The road to discovery is winding

The field of public health has become even more critical in the wake of the COVID-19 pandemic. Public health professionals must balance strategic thinking with compassionate thinking, and must truly be able to collaborate on the state, national, and global levels. Today, we are joined by physician and scientist Dr. Purnima Madhivanan. Dr. Madhivanan is an Associate Professor of Public Health, Medicine, Psychology, and Family and Community Medicine at the University of Arizona, as well as a member of the BIO5 Institute and Cancer Center. She is currently the Director of the MCH program as well as the NIH funded Global Health Equity Scholars (or GHES) Training Program at UA, and she serves as a co-PI for the GHES consortium in collaboration with Stanford, Yale and the University of California at Berkeley. She completed her medical training in India, received a MPH/PhD in Epidemiology from the University of California Berkeley, and completed her postdoctoral training at San Francisco Department of Public Health on Clinical Trials Management. Dr. Madhivanan is an epidemiologist and biomedical researcher examining the intersection of infectious diseases and cancer using -omics technology. Her current work is examining the vaginal and gut microbiome and their role in women's reproductive health. 

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You have been a champion for women and other disadvantaged populations for a very long time. I think that has been the tone for your entire career and life journey, which is really important to me as a woman and as a mom that has daughters. You've been doing that for over twenty years. I wanted you to tell me a little bit about what started you on that path? What makes you passionate about that, in particular? 

When I initially started on this path, I was pretty much clueless. I went into medicine because my family wanted to have somebody in the family be a doctor. I was first-generation, the first person in my house to go to college. I was raised by a single mom who had to raise three kids between the ages of five and one when my father passed away. I have been surrounded by very strong women in my life, and then when I finished medicine, I wasn't sure which direction I wanted to head in, and it was around that time that I took a step back and just wanted to re-evaluate what it is that I wanted to do. 

During that time I was part of this club called the Hash House Harriers. They say they’re runners with a drinking problem, or drinkers with a running problem. During one of those events, a friend of mine said, “There is a doctor who wants help in taking care of her patients.” I wasn't sure what she was talking about, and this was, not to date myself, in the late nineties, and I said, “Sure, I’d be happy to help her.” This was in a pretty urban city with some of the best health care facilities, so when I met her, she was actually running an HIV clinic. This was during the time when patients were being thrown out of hospitals because of the stigma and discrimination associated with HIV. She had taken voluntary retirement from her faculty position, started this NGO, and was caring for these patients, and she had one male doctor. That was it, so she wanted somebody else to help her, along with this male doctor, and I said, “I have a baby at home. I won't be able to work full time for you.” She said, “I'll find you somebody who can take care of your baby. Can you come in?”

At that time, I was going stir-crazy trying to take care of a baby all by myself. Any chance to get out of the house sounded really good to me. I said, “Sure, you find me a babysitter who will care for my baby and I will come, and I'll help you for a few hours.” Within a week, she found me an excellent babysitter who I think of as my soul sister now. Her name is Umsa. She did such an amazing job, even to this day I have such fond memories of her.

I went to the clinic and started seeing patients, just for two hours a day. That extended to three, four, five, six, seven, eight hours, and I was bringing work back home, and that's when my passion for medicine came back to me. The reason was, we had not studied about HIV in medical school. We had really not studied anything about social and psychological issues, or  cultural issues, that can influence social determinants of health and can then influence a person's well being. The women who were coming to me in the clinic were in their late teens, early twenties. They had just gotten married, they had gotten pregnant, and found out they were infected with HIV. Or, they had their husband, who had turned symptomatic, get admitted in the hospital, so we would test the woman. Turns out, she's HIV infected. Or, we find that our patient had just passed away, and when they come to collect the death certificate, we test the wife and she is positive. All these situations affected these young women, 19 to 23 years old, maximum 25 years; and when the husband died, the women were being thrown out of their homes. Because they would have just gotten married and by that time, the man has already turned symptomatic, least understanding the natural history of the disease, that he must have been exposed for a much longer period. The event that took place was the marriage, so this idea that the woman has brought bad luck into the family began. So she's thrown out, and the problem is this young lady, now a widow, cannot go back to her mother's house because she has other brothers and sisters who are of marriageable age. There is a stigma associated with it, and these were the kind of issues I was seeing more than me being a doctor: helping them with the medical problems, cultural problems, social problems, all issues that I had no control over and that I didn't have any training for. 

There were medical students who used to come to India to work with us for periods of three to six months, and one of the students mentioned, “You should be thinking about an MPH.” I was like, what is this MPH? Then I started going and figuring out that this is all about prevention.

I said, “Yes, this is what I need to learn. How can I prevent a woman from getting infected in the first place instead of waiting for her to get infected, get sick, and then come to us as doctors? How can I make myself unemployed so I don't have to be a doctor to deal with these issues?” 

I applied to the MPH Program, I got accepted into Berkeley, and I went and got my MPH, or Masters of Public Health. When I was done with my MPH, I had this breath of knowledge, but not enough depth that I felt I could independently do anything by myself if I moved back to India.

That's when I decided I need a little bit more training, and got into a PhD in epidemiology. Again, with the same plan of going back to India to continue my work.

I was doing my PhD in epidemiology and went back to India to do my dissertation research on the same topic: looking at upstream variables of how we can prevent HIV in the first place in women. There were two papers that had just gotten published that looked at abnormal vaginal flora and how that can increase the risk for a viral infection called Herpes simplex virus 2, which is a huge risk factor for somebody getting HIV. My study was to examine the relationship of abnormal vaginal flora to acquisition of HSV-2, and in the long term, looking at how we can do HIV prevention. That's how I got into this whole field. Nothing planned. 

 

That's an amazing story. A lot of people we’ve interviewed said similar things in terms of getting great training but still having no idea what in practice that would mean. The most comprehensive human success stories are more like yours where you're actually seeing what's happening in the world and with people. 

But I have to tell you, stories like mine don't make great researchers. We don't get grants, we don't. We don't do the sexiest cutting edge technology driven studies that funders are interested in to fund us. So, that's the downside to it.

 

Public health became an animal onto its own being with a pandemic that we all face which we probably weren’t prepared to face. Has the funding for this type of work changed at all in the midst of the pandemic?

When we think about public health, everybody thinks about this idea of surveillance and pandemic, but public health is more than just that. And yes, we did. We did see a lot of money being put into it, but not at the right time. Again, the challenges were trying to reach the people who needed it the most. It didn't happen at the right time. We still have those issues. We went ahead, raced ahead to get vaccinations, but we never for a moment thought, “How are we gonna roll this out in the community? What are some of the issues we should be thinking about?” We completely ignored the social and behavioral aspects that we should have been studying simultaneously as we were developing the vaccines. The problem we have is that we go at one, and we forget that there are these other factors that we should be thinking about. We still haven't come to a stage where we're looking at this in a more holistic manner. We should be employing a systems approach to it, but we're still being very siloed in how we do things. 

It's like if I said “Well, I'm an epidemiologist,” and somebody says, “I’m a social scientist,” and another one says, “I'm this. I'm that.” We can have an intersectional identity. It can be a lot of things, and I think the problem we have is the funding agencies don’t allow you to do that. The funding agencies want you to focus on one disease, one little thing, in order for you to get funded. But when you are a practitioner, you have to think about all the other associated things that go with that disease. I'm not seeing movement in that direction yet, and I hope it happens soon.

 

It seems to be we as a society and as a world, we're so reactive instead of proactive like you're saying, this concept of planning and prevention. If a pandemic doesn't even do it, it's hard to imagine what does shift that thinking. I hope that it starts to shift.

Well, I hate to be the bearer of bad news, but we are going to start seeing more pandemics coming at a much more frequent rate now than before. It used to be once every few years. This is going to become more common now because we travel so much, we are so interconnected. Think about the vaccines. There were so many vaccines here that, for all the political reasons, we couldn't use them, but there were a lot of countries who did not have vaccine access, even till a year ago, and we thought we were so fully protected that we thought life was back to normal. All it takes is for one person to get on that plane and come here. We are still looking at borders and boosters, and these silos. Unless we think that every one of us in this world is going to be in some way related to us, we are not going to address some of these issues that we are seeing now. No matter how great the technology is, we have the best vaccines for COVID right now, but they’re of no use. You're going to start seeing that the virus is mutating, you're going to see more variance. You can have any number of boosters in the U.S., but if a new variant lands up happening in Cameroon, we're all in trouble. I think we have to start thinking more globally along those lines.

 

Let me drill down a little bit, you’re an epidemiologist. Talk to us non-scientists and some of our listeners that are not familiar specifically with that term a little bit more. What does that mean to the field of public health? What kind of ground work do you need to do before you start using epidemiology to investigate a disease or a pandemic?

Well, if there is one foundational idea that underpins almost everything that we as epidemiologists do, it is to understand cause and effect. In epidemiology, demonstrating causality is difficult, so we are very careful. If you ask any epidemiologist, they're very careful about using the word cause. It's a very loaded term, so we are very cautious talking about causality, because it's difficult. Its long and complex natural history of many human diseases, and because we have ethical traditions that say we have to protect human beings, both in health care and in clinical trials, epidemiologists always hold the attitude that all judgments about cause and effect are tentative. They understand that causal thinking demands a judgment, and are always alert to the possibilities that chance, error, and bias can distort or confound these causal assumptions that we make. The ultimate aim of epidemiology is to use the knowledge of cause and effect to break the links between disease and its causes, and to improve health overall.

When we set out to understand something such as a disease outbreak, like what happened recently, we have to first confirm the existence of an epidemic. We have to verify the diagnosis, and we have to develop a case definition, a very specific case definition. Then we have to collate the data we have on all of the cases, and we analyze these data by person, place, and time, which is the epidemiologic trial that we talk about. We develop a hypothesis, and then based on that, we do the data analysis. Based on those findings, we implement control and prevention measures, and we evaluate whether these measures have worked or not, so I guess my answer is, we have very strong traditions, philosophical underpinnings, and methods that serve as the foundation for our field.

One of the biggest challenges that we face in science is replication. We have this issue of lack of replicability for a lot of the findings. One of the things that we always talk about is when you're doing your experiment, when you're looking at something, before you can say something causes something, make sure that there's enough data and evidence that A causes B.

 

I’m a huge consumer of every type of media out there. With everything being an instant, ‘instant news’, on social media, the lack of data and repetitive studies that lead to people believing something is scary.

Yes, a simple example was initially around the pandemic, when the hydroxychloroquine study started coming out. My Goodness! I’m on WhatsApp with a lot of doctors, and I started to get this barrage one night that “Oh, this French study shows that hydroxychloroquine actually helps.” These are doctors, these are my colleagues who are talking about it, and everybody is excited. This was just a preprint, though, this was not even a publication. It was just a preprint, and people hadn't taken the time to go and look at how the analysis was done. What was really evident was everybody in the hydroxychloroquine group who were terribly sick had been excluded from the analysis. That alone should have gotten you to think, “Come on, these are not comparable groups.” I think one of the challenges we have is critical thinking, and if there's anything that we should be teaching our next generation, it’s not about something else that they have to memorize or learn. We should be teaching how to unpack something. How do you use critical thinking to examine some of these issues?

 

That actually leads me to another question. I think because of the nature of this pandemic, everybody now has heard of public health. It's becoming more of a popular study for undergrads and graduate students. Do you see that trend? Could you tell students thinking about exploring this area what it takes to be a good public health practitioner and if there are other things they should think about? 

Absolutely, I would say we need a lot more people coming into this field, and some of the traits that we should be valuing as a public health practitioner is empathy. If you are not going to have that, there is no point in you working in public health. You have to have a sense of community, being able to engage with the community, and understanding your community. Where are they coming from, and how can you be able to contribute without violating some of the issues that they might have, or some of the norms that they might have? This brings me to strong ethical values. You have to be an ethical person, and you have to be responsible. Public health is not a sexy field. There are a lot of no’s and rejection, so you have to be motivated, and you have to believe and be passionate about what you do. Last thing I would say is, you have to be curious.

You have to be curious, and be able to go and examine “why?” Why is it that this particular community has that cancer cluster and not somebody else? 

It's an exciting field to be in, and you can make anything out of it. I mean, here I am. I'm coming in as a physician who hated medicine, but I love what I do now. In terms of undergraduates, we need people from all walks of life, not just doctors and nurses and pharmacists. We need engineers. We need veterinary science folks. We need communication people. We need business people. We need people from all walks of life to be in public health, and I think that's what is so exciting about public health. It's very inclusive, and everybody has a role to play in it.

 

Any students that get to have you as a mentor in this area are very lucky because I think you embody all of those things, and that's an amazing gift. Before you go, I do want to ask. You just mentioned cancer a little bit, and I know that some of your work today is at that intersection of infectious diseases and how that correlates with cancer. Can you talk a little bit about that and where you are in that work right now?

Yeah, absolutely. When you look at what the National Academies of Science, Engineering, and Medicine have said, the pathogens that cause the majority of the currently known infectious disease related cancers are Human Papillomavirus, which is the one that I work in, Hepatitis B virus, Hepatitis C virus, Epstein-Barr virus, Herpes Simplex virus 2, and Helicobacter Pylori. There are several other pathogens, including some parasitic worms, that also cause and increase the risk of some of the cancers. Overall, infections are believed to cause about 13% of all new cancer cases each year, excluding the non-melanoma skin cancers. So, infectious agents. What happens is they can raise the risk of human cancers with different mechanisms. Human Papillomavirus, Hep B, and Epstein-Barr act as direct carcinogens by expressing the oncogenes that can inhibit the upper doses and increase cell immortalization.

In other words, that means these agents are effective on genome instability of cells and can cause the cell to grow out of control. Now, H-Pylori and Hep C viruses can cause long-term inflammation in the body, so this can lead to changes in the affected immune cells, and they produce immune mediators and inflammatory mediators which then lead to causing cancer.

There's still a lot that we have to learn between the links of infectious diseases and cancer, we are just at the tip of the iceberg right now. We're still trying to figure these things out.

 

One leads to the other, but the inflammation piece is being shown to increase the incidence of not only cancer, but brain disease and others. We're so lucky we have people working in this space that is a bit murky right now in terms of causality and connection.

Yep, so I'm headed to India to work on an area related to cancer, but not at the biomedical side. India has a lot of doctors, and we export so many doctors that most of our health care providers here in the U.S. are all Indian origin, right? The challenge we see in India is that once a person gets cancer and they are treated, when they leave the hospital they have no services. They have no support services, they have no support groups, so I got the Fulbright Distinguished Scholar fellowship to go! What I'm going to be working on is trying to understand the psychosocial and community based needs that female cancer survivors would have, because nobody is talking to them about their reproductive health. Nobody is talking to them about their self image. Nobody is talking to them about how they have to live in terms of keeping themselves healthy. I'm going to be focusing on those aspects, more of the social and cultural aspects, of what it means to keep somebody healthy once they have completed the treatment. 

 

That’s amazing, congratulations on the Fulbright, that’s incredible. Thank you for all you do and all you’re doing, and best of luck. 

Thank you, and I want to thank the University of Arizona because I really feel comfortable here, and I feel I have enough people who I can work with. That’s the other thing, having collaborators and having the opportunities. I’m very glad to be where I am, I wanted to make sure I acknowledged that. 

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