An interview with Mirko Zimic

MiniBio: Dr. Mirko Zimic is a principal investigator at Universidad Peruana Cayetano Heredia (UPCH) since 2002, where he focuses on the study of tuberculosis using biomedical, biochemical, biophysical and bioinformatics approaches. Mirko began his career studying Physics at Universidad Nacional de Ingeniería, in Peru. He later studied a Masters degree in Biochemistry at UPCH, and a PhD in Control and Prevention of Diseases, at Johns Hopkins Bloomberg School of Public Health. This was a very productive time for Mirko, when he trained in parallel, in Biostatistics and Genetic Epidemiology. Mirko returned to his country after a successful time in the USA with the desire to contribute to his country’s scientific development, the education of new generations of scientists,  and the improvement of public health. Amongst his various international recognitions, Mirko and his group won the Edmund Optics first prize, in an international competition where they presented their low-cost prototype digital microscope for the diagnosis of infectious diseases. They came ahead of teams from Rockefeller University and University of Virginia. Due to this success, they were interviewed by the Johns Hopkins magazine. In this work, they used basic technology with an important impact in public health.  Mirko developed an inverted microscope built from stock optical components, that enabled low cost, remote and fast telediagnostics of tuberculosis in poverty-stricken areas around the world.

What inspired you to become a scientist? 

To be completely honest, I was sure I wanted to become a physicist when I turned 13 years old. In Peru that’s when one starts the 3^rd year of what we call secondary education. I think a lot was my father’s influence – he didn’t have a degree, but he had a room of tools in our home’s basement, where he would build things. I oftentimes joined him there, and loved watching how he would build things and getting to understand how things work. I could have become an engineer, but my questions were always “why do things work this way?”. I realized Physics was the discipline that could give me answers to those questions. That’s when I decided to become a physicist. 

You have a career-long involvement in biochemistry, biotechnology and microscopy. Can you tell us a bit about what inspired you to choose this path?  

I finished studying Physics, and then moved towards Biology. When I finished my degree, I realized I liked the physical applications in Biology, so I went on to study a Masters in Biochemistry. Unfortunately, I couldn’t do a PhD in Biophysics, as I would have wanted, but I ended up focusing on Public Health and disease control and prevention, that offered me a broad overview of applications in the field of health. Upon coming back to Peru after studying abroad I wanted to apply my knowledge on Public Health to the many needs we have here, especially diseases that affect the poorest. Peru is endemic to many infectious diseases. One of the biggest problems we have is tuberculosis. One of the most important techniques for diagnosis of tuberculosis, developed by the group to which I belonged (in Robert Gilman’s lab) is the MODS test. It’s based on a quick culture which lasts only 7 days, based on a sputum sample. To visualize the MODS test you need an inverted microscope, and a skilled technician who can visualize and interpret the result to give a diagnosis. That’s when my inspiration and momentum came, to join the world of microscopy. We wanted to develop low-cost inverted microscopes, linked to mathematical algorithms for automated pattern recognition that would allow us to reach a diagnosis of tuberculosis, in the most cost-effective way possible. I studied my undergraduate degree in Physics at Universidad Nacional de Ingeniería, in Peru. I then studied my MSc degree in Biotechnology at Universidad Peruana Cayetano Heredia, in Lima. I did another MSc (in Biostatistics) and my PhD in Control and Prevention of Diseases, in Johns Hopkins Bloomberg School of Public Health, in Baltimore, in the USA. 

Can you tell us a bit about what you have found uniquely positive about becoming a researcher in Peru, from your education years?

What I think is that undergraduate education in the most important Universities in Peru, is really strong. This allows many students to go abroad to successfully do their PhDs. The National Engineering University where I studied also opens many doors. The education we receive is very rigorous – in terms of Physics and other Engineering disciplines, we had a very high academic level. It was very formal and rigorous in terms of Mathematics for example. Perhaps in terms of practicals, at that time we had less possibilities than in other countries. We didn’t have a complex infrastructure. That’s why I became more inclined to study theoretical physics. This has changed in more recent years, and students nowadays have a lot more opportunities when it comes to wet lab practicals. This is all at the undergraduate level though. I can’t say the same about postgraduate degrees. We are not yet competitive at the same level as many other countries. That’s why most students at the postgraduate level decide to go abroad. Something important to consider is that most Peruvian young students, before doing a PhD, decide to study a Masters degree in Peru. So once they go abroad, they have more experience and maturity. I think this is an important aspect for their success abroad. But for instance, once I went abroad, it was never in my mind to stay there. I always wanted to come back to Peru, with my newly acquired expertise, and contribute to my country’s research and healthcare. 

Can you tell us a bit about your day-to-day work as a principal investigator at Universidad Peruana Cayetano Heredia?

I’ve been a PI at Cayetano Heredia since 2004. Our group has since grown. We started from scratch – we had a tiny space. I had to bring my own computer from home, and to build others, would have to go to the depot for discarded equipment to get parts to build one machine. The career as an investigator in Peru requires a lot of effort and personal sacrifices. No institution receives you with a full-equipped lab and funding to get started. You are received with a hug and 4 walls. It’s then up to you to get funding for your research. We are raised and established in a culture of grant-writing because it’s the only way to do research. My lab has been lucky to acquire national and international funding, and we’ve remained active within a collaborative network, including people from the Global North and South. We’ve received funding from European and American funding bodies, and even Google has given us funding. That’s how we survive. There’s no other way because we don’t have a solid national program for research (as opposed to other countries in the region like Mexico). Here in Peru, we are often in survival mode, and I mean even personal survival: to be able to support a family, for example. As a professor, if you don’t have a salary add-up in addition to your baseline salary provided by the university, it’s complicated. And this add-up (from funding grants) demands a huge amount of effort. I work with my wife – she’s a molecular biologist and I focus more on the biophysics and computational side of research. So our expertise is complementary. This gives us a certain advantage when it comes to writing proposals, and not everyone is so lucky to have such a solid team, with various areas of expertise. 

Did you have many opportunities to interact with other Latin American groups, outside of Peru?      

Yes, we’ve had lots of collaborations in Latin America. Jose Correa in Mexico is one of my main collaborators while we worked on immune-informatics. Omar Ormachea, from Bolivia, is another important collaborator. He trained in Belarus- in fact he is currently presenting our work in Costa Rica. I have collaborators in Brazil, Ecuador, Bolivia, Mexico. We also have non-Latin American collaborators, the majority in the USA, but also in UK, France and Germany.  In Germany we have collaborators who do Raman spectroscopy, and we have a project to try to identify a molecule that is a resistance biomarker for pyrazinamide, a drug for tuberculosis. All these collaborations have been a truly nice experience. Culturally, it’s easier to understand and get along with other Latin Americans of course. We share many traits and culture and history. A main problem hindering collaborations in Latin America, though, is financing. 

Who are your scientific role models (both Peruvian and foreign)?

There’s several people I deeply admire. I had three professors during my degrees, whom I would consider in this category of role models. Both were very wise, very generous with their time and knowledge. One of them is Prof. Holger Valqui, who was my teacher during my undergraduate degree in Physics. He was a theoretical physicist, he taught us mathematics and quantum physics in a very rigorous way. I admire him very much. He had a huge impact in my generation. Prof. Jorge Arevalo patiently guided me during my master’s studies in biochemistry and encouraged me to apply physics and bioinformatics to biological problems. Later, in my PhD, Dr. Robert Gilman, who was my thesis advisor. He has lived almost 40 years in Peru. He is a Professor at Johns Hopkins and an adjunct professor at Cayetano Heredia University. I think to a great extent, thanks to him, I have had a wonderful career in science. 

What is your opinion on gender balance in Peru, given current initiatives in the country to address this important issue. How has this impacted your career? 

What is observe is that in biomedical disciplines, there are more women. Back in 1994 or 1997, there was already a strong presence of women in these fields. But in the Physics world there is no balance, even nowadays. It’s still a male-dominated field. For instance, I only had one female colleague. 

Are there any historical events in Peru that you feel have impacted the research landscape of the country to this day?

Perhaps it’s not one single event that has had a huge impact in science. 12 years ago Ollanta Humala (the presidential candidate) presented himself during the presidential campaign as a nationalist, and as the leader of a extreme government. Many of us were fearful about this regime, and the threat it might bring to science in the country, based on what we had seen in other similar governments where science suffered because it was seen as a privilege. Fortunately, Humala’s government did the exact opposite. As soon as he became president, he aligned, democratically. He had well-renowned scientists as advisers, and for the first time in the history of Peru, important funding bodies were created for science, and scientific activity was promoted in a really significant way. Previous to him, the local grants you could get in the country was up to, say, 30,000 soles per year (this is the equivalent of < 8,000 USD) for one year only. This was as much as you could get from national sources. With Humala, funding grew to between 150,000 soles and 800,000 soles – this is 300,000USD of that time, for projects lasting 1-2 years. This was, in my opinion, the birth of scientific development in Peru. I think the entire scientific community is thankful to Humala because he empowered CONCYTEC. We started going through a radical change – an enormous leap with consequences we see up to this day. That’s one of the most important historical events I can think of. 

Have you faced any challenges as a foreigner when you have worked outside Peru?

As you know, in the USA, PhDs also include 2 years of classes. These years were tough because I was doing a MSc in Biostatistics in parallel. I was also doing a MSc of Genetic Epidemiology, for which I finished the course work. And I was also attending courses of Biophysics as a visiting student. I was trying to learn as much as possible – like a sponge –  to make the most out of my time there. I think we never took holidays, except for one time we went to New York. The rest of the time, including weekends and holidays, we were studying all day long. This was challenging, but it was a very positive experience. I have very good memories of these times. Dr Gilman had a training grant with which he supported me and my wife while we studied in the USA. 

What is your favourite type of microscopy and why?

I haven’t been exposed to ALL forms of microscopy, so maybe my reply will be biased. I think due to its versatility and applications, I love lensless (digital holographic) microscopy. We have standardized a lensless microscopy method to recognize patterns in the MODS tests for tuberculosis. We just submitted a paper for review now. I think this technique has a promising future for automatic fast diagnostics of tuberculosis. Sometimes we have to reconstruct the holographic image to get specific parameters for z. It’s unexpected but we need to do it. 

What is the most extraordinary thing you have seen by microscopy? An eureka moment for you? 

We once used a confocal microscope to visualize a sample with specific antibodies against cathepsin-L, a protease that is supposedly secreted by oncosphere of the parasite Taenia solum, which generates cysts in the host’s brain, or the Taenia worm. Nobody knew (or knows) how the oncospheres penetrate the intestinal wall to reach the bloodstream and spread throughout the host’s body. This was the topic of my PhD thesis – to study the mechanism of infection of the oncosphere, during its passage through the human intestine. So we cultured oncospheres, and we were able to visualize by microscopy that they secreted vesicles which moved away from the oncosphere and then dissolved. We would see a spark of fluorescence coincidental with the fact that the vesicles were loaded with proteases and these vesicles were then disintegrated. This finding that implies that oncospheres were secreting vesicles loaded with proteases was fascinating. These proteases get dissolved and then attack the intestinal epithelium, perforate it, and allow the oncosphere to traverse the intestinal wall. This video was spectacular. 

What is an important piece of advice you would give to future Peruvian scientists? and especially those specializing as microscopists?

In Peru scientists do not receive the same recognition that they receive in other places of the world. Many people have this notion that if you’re a scientist, it’s because you couldn’t be something better. There’s a cultural barrier in this respect. Parents have a strong influence in their children’s career choices. So there’s a tendency of prejudices against the scientific career. So many potential scientists have followed other careers. Some of those young students have ended up frustrated if they pursued careers for which they didn’t have vocation. My advice would be, if you feel that science is your ‘calling’, persevere and find a way to speak with other scientists who will make time for you and give you their advice. Look for advice amongst Peruvian scientists, who can tell you how their careers are. In my time as a professor, several students have asked for my advice, I have spoken to them, and several years later, these same students came back to tell me they had become scientists. You can’t imagine how happy this has made me. I think you should pursue your dreams with a lot of inspiration and strength. Regarding microscopy, I think it’s one of the scientific disciplines that brings you closest to reality. It allows you to see, with your own eyes, life processes taking place. In other disciplines this is not always the case – you have to believe there’s DNA somewhere and that it amplified. I think microscopy allows you to see patterns, evolution, morphology, changes. It allows you to feel science with your senses. 

Where do you see the future of science and microscopy heading over the next decade in Peru, and how do you hope to be part of this future? 

In my very humble opinion, I have used microscopy to understand diagnostics of tuberculosis and a few other things. I think microscopy plays a pivotal role when it comes to the study of infectious diseases. No other technique has been able to displace it, and I doubt it will be. The big challenge is that you don’t always have personnel with enough expertise to make the most out of those microscopes or of the image analysis process. This opens a new avenue: artificial intelligence. I think microscopy will, from now on, go hand in hand with artificial intelligence, for the automated recognition of patterns. That’s how I see microscopy moving forward in the future. I see also lensless microscopy becoming a key player in the future, in the field of science.  

Beyond science, what do you think makes Peru a special place to visit and go to as a scientist? 

I think Peru is great to do biomedical science –  we have a ton of diseases. We are number one in the world for tuberculosis in terms of incidence, for example. We have Bartonella, Plasmodium, leishmania, dengue, Chikungunya, Chagas disease … you name it. There’s a lot of applications of microscopy for biomedical applications. I hope this changes in the future, but that’s the reality now. Beyond science, Peru is a beautiful country. Peruvian culture is very friendly, very welcoming, the gastronomy is wonderful, the natural diversity too: we have jungles, coasts, sea, mountains – the biodiversity and landscapes are impressive. You can drive 45 minutes and change ecosystems altogether. Many foreign researchers I know have fallen in love with Peru and ended up staying here. 

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