You’re listening to our 17th episode, ‘The Fight Against CF: Breathing Life into Patients.’ I’m your host Simon Floss with Sanford Health News.
The practice of medicine goes far beyond clinic walls. The Innovations podcast looks at the biggest issues facing healthcare today. Each episode offers the opportunity to see the ever-changing world of health and wellness through new eyes. Our leaders offer out of the box solutions to some nagging questions.
Today we’re grateful to be talking with Dr. Michael Welsh, a pulmonary physician who’s a 2020 Sanford Lorraine cross award finalist. He’s worked tirelessly to fight CF, or cystic fibrosis, for years and has discovered a breakthrough in the process.
Dr. Welsh, thank you for your time and sitting down with us today.
Michael Welsh, M.D.: Thank you. It’s great to be here.
Host: First, let’s introduce you to our listeners. What do you do? Where are you from? And, where’s home now?
Michael Welsh, M.D.: I’m a pulmonary physician at Iowa City, the University of Iowa
Host: Go Hawks, right?
Michael Welsh, M.D.: Yes. I actually grew up in Iowa, did some much of my training at Iowa, but also San Francisco and Houston, and came back there. I’ve been on the faculty there for a long time, working on cystic fibrosis, taking care of people with lung disease.
Host: A perfect transition. Let’s talk about cystic fibrosis. Can you explain to those who just might not know how serious and severe this disease is?
Michael Welsh, M.D.: It’s a very serious disease. Let me give you an example.
When I was a junior medical student, I saw a person, first person I saw with cystic fibrosis was in the pediatrics clinic. And you could see across the room that this little seven year old girl was having trouble breathing. You could see it by the way she was using her neck muscles, by the way, her chest was moving. By the way she couldn’t finish a long sentence. You could see it by the foul green sputum she was coughing up.She couldn’t run around and play normally because she just didn’t have the wind. She’d been in the hospital multiple times with IVs.
The sobering thing there was, as we talked about her after the clinic visit with my staff at that point was, it was just how sobering it was to learn that she wasn’t going live to the mid-teens because we didn’t have good treatments. We didn’t have any real treatments to change the course of urgencies. So, cystic fibrosis is a disease that’s very severe. It changes people’s lives. If you pick up any textbook on and look at the chapter on cystic fibrosis in our medical textbook, the first sentence is almost always cystic fibrosis is a lethal genetic disease, and today it doesn’t have to be lethal anymore.
Host: We’re going to get into that in a little bit, but just for more context, off the top of your head, do you know how many people that (CF) affects?
Michael Welsh, M.D.: I think the numbers in the U S are 30 to 35,000 people worldwide around 70 (thousand), I believe.
Host: You’ve discovered the CFTR gene instructs the cells to make a channel for chloride, which is an incredible breakthrough. Can you explain what that means for those who don’t know, and why it’s so critical for patients living with CF?
Michael Welsh, M.D.: So, the gene is sort of a set of instructions, and it makes something. When the gene was discovered, the immediate question was what does it do? There was lots of opinions and controversy and arguments about what it might do, but nobody knew. And, we were able to figure out that it makes a channel.
So, a channel is like a little pore and this little poor lets salt, go through it. And table salt is sodium chloride. And this lets part of that go through the chloride part. So it’s a chloride channel. It’s like a little pore little channel that this chloride salt can go through. That’s important because that can get out into the surface of the lung, the surface of the windpipe, the surface of the bronchi and coat them with this thin layer of liquid.
That’s really important in protecting the lung from infections, inflammation, destruction, it’s sort of a defense. So, we’re all breathing in bacteria. You know, every day we aspirate bacteria from our throats down into our lungs at night. So, we need a really good defense system and in cystic fibrosis, this little channel, once you knew it was a channel, you could then figure out if it’s not there, what happens and how do you, how do you get this lung infections?
Host: That discovery, is that the biggest sense of pride that you’ve had through your career thus far?
Michael Welsh, M.D.: I think there were lots of things that I don’t know if I would say that that’s the biggest, that was really an important one, but, the other things that we were able to figure out is then how does that work? So, he could say it’s like a little pore or channel, but it’s not static. Sometimes it’s open, sometimes it’s closed. So, we figured out how does that work?
The other thing, I think that was there were multiple things, but another one is to figure out, why is it broken? If you want to fix something, you have to figure out what’s broken, right? If your car doesn’t start, is it the battery? Is it a gas tank? Is it an ignition system? Whatever. You can’t fix it until you know what’s broken. The same thing with this genetic disease.
So, we figured out that there’s multiple ways to break this channel. Sometimes the channel never gets made. Sometimes the little pore never opens up. Sometimes it opens up, but it doesn’t really let chloride flow through very well. And sometimes it never gets to where it’s supposed to be.
If you think about an assembly line, yeah, a little widget coming down the assembly line, if you get to a widget and its sort of misshapen, misfolded looks funny, pull it off the assembly line. The cell is a little bit the same, the common CF mutation going down the assembly line being made, being folded, being buffed up, and it looks funny to the cell. It looks misfolded. The cell pulls it off the assembly line. So you never have these channels where you need them. That’s important, because it says, “that’s what you need to fix.”
The other thing there, I think that that helped a lot is we showed you could fix it. So, we showed it for this common mutation that that gets pulled off the assembly line. And there, we learned that we could fix this simply by lowering the temperature of the cells in the lab. Now, normal body temperature is 98, 99 degrees for you and for me, if we lowered the temperature down into the 80’s or 70’s, the channel could make it past the quality control system. It folded a little better. Quality control system didn’t recognize it as abnormal, and it actually got to where it was supposed to be.
Once it got to where it was supposed to be, it actually could work, not one-hundred percent, but pretty darn well. Now, it’s really exciting because it says, here’s the problem. Here’s what the protein does. It’s a channel. Here’s how it works. Here’s why it doesn’t work when it’s mutated in a person, and you can fix it. We can’t fix it. We can’t call people down to 70 degrees. I mean, this is South Dakota We can’t, we can’t cool them down, but it said, instead of calling them, you could make a medicine. If you make a medicine that will fix the problem. So, that ignited drug discovery.
Host: In the midst of all of this research, what was your fuel? What was your motivation? What kept you going?
Michael Welsh, M.D.: I think that people with CF would be the biggest motivation after taking care of them. After having a friend who had a child with cystic fibrosis, that’s a huge motivation. Also, I think that I like very much what I do. I don’t, I don’t really consider it work because I get to chase something to get, to solve problems, puzzles, mysteries, and that’s also a big motivation.
Of course, we don’t always win. We have lots of failures along the way. I think the motivation is I get to work with trainees who, people who are committing their lives to this. I love working with young people. I love working with them because they don’t know what they can’t do. Once you don’t know what you can’t do you can do anything. I’m incredibly fortunate to work with them.
The other thing I think that was really important and a motivating factor of this is that my colleagues and my collaborators. I like to surround myself with critical people. People who will say, well, that’s not the best way to do this. People who will argue with me. That helps us go forward in thinking, “what is the best way?” And we choose the best way. Sometimes we’re wrong and we fail. And then, you back up and you say, “well, that didn’t work. We tried this. Let’s try going around the problem a different way. Let’s try going over it.”
Sometimes you just have to persist, and try, and bust through the problem. But, it’s a combination of all those things: the motivations from patients, your trainees, your colleagues, and the people with CF.
Host: Let’s switch gears now and talk about the Lorraine Cross. What is it like to be a Sanford Lorraine Cross Award nominee? And, what’s this recognition mean to you?
Michael Welsh, M.D.: I love it. It’s humbling, because when I got the call that I was going to be a finalist for this award my first reaction was just so I’m just very excited and honored, but within a couple of hours, I was talking to Kelsey about all the other people who have contributed, you know, all my trainees, all my colleagues, it’s not one person, one person can’t do this. It takes a whole team of people. So, I was thinking about that, and that’s why I talked to him. I talked to David Pierce again, too. It’s exciting to be a finalist, but really you do this because you do this on behalf of all the people who’ve worked with you. The thing is, you do this on behalf of people with CF. We often think about the people with CF, because they’ve really inspired us. They’ve supported us.
I’ll tell you one story. This is about ‘Kay.’ I’m not revealing anything by giving her name, she’s been written up several times. She was really important to us. Kay would come to the lab and talk to the students to help them keep their eye on the ball: this is why we’re doing this because of people like Kay. Kay participated in a lot of studies. I remember one time sitting on a bench with her outside the room where we were going to do this study. It was one of our first gene therapy studies. She was the second person that participated in that. And I asked, Kay, why are you doing this? And she says, “I know this isn’t going to help me, but maybe it will help somebody else.”
I wanted to cry because it’s the most noble of human spirits. That’s what Kay had. I have to tell you Kay died now probably eight, 10 years ago, maybe 12, I don’t remember exactly. Turns out, Kay had a daughter Kay’s daughter got CF case daughter is now benefited from the medicines that Kay helped develop.
We have a picture. We have a little display outside of our lab for K and some of the rudimentary equipment her father built, so she could get missed, you know, treatments that were very effective, but they’re all had, and we have a thing out there for K. We also have a picture of K’s daughter holding a picture of her mother. Both of them are smiling.
Host: Oh, that’s incredible. Thank you for sharing that.
Michael Welsh, M.D.: You’re welcome. That’s why I talk about the people who participate in these studies, and there they are an inspiration to me.
Host: Lastly, here. And speaking of being an inspiration, how would you hope to inspire and motivate future science and medical researchers?
Michael Welsh, M.D.: I tell people all the time, I have the best job in the world. I get to work with young people, great colleagues, get to work on incredibly interesting problems. And in the end, the things that we work on can benefit human beings. I think that it was really important for me was my family. So that that’s really important. They sustain me. They’ve supported me to sacrificed and that’s been really important. Also, I don’t consider what I do work and because I’m chasing something I want to chase. I’m just feeling incredibly lucky to do what I do.
Host: Dr. Welsh, thank you again so much for your time today.
Michael Welsh, M.D.: Thank you. I appreciate you taking the time.
Host: Before we wrap up. I’d like to remind you that Sanford Health Innovations podcast is now available on your favorite podcast apps like Apple and Spotify, as well as our website, Sanford Health News. If you enjoyed this conversation, follow us, give us a thumbs up and share your comments. We love hearing from you and hope that you find these conversations insightful.
Thanks for listening. I’m Simon Floss with Sanford Health News.