Medicinal Research is not just about finding cures for different disease conditions but also about enhancing our understanding of the interaction between a drug and the human body.
Prabhas Jagdale, our next pathbreaker, Pharmacokinetic / Pharmacodynamic (PKPD) Modeling Scientist at GSK (Philadelphia), applies mathematical models to come up with a dosage for a new drug.
Prabhas talks to Shyam Krishnamurthy from The Interview Portal about being introduced to protein therapeutics at ICT Mumbai during his BTech, which made him realize the potential of protein therapeutics in treating and hopefully curing diseases.
For students, the applications of mathematics in pharmaceutical sciences are immense, because the ways in which drugs reach different organs of the body are completely different !
Prabhas, tell us about yourself
I grew up in an army background, was blessed to travel across the country, explore new cultures and meet varied people. While my father was serving in the army, my mom was a homeopathic doctor. I wouldn’t say I was always inclined towards drug development, but definitely had an exposure to medicine. I still remember, when I was a kid, my mom would take me with her to the clinic whenever school was off, though I dreaded being there (it’s not exactly a fun place to hang out!)
When it came to selecting my subjects in 10th, I believe my mom was disappointed when I told her I was not interested in medicine, or more like I was scared to take biology. Even to this day, my mom says I might have been a good surgeon!
My dad’s profession definitely had a big influence on me. Also, the fact that my grandfather was a freedom fighter propelled me towards joining the armed forces. I was pumped up to directly serve the nation as a soldier. There came a time when I was torn between joining the Indian navy as a fighter pilot and being a pharmaceutical scientist. Though I ended being a scientist, I still have an unwavering urge and will to serve the nation.
What did you do for graduation/post graduation?
As a kid, I remember looking at my brother drawing some shapes while studying for chemistry, and I thought that it was pretty cool that he is studying and making drawings in it, haha !! Eventually, I understood that he was writing reactions in organic chemistry and the funny looking structures were skeletal formulas. When my time came, I loved it! Chemistry undoubtedly was and still is my favourite subject (especially organic, physical not so much haha !), not trying to brag (or maybe I am!) here but I did top my school in Chemistry in the 12th Std board exams.
After high school, I went to ICT Mumbai where I pursued engineering in Pharmaceutical Chemistry and Technology. It most definitely was my love for chemistry and to some extent, maybe wanting to be in healthcare in some way or the other that led me to pharma. Here, I was introduced to a bunch of varied fields like Chemical Engineering, Pharmaceutics, Pharmacology and more. This being an engineering course, there was quite a lot of emphasis on “quant” heavy subjects. I still remember there was a subject on heat transfer that I hated to the core. It was in this subject that I learnt about mathematical modelling of different heat transfer processes like convection, conduction and radiation. Just the sound of these processes would make one hate the subject haha!! But you never know how things take a turn, it was this initial training in mathematical modelling that laid the foundation for my career ahead.
What were some of the influences that led you to such an offbeat, unconventional and unusual career?
It was in ICT that I was exposed to research, and I learnt about the impact a small experiment in a lab can have on something as big as humanity itself. In the 3rd year of my course, we were supposed to work on a research project and defend it in front of a panel of professors /scientists. The project I chose was “Targeted delivery for breast cancer”, and the professor I was working under is known to be the toughest professor in the entire university, but he is also one of the best scientific minds I have ever come across. I was doing a literature survey for this project; I came across a therapy where the cells in the body itself produce the drug against the cancer cells. This intrigued me, and honestly, I didn’t understand what this drug was. So, I went to my professor and asked him about this. Being an undergrad, I didn’t know what I was talking about haha, but this question was stuck in my mind and this curiosity got to me.
It was a cascade of many such events and projects that led me to love science, but this one has had the biggest impact on me. After I was finished with my paper for this project, I went and met my professor (the toughest one), and he had great things to say about me. Believe me when I heard him say that he was proud of the work I had done, I felt a charge flow through my body, I started believing in myself and my science.
During this time, I was fortunate that I got ample opportunities to explore the Indian pharmaceutical industry through internships. After my third year, I interned at Zydus Biologics in Ahmedabad, where I luckily worked on one of the drugs that I had covered in the research that I mentioned above. I realized that knowing about a drug, how it acts, how it is dosed, is cool and all, but making one is a different deal altogether. The research I did introduced me to protein therapeutics, while this internship made me realize the potential proteins therapeutics have in treating and hopefully curing diseases. Thus, that internship helped me find the research topic I was passionate about.
As I said earlier, you never know how things turn out. Fast forward to today, the therapy I read about and didn’t understand for the life of me, is RNA based therapy where we program endogenous cells to produce a protein we code for. The world has seen the impact and potential of this in vaccines against COVID19. Luckily, this is one the areas that I work on, I would say it’s been a full-circle, wouldn’t you?
How did you plan the steps to get into the career you wanted? Tell us about your career path
Once I decided to pursue science, the next logical step was higher education. I decided to pursue my MS in Pharmaceutical Sciences. Luckily, I had tons of seniors from my college who had taken this path and were there to guide me. I started reaching out to them, got an understanding of what research looks like in the US (it is very different from what I had been doing in India) and what universities are good for protein therapeutics, which was the research I was interested in. Simultaneously, I was preparing for GRE, writing my SOPs and getting LORs from professors.
I probably wrote about 200 emails to professors, trying to connect with them, letting them know that I was interested in the kind of work they are doing. Most of those emails probably ended up in junk or were never replied to, but there was one professor Dr. Shah from the University at Buffalo who replied in less than 5 mins after I emailed him. There were quite a lot of emails that were exchanged between us. We had a zoom call. I believe I was in awe of the research he did and the impact he had. That was enough for me to catch that flight to Buffalo, New York.
The next two years that I spent in buffalo were the toughest. I was balancing research, academics and on-campus jobs all at once, but this is also where I grew the most as a researcher and as a person.
Remember how I said that I hated Mass Transfer in undergrad. Well!, I was in for a surprise at Buffalo. The toughest subject in the entire course (about 60-70% of the class failed this subject!) was “Intermediate Pharmacokinetic” or famously known as “607” at UB, this subject was all mathematical modeling.
It was the same modelling that I hated to the core, but sometimes we don’t realize our strengths unless we pressure-test them. By the end of my time at Buffalo, I was a pretty good mathematical modeler! To be honest, I have grown to be fond of it so much that I live and breathe differential calculus now. My thesis was on developing a mathematical model for lung delivery of protein therapeutics. This might sound daunting but it’s basically a mathematical/computational model that I have built which tells you how much drug is reaching the lungs.
How did you get your first break?
My first break was a result of the work I did during my master’s thesis that I had explained above. I had developed a mathematical model for the lungs. This work was crucial not just in terms of the impact it would have on development of drugs targeting the lungs but also in terms of timing when it was done. This was done when the entire world was in the grip of SARS-COV2 virus, and humanity had essentially come to a pause. Every major pharmaceutical company and lab was doing their bit to save the world, so was I! I just never realized the impact of the work I was doing at the time; it was only later that I realized that I had developed a framework which was eventually used to decide on the dosing of a drug in humans to treat COVID19 infection.
This work was done in collaboration with GSK and recognized by the scientists from GSK. They made an offer I just couldn’t refuse.
What were some of the challenges you faced? How did you address them?
Ohh this is a tough one! I believe that every student who migrates to another country in search of education faces a mountain of challenges. Right from thinking about funding their education to learning how to cook haha. My journey was pretty similar, but I’ll try to focus more on challenges that I faced as a scientist –
Challenge 1: The first challenge that I faced was learning ! Coming from India, I was used to studying or cramming a day before the exam, from the notes that someone made in the class. I was a scientist now; I could not just ask someone for notes because I was trying to solve problems that nobody has ever attempted to solve. I had to teach myself how to learn from publications, from experiments, from my past experiences. Inferring results from an experiment is a skill, a failed experiment indeed can teach a lot more than a successful one, you need to read BETWEEN the lines I guess! This is true not just for science but for life too, I would say. So, we should try to get into the habit of self-learning.
Challenge 2: I was brought up with privileges that I never appreciated and was never thankful for. I had decided that I won’t take any help from my parents for my higher education, I wanted to do this by myself (never did I think that this is going to be super difficult). Educating yourself in a different country is not limited to self-funding your education, sometimes you have to work to meet your daily expenses. I decided to work so that I at least had money to meet my monthly expenses. But, working while studying was new for me. I started working on-campus in dining. My very second shift was in the dish room. To put it in an easier way, I was cleaning dishes, though I had rarely ever cleaned my own dishes let alone those of others. Getting used to this was tough, I remember questioning my choice to come to the US at one-point haha. Thinking retrospectively, that is the best thing that has ever happened to me. I have started appreciating these small things in life. I have realized that no work is small or big, someone working as a janitor has the same dignity as a CEO.
Challenge 3: Well, this challenge literally broke me at one point, science is tough, PERIOD. I was deep into my thesis, running animal studies, collecting tissues and analyzing them. This data that I generated in animals was feeding my mathematical model. So, it was a cyclic process and my modelling was dependent on the data I generated. I was close to finishing my thesis, I had run what possibly was the last study, in order to graduate. These studies take around two to three months from starting to end, from making the drug to dosing animals to collecting tissues to analyzing them. I was running the final analysis step, this step itself takes about 24 hrs to run the experiment, the results came out and there was no drug. The drug had actually degraded completely, this study that had taken two months had failed. I was this close to graduating, yet I wasn’t!
That was probably the worst night I have ever had, and I am just one of the MANY graduate students who go through this everyday. All of us have had many such sleepless nights, nights full of self-doubt, but as the going gets tough, the tough get going, right? So, if you plan on pursuing science, make sure you believe in yourself and your science!
Where do you work now? Tell us about your current role
I Am working as a Pharmacokinetic / Pharmacodynamic (PKPD) Modeling Scientist at GlaxoSmithKline in Philadelphia, US. As a PKPD modeler, I am responsible for coming up with a Human Dose Prediction. I basically use mathematical models to come up with a dose for a drug that is being dosed for the first time to humans. This dosing is based on a lot of things, like how long does it take for the drug to be removed from the body, how much drug needs to be present in the blood for the drug to show its effect (like relieve the symptoms etc) and more.
What are the skills needed for your role? How did you acquire them?
For one to be a PKPD modeler, one needs to have a good understanding of biology, mathematics, and pharmaceutical sciences. One can’t really mathematically model a disease unless one understands it. So, the work I do is an integration of the roles of a mathematician, a biologist and a pharmacologist. As I had said earlier, as a scientist you need to get into the habit of teaching yourself. I have learnt most of these skills from reading research papers, attending seminars and some from college. So self-learning is the way to go!
What’s a typical day like?
On a typical day, I attend a bunch of meetings with different project teams, each team represents a set of scientists working on finding a cure for a different disease condition. Once I am done with the meetings, I am either learning more about that disease from research papers, looking at actual patient data or am modeling that disease mathematically. Once I have a good understanding of what is happening in patients, my model is validated, and I start running different scenarios and try to guide the projects in terms of how the drug should be designed or what dose levels or dose frequency would be needed in patients.
What do you love the most about your work?
The thing that I love the most about my job is that I don’t work on a single disease, I work on multiple disease areas. One week I am working on cancer, the next on an auto-immune disease or an antibacterial drug. This allows me to have an expertise in varied disease conditions and study different processes in different organs, believe me the way drugs get into the brain is completely different from how they get into the lungs, which is different from how it gets into the bone marrow. Ultimately what keeps me going is the fact that my work is crucial for patients, and I know that I AM SAVING lives!
How does your work benefit society?
One of the values of GSK is to be “Ambitious for our Patients”, and I strongly believe in this. I can proudly say that I indeed am ambitious for our patients!
The work that I do is critical for not just the patients but for all of us. I not only work towards finding cures for different disease conditions but also forward our understanding of the human body and how things happen in the body. I hope that the models I build can be used as a platform by anyone in the world, so that if the next pandemic hits us we’ll be ready to serve humanity.
Tell us an example of a specific memorable work you did that is very close to you!
This is an easy one, it definitely has to be the model I developed during my masters thesis. Remember how I said sometimes we don’t realize the impact of the work we do until much later. Well, when I was developing this model, I just wanted to do it so I could finish my thesis and graduate. As a graduate student, I thought when there are so many experienced scientists in the world, why would someone use my model? I was a young 22-year-old, just getting my handle on pharmacokinetics. I have never been this happy to have been wrong in life!
As I said earlier, this model has been used for dose selection for an anti-covid-19 antibody. GSK has a big portfolio of drugs that target diseases of the lungs, this model is being used for the majority of these drugs now. So, I can proudly say all those sleepless nights, all of that self-doubt has indeed paid off today.
Your advice to students based on your experience?
To anyone who is reading this, there are a few things I have learnt from this relatively short but impactful journey I have had.
Firstly, DO NOT take the EASY way out. Just because you are scared of something doesn’t mean you won’t be good at it, I would have never been a PKPD modeller had I allowed the fear of mathematical modelling to stop me from taking 607. I would rather say, SEEK out the difficult path, because if it’s difficult for you then it definitely is difficult for others too. They too would be scared to take that path, and what will differentiate you from them is that you seek this path out while they run away from it. This choice to not run away and face it head on will most definitely lead you to success.
Secondly, trust in the PROCESS and believe in the VISION someone might have for you. I never thought that the model I was building would ever be used for anything, but I believed in the vision of my professor. I did not know what I was doing and what impact my work would have, but he did. So,
if someone believes in you even when you don’t, trust that person and don’t GIVE UP.
Finally, this is the most important advice and this is what my mentor told me when I was graduating, don’t run behind MONEY. I know, I know this is a cliché, but I have experienced this. Run towards varied learning, valuable experiences and be the BEST at what you do! When people get stuck and need someone to help them out, they’ll pay you whatever you want because you are the only person who can do it. NO COMPETITION you see!
I know I said finally, but definitely want to add something. For all the kids deciding their careers, please do not be scared to take science because it’s difficult or you think scientists aren’t as cool. Science is COOL, the people who do science are even COOLER!
Hope to see you guys grow up to become incredible scientists, do path breaking research and maybe someday some of your works maybe defining for HUMANITY itself.
Hopefully develop more models, publish more and push the boundaries of science everyday!
Really an wonderful interview of prabhas jagdale .proud of the young mind. Thanks for bringing such young talents to thousands of readers site
Great Prabhas. keep it up. we are proud of you. Really nice conversation. inspiring story. happy to read
Indeed inspiring story of perseverance!!