Using Music Based on DNA to Drive Rare Disease Awareness - Dr. Aditi Kantipuly, Professor Stephen Taylor and Casey McPherson

(Begins with music)

Michael Carrese: Believe it or not, what you're listening to there is a musical representation of the genetics of the coronavirus. We're going to be talking to three people today who are actually all involved in creating music based on DNA, and they're doing it to raise awareness for rare diseases. It's really kind of an intersection of the arts, sciences and rare diseases, and we have really just a fascinating half hour ahead of us.

Let me first tell you who's with us on the panel. Dr. Aditi Kantipuly is a physician and advocate with broad-based experience in government, academic medicine, and journalism. Her current work focuses on using the arts to drive health equity in the rare disease space. She's also a Fulbright scholar and author of a book about rare diseases for children called The Zebra Alphabet. She's also a health equity fellow with the Rare Disease Diversity Coalition,

which is the first nonprofit in North America dedicated to serving communities of color diagnosed with rare diseases. 

The gentleman who created that piece of music we just heard is also with us. Stephen Andrew Taylor is a professor of music at the University of Illinois, Urbana-Champaign, who composes music that explores boundaries between art and science. As a theorist, he writes and lectures on African music, data sonification, Bjork, and Radiohead. In popular music, he has collaborated on concerts and albums with the band Pink Martini, among others. His music has won awards from the likes of the Guggenheim Foundation and the American Academy of Arts and Letters. Among his commissions are works for the Spoleto Festival and the Chicago Symphony. 

And we're also joined by Casey McPherson. He's a singer and songwriter based in Austin, Texas, where he lives with his two daughters, Weston and Rose. In response to learning in 2018 that Rose had an ultra-rare neurodevelopmental condition, he founded the To Cure a Rose Foundation and co-founded Everlum Bio, a rare disease lab designed to provide a range of services for ultra-rare disease patients seeking to discover treatments. He's also an advocate of the Sound Health Connection, which is about using music to engage the brain to improve communication and motor function in children with rare neurological conditions like Rose. 

So, thank you all so much for being with us today and let's start with you, Dr. Kantipuly. You are kind of the ringleader of this. Can you kind of give us a grounding, an idea, of what you are doing to use the arts to drive health equity in rare diseases? And then just give us a sense of what's happening with the three of you in terms of collaboration.

Dr. Aditi Kantipuly: Yeah, so I think initially how I got started with the arts was my time in India when I was studying rare genetic conditions. I had met a boy who was fifteen years old and he had progeria which is an accelerated aging condition. At any given time, there are only about 400 people in this world with progeria. When I met him initially, we were talking about hobbies and things he likes and then I just kind of asked him like, “What's your favorite subject in school?” And he told me that, “I stopped going to school years ago because I was getting bullied.” 

You know... what do you really even kind of say to that? Because we all think that education is like a birthright. So, it hit me like a ton of bricks. And so I was like, wow, we really need to change maybe the cultural perspective on the stigma and isolation and how to treat our peers who have differences. That's when the book started, the children's book of The Zebra Alphabet and teaching kids about these rare genetic conditions. 

I shifted into arts a couple of years ago. Then last year, I was listening to a lot of music, putting together playlists, and I came across Stephen's work -- who is just brilliant -- putting these genetic sequences together. I was like, wow, this is like so cool. It blew my mind and I reached out to him with this idea. I was like, “Can we make a song for rare genetic conditions?” Osmosis had announced The Year of the Zebra and big things are happening for the rare community in 2023. He graciously accepted and we were kind of putting this together.

Then, kind of when the track is nearing its end, I was like, “You know, what about doing a concert and trying to sort of showcase this as an advocacy awareness thing?” I was asking in the community again and someone had recommended Casey and so Casey came aboard and he also shared the same philosophy of raising awareness. It turns out he also had made a song based on his daughter's sequence genetic mutation. So we were like, “Oh, that's really cool because this is exactly what we were trying to do.” There was a lot of mutual resonance, so here we are.

Michael: Yeah, just amazing. So, Steve, let me go to you. You get this contact from Aditi and tell us what happens after that. And did you have any interest before, or awareness before, of the idea of trying to create music from DNA?

Stephen Taylor: Yeah. So, I've been interested in science as a driver of music for a long time, and specifically with genetics. I have two kids -- they're both grown up now -- but our firstborn son had Tourette Syndrome, which got diagnosed when he was probably seven or so, and our daughter was born with an extra thumb that got surgically removed when she was an infant. But I just started thinking that something happened with the recipe, you know? And that's when I really started looking into genetic sequences as a basis for what we could either call data sonification or data-driven music.

I was just kind of plugging along, you know, trying this out in various ways...things like the coronavirus or one of my pieces is based on this language gene called FOXP2. There's a bunch of other ones. Anyway, sort of out of nowhere, Aditi emails me and things start happening because Aditi seems like the kind of person that makes things happen. I guess I'll leave it there for now.

Michael: I get that same sense, actually. But just to help our audience, and to help myself understand, how is it you assign a sound to any particular piece of DNA?

Stephen: We call that mapping. DNA consists of four letters, A, T, C, and G and you can map those to anything. I mean, there's even an article in the satirical newspaper, The Onion, which says that scientists succeed in pronouncing the human genome for the first time. Turning it into musical instruments is not that different from just saying the names A, C, T, and G over and over a whole bunch of times. 

So, I did try lots of different kinds of mappings and there were lots of failures. Then I finally started coming up with a few that I thought sounded a little better. Besides doing the letters, of course, you can do things like amino acids. There's about twenty amino acids, and those can be represented with different pitches or different rhythms and so on and so forth.

I like to say data-driven music instead of data sonification because if you really want to make it sound musical, then you're using the data, but it's not meant to be, you know, a graph. Sometimes I do things which are meant to just really have a kind of scientific meaning, but then that's meaningless unless you have a kind of legend or a caption that tells you what the sounds are representing, if that makes sense.

Michael: And actually, let's just listen to a little bit of a sample you sent me. This is Coronavirus 6VLN. 

(music plays)

Michael: So, Steve...fascinating. Tell us what we are hearing there.

Stephen: That’s a small sequence of protein from the coronavirus. It's using amino acids assigned to different pitches, and the lower the pitch is, the more hydrophobic it is -- which means it is afraid of water, and it's going to kind of be on the inside of the protein. If it's a higher pitch, it's hydrophilic which means it likes to be on the outside facing out into the watery cell environment. 

Then there's also a few other things. There's a kind of ratcheting sound, and if that's happening, that means that we're in a beta strand, which is a kind of way that the protein can fold. And if there's a little triangle sounding, that's an alpha helix, which is another way that the protein can fold. So, if you know these things, it’s kind of like a caption for a chart. You can listen to it and get a pretty good idea of what the protein structure is.

Michael: Unbelievable. So, Casey McPherson, let's go to you. I'm trying to figure this out here...you know, you have Steve Taylor in Chicago, you're down in Austin, you both have this idea of turning DNA into music. So, tell us how you came onto this path?

Casey McPherson: Yeah, certainly. So, I've been a professional musician most of my life, and when my daughter was diagnosed with her rare genetic disease, that launched me into a completely different environment of creating a therapeutic for her. Consequently, I'm having to learn genetics, I'm having to learn drug development, but I'm an artist at heart. So, I have used music as a big fundraising tool to try to help fund this drug development for Rose and these other kiddos.

Rose's disease in particular is a point mutation, which just means one letter was off, and so instead of that gene producing an arginine amino acid, it's producing a tryptophan. I got approached by Columbus Children's Foundation as well as the Termeer Foundation and we started talking about raising awareness for these kids, because really none of these children will ever get genetic treatments with our current sort of healthcare pharma model. And seeing as I don't have an MBA, but I have played a few shows in my time and written a few songs, I thought that, well, maybe a way to tell the story is through music.

So, we took some white papers from some brilliant scientists -- I'm sure some that Steven has read as well -- around how you do it. From my perspective, being a pop artist, I was looking for patterns, I was looking for motifs. And so I took my daughter's healthy allele...you know, a girl has two X chromosomes, so she's got one good gene and one bad one. In her healthy allele I was actually looking at the amino acids. What is that the pattern that arginine can give? What's the pattern that tryptophan amino acids can give? How can I create melodies from both of those?

The way I did that, too, is just pretty simply looking at those four letters, but assigning the T to a flat third, because if you're in the key of C, the T is the only letter that doesn't fall into that. So, I assigned T, and then going off of that, just played those amino acids out as motifs. The verse has the mutation motif and then the chorus has the healthy gene motif.

I recorded that song. I’m very interested in music as a way to get people emotionally involved in the story of these children. I see it as even just a human rights, civil rights issue, because we have the technology to cure many of these diseases, we just don't have the structures and pipelines to do it at scale. So, you know, music is a huge way of infiltrating our society and helping us think and be inspired to think differently.

So, Casey, let's listen to a little bit of what you're just describing to us. 

(music plays) 

Michael: I guess I want to know what your reaction was when it was all done and did it capture what you had in mind and what kind of reactions are you getting from other people when they listen to it?

Casey: Well, you know, I ended up having a couple of biotech people actually play on the track. Alan from the Termeer Foundation played some guitar. And so the process of it was bonding, which I thought was very cool, which I've experienced with the Aditi and Steven as well.

We have not released this track yet and Steven hasn't released his track yet. What I hope happens is that we have a platform to tell the stories of these children, these patients. Nobody wants to hear about a sick person. Nobody wants to see someone that's dying, someone that's in pain. You know, our social media just tends to show the highlights of good things that are happening. So, it's been a big challenge with rare diseases. Even with the word rare...we're 400 million people, 200 million children. That's not rare. My hope is that these songs can really make an impact in that and in a larger conversation.

Michael: So, Aditi, back to you. What is your hope here? You've got all of these great elements and you're sort of the conductor of this symphony, if you will. How is this all going to come together?

Dr. Kantipuly: I think what we've discussed so far is we're going to try to showcase some of the tracks that Casey and Steven have composed and sort of put it together. But also another idea was to bring other musicians on board that may have had health conditions and to talk about their personal struggle as well to sort of advocate for health and lessen the stigma. In the long term, I think what I'm seeing is that it's not just like a “one and done” concert to sort of bring in funds like a one-time thing. I want it to be sustainable.

I mean, yes, we are raising awareness for these rare conditions, but I think it's also a really cool gateway. When we talk about health, there's different aspects. There's physical health, emotional health, mental health, and now I think we're going to see the trickling of genetic health. And sometimes that's like even a black box when we're talking about genetics. So, opening those conversations up through music, I think, would be a really powerful way to sort of be more active about our own health and well-being.

Michael: What would you add to that, Steve?

Stephen: Everything Aditi said. And one thing that Casey actually just said really hit home for me is I've been trying to work on this project of turning these genetic sequences of rare diseases into music. The music comes out very sad. Just like Casey said, you know, nobody wants to see a sick person. I think that if we can find a way to make it uplifting at the same time as a kind of artistic expression, I think that would be my dream. I'm still working on that.

Michael: And do you envision doing a fuller scale symphony, or that sort of thing?

Stephen: Thanks to Aditi, pretty much, yes. She's been in contact with some professional orchestras and I think that there's interest in it. You know, it's something that all of us have to deal with and I think there are a lot of people in the mental health community who are musically talented. So, I think that if we can connect with those people, we can maybe make something beautiful happen.

Michael: Casey, you mentioned your daughter Rose and the To Cure a Rose Foundation. Foundations, of course, are always trying to raise money and raise awareness. Talk a little bit about the work of the foundation, how things are going and how you think this might help.

Casey: Yeah, well, the process of developing a genetic treatment is typically pulled out of an academic institution as a proof-of-concept drug. I'm seeing that academic incentives can sometimes be publishing and funding their labs; biotech incentives and pharma incentives are really what's the profit margin on a drug; and as a parent, your incentive is to create a cure for your kid. So, I wanted to be laser focused on that with the foundation. 

We wanted to build a platform -- while we're building Rose's genetic treatment and for her disease -- that we could do this again and again and again in a faster, more efficient process, and so that's what we've done. We've raised enough money and we've created the first proof-of-concept drug for my daughter's disease that exists anywhere in the world. 

Michael: Wow. 

Casey: The problem then becomes getting it into the FDA and the two to four million dollars that it takes to do the required studies. A proof-of-concept drug is a lot cheaper to make than it is to do all the safety work and manufacturing it takes to actually get into a Phase I trial. So, that's where I'm at with that. But I'm very excited about creating a pathway so that for the next parent, for the next Rose, for the next disease that we discover, you know, can all the work that we do begin to create efficiencies and a larger path instead of continuing to just cut down new trails? Can we begin to sort of widen this path for more families and more patients and, ultimately, more cures?

Michael: Now, Aditi, you're a physician, but you're also working on a song yourself about a gene mutation that causes cerebral cavernous malformations. Tell us more about that. 

Dr. Kantipuly: So, around the time that I was having all these conversations with Stephen and Casey and then hearing about their experiences, I was also working with a group in New Mexico. And the New Mexico story is that in the late 1500s, there was a man from Spain who migrated to New Mexico and he passed on this mutation known as CCM -- Cerebral Cavernous Malformations. Typically it's a rare condition, but in New Mexico, there's a higher prevalence. 

I heard the track that Casey had composed for his daughter and it was very moving. It is emotionally riveting and I said, you know, could the same concept be applied to a different condition where we have patients and families that can sort of drive this music? And so right now, I'm working with a local musician and a community member who is personally affected by CCM and they are penning the lyrics to the song. The genre is going to be more like southern country. The idea only came because I met Stephen and Casey. I’m just trying to transpose it to a different community and see how we can expand.

Michael: Wonderful. Yeah. Once you get the creative juices flowing, it can go in any direction. 

Dr. Kantipuly: Right. 

Michael: Casey, I wanted to turn to you as a parent. We have a lot of learners, medical students, nursing students and so forth, and also early career clinicians in the audience. What would you like them to understand about dealing with patients and family members who have rare diseases?

Casey: That's a great question. You know, we live in such an exciting time right now. If you look at the way education works, oftentimes you'll have a solution and it takes nearly a decade to get the training for this new solution. Science is moving so fast right now. If there's one thing for early clinicians to know in their career it’s that genetic testing is so important, even the idea of genetic testing for diseases that don't have current therapeutics because those numbers give people the ability to showcase that this disease is an issue and that brings in more resources. 

So, I'm like, test everyone and test often because new variants show up. Go back to the website a year later. If yours was a variant of unknown significance, go back a year later. It may change. It opens up a pathway of hope and understanding to parents that don't know what's going on with their children. 

The last thing is, is these parents are surviving day to day. And when you become a number --because you've reached the dead end of your health care system -- it is really depressing, you know. And so I think from a clinician standpoint, a nurses standpoint...you have the ability to educate yourself on potential pathways that provide hope. The parents are having to do that because no one else is right now. But I think in the future, we're going to see the medical community really rising to the occasion here. So that's my encouragement. There's so much sort of revolution and innovation that can be done, but we need leaders in every place of medicine to have the courage and the bravery to believe that they can make an impact.

Michael: Well, we're almost out of time, but I do want to give each of you a chance to let people know how they can learn more about your fascinating work. Steve Taylor, where should people go for that? 

Stephen: Oh, sure. You can find me at Illinois.edu, which is for the University of Illinois at Urbana-Champaign. Or I also have a website at StephenAndrewTaylor.net.

Michael: And Aditi, for folks who want to keep track of all this, where should they go?

Dr. Kantipuly: Probably the best ways for people to check out my LinkedIn.

Michael: And Casey McPherson, what about you? 

Casey: You can follow my story at ToCureRose.org and then you can check out some of the music at Alpharev.com and FlyingColorsMusic.com. 

Michael: Well, listen, this has been as fascinating as I hoped it would be, and I want to thank you all so much, not only for spending time with us today, but for this really innovative and important work that you're doing.

Dr. Kantipuly: Thanks, Michael. 

Stephen: Thanks a lot. 

Casey: Thank you, Michael, for having us.

Michael: So, as we wrap up here, let's listen to another selection of Steve Taylor's to give you a sense of the different kinds of music that he's producing from DNA. It's called Winged Helix Cardinal Whale, and it's a representation of the FOXP2 gene. 

(music plays) 

Michael: I'm Michael Carrese. Thanks very much for checking out today's show and as always, remember to do your part to raise the line and strengthen the health care system. We're all in this together.