Sam Rayner, MD - phaware® interview 451

Jan 16, 2024

Dr. Sam Rayner is an assistant professor and pulmonary hypertension specialist at the University of Washington. In this episode, he discusses the different ways physicians can get involved in pulmonary hypertension research. He explains that he is a physician scientist, dividing his time between patient care and scientific research focused on PH. 

My name's Sam Rayner. I'm an assistant professor and pulmonary hypertension specialist at the University of Washington. I'm a physician scientist, which means I divide my time between the clinical care of patients with pulmonary vascular disorders, like pulmonary hypertension, and scientific research focused on pulmonary hypertension. 

I wanted to talk to you today a little bit about the different ways that physicians get involved in pulmonary hypertension research, including the kind of research I do, and delve into what it is like, at least for me, balancing research and PAH patient care, and discuss the importance of having physicians involved in research into complex diseases like pulmonary hypertension.

Physicians are often classified as either being pure clinicians, whose main job is to use their medical knowledge to improve health and help patients, or as being physician scientists who spend a significant amount of time doing scientific research in addition to seeing patients. Of course, this is a simplification and people have many unique careers existing all across the spectrum. But especially in a university setting, careers are often structured based on these categories.

In my case, I've known since before medical school that I wanted to be a physician scientist. I worked in a lab before and throughout medical school at the University of Minnesota under a researcher named Dr. Nobuaki Kikyo, who had both an MD and a PhD. I was fascinated by how much he knew about human health and disease and how he would focus his research to address questions with real implications for human health. When it came to my fellowship training, which is the period of training after residency where I specialized in pulmonary and critical care medicine, I became fascinated by pulmonary hypertension and I knew that this is what I wanted to study.

I felt that in some aspects, PAH was a basic science success story. Here we have a rare disease, which in many ways is very difficult to study in the lab. Yet over three decades we've seen more than 10 therapies FDA approved for PAH via multiple routes of administration with more in the pipeline. We've developed understanding of which groups of patients these medicines work for and which they don't. Most importantly, we're now seeing patients live longer and with a better quality of life. Yet, PAH remains a terrible disease and there is so much more work to do to really understand it and find true cures for the disease, which means there really is a need for people doing research in this space.

I found all this very compelling and I set out to think of exactly how I could study PAH as a researcher in addition to a clinician. Again, an oversimplification, but when thinking of different categories of research that one can engage with, we often think of a spectrum of research spanning from laboratory science, or what we call bench research or some people might call basic science where work's done in a laboratory with cells or animal models, all the way through clinical research on the other end where the focus is entirely on human subjects or clinical data. In the middle of these two sits what's often called translational research, which spans the gap from basic to clinical research and where I've sort of found myself.

When I was learning about pulmonary hypertension and trying to choose a research direction, it was quickly evident that a lot of the prior work in the field had been done using animal models. A lot of important discoveries have been made this way, leading to the therapies that we now have. Yet the animal models that we have don't perfectly represent human PAH, and there have recently been numerous treatments which have shown tremendous promise in these models and yet failed when tested in humans. There also are humane reasons to minimize our dependence on animal models whenever possible in research. For all these reasons, I wanted to try to find a way to build new models using human samples to study PAH in the lab and find new ways to analyze samples that we do obtain from patients.

I was very fortunate at this time to find Dr. Ying Zheng at the University of Washington as a research mentor. She's a bioengineering faculty here and a pioneer in developing engineered models of human blood vessels. The idea is that we can use a variety of micromanufacturing techniques to create patterned tubes in materials like collagen that have the geometry of human blood vessels which we can line with cells, grow in the lab, and create living replicas of human blood vessels. These engineered vessels can then be used to study human diseases or test pharmaceutical compounds. Our work has involved developing new ways to create more sophisticated blood vessel models. I'm now working to develop models specifically of the pulmonary or lung blood vessels that we can use to study PAH. I'm using models that we've already developed to study how human cells from patients with or without PAH behave under environments that mimic what we see in the body in pulmonary hypertension.

One of the exciting things is that it is becoming cheaper and cheaper to do some of these complicated studies on human samples. So things like sequencing all of the RNA or all of the DNA or examining nearly all of the proteins within human cells or human blood or human tissue, that's now something that is accessible to most labs doing research in a way that it wasn't five or 10 years ago. So as the technology advances and becomes more readily available, I think there's more and more work that we can do in human samples. Similarly, the bioengineered models, or what some people might call “organ on a chip” studies, are continuing to advance, become more sophisticated. The hope is that eventually these will become more mainstream and available and things that you just order from a manufacturer and are ready to go and become more and more affordable.

I think we're still in an era where there's a lot of bespoke models where each lab has their own bioengineered model and less of centralized models that everybody's using, although some are becoming more commercially available. But I think we still have some ways to go until we have truly plug and play models that approach the complexity that we see inside of the human body.

It's hard to know what the future might hold. I think we're definitely going to see as these preclinical models using human tissue get better and better, we're going to see new discoveries happen because we're using human tissue instead of animal tissue. I think we're going to see the number of animal studies that we need to do come way down as we can do some of the initial studies using human tissue. Whether we can truly replace in-human studies, it's hard to know. I hope we get there someday. I think we're a ways from that yet just given the complexity of the body and how hard it is to fully match that in the laboratory setting.

At the same time as doing this more basic science research, I've been fortunate to be involved in more clinically-focused research with another mentor and colleague, the director of our pulmonary neovascular disease program, Dr. Peter Leary. We've been doing things like analyzing circulating markers in the blood of patients with PAH and trying to understand how pulmonary hypertension differs across the different causes of PAH. For example, how do patients with idiopathic PAH differ from those who have PAH from lupus or liver disease or methamphetamine use? I'm hoping to combine these two avenues of research moving forward, incorporating human samples into new engineer models.

Doing this kind of research as a physician requires quite a lot of balance, and my day-to-day activities vary quite a lot. Some days, I may be fully in the clinic or hospital. Other days, research demands most of my attention. And some days I may start my day in the hospital and end it in the laboratory. Having specialized in a severe illness like pulmonary hypertension, however, one of my priorities is that I remain available to my patients and colleagues whenever clinical issues might come up. This can be challenging from a day-to-day aspect as it can mean getting pulled away from research experiments or research meetings for clinical issues, often many times a day. This can sometimes be stressful, but actually, sometimes, especially if experiments aren't going well, it can actually be rewarding to be pulled away and be able to be helpful to a patient or another physician and recenter myself.  I honestly enjoy the variety and the opportunity to do something different every day and throughout my day.

Even though a physician scientist's time is divided like this, I really think that researching a disease gives a practicing physician a unique perspective and a unique understanding of a disease like PAH that can help them be a more thoughtful physician. I think the reverse is true as well, that our patients and our clinical care can inform the questions we ask while doing research, and help make sure that the research we do is focused on improving human health. It's not easy balancing these two worlds, especially when considering that physicians may be involved in numerous other activities including education, administration, conferences, et cetera. This is one reason that we're unfortunately seeing less and less physicians doing laboratory science. We are starting to become rare. I worry about this, as I think that physician scientists play a vital role in the research of diseases like PAH. With a disease that's this complex and multifaceted, a practicing physician who knows the disease clinically is going to understand it in a way that a researcher might not who doesn't see patients in clinic.

The flip side of this is that the peer researcher may have cutting edge scientific skills and knowledge to offer beyond what somebody who splits their time to include clinical care might be able to maintain. But a nice facet of modern research is that it's more and more being done by teams of researchers instead of single researchers, and each member of the team can bring in specific skill sets. I really believe that continuing to have physician scientists as leaders and members of those teams is critically important.

I think it really does make a huge difference to be able to put patient names and patient faces to a disease when you're conducting research. I think it makes the research real. It helps you know what questions to ask and why asking those questions is important. It really keeps the research experiments that you conduct focused on helping real people. So I think it helps in a multitude of ways to have that dual perspective. This is an exciting time for pulmonary hypertension research and I'm honored to be able to be involved.

My name is Sam Rayner, and I'm aware that my patients are rare.

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