#75: Can Zebrafish Beat Childhood Cancer?

Quinn: Welcome to Important, Not Important. My name is Quinn Emmett.

Brian: And my name is Brian Colbert Kennedy.

Quinn: This is the podcast where we dive into a specific topic or question affecting everyone on the planet, this planet right now, or in the next 10 years or so. Fucking kill all of us or turn us into something super cool and futuristic like, I guess, controversially Starship Troopers. We are in. Our guests are scientists, doctors, engineers, politicians, astronauts, even a reverend and we work together towards action steps so our listeners can take with their voice, their vote and their dollar.

Brian: Why are Starship Troopers controversial?

Quinn: It's a whole thing. That's a fun talk question, Brian.

Brian: Got it. Hey, this is your friendly reminder that you can send questions, thoughts, feedback and more to us on Twitter @importantnotimp or email us at funtalk@importantnotimportant.com. You can also join thousands of other smart people and subscribe to our free weekly newsletter at importantnotimportant.com.

Quinn: Also leave us a voice message at the link in your show notes. Those are super fun and will include you in the show. Most of them are too weird that we get and we get plenty of them. Appropriate ones, which honestly is saying something if you've if listened to fun talk, appropriate ones, we will include those.

Brian: Really? Because we haven't yet.

Quinn: That's what I'm saying, they're all too weird. That's what I mean. The bar is low. Anyways, this week, Brian, we're getting back into childhood cancer because fuck that, man. This week we're getting technical. We're talking really nerdy about beating childhood cancer with some very unusual and exciting and tiny and glittery, at least to us, resources.

Brian: Yes, we are. Very exciting, very scientific-y talk but it was very cool.

Quinn: Why don't you tell him who stopped by Mr. Brian's neighborhood today?

Brian: Sure. Our guests are Doctors Jaclyn Taroni and Genevieve Kendall.

Quinn: They came on the podcast after listening to previous ones, which is always a good test. They work with probably our favorite place on the planet, Alex's Lemonade Stand to just beat the shit at a childhood cancer. I admire and respect and I'm so thankful for these ladies.

Brian: They were really fun to talk to. It was a good conversation.

Quinn: It was really good. So let's not keep it going. We're already at three minutes for this intro, Jesus. All right. Let's go talk to Doctors Jaclyn Taroni and Genevieve Kendall. Our guest today are Dr. Jaclyn Taroni and Dr. Genevieve Kendall. Together we're going to ask, Brian, can zebrafish cure childhood cancer? Dr. Taroni and Dr. Kenda, welcome.

Jaclyn Taroni: Thanks for having us.

Genevieve K.: Yeah. I'm excited to be here.

Quinn: We'll see.

Brian: I can say you're going to be happy all the way up until we say goodbye. All right. Honestly, thank you very much. If we could just get started by each of you just letting us know who you are and what you do.

Genevieve K.: [00:03:09]I'm Genevieve Kendall and I'm a postdoctoral scholar at UT Southwestern Medical Center. I study a pediatric muscle cancer and I utilize zebrafish models in order to understand how these cancers develop and then implement these models to better identify new therapies that we can use in the clinic.

Quinn: That's pretty awesome. Jaclyn, go ahead, try to match that.

Jaclyn Taroni: [00:03:35]Tough. I am Jaclyn Taroni. I am a principal data scientist at the Childhood Cancer Data Lab, which is an initiative of Alex's Lemonade Stand foundation. My job is to understand how folks like Genevieve and other childhood cancer researchers can use data to answer the really important questions in the childhood cancer field.

Quinn: Awesome. I love it. Some of our conversations are more ethical, some of them are more morality based, some of them are topics that people generally know about, like, why is the ocean cold. Then sometimes there's really technical ones like this. I like to imagine like where if someone said, "Brian and Quinn, figure out how to zebrafish relate to cancer." Where we would start? Literally, what is step one? I cannot even imagine how that would begin. So this is going to be educational for all of us.

Brian: Pretty excited. All right. Quinn is going to go over some context that he's ... I don't know where he's got this information but he'll talk to you [inaudible 00:04:39]. Then you can, of course, correct him at ... I mean, please correct him as much as possible. It really makes me very happy. Then after some context, for our question today, we'll get into some action oriented questions that get to the heart of why we should all care about it and what we can all do to help support you, ladies. Sound good?

Genevieve K.: Sounds good.

Jaclyn Taroni: Sounds great.

Quinn: To be clear, listeners, we've talked about this before, it's kids cancer. If you don't care about it, you're a monster. It should be pretty obvious. Anyways, listen, before we get into that, both of you, we do like to start with one important question to set the tone here on instead of saying, "Tell us your entire life story," if you could each answer, "Why are you vital to the survival of the species?" That would be good.

Genevieve K.: Okay. That's a great question.

Quinn: Be honest.

Genevieve K.: I was thinking about this question because I've obviously listened to your previous podcast and that really, to me, I do what I do because I'm passionate about it and I'm trying to make this world a better place and to help kids. I think even more importantly than that, I'm really dedicated to training the next generation of people that will take up this task and continue this work and continue to spread knowledge and give back. I think that's really what we need.

Quinn: I love that. Paid forward, pass it on.

Jaclyn Taroni: I would say I'm not. I think folks like Genevieve, who are real childhood cancer experts out there training folks, I would say are probably more important than I am. But I'll echo a lot of what Genevieve said, which is, I think as scientists, we want to be in a spot where the folks who come behind us have better resources, tools, training to answer those really important questions. I think, in my position, that's really important to me and something I think about a lot.

Genevieve K.: Jackie really elevates what I'm able to do, though. She's incredibly thoughtful in helping design experiments called Big Data and make the biggest impact that we can make for trying to identify cures for childhood cancer. I think you're being humble, Jackie.

Jaclyn Taroni: Thank you.

Brian: Awesome, I love it. On that note, both of your life work, which sounds like it's fairly complementary to each other, which is awesome, involves doing immense and just incredibly impactful good for a group of young, fragile, just kidding started humans. They haven't been smoking their whole life, they didn't deserve these illnesses that they have. You are truly giving yourself to something greater than you. Thankfully, so many of our conversations are with folks like the both of you. There is a lot of good in the world and we try to expose that and give a voice to as much as we can. For each of you, is there a specific relationship that you can point to that was a catalyst to get you to where you are today to do what you do?

Genevieve K.: I had a really influential biology teacher in high school. Ever since I took this class in ninth grade, I knew I wanted to be a scientist. It was a bit of a road to get to pediatric disease, I started doing research trying to understand how South American bats were related to each other at the genetic level. After that, I realized I wanted to help kids and so ever since then, I've been trying to understand how we can identify new therapies for pediatric muscle disease.

Genevieve K.: It's been incredibly rewarding because I do get to interact with these kids that have cancer and their families through Alex's Lemonade Stand and through being next to a children's hospital and show them what I'm doing and try to make the biggest impact possible. That's really rewarding and motivates me to even work harder.

Brian: My ninth grade Biology teacher was Mrs. Thompson and, bless her heart, she did not make you want to care about science.

Genevieve K.: Oh, no. That's too bad.

Jaclyn Taroni: You could have been on a different path though.

Brian: I think so.

Genevieve K.: You could have been studying bats.

Brian: Yes, exactly. That's awesome. That's really wonderful.

Jaclyn Taroni: For me, I think I got the research bug probably in college. I had a wonderful professor named Dr. Bean who took me in when I was a junior in college and I really got the bug. I feel like my upper level biology courses, I was always so struck by what we didn't know and that led me to go to graduate school. Interestingly enough, I thought I would be an immunologist. When we go to graduate school, in the biomedical sciences, we often do these rotations where we spend a two to three-month stint in different laboratories. The one that I started off in was more computationally focused and I really liked that.

Jaclyn Taroni: I landed in a lab that worked on a rare systemic autoimmune disease and a lot of that work was basically asking the question, which is about, "If I'm working on a rare disease and I want to use techniques like big data that require a lot of cases, how can I leverage other types of data or data measuring things other than what I'm directly setting to learn about the disease that I'm interested in?" That is how I see a lot of what we do at the Childhood Cancer Data Lab. As well as thinking about all this investment that's been made in different kinds of contexts, looking at cell lines, looking at zebrafish, how does that come together to teach us about childhood cancer and that is very exciting to me to put that data to work.

Brian: Do you think the same opportunities to do that, we'll get more into this, would have been available 10 years ago before these advances in algorithms and data calculation and organization?

Jaclyn Taroni: I don't think so. The kind of data we work on, it's called gene expression data or transcriptomic data. Luckily, there's always been a very strong culture of data sharing in that particular realm. But if you look at the expansion, the number of assays that become publicly available over time as sequencing, a particular kind of technology became more ubiquitous, you see it take off like a rocket in like 2008. So it's relatively young in the scheme of things, this explosion of available assays.

Quinn: That's awesome. I'm glad you're right place at the right time. Obviously, a whole lot of people are benefiting from that. Again, just some quick context here. Let me blow through this as mostly catching people up who maybe listen to our previous episode with Jay or did not. So we first dug into pediatric cancer back in Episode 48 titled, "Why the hell does kid's cancer even exist and what can we do about it?"

Quinn: That was with Jay Scott, now a good buddy of mine and the Co-Executive Director of the Alex's Lemonade Stand Foundation, which was started with her very own little lemonade stand by his late daughter, Alex. If you have not listened to that conversation, it is fairly timeless as our best episodes are. I promise it will hopefully inspire you and probably make tears explode from your face as it did mine, all of my keyboard.

Quinn: During that episode, we focused a lot on the ... Just so you guys understand, we'll have 12 different conversations about the ocean, for example, from the Fukushima dump radioactivity into how are the jet stream is changing the ocean to funding to food talks off the coast, so that people really get a fuller context of what's going on because all these things are connected when it comes to pediatric cancer. In that episode, we talked a lot about the the macros. We talked about how cancer is the number one cause of death by disease for kids under 19.

Quinn: Yet despite that, childhood cancer research receives just 4% of funding from the National Cancer Institute. For reference, cancer overall is responsible from what I gather about 29% of American deaths. We discussed how childhood cancer is not just one disease, there's about 12 major types and over 100 subtypes. [inaudible 00:14:01] with cancer when people say we're going to find the cure for cancer. That's not how it works, shit's very complicated.

Quinn: We talked about how there are some cancers kids are more likely to get and the progress we've made against them in research, in treatments, in recovery, and living with it. We talked about Alex and her life and her diagnosis and her treatment and her passing and what all of that meant for Jay and his amazing wife Liz, and and how that changed things for them, obviously, in a number of ways. Of course, we talked about the enormous impact that Alex's Lemonade Stand has had in the fight against pediatric cancers. I'm a big supporter in a number of ways. I know Brian is and listeners, you should be, too.

Quinn: Today, we're going to get into some nitty gritty science, it's going to be fun because Alex has started something new recently. We've talked about a little bit called the Childhood Cancer Data Lab or CCDL, if you're in the know. It is already revolutionizing the way that childhood cancers are researched. On that note, let's dig in a little bit to our completely clickbait title of Can zebrafish cure childhood cancer? Jaclyn, can you finish getting us up to speed I guess, tell me what CCDL is and why it exists?

Jaclyn Taroni: Sure. So the CCDL was started in August of 2017. We are a team of user experience designers, engineers and scientists. Our goal, in essence, is to put big data in the hands of childhood cancer researchers who are poised to make the next big discovery. There are several parts of that. Essentially, there's barriers sometimes to using these data to make discoveries that can be in access, it can be a knowledge.

Jaclyn Taroni: Part of our mission is software, building tools to make these data easy to use. Part of that is training. Genevieve is one of our first training participants and we're very grateful to have her come out and give us feedback on that. Part of it is scientific workflows. So bringing things in from different fields, using our expertise and putting that to work for childhood cancer research.

Quinn: That's awesome. I feel like I've asked Jay this question, either he avoided it, as he does with most of my text messages, or I've forgotten because-

Brian: He does, too? My God, I do the same thing you.

Quinn: This is not that conversation, Brian. We're not doing this right now. How did CCDL come come about? Was there another similar model in another vertical that inspired it? Was it just clear that something like this needed to exist for you guys?

Jaclyn Taroni: Yeah, so I have to definitely give props to Jay and Liz for Jay describes that it just in their gut, they felt like this was a missing piece in the field. But this is definitely first of its kind stuff. There's no other informatics lab run by a funder devoted to childhood cancer, as far as I know.

Quinn: That is super rad. That is very cool.

Genevieve K.: One of the issues that CCDL is addressing is with all of these new sequencing technologies, everybody's potentially using a different platform, a different pipeline, and then they're making the data publicly accessible but it's all in different formats. Then for people like me, it's difficult to harmonize that kind of data and so the CCDL provides this expertise that I can draw on in order to identify data that's important to me and integrate it and then leverage it for my own work.

Quinn: Got it? That's very helpful.

Brian: Seems crazy that it didn't exist before.

Genevieve K.: It's just a lot of people working in silos, essentially, and doing whatever experimental protocols work best for them in their hands. There's no standardized technique, I would say. Jackie can speak more on that than I can really, but ...

Jaclyn Taroni: That's definitely true. It has a bit to do ... I think the CCDL model is powerful because it's happening outside to a certain extent the way data is typically generated. What I mean by that is it's an independent party run by a funder. So I am not an assistant professor, I'm not in academia per se, and I think what we're interested in is we have the room to really focus on the cause, in ways that some folks in academia don't always have the same opportunities because our incentive structure's a little different. If that makes sense.

Quinn: Yeah. I think that makes sense. Yeah.

Genevieve K.: We have the space to focus on. What doesn't work best for us, our particular experiment, we have the space to look more broadly and bring it all together because that is how we are judged as successful.

Quinn: Sure, that makes sense.

Genevieve K.: Yeah. I don't want to rag on academics thing. I don't mean it like that at all.

Quinn: I think most people know that, like academia is a incredible pursuit and an invaluable resource and a just labyrinth nightmare of red tape and things like that. Not even including a case like this, just getting into tenure or anything like that. It's crazy out there.

Jaclyn Taroni: And it's really hard also. It's hard to do what we do. Requires a lot of resource and a lot of expertise in things like software engineering, that folks don't always have the access to resources to do that stuff.

Genevieve K.: Right. I mean, the CCDL is a really unique model. I don't know of any other similar model where they do have the resources and expertise in the same place to tackle this problem.

Quinn: It's almost like the old Bell Labs example.

Genevieve K.: Exactly.

Quinn: I mean, there's a bunch of white guys in that period, which they're great but glad we're moving beyond that. Having those resources in the same building makes big difference. Obviously, 2019, we don't need to be in the same building anymore. I imagine the academia, you probably have those resources in the next building but the effort to integrate with them in any way is probably just infinitely more complicated for a number of reasons. Also, just like you said, you guys are judged and measured very differently.

Genevieve K.: It's true.

Brian: Dr. Kendall, when we first got connected, you responded that you would like to discuss, "Genevieve's use of zebrafish genetic models to study pediatrics sarcomas and the high dimensional assays we focus on in CCDL as part of her experimental tool kit." Let's get into that, to the very basic level, like I am a child, peanut butter and jelly, if you know what I'm talking about.

Genevieve K.: Sure. So pediatric cancer is usually genetically based. There are very few mutations in genes that cause these cancers. The specific cancer that I study is the cancer of the muscle and it's called rhabdomyosarcoma. It's caused when two genes fuse together and form this apparent gain of function protein that acts in the cell to turn off and on hundreds, if not thousands, of genes inappropriately. We've identified this gene as the cause of this muscle cancer now 20 years ago but we have no drugs that target it directly. This is really frustrating to me and how I got into this field. What I do is I take the human form of the cancer gene and I actually use genetics to integrate it into the zebrafish genome.

Brian: So just to dial that way back for both me and as I like to blame them, our listeners who are texting and driving down the four or five right now, why the zebrafish? I need a little more context on that trying to understand. The things that are going through my head are probably very different from how you're about to describe them.

Genevieve K.: No. Zebrafish, although they look very different at the genetic level, they're very similar to us. Over 70% of their genome is conserved with the human genome or is similar to it. Over 80% of human disease causing genes are similar to zebrafish gene, so they're very amenable to understanding human disease and these developmental pathways that take us from a single cell all the way up to an entire organism are very similar. They have a lot of experimental advantages that you don't find in other model systems and one of them is that you can use them for large scale drug studies.

Genevieve K.: A baby fish can develop in one day, which is really fast. You can actually put hundreds of fish in a plastic dish that's the size of your hand and screen 100 compounds at a time for activity in the fish. I literally got into fish because I was sitting in the audience at a muscle conference and these fish couldn't move because they had a mutation in its muscles, and they added a drug to the water and the fish could suddenly move again. After that, I thought I absolutely need to learn how to work in the system. That's how I got into it in the first place.

Genevieve K.: I was shocked to learn that when we insert these human cancer genes into the zebrafish genome, they actually get cancer that looks exactly like the human disease. When you look at the structure of the tumor cells themselves or when you look transcriptionally or at all of the gene expression changes, which is what I do in collaboration with Jaclyn and the CCDL. They're big friends of fish, as I call them, because they have really moved forward all of their software to integrate maybe different types of model systems. Zebrafish are relatively new to cancer research so I really appreciate their dedication to being inclusive.

Jaclyn Taroni: Amazing honor to be friends of fish.

Brian: Oh my God, that's so wild.

Quinn: I think we posted on our Instagram recently, there's a quote that's out there and I can't remember who it is, it might have been Isaac Asimov that said something about, so often science is not about eureka, it's about the greatest discoveries or when someone says, "That's funny." It feels like ... I mean, who was looking for zebrafish to share 70% of our genome or was it just like ... What's your reaction to that?

Genevieve K.: Exactly. The field itself using zebrafish is relatively new, it was a tropical fish enthusiast that started this in the late '80s. There are two different groups that were using fish in Europe in the United States to understand the developmental processes, just a really basic biology of how the cells move during when an embryo was being formed. Then really, in the early 2000s is when they started being implemented to understand human cancers. We're really at the forefront still of implementing these models to understand childhood cancer. We've done a lot in terms of isolating muscle cancer, there's the leukemia models, neuroblastoma models but I think there's still a lot of work to do.

Quinn: Wow.

Brian: Zebrafish.

Quinn: That's amazing.

Brian: How does your research here fit into just the overall structure and goals of the Childhood Cancer Data Lab?

Genevieve K.: Sure. The Childhood Cancer Data Lab has been integral really on a number of levels for me. Like Jackie mentioned, I took there- I guess was that the inaugural training-

Jaclyn Taroni: Yes, the pilot.

Genevieve K.: The pilot.

Jaclyn Taroni: The pilot.

Genevieve K.: The pilot training workshop and it was really incredible. It was essentially like data boot camp. So I went there for a few days and they were trying to make us have knowledge of how to get started on doing these analyses ourselves. They document all of their protocols and make them publicly available so even if you're not at the workshop, you have the step-by-step instructions on how to implement these different types of sophisticated analyses. So that was huge.

Genevieve K.: They're also really cool people to work with and have great ideas. That's important for moving your work forward. Then the other thing that they've helped me with is envisioning how the fish can contribute to pediatric cancer by looking at the transcriptome of the tumors that are generated and how closely they recapitulate the humans in these disease. By transcriptome, I mean, the genes that are turned on and off by this human cancer gene that's in the zebrafish genome.

Quinn: Wow. So what was your experience with data prior to this relationship with CCDL? Was it a big part of your work?

Genevieve K.: Typically, I've collaborated. I'm a big believer and if I'm not an expert, I'd find the expert in order to move things forward quickly. It's been integral to have a fundamental understanding of what needs to be done, the time required in order to do this, and it gave me a framework to build on. Now that I have these articulated protocols online I can really go back and ask them specific stages if I get stuck, how to move forward. I think it provided a good baseline for me to move forward from.

Brian: Fascinating. That's an example of how your work integrates with CCDL. I know it's still fairly new but are there examples of places where you two have seen CCDL work in action successfully, as you'd hoped? Genevieve, you place other examples that you've learned from either that you hope to or anticipated or were surprised by it. Jaclyn, I guess, where have you seen some of your most delightful successes from the system?

Genevieve K.: Well, I was so excited about taking this course that I actually sent my technician and my boss. He went to the next course and it's kind of having a spidering effect where once you train one person, they'll train the next person. The impact of this is only growing. It's not even by taking the course directly but by coming into contact with someone that knows how to do these types of analyses.

Jaclyn Taroni: Yeah. I would say our training effort is less than a year older, we're coming up on one year since Genevieve participated in the pilot. It's wonderful because I always like to say that no one cares about your experiment more than you. I think, we spend all this time studying and nobody thinks about our project or experiments more than we do. To have folks who don't necessarily analyze the data themselves yet, to have them come, get a little more familiar. They're pretty short, folks don't walk out knowing how to do everything but to give them a taste so they feel more comfortable learning on their own and also more comfortable taught having a conversation like Genevieve was saying, with folks who do work on their data with them.

Quinn: So participating with the CCDL, is it sort of a formal partnership or application process? Is it a tool that's accessible all of the time that somebody can log into in the middle of the night when they're feeding their zebrafish? How do you recruit new members to the Avengers?

Jaclyn Taroni: So we do have a tool that you can access in the middle of the night when you're feeding your zebrafish, which is called refined.bio. I don't know how often the feeding of the zebrafish in the middle of the night happens.

Genevieve K.: It doesn't happen.

Brian: You're just not Brian. You have no idea.

Genevieve K.: During the day, three times.

Brian: Depends on your schedule. [crosstalk 00:31:42] They're like Gremlins, basically.

Genevieve K.: They're treated well.

Jaclyn Taroni: Okay. There's a tool called refined.bio and that is the URL. Refined, R-E-F-I-N-E dot bio, B-I-O. That is a collection of data that's been made publicly available through researchers uploading it to government run repositories. What we do with that is we get that data from these government run repositories and then we uniformly process it. So what we mean by that is we've selected certain pipelines that hopefully have pretty general use that then act on that data.

Jaclyn Taroni: We pull from three separate places, we have it come under one roof so it's discoverable all in one place. The idea is that if you know exactly what was done to that data, you can be more comfortable and save time getting the data from us because we're going to tell you what version of the software we use and we're going to tell you why we did that. The idea being, if you want to quickly check something, get preliminary data for your next grant.

Jaclyn Taroni: We've done the intensive work of picking a pipeline and also the actual time it takes to process those samples, computational time. Then you can go to refine.bio, snag the experiment and then see if there's any signal, if it supports your hypothesis, if it validates something that you found in your own data set, for instance.

Quinn: [00:33:28]Brian, you're taking notes?

Brian: I already went to find refine.bio and type in zebrafish, there's 638 results. My day is full.

Genevieve K.: It's exciting.

Jaclyn Taroni: Download them all.

Brian: So cool.

Jaclyn Taroni: Add them to that part.

Brian: [00:33:42]Awesome. What have been the most significant takeaways from CCDL so far? Do we have practical applications yet? Have there been like cool, unexpected benefits or wins so far from either of your perspectives?

Genevieve K.: It's been a surprise to me, and perhaps it shouldn't have been, is the enthusiasm for these training workshops that we're putting on. People wanting to learn this stuff. The last couple times, I believe we've been oversubscribed. I think that surprised me and I think I'm wrong, I shouldn't have. That was not something I was expecting going in.

Quinn: Sketch this out for me. What does a training session look like? How long is it? Where is it? Are we talking about a small classroom? Are we talking about an auditorium? Are we talking about a lab? How many people? Where do they come from? How do they [crosstalk 00:34:42]

Brian: So many questions.

Jaclyn Taroni: We're doing four this year, they're three days long and we're doing four different places. We went to Houston, which is where Genevieve's boss and technician joined us. We just got back from Chicago a few weeks ago, we're going to go to the Bay Area in September and then in Philadelphia in October. Those are three days long. The way this works is the first two days are designed to be instruction.

Jaclyn Taroni: We go through some of the technologies that we work on at the CCDL and are important for Childhood Cancer Research, one of which is called RNA-Seq, now a newer technology called single cell RNA-Seq. We show folks how to process and analyze that data and kind of give them a starting point set of tools. Then on the last day, that's designed for us to be in the room, unstructured time, work on your own data or otherwise practice skills that you've learned in the first few days.

Quinn: That's what I do with my six-year-old.

Genevieve K.: It's pretty intense. You bring your own data. There's practice. They have practices that we go through together and then on day two, they say, "Go for it." On day three, you have to do a presentation to this group. I think it's maybe 10 to 15 people. Jackie, is that about right?

Jaclyn Taroni: Yeah. Yes, has been around 15 people up to 20.

Quinn: Because you said you're oversubscribed, right?

Brian: Packing the place in.

Jaclyn Taroni: Yeah.

Genevieve K.: It's probably more than when I was there for the pilot.

Jaclyn Taroni: Yes it is. It is more.

Genevieve K.: We got a lot of attention from really smart people like Jackie. At the end of the day, you need to have been successful enough to analyze your data in order to present it to the group and talk about an intelligent way what you've done. I would say Jackie also teach good practices on how to code, too, which is important.

Jaclyn Taroni: I joke that I'm borderline militant about but kind of stuff. I need to be able to read it to find the bugs. I'm a big believer in that. It's probably a bit much.

Genevieve K.: I thought it was great.

Quinn: We can have an offline discussion about that. That's basically how I treat our workplace and Brian really just love it. That's really cool. I know Alex's funds a lot of research. Are these folks that are showing up, do they already have relationships with Alex's? Are these mostly incoming calls? Are they outgoing calls? How are you sourcing these geniuses?

Jaclyn Taroni: I don't have the exact breakdown but quite a few investigators do already have some kind of relationship with Alex's. But I do believe there are some folks that are not funded by them or not in Alex's funded labs. For the most part, yeah, quite a few of them have some experience with Alex's already.

Quinn: Got it. It's probably an interesting sourcing ground to find new folks as well on the other hand, that Alex's might be a partnership with.

Jaclyn Taroni: Yeah, it could be. I think it definitely ... If you are not already familiar with our organization, coming to our training will make you familiar for sure. We say where we're from because that's polite and a normal thing to do when you're meeting people. For the most part, I think people might be more inclined to either seek maybe collaborations with us at the CCDL in the future, if they get to know us. Genevieve, you can stop me if I'm wrong. Maybe you're ...

Genevieve K.: No. Are you kidding? I would love to collaborate.

Jaclyn Taroni: Yeah, we're going to get it up right now on the call.

Genevieve K.: It's happening.

Brian: Are most of the, love the word investigators, are they US-based? Are they international? What's the breakdown there?

Jaclyn Taroni: I think because we've been pulling or at least contacting folks that are in our sphere already, that is mostly US-based folks because that is traditionally how Alex's has funded investigators.

Brian: Got you. So let's talk about the hard stuff. Where are you both ... I realized again, you don't do the same thing but your jobs to complement each other theoretically and practically. Where are you running into obstacles? Do you find things running into the ground or have been difficult so far with CCDL or, Genevieve, with your own research either in collaboration with CCDL or otherwise?

Genevieve K.: That's a great question.

Jaclyn Taroni: Go ahead. I'm sorry.

Genevieve K.: Go for it, Jackie.

Jaclyn Taroni: I would say what I didn't talk about, something that also surprised me going back to a little bit what we were talking about earlier, one of the projects that I finished up and published in the last year was a project that essentially looked at training a machine learning model and extracting patterns from a large collection of essentially random human data and then applying it to rare diseases like childhood cancer. What we saw is essentially that you were able to learn more pathways or get a higher resolution look into the rare disease data, even though that model had never seen the rare disease data before.

Jaclyn Taroni: That's been really exciting and I think speaks to how something like refine.bio that we're using could be really useful, even though the bulk of the data that's in that resource is not specifically looking at childhood cancer data. So bringing this new idea, this conceptual advance, if you will, that was a challenging project and really exciting project to work on. I'm excited to do that, maybe looking at zebrafish in a similar way and transferring over what we've learned to human tumors. I think all of that is very new and sometimes when things are new, they're hard but definitely, an exciting place to be.

Genevieve K.: I think one of the biggest obstacles that we face is really understanding what genes are doing in a tumor. When you go to a clinic and you get clinical genomics done on your tumor, you'd get a report with different mutations in cancer causing genes. But if these mutations are one base over, and they don't have a described animal model, then you can't call them as being positive.

Quinn: Could you explain that for a basic human being?

Genevieve K.: Sure. A lot of times, we get these reports back from clinical sequencing efforts and you just have gene lists. There's a band of genes that you found an exact mutations and other tumors and these are causing the tumor, probably. Then you have a bunch of passengers, which is mutations that we have no idea what they're doing but they're there. That's really why I've tried to integrate myself into a clinical community because what they can do with the fish model is take these mutations that we're not sure what we're doing and then build zebrafish avatars of human disease and try and understand how the genomics of a human tumor will play out in an animal model.

Quinn: Interesting.

Genevieve K.: It's a way to functionally validate what we're seeing from patient tumors. Putting it into the fish, seeing the presentation of the disease, potentially how it responds to different therapies or combinations of therapies. Then the goal for me would be one day moving that back into the patient after testing it in the fish.

Brian: How often does research or results not translate from the zebrafish over to humans?

Genevieve K.: I mean, it happens in all models. For example, the sepsis model, mouse wasn't predictive of what was happening in humans. So it's bound to happen in zebrafish as well. There was a really exciting paper recently where they took a specific mutation they found in a human with lymphedema disorder, put it into the fish, screen drugs on the fish, found a drug and put that drug back into the single patient and improve their course of disease. It is possible to go from fish to human directly, in terms of drugs that you're finding that are potential therapeutic options. For drug development in cancer, there's a lot of failure once you reach clinical trials. To me, the best drug has activity in multiple model systems and that's the burden of proof you should use to move forward.

Quinn: Sure. I was just thinking, someone created, some frustrated researcher ... I'll have to find this, created basically a Twitter bot ...

Genevieve K.: In mice?

Quinn: ... in mice. It's so great because we talk about that all the time and it's easy as I go through and try to find the biggest news and most impactful news possible, the most truthful and validated news and often, we're linking straight to journals and things like that. Because you see these headlines sometimes in respected publications, because they'll go from a paper to a journal to getting picked up by a science blog to getting picked up by the New York Times and then it's a headline like Alzheimer's Cured. You're like, "What the fuck?"

Quinn: If you really dig into it, it's like, "Alzheimer's cured in mice." Again, the context is helpful and that's why I was just curious because again, we use mice because it is so close and it's really crazy. The zebrafish, obviously, is proving similar but obviously, there are going to be times where it doesn't translate.

Genevieve K.: Absolutely. That's why it's really important for me to validate everything I find in patient tumor data, are these genes important for overall survival in patients. That's my stop gap, essentially, do I move forward with this or not. That's why I've really partnered with the CCDL, to filter the things that might be most important to move forward with because I don't care about fish disease, I care about [crosstalk 00:46:00]

Brian: I love zebrafish.

Genevieve K.: I do care because I want them to be healthy. I want them to get cancers that recapitulate human disease.

Quinn: How many zebrafish have you put in your Amazon card since this conversation started?

Brian: Is that how you buy fish? Come on.

Genevieve K.: Just go to your local pet store. It's the same fish, it's like an inch long.

Brian: I thought it's beautiful if it's little striped. I grew up with a lot of fish in fish tanks in my house and I loved it. You can just sit there and stare at them, they're beautiful.

Quinn: You could have been solving cancer this whole time.

Brian: I was like, "Damn it."

Quinn: I don't want any excuses. Do you think these ladies made excuses for being 11?

Brian: No, I'm sorry.

Quinn: Well, you know what, we'll take this off, we'll deal with this.

Brian: I'm sorry doctors and Quinn. Has CCDL inspired other organizations to undertake similar endeavors? Or if not, where could you imagine this model going into other areas of cancer research or just medical research in general?

Jaclyn Taroni: It's a really great question. I don't know. I'm not sure that I've seen this exact model. It's still early days, it's early days. But I think it is useful to have an interdisciplinary team that has funding from a research organization to do this kind of work. I could see, of course, I'm biased but I could see this model being really powerful because there are some problems that are difficult, require a lot of resources and that they won't necessarily get attention in academic institutions or industry or what already exists.

Jaclyn Taroni: So I could see it being something that crops up more, I think. Hopefully we're very successful and people look at us and they're like, "We want to do that for our community." That would be great but I do think it's early days. I think, early days or not, we've processed a lot of samples, we're getting our training program up and running and I'm super excited about it. I hope we are in a place where folks look at us and go, "Wow, I really want to do that for our community."

Quinn: I don't know if you guys have this in Philadelphia but Brian is quite good at ... Do you guys have the guys who stand the street corners that flip the arrow sign up and down and dance with it to point people to come to the car wash? He could do that for your training sessions but if you guys don't have those, I can think of another analogy that's perfect. You talk about interdisciplinary, he's got a lot of skills.

Jaclyn Taroni: Yeah, I think there's ... Maybe we're a little tight on sidewalk space for that move but get him a clipboard maybe. Clipboard model is quite popular.

Genevieve K.: Typically, CCDL has an information booth at big cancer meetings so I see a lot of opportunity there for sign flipping.

Jaclyn Taroni: That's true. We should fly you in.

Brian: I'm in.

Quinn: I was kidding 10 seconds ago, now I'm not. This is dead fucking serious. We will come and wear t-shirts or crop tops or I mean, whatever gets the job done.

Jaclyn Taroni: Well, we should do some user testing and see what really works. We're about that here.

Brian: Well, let us be your guinea pig.

Quinn: Jay also has to be involved in this so I'll make sure we [inaudible 00:49:37] them without telling him.

Genevieve K.: Good plan.

Brian: All right. Let's get into our action steps. We like to provide very specific action steps if we can that our listeners can take to support your mission with their voice, their vote, and their dollar. So let's get into that. Let's start with voice. What are the big actionable specific questions that we can all be asking of our representatives that would help support your missions, ladies?

Quinn: What should they say?

Genevieve K.: Okay. Obviously, there's federal funding agencies for scientific research, primarily, the NIH for health and the NSF. Advocating for increasing the budget for both of those organizations makes a really big impact on what we're able to do. Right now at the National Cancer Institute, which a lot of grants to researchers at academic institutions, the funding line is I think at 8% of submitted grants are accepted for funding. It's an even smaller percentage, that's a lot to childhood cancer but we're missing out on a lot of great science because of that and it's a budgetary constraint.

Quinn: I was going to say, is it just purely a funding constraint that knocks out 92% of requests or is it a low quality of entry or ...

Genevieve K.: It is. No, there's a lot of great science that is being missed out on and it's just the budget is it is what it is. It's getting more and more competitive now to get funding. Sorry, the foundations like Alex's Lemonade Stand have made a huge impact on what I'm able to do. The grants that they get for young investigators really propelled them to be able to do the kind of creative translational research and then they have an A award that propels you from a postdoctoral position to faculty as assistant professor. They're really trying to build the next generation of cancer researchers.

Quinn: I wish there was a way to almost make some publicly available/searchable list. Almost like, I mean, I hate to use this as an example because it can go wrong so easily but a Reddit almost uploading systems, like all the projects and research that don't get funded that, like you said, so much good science is not happening. To put those out there so people see like, "This is why you need to get your representatives to vote for more funding." Because these are, quite literally, these specific things that are not happening because of that.

Genevieve K.: Exactly.

Quinn: Brian, can you put that on your list?

Brian: Absolutely. I want to go to dollar, too. What can everybody do to support you with our money?

Quinn: If only there was a foundation that you guys haven't mentioned where people could send their money to express their support system for once. [crosstalk 00:52:55]

Genevieve K.: Sure. Jackie, do you want to take this?

Jaclyn Taroni: Yeah. Alex's Lemonade Stand Foundation. Bam.

Quinn: What's the URL for Alex's Lemonade Stand foundation?

Jaclyn Taroni: alexslemonade.org.

Quinn: Beautiful. This is the moment where I'm going to pimp LA Loves Alex's Lemonade Stand Foundation. Have either of you come to that event yet?

Brian: Incredible.

Genevieve K.: Yes, it's amazing.

Jaclyn Taroni: Yes, it was great.

Quinn: Are you coming this year?

Genevieve K.: I don't think so. I'm disappointed.

Jaclyn Taroni: I'm not, yeah.

Brian: Whoa. They're busy.

Quinn: Where are you girls got going on? I know but it's a fun time.

Genevieve K.: It is, I would love to.

Quinn: It is fantastic. It is one of our favorite things. Brian, when did I [crosstalk 00:53:48] into this? Last year or two years ago? It is such a impactful moving event for everyone. What is it, Brian? September 14th this year?

Brian: Yep.

Quinn: Is that right? September 14th, Los Angeles. It's at UCLA. Regular tickets are 100 bucks or something like that. You get unlimited food handed to you by 100 of the greatest chefs in America/the world. There's 20 incredible mixologists, there's a wine area. Then there's also Jay and Liz and their children, their sons up there talking and other very small cancer patients and survivors up there talking. You're drunk and crying and just throwing money at this incredible organization. It's sunny and it's beautiful and everyone is having just the greatest time for such an incredible event. I can't recommend enough.

Quinn: So if you've never come, please check it out. It's called LA Loves Alex's Lemonade Stand. The past few years, they've raised a million dollars on the day each day for efforts like this to fund CCDL and other research. They also support travel funds for families that can't afford it because it is an unexpected life expense and it's really fucking expensive and the whole family's affected and someone's got to help out with that and they do. Please check it out. It's pretty fantastic.

Brian: We'll be there. Important, Not Important will be there.

Quinn: We will definitely be there. If you come, we will find you. Not like a bad word but like an excited "We'll take it together," way.

Genevieve K.: Is that an ominous?

Quinn: No, no, no.

Brian: We just want to eat food with you and drink drinks with you and cry with you. That's all.

Quinn: And thank you for what you're doing. A lot of crying. A lot of crying. Brian, take us home. Ladies.

Brian: Seriously, thank you so much for being here. This has been so fantastic. I can't wait to see what else comes out of the CCDL as it grows. Can't believe it's only been a year or not even a year yet?

Genevieve K.: August 1st 20017, I believe.

Quinn: What year is it now? [crosstalk 00:55:49] It's almost two years old.

Genevieve K.: It's almost two years old, yeah.

Quinn: We're going to have a birthday party.

Brian: There will be a time when we email you after this conversation to say, "Who else should we talk to? Do you know anybody else that is trying to change the world and solve kids cancer or cure ..."

Quinn: Anything.

Brian: I mean, anything, just all of the things.

Quinn: People who inspire you.

Brian: Yeah. If there are people that to come to mind, please pass them along. That's how we get some of our absolute best guests on the show. Now it's time for our Not a Lightning Round.

Quinn: Not a Lightning Round. It's just a couple more emotional questions and then we'll let you guys get out of here. To both of you, to each of you, when was the first time in your life when you realized you had the power of change or the power to do something meaningful?

Jaclyn Taroni: Yeah. I think it went back to ... What year was the Young Investigators Summit in LA, Genevieve? Do you remember?

Genevieve K.: Oh, gosh. I think it was '16 or '17.

Jaclyn Taroni: '17? Yeah, just like meeting all of these investigators who are about the same career stage as me because I was a postdoc at the University of Pennsylvania at the time. Just meeting all these childhood cancer researchers and their passion for their research was just like infectious. Understanding that this initiative was getting underway and being part of this exciting science, helping these folks like do what they're so passionate about and what answer really important questions.

Jaclyn Taroni: That YI summit, that's where I met Genevieve, for the record, too. It was really wonderful. I think it was such a great introduction to the foundation and it's why I'm just working with these scientists who are so talented, so passionate and I was like, "I can help them, I can be part of this."

Quinn: Awesome.

Genevieve K.: I'm trying to think of a specific instance. Like I said, my biology teacher was really influential on me in high school, and I was always gravitated towards an incredibly challenging problems like childhood cancer because I feel like I can make a big impact in the area. I think this manifested early because this is really random but on our senior year in high school, we had to give each other awards. This person I barely knew gave me an award that she had self-named, that I was the most determined person. I think it's true. I'm very determined. I think I just have been manifesting that for a while unintentionally but I am very focused and I do think I can make a big impact by staying the course.

Quinn: That's awesome.

Brian: Since we're talking about it, my senior awards were most hair color changes and craziest.

Quinn: Thank you, Brian. That's so helpful.

Brian: Well, we were on the topic.

Quinn: Yeah, yeah, yeah. People whose name starts with Doctor, let's limit this one to that.

Brian: Got it.

Quinn: Who is someone in your life that's positively impacted your work in the past six months?

Genevieve K.: Well, that's easy for me. My postdoctoral mentor is James Amatruda and I highly recommend you speak with him as well. He's the most intelligent, kind person that you'll ever meet. He's been just completely instrumental and letting me have freedom of thought and be independent. Now, I'll be starting my own lab in the next six months, so he's an incredibly inspiring person.

Quinn: Awesome.

Jaclyn Taroni: You should absolutely talk to him. He's great. It was so rad having him for training. I would say the director of the CCDL is Dr. Casey Greene. I was a postdoc of his before I got started here at the CCDL full-time. His vision for the lab and shaping it and assembling this team of designers and developers and scientists, it's been incredible to watch and to be a part of.

Quinn: I love it.

Brian: Awesome. Ladies, what do you do when you feel overwhelmed? When it's all too much and you need deal and relax?

Genevieve K.: Sure. So I recently joined this women's only gym and they do fitness classes there. I have one this morning, actually. That's a good way to burn off some energy really.

Quinn: What's your class of choice? Is it like Zumba, Pilates, what are we talking about?

Genevieve K.: No, it's called ... It's actually designed for athletes who do rowing, run wind sprints, a lot of lifting. I do the whole spectrum. It's been fun. You have to challenge different parts of your brain and so the other thing I do is take naps sometimes.

Jaclyn Taroni: Nice.

Genevieve K.: I love to go outside and hike, too.

Quinn: I love that. I've been trying to get Brian to do ... What's the word Brian? Cardio? Cardio?

Brian: No. Get out of here.

Quinn: Its new to him but we're working on it. We're working on it.

Brian: He tries to get me to do these Spartan races where, I don't know, you're running for days and you're in mud and you're climbing walls. Let me run on the treadmill.

Jaclyn Taroni: Is this consistent with Jay's comments about Quinn and ...

Quinn: That's unfortunate. I did not know what he told you. I've got some fun plans for him for this year. It's going to be great.

Jaclyn Taroni: I won't tell.

Quinn: Yeah. Please.

Jaclyn Taroni: I think my answer to that question proves why Genevieve was most determined and I was not as a senior in high school. But yeah, I have been very much enjoying Red Dead Redemption Two.

Quinn: Oh, that's so good.

Jaclyn Taroni: Yeah. That's been really past couple months, it's been great to kind of escape to that.

Brian: Can you do that in VR yet? Is that a thing?

Jaclyn Taroni: I have no idea.

Brian: I just want to be in that world.

Jaclyn Taroni: It's beautiful. There's horse ...

Brian: Yeah.

Quinn: My buddy, friend of the pod, Seth, one of his good friends voices the main character and has said he basically can't go out in public because the game is ... I mean, so many people play that game and not just played the game, we're not talking about Mario Brothers. They've spent hundreds of hours.

Jaclyn Taroni: It's so many hours. So many hours.

Quinn: So when he opens his mouth, people are like, "Holy shit." Blows movie stars out of the water.

Genevieve K.: I feel so ignorant because I did just have to Google what that was. So I'm a little embarrassed by that.

Brian: No, it's okay.

Jaclyn Taroni: It's okay.

Quinn: It's okay. It's okay. It's pretty fantastic, though. I was just like, "God, that's such a weird thing." Anyway, it's a great game.

Jaclyn Taroni: Such a good game.

Quinn: Okay, Brian.

Brian: Great game. Here we go. If you could each answer this question for me, please. If you could Amazon Prime one book to current President of America, Donald Trump, what would that book be?

Quinn: We've had everything.

Jaclyn Taroni: Nonviolent Communication is what popped into my head.

Genevieve K.: I want to go with Alex and the Amazing Lemonade Stand just to show how one person can make a positive change on this world.

Quinn: That's awesome. Both of those are fantastic. We've had everything from the constitution to coloring books.

Brian: Just everything.

Quinn: Awesome. Well, listen, this has been long enough. There's all kinds of cancer that hasn't been cured since we've taken an hour plus of your time. So we're going to let you guys get back to it. We cannot thank you enough for your time today and for everything you're doing with each other in your own endeavors and what's to come because I know you're just getting started. No pressure. So thank you and I hope to see you at an Alex's event this year or next year somewhere. And when you get that lab started, put in a couch because Brian will come sleep on it.

Brian: No, I'll do the sign spinning thing. [crosstalk 01:04:59]

Genevieve K.: You're welcome. You're welcome to come join.

Quinn: It'll be great. He'll do any job. Thank you guys so much. We really appreciate it. We'll check in down the line and see how everything's going.

Genevieve K.: Thank you. Super pleasure.

Jaclyn Taroni: Thank you for having us.

Quinn: Thanks to our incredible guest today and thanks to all of you for tuning in. We hope this episode has made your commute or awesome workout or dishwashing or fucking dog walking late at night that much more pleasant. As a reminder, please subscribe to our free email newsletter at importantnotimportant.com. It is all the news most vital to our survival as a species.

Brian: You can follow us all over the internet. You can find us on Twitter @importantnotimp.

Quinn: It's just it's so weird.

Brian: Also on Facebook and Instagram @importantnotimportant. Pinterest and Tumblr, the same thing. So check us out, follow us, share us, like us, you know the deal. And please subscribe to our show wherever you listen to things like this. If you're really fucking awesome, rate us on Apple podcast. Keep the lights on. Thanks.

Quinn: Please.

Brian: And you can find the show notes from today right in your little podcast player and at our website, importantnotimportant.com.

Quinn: Thanks to the very awesome Tim Blaine for our jam and music, to all of you for listening. And finally, most importantly, to our moms for making us. Have a great day.

Brian: Thanks, guys.