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Credit: Kim Foley
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Interview of Ksenia Blinova by David Zierler on May 28, 2020,Niels Bohr Library & Archives, American Institute of Physics,College Park, MD USA,www.aip.org/history-programs/niels-bohr-library/oral-histories/XXXX
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In this interview, David Zierler, Oral Historian for AIP, interviews Ksenia Blinova, acting assistant division director, Office of Science and Engineering Laboratories, Division of Biomedical Physics at the FDA. Blinova recounts her childhood in Tula, Soviet Union, and she describes the “physics” and “lyrics” educational scheme that splits school children into either a science or humanities focus. She describes her education at Moscow State University, where she became interested in physics and where Victor Yuzhakov and Svetlana Patsaeva were her graduate thesis mentors and where she developed her expertise in fluorescence intensity. Blinova discusses her postdoctoral work at the NIH where she was mentored by Robert Balaban in the Cardiac Energetics Laboratory. She describes the fellowship opportunities stemming from NIH-FDA collaborations that led to her initial work at the FDA, where she learned both biostatistics and took training in regulatory issues. Blinova discusses her subsequent work in electrophysiology and induced pluripotent stem cells, and she describes some of the challenges in ensuring that medical devices are certain to be safe and effective for patients. She describes how physics is applied in her division, particularly in computer modeling, and she describes her interest in developing human cell research as an alternative to animal testing. At the end of the interview, Blinova describes how she plans to remain close to the research as her administrative responsibilities increase, and she explains the promise of her current work on cardiac ablation for patients suffering from atrial fibrillation.
This is David Zierler, oral historian for the American Institute of Physics. It is May 28th, 2020. It’s my great pleasure to be here with Dr. Ksenia Blinova. Ksenia, thank you so much for being with me today.
Hi, David. Thank you for inviting me.
OK. So, to start, please tell me your title and institutional affiliation.
I work at the Food and Drug Administration’s Center for Devices and Radiological Health, and with the Office of Science and Engineering Laboratories in the Division of Biomedical Physics. Currently I’m acting as the assistant division director there.
OK. Now, let’s take it all the way back to the beginning. Tell me about your family and your early childhood in Russia.
[laugh] I had a mother, father and a brother. I wasn’t born in Russia, actually. I was born in Soviet Union. The country doesn’t exist anymore, as you know. What do you want to know about my childhood?
Let’s first ask, where were you born in the Soviet Union?
I was born in Tula. It’s a city about a hundred miles away from Moscow.
And where were you parents from?
Both my parents were from Tula’s region. My mom lost her parents during World War II and was raised in an orphanage. My father’s parents, my grandparents, I knew them very well, lived in a small village in Tula’s region. Both of my grandparents were elementary school teachers and I spent many summers with them when I was a child.
What was your education like growing up? Did you go to a public school?
There were only public schools in the Soviet Union. Education was free for all, including college. Admission to top universities was quite competitive, though, and you had to do well at the entrance exams. College students got paid a stipend in addition to being provided with a free dorm room. In the years I was in the university, the stipend equaled to the bus fare I had to pay to get from the dorm to the university. It wouldn’t cover anything else, food or anything above that, so most of us had to combine working with studying.
At what point did you realize that you were good at math and science?
[laugh] I’m not sure I’m good. I enjoyed math mostly, probably more than physics while at school. I don’t think I had much choice in terms of career. In Russia we like to split people into two categories: Physics and Lyrics. STEM-oriented people would be in the “Physics” category and the other part would be “Lyrics,” or humanities-oriented people, good at and interested in literature or arts or anything related to language. And it became evident that I’m not that good at language very early on. [laugh] So that automatically put me into the “Physics” side. I was torn between STEM and piano in high school, but my dad also had a saying “There are only two careers, one is science, and another one is cabbage selling.” Playing piano naturally equaled to cabbage selling and I did not want to sell cabbage, so I became a physicist.
Physics became my only choice. [laugh]
What were your parents’ professions?
They were both engineers.
Oh, so you had science in the family that you were exposed to?
Yeah. My older brother is also a physicist by education. He didn’t pursue a career in physics, though. It was really hard to remain in research in those years. It was almost impossible to do science and support a family, so he became a businessman. But his education is in physics.
Now, when you were thinking about college, were you thinking specifically about studying physics?
I would say I first selected the college and then the specialty. It happened that we went on a visit to Moscow and I saw the Moscow State University and fell in love. And then I was looking at different departments and physics became one of the top on the list. I actually went to a public school with physics concentration where there was an excellent physics teacher. He was also a philosopher and quite a character. [laugh]
Did you immediately connect with physics once you started learning it? Did you feel like this was something that you would pursue for a career?
I wouldn’t say so. Even to this day I do not consider myself purely a physicist. Not the type that works with atoms and energy and relativity theory. I was always inclined towards living things, so if anything, I would probably called myself a biophysicist.
Of course, of course. So what college did you go to as an undergraduate?
I graduated from the Moscow State University named after Lomonosov. The school is widely considered the most prestigious educational institution in Russia - the Russian Harvard.
You must’ve done very well in high school to get to go there?
I did pretty well. I maintained straight A’ ts at school, graduating with a Gold Medal, and got the highest score at the first entrance exam to the University in math. Combined, these got me automatically admitted and I did not have to take neither physics nor essay writing admission tests. I’m not sure what would happen if I had to actually take those exams, perhaps I would never end up at the Moscow State University and you would not have to interview me today. [laugh]
Now, in the Russian system, do you declare a major right away or do you sort of learn generally and then you get more specialized later on?
Yeah. You start with studying general topics in math and physics, like linear algebra, calculus, mathematical analysis, or mechanics, thermodynamics, electricity, quantum theory and so on. Sometime in your fourth year, I believe, you adopt a more narrow specialization. For me, it was optics, specifically molecular fluorescence. And then you start your own research project.
Is there a senior thesis for undergraduates?
Yeah. When you get your master’s degree, there is a thesis that you have to defend, and you get a degree in physics.
So there was no thesis for the bachelor’s degree, just for the master’s degree?
No. Right. We actually couldn’t get a bachelor degree. You couldn’t exit the program after four years. It was a five-and-a-half-year program, and everyone got a master’s degree at the end of it. It was called differently in the Soviet era; I believe now it is closer to the international standards, with bachelor’s and master’s degrees available.
Mm-hmm. And who were some of the most prominent professors in the physics program at Moscow State when you were there?
You got me. [laugh] Prominent professors? I remember mostly my—
Well, who did you work with? What professors did you work with?
Right, my mentors were Victor Yuzhakov and Svetlana Patsaeva. They were my master and PhD theses advisors. I learned from many other faculty members, Anatoly Akimov, and Anatoly Baranov. Professor Leonid Levshin led the molecular spectroscopy research program when I was working on my Ph.D.
As an undergraduate, was the program—was there more of an emphasis on theoretical physics or experimental physics?
Well, there were limited resources for purchasing laboratory equipment, or getting computer access. I would say our education was very theory-based, but at the same time, the limited experimental resources forced us to be very creative. I remember my experimental setup used a lot of Play-Doh to hold it together and things like that. [laugh]
We also had to be creative with experimental approaches which sometimes led to novel method development. Part of my project was to measure fluorescence lifetime. Our lab did not have any picosecond or nanosecond equipment, but we had an instrument that could measure fluorescence intensity, and actually my work was in developing a method of measuring fluorescence lifetime based on the laser-induced saturation of the fluorescence for organic molecules. As you pump more energy into your sample, at high enough excitation densities, dependent on the sample fluorescence lifetime, non-linear effects can be observed, and you can use the spectroscopy of the saturated fluorescence to estimate the spectral characteristics of your sample. Sometimes budget-restricted, forced creativity can yields a new useful method, I guess.
Now, what kind of work was your advisor involved in at that time?
Well, he was really focused on teaching, at this point of his career, I think. We also had mechanics, optics, electricity and other labs for undergraduates where he would teach the practical research skills.
Mm-hmm. Now, at what point did you think that you were going to go on to graduate school? Did you ever consider ending your education in physics as an undergraduate and pursuing a job from there, or was your track always to go on for the PhD?
[laugh] It was actually my husband who convinced me that I needed a PhD. Not that I wasn't interested, it was actually really hard to pursue this type of career in Russia at that time. Most of the universities lost a lot of young scientists to immigration or other occupations in those years. It was just impossible financially to work in science.
Was the collapse of the Soviet Union a part of the issue?
Absolutely, yeah. So that was the same process that started with the Soviet Union dissolution, followed by a deep financial crisis, racket gangs growth, terrorist acts, and Moscow apartment bombings, Wind of Change, you know. It was a very interesting and tough period in Russian history. I hear that it’s gotten much better since then, but this is the Russia I remember.
So it was your husband who convinced you to go for the PhD because—well, probably, he thought you were good enough to do it, and second, 'cause it was probably better for your career?
Yeah. He's actually from Moscow State University, as well. He's graduated from the Faculty of Biology. And it was very popular pathway among the young biologists in Russia of those years - to get a PhD degree and come to US for the postdoctoral training. And it wasn't actually something I have ever planned for myself, but I wanted to be with him. [laugh] And it's really what had me driven towards obtaining my PhD. It was a lot of work. Maybe I wouldn't do it if I knew.
[laugh] It was hard.
Now, when you were thinking about your PhD topic, were you already specific in your interest in biophysics or that came later on?
Yeah. My focus for PhD was also mainly in fluorescent methods, but involved complex organic molecules and amino acids as biological targets.
Did you stay with the same advisor?
The whole way through?
Yeah. [laugh] I guess I'm lazy.
What was your dissertation on?
That's a good question. I don't remember; it was in a different life. Let me look up the title. Photophysical Processes and Molecular Association in bis-cyanine solutions. Bis-cyanine dyes first synthesized in this work are a “sandwich” type molecule with two parallel chains bonded by two links. Depending on the angle between those two components, the fluorescent properties change in a way that can be predicted theoretically and checked experimentally. I would have to refresh my memory to give you more details. That was a very long time ago. [laugh]
That's OK. That's fine. That's fine.
It's been a while.
What was the defense like? Is there an oral component to it? Did you have a committee that you'd have to speak to and talk about your work?
Yeah, yeah. I think it may be very similar to what the process is here. So you're supposed to have a certain number of publications. You send your work to several reviewers before the defense, internal and external. You have an official opponent who is supposed to criticize your work, and you're supposed to respond. There is an oral presentation, and then there's a voting, so you have to leave the room and they vote on your defense.
Were you nervous?
Yeah, of course. It all went well, and I got all—what is it? Like, they have black balls and white balls or something like that to vote, and I get just 100% of the metaphorical white balls.
OK. So what is your plan after you defend? Are you thinking about a postdoc in the United States?
Yeah. So, after the defense, I almost immediately moved to the US, and actually moved first to join my husband who already had a postdoctoral position at the NIH. I was in the country maybe for a few months before I started my own postdoctoral fellowship. It was at the NIH, too.
So that was your first position in the United States, at the NIH?
And where in the NIH were you?
It was at the National Heart, Lung, and Blood Institute. My mentor was Dr. Robert Balaban.
We talked about Dr. Balaban a little bit.
Yeah. He's probably the first person who made me really excited about science by showing me all of its possibilities. He was also super enthusiastic about lab research, and this was contagious. In general, my selection of a new research subject or where I would channel my energy was often influenced by the people who I worked with and who I was inspired by. [laugh]
I'm curious, Ksenia, how was your English when you got to the United States? Were you speaking English well at that point?
Dr. Balaban said my English was OK. He was the first person to interview me in the US, and after I got the position, he immediately sent me to an English class. [laugh] So that says a lot, I guess. I actually had some experience working in a British company before I moved to the US, and that maybe made my English slightly better than of an average person from Russia at that point. At least I had a bit of oral practice though.
And why NHLBI, why were you a good fit for there? How did your background fit in with what was happening at that institute?
So the lab did a lot of optics and fluorescent studies, so that was the connection, even though in Russia we didn't have any luxury of having high-end instruments. I've never seen confocal microscope before I came here. But, theoretically, I understood how it was supposed to work. I understood fluorescence physics pretty well, I thought. So I guess that was the connection, because most of my postdoc studies involved optical imaging of some sort.
Now, when we initially talked, we talked a little bit about whether Dr. Balaban was a physicist or not. And you think that he is.
[laugh] Well, I was surprised that he was not on your list of NIH physicists to interview. Up until I was about 20 years old, I thought that it was my father who said that “science consists only of physics and stamp-collecting.” (Blinova editorializes later: I have since learned that it was Sir Ernest Rutherford who said that first.)
Bob Balaban is clearly a scientist and then, in my mind, he's a physicist. He understands physics and math behind physics. You may argue that formally his degrees are in other life sciences, chemistry and physiology, I believe, and, of course, he has a very deep knowledge of biology, physiology and pharmacology, but when he was talking to me, he was speaking my language, physics.
Yeah, yeah. What were some of the big research questions that the lab you were working with were asking?
The lab was called the Cardiac Energetics Laboratory, this is the one that Bob Balaban started, and I believe continues to lead at this point, so anything related to energy transfer in heart cells, such as mitochondria, would be the subject of research. So, during my training there, I worked with some great folks who taught me how to isolate cardiac cells from rabbit hearts and mitochondria from pig hearts. These were our primary animal models. It was interesting. And then doing all kind of studies, biophysical, metabolic and optical around these models.
And how long were you at the NIH?
For about six years.
And it was not a postdoc the whole time. Were you converted over?
It was pretty much postdoc the entire time. I may have started as a visiting scientist or something like that, and then I was switched to IRTA after I got my Green Card. This is a fellowship program at the NIH, probably still exists, but technically it was a postdoctoral training.
And what was your feeling about the NIH? Was it a collaborative place? Did you take advantage of being able to work with researchers in other institutes?
It was absolutely amazing. That's the best place in the world to do science and research. Maybe—it didn't hurt that Dr. Balaban was my mentor, so that opened a lot of doors, as well. I remember, at some point, we needed to isolate a specific protein complex. I had zero experience in that, but he was able to connect me to a person to a different center whose entire career was in protein purification. Not just protein purification, but he was definitely an expert in this. And he would spend time teaching me how to do that. It was such a great learning experience. And then, when I realized that one of the chemicals that we were using for gel electrophoresis was blue and we wanted it to be transparent, Dr. Balaban connected me to a group that was able to synthesize the same molecule but colorless. He had a lot of connections and he was very generous with them, and I think his students could always get the resources they needed. That was the biggest difference. In Russia, nothing was possible and here, of course, opportunities were much better.
So I'm curious, at some point a postdoc in the United States stops being a temporary kind of thing and it starts to be, this is your life, this is where you are now. When did that happen for you in terms of thinking you and your husband are going to make careers and a life for yourselves in the United States?
Well, initially I was coming here for two years. That was our agreement with my husband. I'm, like, "OK. I'll give this two years, but after that we are coming back home."
So that was your intention? Your intention was to go back home?
That was absolutely the intention, yeah. [laugh] I don't know how many years now we've been married for—about 18 years now, so, yeah, I'm still here. And now I'm not planning on leaving. It may have played a big role for me that my kids were born here, and that they are as American as it gets, I guess.
And it's home to them, and it's now home to me, as well. I'm not considering moving back, not at this point.
Did you think that you were going to make a career at NIH?
I don't know. When I was leaving the NIH, I felt like I still had my career goals being formed. Up till then, I spent most of my time in basic research, but I was also starting to get curious about some adjacent areas. . While still at the NIH, I took some classes at the FAES school in public health, technology transfer, intellectual property and patents and such. So the FDA came up very naturally, in addition, it was literally, like, next door. At that time, the Food and Drug Administration had some research labs that were located right at the NIH campus. So I would meet some FDA-ers during lunch breaks, and this was how I learned about some exciting fellowship opportunities with the FDA. The transition was very smooth. I guess I was being lazy again. I even continued to park in the same parking spot when I moved to the FDA.
So what was the actual transition for you? Did you get a formal job offer? Was it a research fellowship? How did you make the transition to FDA?
Yeah. I first joined as an ORISE fellow at CBER, the Center for Biologics Evaluation and Research at the Food and Drug Administration. But I was in this position only for about a month and then the FDA Commissioner Fellowship call for applicants came out, and I applied, and I was selected. That was an inaugural class of the two-year program. That was a very interesting program. It was specifically designed for future FDA-ers of different sorts, if you wanted to be a reviewer, or you wanted to be a regulatory scientist or maybe interested in the policy making. It was a very comprehensive training. Part of it was just classes and classwork, but we also had a research project that we did with an assigned preceptor in one of the FDA centers, so that was an awesome learning experience, that I thought would continue for two years And then - as they say - , “once an FDA-er, always an FDA-er”. [laugh]
And that's what happened to me, I think.
So you took classes? Was it like graduate school all over again? What kind of classes?
That's right, it was a bit as a graduate school, yeah. But the topics were completely new to me. Even when I was a postdoc, I felt like I was missing a lot of biology training, biostatistics training. Some things are very strong in Russian schools, so math and physics have never felt like I missed something. I was good at all that, maybe better, but there are things that, at least at my time, it wasn't focused at all. We don't get any biostatistics, for example. And just because I was in physics department, I never got any biology or physiology. So I took some classes at the FAES school. This is like—I don't know if you know, but it's a school affiliated with NIH. And many of the professors are actually NIH-affiliated scientists.
What does FAES stand for?
Foundation for Advanced Education in Science. It's a graduate school, so for somebody who already had a degree, but wanted to supplement their knowledge in a specific field. Bob Balaban would send a lot his fellows to this school. It’s located at the NIH campus, and it's a very good program. So I took some basic biological courses, like biochemistry or immunology there, something that I felt was missing. But the FDA Commissioner’s Fellowship offered classes that were very different from anything I took before. It really started with laws and regulation that guides FDA decision making. And we took clinical trial design and some professors from Duke University, and Johns Hopkins University would come and teach us for, like, six months in a row, covering topics such as epidemiology and biostatistics. That was my first serious course in biostatistics. It was all new and I love new stuff, so I totally enjoyed it, really loved it.
And I assume you're becoming familiar with the regulatory issues, as well?
That was part of the training, as well. So, at some point, a representative from each center would come to teach—and FDA, as you might know, covers a lot of products. It's food, it's drugs, it's medical devices, it's biological products, now it's tobacco products, as well. They also have Center for Veterinary Medicine. So several people from each center would come and present to us some case studies relevant to their specific center. It was very interesting.
Did the FDA feel like a bigger place than the NIH?
Not in terms of size maybe, but what was very attractive to me, that you could feel that your research would probably have almost immediate effect, while NIH is more focused on fundamental science, and you may never see the fruits of your labor, at least not in your lifetime. Here, you're just forced to do something—at FDA we don't do basic science at all, so every scientific project is always relevant to a specific drug or medical product to be on the market. It's a very applied research.
What happened after the end of your two-year fellowship? What position did you move into then?
So, after commissioner fellowship, I worked—so the center was in CBER, as I mentioned, so my research was in vaccines and actual vaccine adjuvants and—
What is that, "adjuvant"? What does that word mean?
Oh, adjuvant, it means that you have to enhance the effect of the vaccine. So the modern vaccines are super pure. It's not the attenuated live virus that you're working with. It can be just one protein. So, by itself, it often doesn't induce the big immune reaction. And, for a vaccine to be effective, you want a big reaction. And modern vaccines are mixed with these adjuvants that are known to induce immune response. And, of course, those adjuvants have to be very safe and very efficient at the same time. Prophylactic vaccines are given to healthy kids and adults, so the risk tolerance is very, very low in this field. At the same time, you want your vaccine to be effective.
I'm curious if CBER is involved in vaccine issues with coronavirus today?
Probably, yeah. That would be the center to review the safety and effectiveness of the vaccine.
And then, where did you move on from CBER? Where'd you go next?
I believe a scientist from CDRH, my future mentor, came to our Commissioner’s Fellowship final presentations. And, somehow, he knew about my prior publications and he knew that I could isolate cardiomyocytes. And, apparently, it was a needed skill. There is a little bit of art into isolating live and happy, healthy cardiac cells. And he needed this for his lab and for his research, and he just found me, and we started talking, and this is how I moved to CDRH. His interest—my new mentor's name was Richard Gray. He has a long career in academia before he joined FDA. His primary interest and expertise is in cardiac electrophysiology, and I learned a lot from him about the heart from this perspective now.
Was the FDA commissioner fellowship—did you feel like it put you on a leadership track? Was that part of it, training the next generation of leaders at the FDA?
Probably. We were treated very well there. It was the inaugural class, the first year the program was running. It is still going on, selecting students every two years. But we were very special as a first class. I stay connected to some of my classmates to this day. The Commissioner would talk to us quite often, and we felt that the education that they gave us—the program was so well thought through and put together with such love and dedication. It was awesome. It didn't mean that we were guaranteed any sort of a position at the FDA, but most of the us stayed with the FDA at least for some amount of time after completion of the program, and many of the graduates are actually in leadership positions now in the agency.
Now, for the first two years when you moved over, you were an ORISE fellow again?
Right, right. And what is that program? What does that stand for?
It's Oak Ridge Institute for Science and Education—it stems from the US Department of Energy. It's just the mechanism that allows us to bring for training people who are interested in regulatory science. I have several ORISE fellows myself now. So the purpose of it, it's usually one or two years fellowship. Sometimes it can be longer. I think it's limited to five years after your last degree. And the training—they're mostly doing research and participate in whatever lab they're joining, but also getting some regulatory perspective in this time, how FDA works and what our goals are, and how we do regulatory research.
Now, in 2012 you become a staff fellow. Is this within the division of biomedical physics?
Actually, I stayed a long time in this DBP—about nine years now, I think—in different capacities here. I started as an ORISE fellow, then I was a staff fellow for several years. It also has another fellowship —so called MDFP or a medical device program is also a fellowship, also is a staff fellowship, but it has more structured research project. And then, I believe, they converted me to a government employee a few years later. And, at that point, I already was leading and managing the electrophysiology and induced pluripotent stem cell lab. And most recently, I started acting as an assistant division director, so all within the same division.
Right, right. Now, as acting division director, are you now at a point where you're not conducting the research anymore, you're managing other scientists, or are you still involved in the research?
I'm still involved in the research. I'm a very low-key director. [laugh]
I'm very involved with experiment design and I’m still doing some experimental work myself. I probably spend less time in the cell culture hood and pipetting these days, but I still feel like I understand every detail of what we're doing and can give a hand, if needed, these days.
So let's talk a little bit more generally about the division of biomedical physics. So what is the overall mission of the division, would you say? What is its main function?
Well, as the part of OSEL, our mission is to accelerate patient access to safe and effective devices on the US market through the best in the world regulatory science. What we are not trying to do is develop new medical devices. We're involved with the review of medical devices, but the main thing that we're doing, we're trying to identify assays or methods that would help in the review of new devices. So if you have a new technology, and reviewers who are not working in the labs anymore may not have hands-on experience with it, this is where OSEL can provide consulting reviews, and we're trying to maintain a good collection of experts in different areas, and also do some forecasting on what technologies might be coming to FDA doors soon and build expertise in those new areas, as well.
What is your role specifically in all of this?
Well, my current role, I guess, is to support, nurture, and guide the fellows who are under my supervision, but I'm also not giving up on my research —about half of my work is leading my research lab, and we have several research programs going on, which all are on hold mostly due to COVID.
Right. So you're not able to go into the office these days, either, I assume?
Right, yeah. We are teleworking as much as possible. So the doors are only open for COVID-related research right now, which is deemed essential. But, yeah, we started to discuss some reopening plans, so hopefully in some foreseeable future we'll start to do some experiments.
So the main focus of the division is on medical devices?
Absolutely. The whole center is working with medical devices. Medical device has a very broad definition. It can be an in vitro diagnostic test or software. It's not necessarily something complex as a surgical robot, it could be a tongue depressor or gloves, but everything rotates around medical devices. We are also involved with combinational products, when device is used to, for example, deliver a drug or a vaccine, in this casa we work with other centers on the review of the product.
So where does your office come in in terms of the approval of the medical devices? Are they already approved by the FDA, or your office is involved in part of that approval process?
We can work on different stages of the medical product lifetime. So most often OSEL is involved with early submissions we have this mechanism for pre-submission, where a company has an interesting idea or maybe an early device prototype which hasn't been through much of a testing yet, and they want to talk to the FDA. And it's a great idea to talk to FDA early to maybe plan for the future regulatory review of the final device. So OSEL is often involved at this early device development stage, but we also look at ready-to-go-to-market devices and also post-market research is also common at OSEL.
Do you work with human subjects at all in terms of determining safety? How do you know if these things are safe if you don't work with human subjects?
So let me step back. FDA usually doesn’t test any devices. It's not like a company has to send us a device and we test it and then we say, yeah, it's safe. We actually review the data that the manufacturers of the device submit to us. We have to trust this data. We look at the raw data, and we look at quality of the submitted information. So CDRH is a large center and, I don't know, maybe 80% of it is reviewers who never go to the lab. But there is a small part, maybe not even 20, maybe 10%, of CDRH is also where we have scientists who spend some time in research laboratories. And our help to reviewers comes in the form of consulting reviews. So, if the lead reviewer sees something that they need our help with, they would send us a document, we will review it and give our prospective or identify potential deficiencies in the current submissions. And, of course, OSEL’s input can play an important role in the regulatory decision.
Now, in terms of getting a bigger understanding of the overall process, so a company comes to the FDA and then that's the beginning point. And then the end point, there's some final decision on what the FDA says about the product. Where is your division in that sequence?
So our division can contribute anywhere. We can participate at each stage of the review process. Whenever our help is needed. Sometimes it's very early on, but, again, we even look at the approved products that are already on the market, or maybe after approval there was some safety signal and that justifies some research to be done to understand where the signal comes from, for example, can it be related to a design or a material change? And what needs to be done to ensure the device remains safe and effective, and what implication that signal may have on the future devices. So things like that can come at any stage.
So that means that you're really involved in any stage of the process. It doesn't mean that there's always, like, one place where your office is involved. You could be at the early stage, you could be at the end stage?
That's correct. It doesn’t mean that we're involved with every single device being approved or reviewed, because many devices just use well-established technologies, and that doesn't need a review from OSEL in most cases, 'cause reviewers are well trained and have all the knowledge they need to make a decision. We are mostly involved when there's a complex device or a novel device, or something unexpected is happening which needs some digging in and deep knowledge about an area.
And is all of the information coming from the companies themselves in terms of the data, or are you getting information also from health professionals or even patients themselves?
There is a mechanism to get all kind of input, and one of the mechanisms is to have an advisory panel meeting, and usually all sides are involved with those. The company presents the technology, you hear from physicians who may be participating in clinical trials and learn from their experience what they think about the device. And usually the patient groups are also represented, and they say—it's very important for us. The thing that you have in your mind when you think about what a tolerable risk would be for a patient, may be very different from what an actual patient thinks about it. So now we're really trying to have the patient the power to decide what an acceptable risk is for them, as long as it's an educated decision. This is part of our work. So, at many companies, they don’t necessarily generate all the data by themselves, but there are established CROs, or companies who do some sort of testing as a business. So those are often well established and accredited parties that we trust to do good testing.
So can you walk me through an example of—I mean, the overall mission is ensuring safety, I assume. Is that the bottom line, making sure that medical devices are safe?
Well, safety and efficacy. Safety is usually the main concern in the initial testing, but they also don't want to approve a device that is not working, even if it's totally safe. It probably wouldn't do immediate harm by itself, but if it doesn't work, it probably means that you won't get the treatment that might be helpful to you. So efficacy is also important.
So I wonder if you could walk me through for both cases, a case where—and speaking in general terms; we don't have to speak about particular companies or devices—but just to give a better understanding of your office's involvement in making sure that a given device is safe, how do you do that?
Well, many of my colleagues are maybe in the clinical data that companies submit, so we look at bench testing, any in vitro test they might have done. There are people who are experts at looking at animal data with any safety signals that were noticed during the preclinical testing. That's the big part of what OSEL does. There are also related issues and there are experts in fields like, will this device be compatible with the environment? For example, electromagnetic compatibility. Will this device interfere with the setting if it's to be used in ICU, for example? If anything that will prevent this device from functioning normally, that kind of questions.
So is it a different process in terms of safety and efficacy, or is it one process that determines both?
My understanding is that, in the early stage or phase of clinical trial, safety is the main focus. And then, before the device is actually approved, you also have to show—well, it depends on the design of the study, but in some cases, you have to show superiority or noninferiority to the existing standard of care. It depends on the treatment and disease.
All right. Now, maybe this is going to be a hard one for you to answer, but it's in the title of your division anyway. I'm not making it up. It's the Division of Biomedical Physics, and you have a PhD in Physics, so I must ask: How is physics used in the capacity of your job? How do you act as a physicist in this division? How do you use physics to do your job?
I'll tell you how the division uses physics. We have people who are much more physics-oriented in my perspective than me right now. Well, my physics and use of physics is limited to imaging. Everything that I do is connected to some sort of optical probe or high-resolution imaging of the cell, things like that. But there are also people who are maybe engineers by education. We have a lot of engineers in the division, or biomedical engineers, so they are trained in physics and math. And we also have people who do computational modeling, and that requires a lot of understanding of physics and math. But also, there are divisions that are doing material science research, they're probably more like chemistry, but nothing exists without physics. [laugh]
So maybe this is another hard question since you had difficulty with your dissertation, but it's more recent, so you can't say you have a bad memory on this. What do you feel like your biggest contributions at the FDA have been?
So, at the FDA, I think what my main contribution would be the development of alternatives to animal testing. This is why a lot of us working with human models. There are many reasons to avoid animal testing, and one of them, probably the most important one, is that the results are not always translatable to clinic. Because (animal) species are different and—I don't know about other organs, but clearly mouse’s heart, especially, is very different from human heart in many regards. So my contribution was in developing this lab that almost exclusively uses human cells now. And these cells are coming from induced pluripotent stem cells, and stem cells that are not the same as fetal stem cells, so there are not any ethical issues connected to this type of research. Those induced pluripotent stem cells are received from adult donors from just a blood sample, for example. Donors have fully consented to donating the samples. And now technology allows us to reprogram those cells into the pluripotent stem cell state, and then you can use them to differentiate to potentially any tissue type, heart, lung, or nervous system, or hepatocytes, liver cells, whatever you might be interested in. And those cells will carry the donor-specific genetic information, so there is the potential to use them for personalized medicine or to develop an in vitro test that would predict individual response to treatment.
So Ksenia, I'll ask you one last question, since we've brought it right up to the present. What do you want to accomplish in the future for your career?
Well, as you know, I'm now exploring this management part of life, and I had been very lucky in my life and had very good mentors and supervisors that really shaped my career, and I hope to give back to my fellows. But also, I'm not going to give up my research, and I think we have very, very interesting projects in development.
You want to be the Dr. Balaban for your fellows, right?
Oh, that's not possible! [laugh]
Nobody’s as good as Dr. Balaban.
So what are these projects that you're excited about for your fellows?
So one of the areas that we're looking at right now is cardiac ablation. This treatment is used for patients with atrial fibrillation. And the idea is to scar heart tissue to stop this abnormal propagation of electrical activity. And usually, or conventionally, the scarring of the tissue is done through delivering heat or cold to the tissues, so you cook part of the tissue and that brings a scar on the tissue. Now different types of energy are being proposed, and one of them is delivering pulsed electrical field which would induce electroporation of the cells. Electroporation is the process of creating small pores in the cell membrane that eventually leads to cell death. And the promise of this technology is that it will be faster, it will be not thermal, so there may be no side effects to surrounding tissues, and some preliminary data also suggests that it may be specific to cardiac tissue.
And the idea behind our research project is that is has been measured in different animal species and following different protocols (so, unfortunately, there is no comprehensive study), that the electroporation threshold may be lower for cardiomyocytes as compared to, for example, neurons or lung tissue. That would give you an opportunity to very precisely ablate only the parts of the heart that you actually want to. There is no chance of damaging surrounding tissues like phrenic nerve or the esophagus. One of the most serious—rare but serious—side effects of cardiac ablation could be esophageal fistula, so a hole in the esophagus. This is usually life threatening. So with this new device —or devices, potentially, that risk can be avoided. But we want to look at this in a more systematic way to generate data that would support selection of specific parameters for electroporation-based ablation. We actually want to look at the tissue specificity in human tissues, because none of this data exists. And eventually, we want to develop a medical device development tool. This is the mechanism for us to develop and validate a specific assay that can then be potentially used by anyone in the field, but which will be helpful to the FDA reviewers, and will hopefully reduce the amount of animal testing or clinical testing, shifting some testing towards in vitro studies.
Now, I was glad to hear you say that you don't want to give up the research, even if you continue on in the administrative side of things. How are you going to do that? That's always the challenge, right? As you move up the ranks, it's harder and harder to stay with the research. What's your plan to be able to do that?
I would really never consider giving up science completely. It would be too boring. Science is the good and stimulating part of my life. [laugh]
So what is the research? What's the research that you want to accomplish into the future for yourself, for your own interests?
Well, I want to really explore the potential of the stem cells to the extent possible. It's a very exciting discovery. It got a Nobel Prize, in medicine in 2012, I think, very soon after its discovery in 2007. So you see how quickly the field realized the potential. But, from my position at FDA, I want to see how those cells can be used to advance the review of the devices, drugs, or other medical products. While these cells are human by nature and they resemble actual human cells, there are also challenges with them, such as how reproducible and mature they are. There's a lot of work to be done in this area. And I'd like to be this contributing person from the federal regulatory agency, maybe inviting people to think early on what the implication would be for the use of these assays in the future regulatory review.
So what would be a concrete example of success as you envision it for this research?
I can imagine two. First, that using these in vitro early studies, you'll be able to faster identify potential safety concerns, or maybe even alleviate some of the potential concerns and move forward some potentially safe and efficient devices or treatments to the market. But the other very attractive thing of this is in development for the personalized medicine area. So right now, we really treat every patient following pretty much the same approach based on his, I don't know, demographic, age, or history. But you're not going down to the specific genetics of each person. If you could use your own cells and predict your individual response, that would be, I think, a great thing. So, very interesting science.
Well, Ksenia, thank you so much for spending the time with me today. It's been really a great pleasure talking with you. I really appreciate it.
Sure. My pleasure. Thank you.