Tackling COVID-19 with research and science communication

Infectious diseases are the leading cause of death in developing countries and ignite grand challenges like pandemics. BIO5 researchers are working to develop better prevention, diagnostic, and treatment strategies to decrease the global burden of these diseases. BIO5 member Dr. Deepta Bhattacharya is a professor of immunobiology, and associate professor of surgery, genetics, and cancer biology. Dr. Bhattacharya merges stem cell biology and immunology to understand the development of white blood cells and to devise novel strategies to fight illnesses such as COVID-19, influenza, and Dengue virus. 

Can you share a bit about your path into science and how you got to be where you are today?

I know that there are some people who are planners and think, “Okay, this is what I’m going to be doing with my life,” and I cannot honestly say that that was the journey for me.

I come from a background of mathematicians - my father was a mathematician and he's emeritus here at UArizona, and my older sister was very much mathematically inclined as well.  She actually worked for the Department of Defense as a mathematician and computer scientist. I always felt in some ways like the black sheep of the family because it just didn't come that easily to me. It was easy enough when I was in elementary school, but then it got harder and I started to think, “Well, maybe this isn't really quite my strength.” Particularly as we got into college, it just stopped making nearly as much sense to me. I think that's one of the things you recognize from mathematicians - the numbers are almost like a language to them, and I just didn't feel that intrinsically.

So, how did I actually end up in this? It’s a strange journey. I was really much more interested in chemistry and some computer science, mainly because I liked playing video games more than anything else at that point. I went to Indiana University as an undergrad, and I was thinking that I was going to do chemistry, but then oddly enough it had this weird language requirement, whereas as a chemistry major you could only take either German, French, or Russian as your foreign languages. I had four years of high school Spanish and had taken some more in college, and it seemed a little silly to me, so I changed my major from chemistry to biochemistry which allowed Spanish as a foreign language. 

That started to get me to take more biology classes as part of the requirements for the major alongside all the hard chemistry I was wanting to take anyway. I started like it – my teachers were good, I liked learning about evolution, molecular biology and genetics. 

Then I ultimately came to a difficult decision when I decided that I was going to go to graduate school, which was what I would study in graduate school. When I started reading the descriptions of the different schools and what they were doing, I just found myself being pulled and drawn more into biological science.

Then I got in as a student at UC Berkeley, and that's when I first started to get into immunology.

Your research merges the fields of stem cell biology and immunology to understand the basic biology of lymphocyte - or white blood cell - development, with the goal to ultimately develop creative translational strategies to combat infectious disease. Tell us about how you got into this field. How did you get into this field, and what are some of your current projects?

After I finished my PhD, I just wanted to do something a little bit different. Because my wife was still in graduate school at that point, I wanted to stay in the Bay Area. Throughout graduate school, I had read papers by Dr. Irv Weissman, who is a professor at Stanford and one of the leading voices in stem cells. 

Around that time, there were ballot initiatives to try and get state money to do some regenerative medicine work, and Irv was one of the leading voices behind that. I decided that I would like to try and do a postdoc in his lab if he would have me simply because I just thought the stuff he did was cool.

What his lab primarily did were stem cells of the adult type - hematopoietic stem cells. These are the stem cells that we all have. They live in our bone marrow and they're responsible for generating all our blood cells, because those cells die pretty often, and they need to get replenished. 

I did a lot of basic work in understanding how stem cells give rise to some of the immune lineage cells, which are part of your white blood cell system. Things went well in my postdoc, but I didn’t feel like I was wedded to an academic career per se. What ended up happening is I got a job offer at Washington University in St. Louis out of my postdoc, which seemed like the best opportunity to continue to do some cool stuff that I felt like doing.

So again, it was not a straight and narrow path into this career. 

One of the things that I realized is that when you start an academic career, it's difficult to carve out your own niche. I thought that the best way to do that probably would be to merge some of the things that I did as a graduate student in basic immunology about how antibodies get made along with some the stem cell stuff that I had done as a postdoc. It took me a long while to figure out how best to merge those things, but that's how I came to this in the first place, and why we merged two fields that superficially don't seem to have a whole lot to do with each other.

It seems like you got into this field at the right time. 

I caught it at the right wave, I suppose. Right around the time that I was a postdoc, the International Society for Stem Cell Research came into its fruition, and now it’s a thriving professional organization that's devoted strictly to strengths to stem cell research.

At the same time, there was a lot of excitement, but also a lot of controversy, around the cells.

There were some restrictions around embryonic stem cell research, and then all of a sudden, they came as an alternative to induced pluripotent stem cells, which later led to the Nobel Prize. 

It was a really exciting time to be there. Groups all around the country were figuring out protocols of how to turn pluripotent stem cells into different cell types of interest like beta cells in the liver to retinal cells in the eye. It was just a lot of really fascinating things where people were merging the basics of developmental biology that we've learned through decades of basic work and then applying that to stem cells and then being able to turn them into whatever you want.

That was to me was the really interesting and critical thing.

Whereas I’d worked in this adult stem cell field of how blood cells get made, when I started my own lab, we started to move over to the pluripotent stem cells stuff because then it's only your own imagination that constrains you - you can make whatever you want. That's where I started to think about what we can do with the cells that merge the things that I’ve learned during my training.

We started to think about how we actually turn these stem cells into antibody producing cells, because what we certainly know is that some vaccines work great while others don't - we still don't have an HIV vaccine and yet we what we know is that there are some people who, mainly through fortuitous chance, are able to control the infection without any antiretrovirals mainly because they make these crazy antibodies that the standard issue person is not going to be able to make.

Then we started to think that for the diseases that you can't vaccinate against, what's the alternative? Can we synthetically build immunity? If a vaccine won't do it for you, if a vaccine isn't instructing your immune system in the right way, can you actually provide the cells that would confirm immunity?

That's then how we got to this space here where we're still very much interested in the basic biology of what it takes to make a good antibody response. That also then gets plugged into some of the workflow of the people who work on stem cells and saying, “Here's what we learned in the basic biology, so here's what needs to happen to be able to make a good antibody producing cell. Can we now build that into our workflow and then coerce those pluripotent stem cells to do just that?”

You shifted your research to work on various aspects of the COVID-19 pandemic – can you talk a bit about that?

I think the advantage from our standpoint was that it actually wasn't that much of a pivot. The majority of the lab still works on basic immunology, and we study viruses and antibody response to different viruses. 

The family of viruses that we’ve probably done the most work on are the flaviviruses, so that's West Nile virus, Dengue virus, Zika, Japanese encephalitis virus. I think my virology colleagues would probably have a heart attack if I said this, but again, from the perspective of an immunologist, a virus is a virus in terms of how and what we do with it. We're really more interested in how the host responses once the virus infects, and so there are certainly some similarities between these flaviviruses and SARS-CoV-2 - they're both RNA viruses and they both mediate acute infections.

A lot of the workflow, tools, and techniques were really already pretty well established in my lab, so I would say that it wasn't actually very much of a pivot at all if you look at it from that perspective. On the other hand, everything that we've done up until this point was pretty basic things we do in the lab.

When it became clear in late February, early March 2020, I started talking with Dr. Janko Nikolich-Zugich, my department chair who also studies viruses, about what we could do. At that point, it was clear that it wasn't going to be geographically constrained to certain places - it was going to get everywhere, and it was going to come here. 

We really wanted to be able to contribute in some way. We started talking to some of our physician-scientist colleagues at Banner and the UArizona College of Medicine about making sure everything was in place so we could collect samples from people who unfortunately landed in the ICU and help contribute in some way to help us understand what it is that makes people really sick.

We got a pilot grant from BIO5 to do some of that work. What happened is that word of that got out. Our intent was just to test a handful of people for their antibodies just to make sure that they really did have COVID-19 and not something else - that was really our only ambition at that point. But when the word got out and the Arizona Republic picked up on that story, it piqued the interest of some key governmental leaders who then came back and talked to President Robbins about whether or not we’d be willing and able to expand that.

At that point, we kind of got “volun-told” to expand our efforts at that point, because again, we were only planning on doing a few dozen of these, and then we were at about maybe a few thousand people on campus that then became 250,000 for the state.

I want to make this clear is that that's not something that one lab or even two labs can do. We don't have the capability of doing them, particularly for clinical tests, we didn't have the background for that. I think I get way too much credit for that particular test. Dr. Dake at UAHS gathered together this amazing team of people who had all sorts of different expertise, from people who knew how to deal with regulatory issues to make sure that everything we were doing was sound legally, to Ryan Sprissler’s team at UAGC who had a CLIA-certified lab where they could run these tests, and Matt Kaplan to be able to build up the robotics.

If you look back, our role on the development of those tests was very small in the grand scheme of things - it was really was just such a huge team effort, and I think that when you look back at that effort, it just so obvious that the whole is so much greater than the sum of the individual parts because there's no way any of us could have done this alone.

It's almost laughable how modest our ambitions were at the very beginning, because now, you see what we were able to do because of all this effort that people put in. We are at the forefront, we learned things much more quickly than other people who don't have this infrastructure built up.

You’ve been a prominent voice throughout the COVID-19 pandemic on local and national news regarding masking, testing, vaccination, and other ways to mitigate disease spread. What has that experience been like for you?

None of us are trained to do this - primarily we're trained to do science - how to conduct experiments, how to do good experiments, how to interpret the data - we're not trained to talk to the media. I think at the very beginning, I would be almost sick with nervousness every time I had to do an interview with someone because I didn't know what I would say. It was just such a terrifying thing for me to get up there and have to talk to someone who could use anything that I said in whatever way.

You can check with my wife on this, I would be sick with nerves leading up to an interview, but then what started to happen is that I think I recognized that a lot of science journalists are not doing political reporting - they're not looking for “gotcha moments.” They're trying as best as anyone else to communicate the facts to people, so then you start to recognize that we're all on the same side, and that brought my nervousness down a little bit.

I also learned that you really have to assess the situation, given your own expertise and background, and call it like you see it. There were times where I was confused by some of the public health messaging coming out of the CDC - I still am sometimes. At the beginning, I felt a lot of pressure that I had to conform to the party line, but at this point, for better or for worse, I don't feel that way anymore. I'm an immunologist and I'll call it like I see it from the perspective of an immunologist. 

Over time, I have built up relationships with a lot of the reporters - we know each other well - and it becomes a lot less stressful to be able to talk to some of these people about what I’m seeing.

I think one of the key things that I’ve learned stylistically is that I don't come at this from the perspective that this is going to be too complicated for people to understand. If it's complicated and it's really important that you make it understandable, rather than gloss over the facts and say something inaccurate. My experience has been that people who are actually reading and listening to the interviews are trying to understand, and it just seems like the appropriate thing is to speak to them like they're adults, good or bad, and explain why I’m thinking what I’m thinking with the proper level of uncertainty.

We've all gotten things wrong during the pandemic, but it's really important to explain why you think the things that you're thinking. I felt like a lot of public health messaging at the beginning was just preparing people for the worst all the time, even when I don't think that was actually warranted, so I've just tried to call it straight and the style has worked as best as I can tell.

I'm proud to be here. I don't think I would have gotten the chance to be able to be part of this amazing team anywhere else. It has been a rough ride with the pandemic globally, but I think the UA has given us the opportunity to shine. 

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