I’m going to take the afternoon off to sit in a doctor’s office and be seen.” And sure, for people who have free time or discretionary time or have jobs where they can take time off, that works. But instead we configure a system, and people don’t show up for appointments, and we’re too ready to blame them instead of to wonder whether or not we’ve configured a system that’s optimal for people to be able to participate in.

So I think your points are so important. I wanted to key on one thing. I know it was so interesting. So you say if we could make it more like hypertension, in a way, destigmatize it. But those of us, I’m a cardiologist, those of us on the hypertension side say, “Why can’t we make it more like HIV so that there’s a sense of urgency?” You look at Africa, one in three women, one in four men, we published a study recently across 37 countries in Africa, have hypertension.

Among those who do, only 15% of women and 8% of men are treated. Only 7% of women and 4% of men are controlled. And the absolute case count has nearly doubled in the last two decades, and men are worse on almost every access that you look at. So Africa now has about 390 million adults with hypertension. Fewer than one in 10, like I said, is on treatment. So why is it that we can get all animated about HIV, but if you look at the number of people who are dying in Africa, many more are dying of hypertension and many more at risk? Now, I’m not suggesting moving resources from one to the other. They’re both important, and we obviously want to be able to value every life and try to help every person. But for some reason, the noncommunicable diseases lack that sense of urgency.

We didn’t get a PEPFAR for hypertension in Africa, we got a PEPFAR for focusing on infectious diseases. And so I’m just wondering what your thoughts are about that, because for me, this is a number one threat. And by the way, it still is the leading cause of death in Africa now. I mean, hypertension, cardiovascular disease, cardiovascular disease and stroke all wrapped together, and these risk factors aren’t being addressed.

Ingrid Katz: I totally agree, Harlan. One of my colleagues who worked with me at PEPFAR, he had just written in a Substack about, “We need a Marshall Plan for global NCDs,” and I really agree.

Harlan Krumholz: And NCDs, non-communicable diseases for people listening just because they... Yep.

Ingrid Katz: Right. And I think we’ve made a mistake in many ways, us, the global health community, to have such a strong emphasis on infectious diseases that we’ve essentially neglected the major killers of people globally of adults being noncommunicable diseases. And again, I think a lot of that weight has shifted because of the emphasis we have made towards reducing mortality from HIV. That was clearly a leading killer, particularly in Southern Africa. But if you look at the global statistics now, I completely agree with you, Harlan.

Harlan Krumholz: I will say, by the way, the themes are the same, which is that this connection between what we know works and as Howie said, we know the problem, we have affordable meds now, but still, we’re having trouble translating to people who could benefit. Same themes.

Ingrid Katz: I think the urgency piece to get to that aspect of your question is something that’s very much built into our HIV response. And it was built there from its insemination, right? Because if you recall, some of us are old enough to remember the HIV activist movement of the ’80s, right? That was the nascency of all of this, all of the work that we do. It drove our scientific response. There were die-ins at NIH. There were, of course, ACT UP. There was TAC in South Africa, Treatment Action Campaign. So there was a lot of activism at the core, and scientists and clinicians were coming right alongside. But at the end of the day, they were the heartbeat of our HIV response and also what pushed the White House and George W. Bush to create PEPFAR. There was a lot of noise about the global inequalities between folks who could have access to lifesaving medications in the United States and Europe and nowhere on the continent.

And so in many ways, that is what underpins, I think, the consistent messaging around the urgency, that we were rooted—and still are, if you go to our major HIV conferences, I’ll be at Rio in July for our International AIDS Conference, there will be activists there. They will come up on stage. They will sound the alarm about things that are concerning to them, and that’s their job. They see that very much as their job, and they are very much integrated into all of our spaces, whether they’re in communication with government, whether they’re activists speaking with NIH. We had leaders at NIH who ultimately welcomed them in and said, “We want you here.” And I do think some of the most active spaces, you think about, for example, my understanding is communities like the breast cancer awareness community took a playbook from the HIV community. So we need a lot more activism to support breast cancer research and treatment.

And before that, it was much more stigmatized. People didn’t want to talk about breast cancer. So in many ways, I feel like we need a hypertension moment. We need activists there for the cardiovascular community. I mean, cardiovascular disease has undergone such... I mean, I’m a physician too. So while I’m not a cardiologist, I appreciate the tremendous advances that we’ve made in cardiovascular research and clinical care. And when you look at it from a population level, there’s a huge mismatch. We have this incredible science. We could absolutely, I think, end hypertension, certainly as a killer, we should be able to treat hypertension successfully for the vast majority of people, and we’re not quite able to do that at a population level. So I guess my question to you, Harlan, because I talk a lot about the stigma that surrounds an HIV diagnosis and the getting care that people need, in your opinion, what do you think is holding back countries from really advancing a Marshall Plan or being able to really elevate care, chronic care, for hypertension?

Harlan Krumholz: Yeah, I think it’s the distance between the intervention and the reduction of risk and being able to show people that actually there is a big ROI that’s not so far in the distance. I mean, when you have asymptomatic conditions that you’re trying to... and what I’m talking about are the risk factors. So hypertension or whether it be lipids or whatever it is, getting people to galvanize treating obesity now is the same issue. And obesity, of course, does have some outward manifestations and can provide some limitations to people that would motivate them to want to undergo treatment, but hypertension doesn’t. I think it’s like you said, I think it was the activists. I think people just get mobilized around infectious diseases in a way that is harder to do when they’re not communicable, when people don’t infect each other. But we’ve got to be thinking on a social level, they actually are in a way communicable.

I mean, Nicholas Christakis had this idea about obesity being a social phenomenon. And I think that would be same true with all these other risk factors. And I think just getting people to understand, the policymakers and populations, about the massive benefits that can accrue to trying to lower risk without sacrificing a lot of quality of life. We’re not telling people you have to give up a lot. It’s just being attentive to these risk factors can make a huge difference.

Howard Forman: I do think it’s worth mentioning for our listeners, though, that from 1993 to 2003 roughly, South African life expectancy, which had been going up over time, dramatically dropped by over 10 years suddenly. That’s a jolt that you can’t ignore. Even though as you’ve pointed out, Harlan, the overall morbidity from hypertension may be comparable, but it didn’t happen suddenly that way you could see it in your neighborhood where people are dropping dead.

Harlan Krumholz: Well, people suffer from HIV. Look, I am not trying to create a competition between the two or to suggest fewer resources should go to the infectious diseases. I’m only thinking out loud with you guys about how we also make sure we’re keeping our eye on the ball.

Howard Forman: The burden is there.

Harlan Krumholz: And by the way, that was affecting a lot of young people, and that gets people’s attention too is that those deaths were many... there were many fewer people than you would’ve gotten with cardiovascular disease. There were many more years because they were people who were suffering and dying at much earlier points of their life. So that’s another facet of it.

Ingrid Katz: And I think it’s also multigenerational with HIV when there was such a massive loss, and then children were orphaned, and then they were born with HIV. So there were so many layers there. And I said, if I ever write the story of South Africa during that period before PEPFAR, I would title it “Funerals Are for Wednesdays,” because there were so many people dying, they couldn’t hold funerals on the normal days of the week that they would, which would be the weekend. And all these things stacked up so people could only hold a funeral on Wednesdays. To me, that is so devastating to imagine that you couldn’t even say goodbye to your loved one on the standard day of the week. That’s how bad it got for South Africa.

Howard Forman: I want to pivot to a different topic, but related, and that is, right now there is a growing Ebola outbreak. It is very difficult for us to know how bad this will be, but it looks like it’s on track to be the second-worst Ebola outbreak, and we’re going to learn a lot from it. But one of the criticisms that you hear from people in the DRC is, “Why are you all giving us all this attention over this one disease now when there are so many devastating things happening to us including civil war or at least military incursions and traumatic harm and disease harm from other diseases?” And by “DRC,” of course, we mean Democratic Republic of Congo. We’ve mentioned it a few times over the last few episodes.

What is the answer to people to explain why it is so important for the United States to care and for the greater global health community to care about what’s going on in the DRC, in the adjoining nations that have been affected and beyond?

Ingrid Katz: Yeah. So the point you raise about the global attention to pandemics is real, and I don’t want to discount the absolute urgency that we are facing with the Ebola epidemic right now. It is serious, and I think we need all hands on deck because there is too much at stake. And I would say part of the reason we think about this and why we engage so fully as Americans is that we know that viruses don’t stop at borders, right? We know that from COVID, certainly didn’t stop at a border. And so anytime that we’re addressing an infectious disease that is lethal, we have to be thinking about the entire globe. In something like Ebola where it is intensely transmissible and essentially terminal without tremendous intervention, which we certainly don’t have the capacity to do in such a resource-constrained setting with, as you said, violence, we have a situation where there’s essentially, it’s an uncontrolled epidemic unless we work to essentially end it collectively, and even then I think it’s going to be very hard to staunch the flow.

I think the larger picture of why do we all rush in for these epidemics and then pull away when that’s been quelled and not pay attention, I think as a global community, I’m not saying just the United States, during these other times, I think that is actually an area of deep concern. I’ll use, for example, South Sudan as a place, is under deep, deep duress right now. I mean, they’re under such extreme circumstances. They have essentially no functioning health system whatsoever. So if you were to go to one or two of the remaining health clinics that are open, there would be nothing there for you. So to imagine that as an American, where we come to a clinic, even if we have to wait to get there or we have to go through, sometimes we have to go to the emergency room because we need to get care faster than we can get it in a clinical setting, we never question, will there be a physician or a nurse there? We never question if the medications will be there that we need.

And I think when we neglect countries that are in these extreme circumstances where we essentially say, “Well, that’s not our purview,” if you’re just thinking about the United States, which I personally prefer not to do, I prefer to think of our whole globe. But if you’re just thinking about the United States, I mean, this is a bomb ready to explode because any infectious disease will immediately take off into the neighboring regions because there is absolutely no way to contain it there. And so we’re left in these incredibly dire circumstances, certainly for the people who live there, but for all of the surrounding spaces. And often there’s conflict on the borders of all of these places. So there, it’s very porous. People can come and go.

So we saw that with transmission into Uganda, and all of the countries that are surrounding DRC right now are quite concerned about the potential for spread. So we have lots of reasons that are both, I think, I would say critical for our collective wellbeing on this planet, but also of course for the people who live there and for the surrounding communities.

Harlan Krumholz: One thing, I wanted to go back to the South Africa example for a minute because you have such deep expertise there. And it seemed to me to be an example of the role of government and both how it could promote adverse... you know, how do I say it? It amplified the pandemic, the epidemic of HIV for a long time before it pivoted to help partner with others to actually control it. And it showed really the key importance of the government. Maybe can you talk about that a little bit? Because for a long time it was taboo to talk about HIV in South Africa, and ignoring the problem I thought was what led to its amplification, but there was ultimately a pivot where the government realized it had a role to do. Can you talk a little bit about that time before, and what was it that changed the government so that they moved from non-evidence-based ignoring it, not wanting to even talk about it at all to a point where they actually engaged positively with it? What happened there?

Ingrid Katz: Well, I mean, Mbeki was essentially an HIV denialist, and his minister of health certainly didn’t help matters at all. It was complicated because Mandela passed Mbeki the mantle of the presidency, and people actually credit Mbeki for doing a lot of very progressive economic reforms in the country. But when it came to HIV, this was such a blind spot for him, and huge troves of misinformation were spread. And I think I completely agree with you, Harlan. And there are data to support that statement that were done by investigators at Harvard to show that, yes, under Mbeki’s watch, hundreds of thousands of people probably needlessly died because the message that was being propagated was this is not real, this is a curse from the Global North or you could treat it with garlic, any number of strings of misinformation. And we, of course, weren’t helping matters because access to treatment was not widely available.

So you had this kind of perfect storm, and you see it again and again with global pandemics of constrained access, whether it’s to a therapeutic or to a vaccine with misinformation that now gets put on warp speed with all of the ways that were interconnected globally and the spheres of information that people all live in that are separate from one another. And you had people who did not, even when they had options to avail themselves of treatment, were not necessarily accessing it. Now again, stigma being, I think, one of the major sources of non-engagement in care, but I also think this piece of misinformation, it got integrated into the psyche of people that was very hard to lift off. And so when there was a change in leadership, so Zuma came in, different presidency also had some challenges in that ecosystem for sure, but did not have as a regressive stance around HIV.

And so at that point you could imagine, and again, when PEPFAR came in, and this is where I think your question around or your comment around governments is so key, Harlan, they essentially had to build a parallel system adjacent to government clinics because the government was not welcoming in PEPFAR at that time. Other countries were able to integrate PEPFAR in different ways because the government said, “Yeah, we could use you here.” But in South Africa, that was not the case. Academics, NGOs, activists said, “Yes, please come. We will work with you.” And still, many of those folks are there today.

Some of them are my closest collaborators and friends who worked very closely with PETFAR in those early years, many of whom were clinicians who... I have a friend, a clinician, the resources were so scarce for antiretroviral therapy. When someone was on treatment as a last-ditch effort, because they got it at the end of their life and they died usually from IRIS, which is like an immune reconstitution syndrome, they would literally drive to their house, take the meds, put them in the back in the trunk, drive to the next person’s house, and give them those meds that were still left over because people were so desperate to try to get treatment.

Those people said, “Yes, PEPFAR, please come in. We need antiretroviral therapy here.” At that point, the government was very mixed in terms of how they were receiving PEPFAR. Now, when Zuma took over, there was a shift, and I think it was so fortunate that I think people were then able to lean in. But again, I completely agree. You cannot underestimate how critically important it is for governments to have the backs of their people in terms of prioritizing health investments. And I think part of where the struggle now lies... you know, when we go back to Abuja and we think about these commitments that countries made to support the health of their people, to make commitments in their budgets as a percentage of their GDP to commit to people’s health and wellbeing, what you find is that it often can be deprioritized because they have so many other demands on a constrained budget.

And so this is going to be where the rubber hits the road right now. In this moment, we have to be watching that so closely. It’s a big risk.

Howard Forman: In our last minutes, I just want to give you a chance to say, what are your hopes, dreams, aspirations for global health at Yale? Because I think that there is so much opportunity.

Ingrid Katz: Oh, thanks. Thanks, Howie. I can’t tell you how happy I am to be here. This community is so robust and vibrant. And part of what I love about Yale is it is a full university of people who are engaged here. I mean, we have, of course, the folks on the biomedical side, the School of Medicine, School of Public Health, School of Nursing, but then we have folks like you at the School of Management. We have others in the Law School. There are economists, there are political scientists. I think when you bring cross-disciplinary expertise to bear, that’s where you can see the most opportunity for change. And so my hope is that Yale really gets to lean into this moment. I think there is a huge need for academic partnerships around the world. And I think there’s tremendous expertise on campus here. Lots of people have been invested in this space for decades with deep partnerships.

And my hope is to help grow the full arc of this university so that we really elevate the collective and support cross-disciplinary collaborations, both here and globally.

Howard Forman: We are very lucky to have you.

Harlan Krumholz: So wonderful to talk to you. Thank you so much for joining us.

Ingrid Katz: So great to see you. Thank you.

Howard Forman: We were so lucky to have her.

Harlan Krumholz: Oh my gosh. What a terrific individual.

Howard Forman: Yeah.

Harlan Krumholz: Yeah, I know. It’s like Yale attracts wonderful people. She’s super. Hey, let’s get onto another favorite part of the podcast for me. What is Howie Forman thinking this week?

Howard Forman: Yeah. So when I was nine or 10 years old, I wrote a biography, as one does in grammar school about Linus Pauling, and I fell a little bit in love with this man. I mean, he had two Nobel Prizes, Chemistry and Peace, both unshared, the only person in history to pull that off. And Pauling was certain that vitamin C was close to a miracle, that it could prevent the common cold, fight cancer and more. And as a child, I absolutely believed him, and I followed this for a long time. He was wrong, and the story of how wrong is playing out in the journals right now. For more than 50 years, vitamin C has been tested as a cure-all, and it has mostly failed in colds and cancer and sepsis. This month, JAMA published the VICTORY trial, a rigorous international study of high-dose intravenous vitamin C in patients with severe burns.

The researchers had real reason to hope. Instead, they had to stop the trial early, not for lack of benefit, but for harm. Twenty-eight-day mortality was nearly twice as high in the vitamin C group, 15% versus 8%. The accompanying editorial was titled simply, “Time to Stop.” So you might conclude that vitamin C does nothing, but that same month, New England Journal of Medicine: Evidence published the other half of the story. A seven-year-old girl with six weeks of leg pain and a limp. She was worked up for leukemia for bone cancer. Her MRI lit up in ways that mimicked other diseases. The answer turned out to be scurvy, vitamin C deficiency from a diet with almost no fruit or vegetables. The cure was essentially an orange. Within three weeks, she was walking normally again. There’s the whole lesson in two papers. Vitamin C is essential. Its absence is a genuine treatable disease, but essential is not the same as curative in large doses for everyone.

Pauling, brilliant as he was, collapsed those two ideas into one. The same molecule is one of medicine’s quiet heroes and one of its most stubborn cautionary tales. It took 50 years and a two-time Nobel Laureate getting it wrong to tell the two apart.

Harlan Krumholz: Thanks. To me, Howie, first of all, I mean, we have to salute both what Linus Pauling’s accomplished, but can I say, no one’s perfect? I mean, but he did feel very strongly about this and he did put this into everyone’s thinking. But to me, it’s not just Linus Pauling, it’s this whole belief around multivitamins. And for the general adult population without nutritional deficiencies, most vitamin mineral supplements have not been shown to prevent cardiovascular disease, cancer, reduced mortality.

Now you’re looking at it very specific—burn victims, for example. I mean, but it’s still the millions and millions. We can’t get people to get measles vaccine, but the number of people who are bought into this idea about vitamins is just remarkable. And that’s multivitamins, vitamin D, vitamin E, folic acid. Again, unless there’s a nutritional issue, it’s just remarkable. Now, I remember growing up, people were always talking about vitamin C and the common cold. And Howie, that didn’t pan out either.

Howard Forman: Didn’t pan out. And today I was visiting with my father, and I reminded him that’s what got me interested. My father is probably who told me about Linus Pauling, and for years my father took vitamin C. For that reason, we believe that this brilliant man must be right, and we’re just a few studies away from proving it.

Harlan Krumholz: Yeah. And I think it’s for some reason, and we’re talking about peptides now, right? People injecting these peptides, and it’s taking off. But antihypertensives, I mean, a lot of people do take hypertensives, but we still have this big gap when we’ve got something that’s such a big benefit. It’s the same thing as we were talking about with Ingrid. It’s about how do we manage this information gap or this belief gap where the belief versus the evidence? I think that the story that you’re telling is both an important tale about the value of research and really testing our assumptions. Like I said, Francis Collins always says, “Science is progressive and self-correcting.” We need to do the studies, and then we need to help people understand where’s their evidence, and where’s that? People can do non-evidence-based things if they want, but they just need to understand there’s a difference between that which we know about and that which we don’t.

Howard Forman: That is absolutely right. And I think we’re going to keep coming back to this theme at times because we should follow data, we should follow the science, we should iterate, and we should be willing to admit when we’re wrong. We should be willing to admit when we don’t have certainty, and certainly we should also stop doing things that don’t work.

Harlan Krumholz: And to be humble enough to say what we’re saying is what we know now. It may change.

Howard Forman: Right.

Harlan Krumholz: Anyway, things we know work and don’t work now.

Howard Forman: Yes.

Harlan Krumholz: You’ve been listening to Health & Veritas with Harlan Krumholz and Howie Forman.

Howard Forman: So how do we do? To give us your feedback or to keep the conversation going, email us at health.veritas@yale.edu or follow us on LinkedIn, Threads, Twitter, Instagram, wherever you want to find us.

Harlan Krumholz: And give us feedback. We love feedback. Feed us. Tell us how we’re doing. We’d love to hear from you.

Howard Forman: Health & Veritas is produced with the Yale School of Management and the Yale School of Public Health. To learn about Yale SOM’s MBA for Executives program, visit som.yale.edu/emba, and to learn about the Yale School of Public Health’s Executive Master of Public Health program, visit sph.yale.edu/emph.

Harlan Krumholz: And a hat tip to our superstar Yale undergrads. Donovan Brown’s with us today, did an amazing job. Today, Gloria Beck, also amazing. Our great producer, Miranda Shafer, and I get to work with the best in biz.... You know, my wife, Leslie, she always says, “I love when you call Howie ‘the best in the business.’”

Howard Forman: I do too. It’s so sweet.

Harlan Krumholz: I do it because it’s so true. It’s so true.

Howard Forman: No, you’re very kind. It’s going right back at you, and I appreciate you very much, Harlan. I hope you have a great week.

Harlan Krumholz: All right. Talk to you soon, Howie.

Howard Forman: Thanks. Talk to you soon.