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E4: Who is the Honey Badger?

Kenneth L. Scott was a cancer genomics researcher for CCG’s Cancer Target Discovery and Development (CTD2) Network and a professor at Baylor College of Medicine. Also, he wanted to be a honey badger. Colleagues and friends discuss Ken’s grand vision for precision oncology, his experience with rare cancer, and his unique relationship with the honey badger.

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Additional Information

Interviewed on this episode are Tim Heffernan, Caitlin Grzeskowiak, Samuel Tsang, Ben Deneen, Gordon Mills, and Laurel Scott.

Cello Suite No.6 in D major (BWV 1012) by Johann Sebastian Bach is performed by Pierre Fournier. Other music on this episode is by Loyalty Freak Music and Komiku.

Pictures of Ken Scott shared by friends and family.

Ken Scott prior to his sarcoma diagnosis.

Credit: Laurel Scott and Benjamin Deneen

Tim Heffernan and Ken Scott have drinks before Ken's first round of chemotherapy.

Credit: Tim Heffernan

Ken Scott with lab members Caitlin Grzeskowiak and Samuel Tsang prior to starting chemotherapy.

Credit: Samuel Tsang

Ken Scott with his physical therapist after his hemipelvicotomy.

Credit: Tim Heffernan

Episode Transcript

SONG: ["Cello Suite No. 6 in D Major, BWV 1012"]

PEGGY WANG: In 2011, there was a video. Juxtaposed against joyful and triumphant classical music is a small animal, about the size of a raccoon, running around, digging, being rather aggressive towards birds and jackals. It quickly becomes clear that this animal will attack and eat just about anything in its path. Mice. Bees. A snake thinks it can hide in a tree. Nope.  At one point, the animal picks a fight with a cobra snake and gets bitten, and passes out. You think okay it's dead. But moments later, it just wakes up and starts sleepily eating the cobra. And this animal if you don't know, is known as the honey badger.

SONG: ["Friend to Friend"]

PEGGY: I'm Peggy Wang, and this is Personal Genomics, a podcast from CCG, the Center for Cancer Genomics at the National Cancer Institute.

Someone who really loved that viral honey badger video, and honey badgers in general, was Kenneth L. Scott, a professor at Baylor College of Medicine and a cancer genomics researcher for CCG's Cancer Target Discovery and Development program. In fact, many of Ken's colleagues and friends have come to think of him as a honey badger. On today's episode, we try to figure out how that came to be.

TIM HEFFERNAN: Ken was the most spontaneous person, you know I've ever met.

PEGGY: This is cancer researcher Tim Heffernan.

TIM: I am a dear friend of Ken Scott's. We first met each other in 2005.

PEGGY: Tim was interviewing to join a lab at the Dana Farber Cancer Institute in Boston, where Ken was already a postdoc.

TIM: Ken was instrumental in my recruitment to the lab, he was the one who hosted my visit. When you're recruiting for a post-doctoral fellowship, you're always asked the same question, you know, what is your interest in this lab. But Ken was uh was very spontaneous. And we started lunch with him asking me um why wouldn't I join this lab. It really made me think, you know, why wouldn't I choose this lab. It had tremendous opportunity, a fantastic mentor. That was his way, he really challenged you to think differently.

PEGGY: And Tim and Ken really got to know each other over that first lunch together finding out that they were…

TIM: Very much similar people, maybe different different physiques, you know, Ken's a big dude, he was like head and shoulders taller than me. But uh, we were very much aligned with our scientific thinking. And then also on a personal level, sports and family and then comparing and contrasting our lives growing up. Me being originally from Boston, and him being from Texas.

That lunch was important, it was it was over two hours long, and he got up and paid that bill and started dancing right there in the middle of the restaurant, and it was as if he had his own personal dance floor.

PEGGY: What kind of dance did he do?

TIM: He just wanted to prove that he had rhythm, he didn't prove that he could break dance till several months later. That was the spontaneous nature of Ken Scott that you know, nobody can tell him that he can't dance in a restaurant, right?

PEGGY: For many researchers, being a postdoc lasts several intense years.

TIM: You know there's obviously the science, there's obviously the mentor, but it's also the people. I was looking for an opportunity to work with people that that I could certainly get along with and interact with and share this experience over several years. And meeting Ken that day you know really put things at ease. I knew leaving you know the lab that day that that I was gonna work in that lab and Ken and I would be, would be really good friends.

SONG: ["The road we use to travel when we were kids"]

PEGGY: Tim and Ken spent a lot of time together over the next few years.

TIM: Ken and I, we sat back to back and we were both in the lab early in the morning. Ken was always there first and he got to choose the music. So you would have everything from heavy metal to rap to pop to teen pop. He had a pretty eclectic musical taste. We were very serious with respect to our science, but you know we worked hard we played hard.

In that particular room of the laboratory, it was four of us and uh Ken was able to convince some of our technical staff that we had a uh, boy band. And Dana Farber is located on Binney Street in Boston. And so we called this band, “The Binney Street Boys”. When we were asked to prove it he would break out into song and uh and really start dancing and amazingly I think people actually believed us. You know, we almost believed we had a boy band.

PEGGY: So did you join in and do some a capella?

TIM: Oh you didn't have a choice. When Ken said all right here we go, you had to join in that was just the way that it worked.

Very early on Ken had this vision of functionalizing the cancer genome.

SONG: ["Traveling in your Mind"]

PEGGY: “Functionalize,” a term Ken liked to use—meaning to…

TIM: Wade through the hundreds to thousands of genes mutated or deregulated in a particular cancer, identify the specific set of genes that we call drivers…

PEGGY: And once you've figured out the key changes, work out…

TIM: What the mechanism was, how they were contributing to cancer pathogenesis.

PEGGY: It's worth taking a moment to appreciate that today, this type of functional work is prevalent, enabled by sequencing and other modern technologies. But Tim and Ken were having these brainstorms in 2005.

TIM: This was rare at the time. We were using very low-resolution technologies, looking for amplifications and deletions and these would be large sections of chromosomal arms.

PEGGY: Meaning, each data point would tell you about not a single gene but…

TIM: 200, 300 genes. You know we needed to think more creatively on how to functionalize that data to identify which of those genes is contributing.

PEGGY: As a postdoc, Ken started to develop high-throughput platforms for screening cancer genes.

TIM: He was a technical wizard. He would draw it out on a whiteboard and in a matter of weeks he would have the prototype system up and running. When I talk about the technologies that he was thinking about building, this was not about what he needed. It was about what the field needed. He had an incredible ability to understand and appreciate the gaps and the challenges and then strategically develop technologies that would address those challenges.

PEGGY: Eventually, Ken moved to Texas to work at Baylor College of Medicine, where he started his own lab.

CAITLIN GRZESKOWIAK: My name is Caitlin Grzeskowiak. I was Ken's graduate student. The first time I met Ken was during my graduate school interview. I walked into his office and he was leaning back in his chair with his cowboy boots like on his desk. He had a collection. He called them postdoc skin boots.

SAMUEL TSANG: On the Skype interview, I put a very formal, nice picture of myself of course.

PEGGY: But Ken's profile picture, he was…

SAM: Riding a motorbike and then they have some like a cloth wrapping their head. And then he also make a funny face in his profile pictures, too.

PEGGY: This is Sam Tsang, he was a postdoc in Ken's lab.

SAM: When I moved here at the first few weeks I stayed in the hotel and I knew nothing about this country. And he was very nice to drive me around Houston to show me around. He helped me to find an apartment and also set up the electricity. Basically, the first day I saw him he already took me around to do all these things so at the end of the day I had my apartment secure and also I got a mattress.

PEGGY: Like a full-package welcome.

SAM: Yea.

CAITLIN: When I talked to him in my interview, he basically just told me about this woman, she was doing this really cool like epigenetic study. And so he really convinced me to join this other lab. And then she left Baylor and so I needed to find where else to go. And he was like you're welcome to come back and join.

SAM: Ken sometimes still joke about like how she refuse to join the lab and she crawled back later on.

CAITLIN: He was really um very fun-loving, had a good sense of humor.

PEGGY: So what was it like to be in Ken's lab?

SAM: He likes to work in the lab occasionally and then turn on the radio really, really loud. I think the entire floor can hear the music. I didn't know much about American music at that time, from what I heard from others those are not music that anyone else would appreciate.

CAITLIN: He was pretty into the honey badger. It was definitely a funny, inside joke for the lab. He actually had a stuffed honey badger. You could press the paw and it would basically like throw insults at you.

SAM: I think it just appeared out of nowhere one day.

CAITLIN: Like Sam brought him a western blot and he looked at it and he didn't like it, and he pressed the little button, I didn't even know it talked, but then, all of a sudden I heard this expletive coming out of this stuffed animal.

SAM: One of the reason why people like to talk to him is because he is very happy all the time. Just being around him can make you happy.

CAITLIN: He was really kind of a doors always open kind of person and he really meant that and you knew it.

SAM: In Ken's lab we do genetic screens.

SONG: ["Traveling in your mind"]

SAM: And we study a large number of gene mutations and fusion genes and we are very good at making these in large numbers so that we can study them systematically.

PEGGY: They developed a technology that served as a foundation for these screens…

SAM: Called HiTMMoB. It stands for high-throughput mutagenesis and molecular barcoding.

CAITLIN: The lab was really focused on developing the technology that made it possible to participate in all of these different research projects. That allowed us to investigate metastasis, tumor initiation, primary tumor growth and development. A variety of projects.

PEGGY: One thing Ken emphasized to his lab mentees, was…

CAITLIN: How you effectively develop collaborations, how you can help others with their work, and in turn help you with yours and have that amplifying effect.

SAM: See how can we can do more things together. This is very beneficial for the research environment that we have the resources to share.

CAITLIN: Having that strategy and vision of seeing how you can be helpful with others’ research will also help elevate you as a scientist.

PEGGY: One of those collaborations was with Benjamin Deneen.

BENJAMIN DENEEN: You know, he was doing these hardcore Ironman competitions, did you know that? He had the whole family life, a high profile, high operating lab, and then he was taking the time to wake up at 3 a.m. to go swim a mile, and then bike 50 miles. I don't know when the man slept or how he slept or what.

So my name is Benjamin Deneen. I am a professor at the Baylor College of Medicine. I was one of the few people at Baylor that studied brain development and brain cancer. We sort of had this instant connection, this instant chemistry between us.

PEGGY: Ben and Ken met at a monthly pediatric cancer meeting at Baylor, and that…

BEN: Led to us having coffee, having lunch, and just brainstorming random, crazy ideas. Those conversations were some of the best conversations I've had scientifically because I learned so much from him.

What really kick-started our collaboration was the state of Texas has these calls for grants every year. He and I decided just to throw one in there just to see what would happen. It was just these crazy ideas where we were going to take functional genomics and do it in the developing brain.

PEGGY: They were going to study glioblastoma, but…

BEN: Not in a dish but in an actual developing mouse brain.

PEGGY: Even now, genetic screens most often take place in cell lines, cells that grow in a dish and are easier and faster to handle. But Ben and Ken decided to combine their technologies and do it in an animal model—mice.

BEN: And somehow we got it.

SONG: ["Traveling in your mind"]

BEN: And it speaks to Ken's brilliance really because he's the one who had all the concepts. .I was actually very hesitant to do this because I didn't think that it was really gonna be all that interesting. I was like well we're gonna screen variants and what are we gonna find? If we find a new driver, so what? And I have to concede he dragged me kicking and screaming into this project.

PEGGY: Another collaborator on board with the Ken's ideas, but more enthusiastically, was Gordon Mills.

GORDON MILLS: I think to a degree I've ended up in many cases being the cheerleader, saying okay let's keep pushing. If it didn't work, let's go back and find a way to make it work.

I'm Gordon Mills. When I met Ken Scott, I was the chair of systems biology at the MD Anderson Cancer Center. It only took a few minutes to realize that this was a very special young scientist. He walked in and there was a clear presence. I would say that I probably learned as much or more from him than he did from me in terms of science.

One of the challenges that we have today in precision oncology is trying to understand the functional consequences of the mutations that we see in patients’ cancers. The community has sequenced now tens of thousands of cancers and have identified over three million different mutations and genomic aberrations in those patients.

PEGGY: A lot of important work has been done in sequencing the tumors of patients, essentially creating long lists of gene alterations. But functionalizing a list—whittling it down to the drivers and figuring out how exactly they contribute to cancer, is difficult and time consuming. And Ken wanted to create ways to do this quickly and systematically.

GORDON: If you're going to characterize a large number of genomic aberrations, you need a way to make them at scale and…

SONG: ["Traveling in your Mind"]

GORDON: Using an absolutely wonderful technological platform that he had built—he called it HiTMMoB—we characterized over a thousand different mutations and fusion genes in terms of whether they altered the mechanisms by which cells grew, survived therapeutic stress, and frankly, from that more than doubled the characterization of what was available in the world at the time. So Ken contributed massively to understanding what we would do for an individual patient.

PEGGY: Here's Ken's friend Tim again.

TIM: He actually did an experiment where he generated all of the mutations identified in a single patient's tumor.

PEGGY: Functionalization work can sometimes take years. Ken wanted to condense that and show that it is possible to identify unique mutations for a single patient in a short amount of time. And those unique mutations were potential drug targets specific for that patient. 

TIM: And so his vision evolved to truly patient-centric: could he develop a system that would enable new identification of mechanisms that were driving a specific patient's tumor, and is there a way to rapidly translate that data into a new more effective therapeutic?

CAITLIN: That that was really at the forefront of what he thought was possible, that we could actually identify in real time any kind of genetic aberration and put them into either basket clinical trials or really be able to focus in on how their specific mutations or aberrations are affecting their treatment outcomes.

TIM: We were at my house and we were watching the Super Bowl. Ken and his wife Laurel and his kids had come over. And he had mentioned that his hip was bothering him. And my wife who's a physical therapist, he asked if she could do some activity tests and she thought that you know it could just be tendinitis or something associated with him participating in a triathlon. She had suggested that maybe he goes in and gets this tested out by a specialist.

CAITLIN: I remember getting an email from him. I don't remember what the subject line was but it was just one word, basically telling us he had some news to share.

SAM:  I thought it was something like he bought a very expensive machine for the lab and we need to think hard on how to use it. So we all went to the meeting room the next day.

CAITLIN: We heard somebody get off the elevator and coming in crutches. I thought at that point he just like maybe injured himself because he was training for, I don't know, maybe his like third Ironman or something. And um he came in in his crutches and he just said, guys I have bone cancer. And that was how we found out.

SONG: ["Beach”]

CAITLIN: I think it was really just shocking so once he told us, I mean a lot of people were crying and it was mostly like, do you guys have questions.

SAM: We were all very surprised because he looked so healthy and he's big and he is in really, really good shape.

CAITLIN: He was very young.

SAM: We didn't know what to expect, and he told us he is going to get more medical exams, figure out what’s the treatment plan. He also told us our job is secure so we wouldn't need to find another lab right away, things like that.

CAITLIN: I just kind of went and took a walk and thought about mostly his family, I mean he has two kids and also nobody really knew if he was gonna be able to continue working or it was kind of all up in the air.

PEGGY: This is Ben, who was working on the brain cancer project with Ken.

BEN: We got the grant, got funded, and then we were off and running. About three months after, there was a major storm in Houston. My house completely flooded out. I was feeling bad for myself and then like a week later, he calls me. He's like dude I got diagnosed with cancer. And I was like holy, what else can happen? It was just a really bad week.

PEGGY: Soon after his diagnosis, Ken started chemotherapy.

TIM: He called me up and said, hey I have an hour before I start this, do you wanna have a drink? He was drinking scotch, I had one scotch and a beer. This was very early on. You know he sort of opened up about what he was thinking about this disease, and the course of treatments and just really wanted to express that he was gonna fight this as hard as he possibly could. He never felt sorry for himself, or he never expressed it. He just wanted to talk about what he was gonna do. You know this is my goal, this is my challenge. And we toasted to that. And uh I think the shock had worn off and it was now you know, game time.

SONG: ["Enby"]

TIM: Let's do this. Let's have a drink. I'm going, i'm going upstairs. And so it was really the battle that he was about to, about to start.

CAITLIN: Once he got diagnosed and he had in his mindset, how do I beat this, it was like nothing's gonna stop me. Like he plowed through everything. And always asking for like what's the most I can do. What's the most intense treatment you can throw at me, I'm gonna do it.

His whole family, too, had these little bracelets made that were like "honey badger spits out sarcoma." On that version that's what it says [laughs]. And it was all in that spirit of like, this is nothing to a honey badger.

BEN: His productivity actually increased during that time because [sigh] he couldn't do the triathlon stuff anymore, as much. He just diverted all that energy back into his lab and into his family.

SAM: Did you know Ken, like while he was sick, he still got a couple of grant including an R01?

BEN: He said that that you wrote his best R01 on chemo brain because he was relaxed and didn't care [laughs].

CAITLIN: He was holding meetings in his hospital room. He really wanted everything to just continue on normally and was always answering emails and responding to things the way that he could.

He called me when he was having his biopsy done and he said, Caitlin I have a favor. He was like I need to drop off my tumor and I was like what a weird phone call to get.

TIM: I remember him calling me and saying I'm on the interventional radiology table and I just asked the doc to take another pass of my tumor so I can take a chunk of this tumor into my lab. Isn't that honey badger? And of course it was.

CAITLIN: He delivered it to the lab and we put it in our freezer until he knew exactly what he wanted to do with it. I remember I labeled it, I just wrote “Ken's tumor” and the date.

TIM: His first discussion with his doctor, it was made very clear to him that you know this this disease doesn't have a standard of care. You know there has not been enough patients to run a trial so they were essentially going to use a particular chemotherapy that anecdotally had shown responses in some patients.

As scientists, particularly cancer scientists, we know a lot about this disease, so we ask very different questions. And so Ken immediately started asking questions about why I have cancer.

SONG: ["Ambiant hope"]

TIM: You know, I want to sequence this tumor, I want to establish an animal model, I want to establish a cell line.

PEGGY: Ken started to study his own cancer, and Gordon and Tim joined the effort.

TIM: Ken had so many friends and colleagues and when the news broke around the medical center here in Houston, you know everybody was involved. This was personal for us.

GORDON: I gladly put my efforts into characterizing this. A much broader community stepped in and said, I have ideas, I have concepts. Can you send me a little bit of tissue, can you make a mouse or a cell line. We extensively characterized that sarcoma. We set up a collaboration with multiple people around the world to look at ideas that we could do. Major leaders stepped up and said I'm going to do this. Without question. But it didn't help.

TIM: He had a very rare mutation um that activated a number of pathways that Ken had defined.

GORDON: We didn't have any really exciting targeted therapy or immunotherapy that we could move forward to help Ken.

PEGGY: With the help of colleagues and friends, cutting-edge scientists in the field, Ken identified the mutated gene responsible for his sarcoma. However, there was no known drug for his disease.

SONG: ["Beach"]

GORDON: It is extremely hard when you realize that despite all of the work we've done, all that we have learned, all of the effort that we have put into this, so much of the time we don't succeed.

TIM: We didn't have the therapeutic specifically for him, and it was ironic. Unfortunately, um you know we failed him and that was I think the most heartbreaking in a sense.

PEGGY: What is it like, to figure out exactly what is going wrong with your body, but not be able to do anything about it?

TIM: He underwent 24 cycles of diverse chemotherapies, but he never lost you know his passion, he always wanted to learn more.

CAITLIN: Ken was very open about what was going on. I mean he's very transparent with us about how his disease was progressing. Every time he got an update from his oncologist he would let us know, so we were always informed.

TIM: He was always positive. The eternal optimist. And he knew this was just, you know a bump in the road. This was a challenge that he was going to have to face but he was going to make the best of it.

CAITLIN: He had still had a positive outlook about even getting an infection in the hospital after his surgery.

PEGGY: Ken had a hemipelvicotomy—where part of his pelvis was removed. This is a tough surgery, with a long recovery and rehabilitation process.

CAITLIN: He told us about these studies that he was reading from like the 1800’s about how some folks who had infections after their surgeries, their tumors went away because they had these immune reactions and he was thinking about, oh there might be hope for me because I'm having this crazy fever. He was just really optimistic, had a lot of hope.

SAM: There was a chance that he could have the entire leg removed with the pelvis, but he got to keep it at the end so he was happy. He actually showed us some videos, like a guy with a similar situation did training and then could go back to a certain level of physical activity so he was pretty optimistic about it. With his positive energy around like the room, I was like, totally believed that he would be fully recovered from it.

TIM: I visited him in his recovery room. And coming back to the honey badger, he said, I’m gonna get up and I'm gonna walk again. Now this was a this was a serious surgery. That was the time where I told him that you know, he should take it easy and let himself rehab and get better. But uh every day that he spent in that hospital was another day that he wasn't going to be at home with his wife and kids or it was another day that he wasn't going to be in his office talking about the next experiment. And so he knew that he had to get out of it. But that was a major surgery, and those discussions were hard.

GORDON: It is very hard to visit an individual who was as robust and strong as Ken when he is struggling with a disease that is really, really difficult. Often the patient has a far better way of dealing with this than the people visiting him. We want to let the patient teach us what is important, and indeed, Ken was just an outstanding example of someone who was not going to let the challenges that he was undergoing affect his interaction with people.

He wanted to talk about science, he wanted to talk about the future, he wanted to talk about what we could accomplish. He did not want to focus on Ken. This gave him a reason to deal with the pain, the problems, and to fight as hard as he did.

PEGGY: Ken learned to get himself around on crutches soon after the surgery.

TIM: He was up, out of bed, assisted, but he was you know walking around the hospital floor.

CAITLIN: Yeah and not even that long afterwards. I would say like his progress was really accelerated from what I remember.

PEGGY: He went back to work. And a couple of months later, he had his first scan.

BEN: I think it was like maybe two or three months later because he had to go off of chemo after the surgery because you can't recover from that surgery and have to be on chemo, that's just too much for the body to take. And so we got off surgery, the tumor came back, and we kind of knew that this was going to be the end.

SONG: [“Sunset on the Beach”]

TIM: This was uh obviously a disappointing discussion, but uh he was very clear. There would be no additional treatments and uh he would enter hospice care. It was hard on him because again, he was the ultimate competitor. He was somebody who would accept any challenge and this was the ultimate challenge. This was the life challenge.

GORDON: It became clear not very long afterwards, while the therapy gained time it really was not going to be curative. Ken at that point never, ever said a negative thing, never was down, still came to meetings even if he had to come in and not feel well or need support from a cane.

SAM: After the surgery he was on crutches. I remember the meeting that was supposed to be me and him and some other collaborators. And we all knew he was pretty sick at that point but he was still in the meeting. But he had to leave in the middle because he was too sick. Some of us walked with him to the parking lot to his car. I'm sure he was feeling horrible but he was still trying to come back.

PEGGY: Did you guys like try to tell him to try to take it easy? Like was it hard to try to tell him to rest?

SAM: I personally didn't tell him that because I think he actually planned everything very well for himself, for us, and also for the family. All the other times I think he handled it like pretty well. He always try to work against his body condition. Most of the time he succeed. Of course, I wanted him to stay at home and just relax but he just tried to do a better job for us I think.

CAITLIN: He always kind of thought about everything like two moves ahead and he always knew how strategically to manage his own time. I don't think he had a hard time figuring out where to put his efforts. I don't think he had a difficulty with that.

GORDON: He did an incredible amount during that period to make sure that everyone in his laboratory had a career plan, career options. Just an incredible effort and planning for a future that he knew he wasn't going to be part of.

BEN: it speaks to his humility. He was genuinely worried about this. He and I had several conversations where he was like freaking out, not about himself but about the career paths of students and technicians and postdocs. He really made sure his people were taken care of.

CAITLIN: He had said this to us actually. He was like, I'm just really sad that I won't get to see how your careers develop because I’ve, you know, I have such great people in this lab. That was the hardest part for him. Was like we were all gonna go off and do things and you know he wasn't gonna get to see where we all landed and I think that was difficult for him.

PEGGY: In early November of 2017, Tim received a call from Ken's wife, Laurel.

TIM: His you know final weeks, final days, Ken was was suffering from a lot of uh you know, the treatments that had taken their toll on Ken. He was put on palliative care and Laurel was, you know she's a physician. She was taking care of him from a personal level as his wife and with an incredible amount of faith and love but also as a trained physician and really making sure that he was certainly taken care of, and he was pain-free and comfortable and that to me is really special.

 I did get to say bye to Ken for the final time, and we embraced, uh it was quite emotional. But I knew even when I was leaving that room that Laurel was gonna be by his side and taking care of him up until the last minute and that's exactly what happened.

PEGGY: Caitlin received a call from Sharon Plon, who had taken over as her mentor.

CAITLIN: Um, he passed away on November 9th and I got a call from Sharon. And she told me. She called me because my defense was actually the next day.

PEGGY: The next day was Caitlin’s thesis defense: her oral final exam for her PhD.

CAITLIN: And she wanted to make sure I could still defend.

PEGGY: Did you defend the next day?

CAITLIN: I did. And um they made the announcement at that point too about his passing.

SONG: ["You yourself and the main character"]

CAITLIN: I think the department sent out a notice, um so my thesis defense was packed with people. It was really nice.

PEGGY: Oh wow.

CAITLIN: You know it was funny because like I had gone to other defenses and I was like people get so emotional I'm not gonna cry. But it was, it was challenging.

PEGGY: So did any of the committee members grill you?

CAITLIN: [laughs] I know, right. I was actually grilled on a couple of things and I appreciated it at the time because it kind of helped you know transition everything in from like a emotional point to like oh we have to get back to business. His wife was planning to be there. She wasn't able to come because of the funeral arrangements but they set up a live stream for her. I think that was like important to her to kind of see that through for him.

PEGGY: Ken was 43 years old.

SAM: He was such a good person, good mentor and good researcher, and he was so young when he died, so I felt like he would have way more contributions to research if he could have lived. That’s my frustration.

CAITLIN: It all would have been so different if things had gone the other way but to me it's like his story, I think is like cut short in a way. I feel like he was just getting started.

PEGGY: When Ken got his first scan after the surgery, he knew he had to start preparing for the end of his life. What is it like to close out your lab, when you're just starting out?

SAM: So Ken makes the plan, like I said he's a very good planner. He basically just share everything out.

PEGGY: Ken arranged for another PI to take over his lab space along with one of his grants.

SAM: For two labs to merge, we need to allocate a space for the equipments that they have.

CAITLIN: What actually kind of transitioned in that way of like we needed the same reagents and materials and lab notebooks to be there.

PEGGY: Ken made sure there was funding for his trainees to stay in the lab with the new PI until they decided on their next moves.

SAM: I stay a little bit longer after they moved in and worked with the new people.

CAITLIN: There was a period in between where I needed to wrap up some experiments before I started my postdoc.

PEGGY: And then there was the lab's gene library. A valuable resource Ken's lab had assembled and used as a building block for many of their screens. Ken wanted to make sure it would be well-cared for and utilized in its next home.

SAM: We built it in the lab. It's like 35,000 bacterial stocks, so it's a huge library that needs freezer space and also a lot of database informations.

PEGGY: Ken found another lab to care for the library and manage its sharing. 

SAM: Ken wants to give it to Baylor as a resources so everyone can use them. We also need to teach the receiving lab how to handle it.

CAITLIN: He also um helped his research technicians move over to into the lab that took over.

SAM: Also connect us to collaborators and labs to make sure we all have a place to go

CAITLIN: He prepared letters of recommendation for all of us in the lab and kind of put his situation in there and said, this is my kind of letter and perpetuity of recommendation.

PEGGY: Sam moved to Gordon’s lab.

SAM: I'm really glad that Ken connect me with Gordon.

SONG: ["Ambiant hope"]

SAM: My goal is to learn more about proteomics and find a way to combine the genetic technologies from Ken's lab with the proteomics. I am working on developing a time-lapse imaging system. We can do a drug screen on the patient samples, then we can tell whether the patient cell is sensitive to the drug or resistant to the drug. By combining these two then we will have a better understanding of the cancer biology and find a better way to predict the drug response.

PEGGY: Caitlin went on to her postdoc, but afterwards…

CAITLIN: I made the decision to move from my postdoc to a role that works on policy, in large part I think inspired by Ken's struggle. You can find your mutation or your driver behind your cancer, and you can find a drug.

PEGGY: But even if you're lucky enough to do those things…

CAITLIN: To figure out how to get that therapy takes time and I think that patients don't have time and there's so many barriers that are created not through science. That's something that I think about a lot when I do my work now.

PEGGY: For Ben he continued their glioblastoma project. They completed the screen that Ken designed, and identified possible driver mutations—mutations that contribute to glioblastomas in mice.

BEN: I was being the skeptic I was like, I bet you they're all gonna be the same, who cares.

PEGGY: But then they took a closer look at those tumors.

BEN: Our jaws just dropped, like we didn't believe it. You have related variants that differ by a single amino acid that are thought to behave the same, but the tumors that they make are fundamentally different. And once I saw that, I was engaged a hundred percent and I was no longer a skeptic. Ultimately, I have to say he was right, that it was worthwhile doing these experiments that I was very skeptical of right. And what's really sad about that is that was around the time that he passed away.

PEGGY: Yeah, you never got to tell him, you were right.

BEN: He was right yeah and I never got to say that. I was actually really, now I'm getting sad thinking about that. We never got a chance to share with him how cool it was that you had related variants that behave very differently which is surprising, and it speaks to the need to functionalize all these different variants.

SONG: [“Sunset on the Beach”]

BEN: The bigger idea that we had that we never actually got to, which is really disappointing, but it's something that I'm hoping that we can start, is to do this on patient-specific mutation sets. Pediatric glioma has roughly thirty or forty mutations per tumor.

PEGGY: Few enough mutations, that they could test all of them in the lab, using the mouse system Ken designed, and figure out which ones are important for their cancer—on a per patient basis.

BEN: So the idea would be to recapitulate all the mutations, throw them into a mouse and ask which ones are drivers and which ones are passengers. This screen was basically proof of concept that we can do it on a large on a large scale and that we could apply the technology to do any patient specific cohorts.

PEGGY: Ben continues to collaborate with Gordon, along with many other researchers across different fields, brought together originally by Ken.

BEN: It really speaks to Ken's you know gravitas or his magnetism. He was a larger-than-life personality and I miss him dearly. There's no way that I could I could pull this off on my own [laughs].

PEGGY: Gordon, who now is at the Oregon Health and Science University, continues to work on many of the concepts that he had originally started with Ken.

GORDON: When Ken passed, in his honor, we renamed the project that he and I led, and now Ben Deneen and myself lead, to “The Honey Badger” project. Ken had a rare and difficult sarcoma, there's really very little known about what you would do for sarcomas that change therapy management. We have now developed probably one of the first and useful sarcoma models that we can explore in animal systems. We had a new patient last week who had an unusual fusion gene, one that had never been characterized before, and we're using the technology that Ken Scott developed to do that characterization.

SONG: ["Ambiant hope"]

GORDON: We have just published and extended in our database the largest collection of genomic aberrations that have been characterized. He trained an incredible group of people and those people are now setting up their own laboratories their own projects and embracing the concepts that Ken brought forward in terms of collaborations, innovation and making a difference. Seeing what happens to the Ken Scotts of the world to other patients and really saying we have to do more and we have to do it faster, it’s a driver.

PEGGY: Tim is now at the MD Anderson Cancer Center.

TIM: Uh you know maybe 20, maybe 30 percent of patients actually match to an available therapy. Ken and I always saw that as you know a challenge that wasn't good enough.

PEGGY: Finding the drivers of any given tumor and figuring out how they work is difficult, and this is just step one. To take things to the next level, and truly be able to carry out precision oncology on a per-patient basis, there needs to be an actual drug.

TIM: We may be able to identify the key dependency but if it's not therapeutically tractable or there is not a drug in the pharmacy to target that specific mechanism, it doesn't necessarily help the patient. And again one clear and real example of this is Ken. We did not have a drug to give Ken, specific for his disease and I think that that's something that continues to motivate us. What he envisioned was a day where a patient would come into the clinic, a biopsy would be taken, as the patient undergoes maybe standard of care therapy. Ken could work in the background to identify new therapeutic opportunities that would benefit the patient.

PEGGY: Tim continues his work in the drug discovery space…

TIM: To build systems that would allow us to identify nodes that we could exploit therapeutically, to identify a new unprecedented gene that may be contributing to cancer pathogenesis, to validate that finding and then enroll those targets into an active drug discovery campaign. And my investment in this space was born out of early discussions with Ken.

BEN: He was in my office one day and like we're talking. He's like have you seen this honey badger. I'm like, uh yeah. You have to look at this. And so we spent probably 15-20 minutes in my office looking at the honey badger thing he was going on and on about it. Like it's great and how he wants to emulate the honey badger. It was the first time I'd actually seen the whole thing. And then he starts going into the analogy, and I'm just like dude you're crazy [laughs].

PEGGY: Wait was his analogy, what were some of the parts of his analogy?

BEN: Part of it was, you know resiliency, right. Cause your papers will get rejected, your grants get rejected, your hypothesis is not going to be correct and your experiments are going to fail. So you've got to be resilient and just keep moving forward. And the other part of it is doing whatever you want to do. Cause that's what the honey badger does, right? There's a million reasons not to do any experiment. I can talk myself out of any experiment at any given time.

You have to just be like, I don't care what other people say, I'm just going to do it because it makes sense to me. And Ken definitely embodied that.

CAITLIN: The resiliency and the just, I don't care what anybody thinks of me. I think that was Ken all the way, like Ken didn't fit a mold, you know. He didn't care if people thought he was this you know Texan football player who is now trying to do science. He was really about, we do good work, we do high quality work, we do ethical work, and had an intense focus.

It's just the toughness there, he didn't let anything get him down. When I think about a honey badger it’s just the ability to just move through adversity no matter what and have laser focus on your goal.

TIM: It was almost as if he was waiting for somebody to tell him something couldn't be done. This is a stressful business, you know what I mean? It's this never-ending cycle. But Ken saw it as you know, the next adventure. You know what I mean, he has partaked in new dances and new skits with his lab. Him signing up for what's called the death race in the mountains of Vermont, you know what I mean. It’s called the death race. He was just that type of person, he was just so passionate about life. And he lived on the edge, and he was honey badger through and through.

You know every time I see the honey badger, I hear the words “honey badger”, I immediately think of him. I always associated Ken with the honey badger prior to the YouTube video or the football player from LSU.

PEGGY: He talked about being the honey badger before, before the video?

TIM: Oh yeah, yeah. And Ken put me on to the video, as to say, okay this is what I'm talking about. Even today, you know it's almost three years since he's passed and I know that if I walk through my lab and start talking about honey badger everybody knows who I'm talking about.

PEGGY: So, your interactions with him were you know more professional, as you said, but did he tell you about the honey badger? And show you that video? [laughs]

GORDON: [laughs] I think that you don't want to take this too far. We use the honey badger in his honor, but it's not really the full description of the breadth of Ken Scott. Yes, we clearly did discuss just how striking the honey badger is considered to be the toughest animal pound for pound on Earth. He absolutely was struck by the power the strength the willingness of this animal to compete and I think in his Ironman life he was that competitive. But the other aspects of him are incredibly important.

SONG: ["Sunset on the Beach"]

GORDON: In science he was a collaborator, it was interactive. He cared for everyone around him in a way that is truly exceptional.

TIM: Beyond the break dancing and the the Ironmans and obviously his incredible science, I think he was a model person and he was a human that I think a lot of people would strive to live up to. We became great friends, great colleagues. We bought a house in the same neighborhood so our kids grow up in the same schools, and it's it's wonderful to see. But I do miss my friend, I miss him a lot. He has certainly left an incredible legacy that continues to inspire me everyday.

PEGGY: Ken's trainees have moved on in their careers. And many have also started families.

SAM: I just wonder if, because I have a one-year-old daughter. She keeps yelling all the time. I hope that’s fine if you hear some screaming at the background.

PEGGY: Oh sure, that’s totally fine.

SAM: Yea there's actually one thing I really want to share. Things that impressed me a lot is when he got diagnosed, he said it multiple times that he wants to make sure his kids won't feel like they won't have a father growing up. To think ahead how to provide the best, not financially, physically, but also emotionally. To emotionally support the kids and his family, that's something I also learned from Ken a lot. He wrote like birthday cards for every year for the future years and he also make a video of him dancing with his daughter for her wedding. Because he knew he's not gonna be there.

LAUREL SCOTT: He didn't tell me doing that until like the very end so that I would know but I didn't know he was doing it while he was doing it.

PEGGY: This is Laurel Scott.

LAUREL: My name is Laurel Scott. I am Ken's wife. We were married for 19 years and he was the absolute love of my life.

He wrote them birthday cards for every birthday up through age 25 so every birthday they'd get a card and pictures that he chose to put in there. He left videos for them, he and my daughter actually went to a wedding reception venue around here all dressed up and a professional photographer and videographer came out. So she won't have her dad at her wedding, but she'll be able to play this video of them kind of having that first dance. He actually left notes hidden which I found over you know the last few years just random places.

We were playing the board game, we opened it up and all of a sudden my daughter was like, oh my gosh it’s a note from dad! We're like what, what? We're all trying to grab it and read it, you know the three of us and it’s like, it's so exciting it's like you just found a hidden treasure.

For somebody to do that when they are you know in the midst of you know really miserable physical suffering and just knowing that everything that they've worked lived for their whole lives is just sort of coming to an end. But that was what his focus was because he just felt such strong love for them.

SONG: ["Sweet me"]

LAUREL: His research has continued and been published and the kids and I are thriving despite the fact that you know, we have this tragedy in our lives. It's just it's all the stuff that he set into motion to be sure that everyone would be okay.

About him being the honey badger, it started out all was just being fun and light-hearted because of the way that he faced life. And it didn't become like a more serious role until he was sick. Everything he did every day was crazy and honey badger don't care kind of drama. Like climb on the roof and trim the palm trees while he was wearing a backpack of chemo. I mean, there’s lots of things like that, but honestly, the way that he handled his illness and how he fought it. That has to be the most incredible, brave, it’s okay I got this situation that I ever saw. There actually is a stuffed honey badger that we have in our, [laughs] in our house, that says some rather inappropriate things. I think that’s just sort of a term of endearment that a lot of his science friends call him now.

I think sometimes it seems like people are maybe just remembering the good things because he's gone, but the reality is that's really how he was.

Family was always first to him. He was always there for anything that we needed, if you know the kids had a game, a performance. You know not just when he was sick and realizing, okay I've got to make every minute count. I mean he really lived his life that way before he ever was diagnosed with cancer.

My son is a mini-me to his dad. He just has the exact personality, just happy-go-lucky, just whimsical, he loves jokes and pranks. And our daughter has these just absolutely perfect pieces of him. You know his humor, his sarcastic wit, courage. Really I see him everyday just by watching the two of them as they go through life. Sometimes one of their facial expressions will be exactly his facial expression. It's really actually pretty cool to see and I just think that they are amazing and they have shown such strength and such fortitude and there's such loving generous kind people. That’s what we worked so hard to instill in them.

PEGGY: What is it like to prepare for the end of your life, during a whirlwind like cancer? I spent a lot of time talking to Ken's colleagues, trainees, and friends...

TIM: Nobody can tell him that he can't dance in a restaurant, right.

SAM: Not music that anyone else would appreciate.

PEGGY: And his wife…

LAUREL: Honey badger, you know its like [laughs] oh my gosh.

PEGGY: More people than could be included here on this episode…

JOANNA OZGO-WARDWELL: Just the dogged way he went about getting his way.

TURGUT DOGRULUK: In a brand new lab that has limited resources.

PEGGY: To try and understand what he might have been might have been feeling, physically…

SAM: So you can imagine how unwell he was.

PEGGY: And mentally.

CAITLIN: He wasn't gonna get to see where we all landed and I think that was difficult for him.

PEGGY: It's hard to get underneath the thick skin of a honey badger. But here's what I do know. He must have been busy.

SAM: Like I said he's a very good planner.

GORDON: Career plan, career options, helped them make sure.

PEGGY: He must have really focused on the things he cared about.

BEN: Freaking out, not about himself but about the career paths of students and technicians and postdocs.

TIM: He would always switch the conversation to how you were doing, how your family was doing.

PEGGY: While others slept, he was preparing, building…

CAITLIN: He would email us at like 3:45 in the morning.

JOANNA: Ken stayed up all night and made sure that I had a letter.

PEGGY: Setting things in motion.

LAUREL: Notes hidden which I found over you know the last few years.

PEGGY: Today, 3 years after his death, we are still seeing pieces of his research, his hopes and dreams being carried out.

CAITLIN: Inspired by Ken's struggle.

BEN: It speaks to the need to functionalize all these different variants.

TIM: Ken and I always saw that as you know a challenge that wasn't good enough.

GORDON: Seeing what happens to the Ken Scotts of the world and really saying we have to do more and we have to do it faster.

PEGGY: There is just no way anybody could succinctly capture all of one person's impact on the cancer research world, on the lives of their colleagues, mentees, and friends, on their family. But everyone I spoke to agreed we could try to explain Ken, in the way of the honey badger video.

BEN: I'll just start from the top? Okay.

SONG: [“Cello Suite No. 6 in D Major, BWV 1012”]

BEN: This is Ken Scott. Watch him run, swim, and bike.

TIM: Watch him screen, collaborate, innovate

GORDON: Watch him train and mentor. He is incredible…

JOANNA: He’s pretty crazy

TURGUT: He’s pretty hardcore

TIM: He’s pretty intense, and awesome

KATHLEEN KONG: Look he runs all over the place

TIM: Whoa, watch out says the neighbor

SAM: Oh he’s blasting music in the lab

CAITLIN: Oh he’s got a backpack full of bricks

TIM: Oh he’s rolling a giant tire

DANIELA MORENO: Oh Ken Scott is just crazy

GORDON: Oh Ken Scott is just crazy

BEN: Ken has placed in ironman competitions

SAM: Wow, Ken has placed in ironman competitions

GORDON: He’s also gotten career development awards and prestigious grants

TIM: He doesn’t really care,

CAITLIN: If he’s set a goal, he’s going to do it.

JOANNA: If he’s set a goal, he’s going to do it.

TURGUT: Now look he’s there at a Tae Kwon Do tournament.

JOANNA: Now look…

DANIELA: He’s there at a choir performance.

BEN: Look he’s doing his 4am workout.

SAM: He’s sending email while he’s doing it. That’s impossible!

DANIELA: He just doesn’t stop.

CAITLIN: He just doesn’t stop.

GORDON: He just doesn’t stop.

TIM: Ken has a fairly long body, but a distinctly thick set of broad shoulders,

JOANNA: And you know, he does the worm,

SAM: Transitions into a windmill,

TIM: And tops it off with a perfectly executed backspin.

TURGUT: Now look here’s two million aberrations found in cancer patients that have not been functionalized.

CAITLIN: You think Ken Scott cares?

TIM: You think Ken Scott cares?

BEN: You think Ken Scott cares?

JOANNA: Nah,

SAM: He doesn’t.

DANIELA: he goes right in and designs a high-throughput screen to figure it all out.

KATHLEEN: He doesn’t care about being wrong, he just tries again.

CAITLIN: Nothing stops Ken Scott when he sets a goal.

JOANNA: Nothing can stop Ken Scott when he’s set a goal.

TIM: Oh, that’s so honey badger.

CAITLIN: Now see what’s interesting is other researchers…

SAM: They might be skeptical of his large-scale, disruptive approaches.

JOANNA: They say, I don’t think the technology is really there.

BEN: I guess we’ll give it a shot.

TIM: Cancer biologists,

BEN: Neuroscientists,

CAITLIN: Developmental biologists,

JOANNA:  They say hah, alright Ken,

KATHLEEN: Alright, Ken,

GORDON: Go for it. And you know what, computational biologists say it too.

BEN: But Ken gets them to all join in and now they’re a real team.

SAM: A real team.

TIM: That, too is so honey badger.

DANIELA: That’s so honey badger.

BEN: That’s so honey badger.

TURGUT: At nighttime, Ken writes emails, papers, and grants…

TIM: And then some fictional stories cause he doesn’t much need sleep.

SAM: He really doesn’t need to sleep.

CAITLIN: Oh, little does Ken know, FYI he has chemo brain.

JOANNA: While he’s writing, the poisonous venom is seeping through Ken’s body and he passes out.

BEN: Ken is gonna pass out for a few minutes.

KATHLEEN: And then hes gonna get right back up and start writing all over again.

SAM: Look at this.

JOANNA: Look at this.

BEN: Look at this, like nothing happened.

JOANNA: Like nothing happened.

TIM: Ken gets right back up and continues writing.

TURGUT: And of course, what does Ken get later?

GORDON: An R01.

CAITLIN: That’s so honey badger.

KATHLEEN That’s so honey badger.

SAM: Oh, that’s so honey badger.

JOANNA: That’s so honey badger.

GORDON: That’s so honey badger.

TIM: And that is Ken Scott.

SONG: [“Sweet You”]

PEGGY: A big thank you for all the generous, kind people who joined in to do some honey badgering, for taking lots of time and opening up to share their personal stories and memories about Ken: Benjamin Deneen, Caitlin Grzeskowiack, Daniela Moreno, Gordon Mills, Sam Tsang, Subhashini Jagu, Joanna Wardwell-Ozgo, Kathleen Kong, Kwanha Yu, Tim Heffernan, Turgut Dogruluk. And of course, Laurel Scott. Isn't she honey badger?

For more information about this and other episodes of Personal Genomics, visit our website at cancer.gov/personalgenomics. Questions or comments about this podcast? Wanna share your story about research? Email us at nciinfo@nih.gov. Be sure to mention the Personal Genomics Podcast. If you like the show and wanna hear more, please subscribe and share it, and leave us a review.

Personal Genomics is produced by me, Peggy Wang, under contract and with help from Center for Cancer Genomics staff. We are a production of the US Department of Health and Human Services, National Institutes of Health, National Cancer Institute.

You know, I was so pumped to drop another episode of the podcast, I was telling Gordon how excited I was, you know it’s great, I wanna make more episodes and tell more personal stories and he was like…

GORDON: [laughs] I think that you don't want to take this too far.

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