#34: Electrocuting the S#!t Out of Cancer.

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

Brian: And my name is Brian Colbert Kennedy.

Quinn: Our topic today: electrocuting the shit out of cancer.

Brian: One of the cooler topics, I think.

Quinn: Yeah. Our guest today is almost double doctor, Theo Roth.

Brian: Jesus.

Quinn: He's a MD/PhD student candidate at the University of California San Francisco. He's worked at the National Institutes of Health and Stanford. Let me tell you, he's figured out some pretty cool shit, Brian.

Brian: Yes he has.

Quinn: Brian.

Brian: Yes.

Quinn: Ready?

Brian: Uh-huh.

Quinn: Pop quiz.

Brian: Okay, great.

Quinn: If I said, "Brian, how are you going to electrocute cancer?" Go.

Brian: I would take a person with cancer and there's gotta be something, like not an electric chair obviously, but some-

Quinn: Nope, this is going so bad.

Brian: Some sort of nice, gentle way to electrocute their body and maybe somehow it's getting in and only directly targeting the cancer. I'm just a guy! I don't know!

Quinn: Sweet Jesus.

Brian: Ugh! Okay, so don't put me in charge of that.

Quinn: With how shitty you feel right now, would you do that to yourself if it said you'd feel better?

Brian: Yeah.

Quinn: Right then?

Brian: Wait, what I just described?

Quinn: Yeah.

Brian: Oh, I don't know. That sounds bad.

Quinn: That sounds like, "Wow, how did that get in there?"

Brian: Even when you accidentally touch a bad cord or whatever and you get that millisecond of a shock, it's so awful. I don't want to feel that.

Quinn: Mm-hmm (affirmative). My kids like to, you know, you gotta put the little things on the electrical outlets to block them?

Brian: Yeah, yeah. The little plastic? Yeah.

Quinn: First of all, they figured out how to take them off so quick, little MacGyvers. And then one of them will just keep eye contact with me, making sure I see him-

Brian: Oh my god.

Quinn: Reaching up with an increasing grin on his face as he looks to stick his finger in. He's like, "You're going to watch me die."

Brian: Ugh!

Quinn: "Deal with it."

Brian: I love that in their mind, it's like they don't realize that there's actual harm that could happen.

Quinn: Oh, fuck no.

Brian: They just know that you don't want them to do it, so it's like this, "Hey, look at ... "

Quinn: Yeah, yeah. They have no context. Look, they literally don't know what time is.

Brian: Yeah, yeah. Right.

Quinn: They don't know until a month that they have hands and feet. 

Brian: Oh my god.

Quinn: They keep seeing hands and feet and getting terrified because they don't know it's theirs. The context for self-harm, nothing. Doesn't exist.

Brian: Yep, yep.

Quinn: Doesn't exist. Like, "Don't jump off this." They can look down and be like, "Probably not, but I'm going to do it anyways."

Brian: "Maybe I should jump up there."

Quinn: But electrocution, way the fuck beyond their scope of comprehension.

Brian: Oh, it's so bad.

Quinn: Doesn't excuse being a dick about it though.

Brian: I used to have one of these fake lighters.

Quinn: Cool!

Brian: Yeah, yeah, it was really cool. Instead of lighting-

Quinn: Was this last year?

Brian: No. I bought it from a man selling it on the street when we took our 8th grade trip to Washington DC. Fake Oakleys and these lighters-

Quinn: Cool.

Brian: That, instead of it creating fire when you press the button, it just somehow buzzed you. It was the best. I really got some people! 

Quinn: Oh god, Jesus. That's amazing, that's amazing. Teddy's here with us again.

Brian: Sweet Teddy.

Quinn: Hi!

Brian: He was dreaming during the recording.

Quinn: Can you guys hear that tail hitting the ground? Hey Ted.

Brian: Oh, I hope that comes through.

Quinn: Yeah.

Brian: He's just so happy.

Quinn: He's the best. He moved a foot and a half for some reason in the middle of the recording. Unclear why.

Brian: Just to do the same thing, just lay.

Quinn: Just in a different spot.

Brian: He's so cute.

Quinn: Last note. It is talking about cancer today. It's going to get kind of wonky. It's super fun though. It is Children's Cancer Awareness Month now in September. We're not specifically just talking about children's cancer, but we're talking about all of it. You should note that children's cancer receives 5% of federal cancer research funding, 5%.

Brian: That doesn't seem like enough.

Quinn: Which is not great. So contribute to places like Sloan Kettering and Alex's Lemonade Stand to help fund research, and treatment, and travel for those folks. Fuck cancer in the face. 

Quinn: That's it! Let's go talk to Theo.

Brian: Let's go talk to Theo.

Quinn: Our guest today is Theo Roth and together, we're going to talk about electrocuting the shit out of cancer. Theo, welcome.

Theo Roth: Thank you. Thanks for having me.

Quinn: For sure.

Brian: Very happy to have you here. A great place to start would just be tell us who you are and a little bit about what you do.

Theo Roth: Yeah. Maybe not the type of person that's always on podcasts, but I'm actually a student. Call it MD/PhD student, so I'm training to get a medical degree. But currently though, I work in a lab with a physician named Dr. Alexander Marson.

Quinn: You couldn't settle for just one degree? You've gotta go for two at once, pal?

Theo Roth: Well, that's the discussion that gets very, very technical and complicated very quickly, which is exactly the kind of stuff that people who do MD/PhD degrees like, so.

Brian: Yeah.

Quinn: Right. Good news is you're the right person for it. Cool, okay. So you were saying you were working in a lab with who? Who's this chump?

Brian: Marson?

Theo Roth: Yeah. I work with a person who already has their degrees after their name. His name's Alex Marson. He's the guy who's the head of the lab. Together, we come up with ideas about experiments, and then I go in, and my day job is to go do those experiments.

Brian: Where in the world are you guys?

Theo Roth: Yeah, we're at the University of California San Francisco.

Brian: Hey!

Theo Roth: It's a beautiful view out over the Pacific Ocean, which we tend not to look at very often because it's covered in fog.

Brian: We know what you're talking about.

Quinn: Well, at least it's there. That's not like our view, beautiful Ventura Boulevard. Awesome man. How long have you been there?

Theo Roth: I'm starting my fifth year at UCSF. I've been working in the lab though for the last two years or so.

Quinn: Okay.

Brian: How much more you got left because you get all the fancy letters?

Theo Roth: Yeah, it's always a question that parents, especially, are the ones asking. Probably one year before I finish up my work in the lab and then two more after that to finish the medical degree.

Brian: No problem, you're almost there.

Quinn: Yeah.

Theo Roth: After a while, it all blends into the same.

Brian: Three more easy years.

Quinn: Right, and then all your life is gone. Perfect.

Brian: That sounds fantastic. Yeah, I guess we don't have a ton of students, but I believe we have had students before and it is ... The conversations are just as intriguing and mind blowing as with anybody, so very happy to have you and clearly you're working on something, eh, pretty important.

Brian: What we're going to do today is ask you some questions. The goal here is to, by the end of this, make sure that our listeners have some solid ideas on what they can actually do, physical action steps, to help support you and everybody that's doing what you're doing and fighting what you're fighting for. We're going to do that, if that sounds okay.

Theo Roth: Yeah, sounds great to me.

Quinn: Yeah, sometimes those specific actions get down to, "Sweet Jesus, do this thing to save the planet," and, "It's all melting. Help, everything is on fire," and sometimes it's like this, which is support basic science and funding of labs and things like that so they can know where their dollars are going.

Quinn: All right Theo, we start with one pretty important question, something to set the tone of the conversation. Instead of saying, "Tell us the remainder of your life story," we like to ask, "Theo, why are you vital to the survival of the species?"

Theo Roth: I don't know if me, myself, is the key factor here.

Quinn: Well, that's the point of the question, but go on.

Theo Roth: I'll answer for maybe students in general. 

Theo Roth: It's that most of the work that's done to advance our knowledge, our understanding, is being done by students. That's something that's very accessible for lots of people. It's harder to see how to become the person who cured cancer; it's easier to see how to become a student at the university that's in your city or in your state. It's important for, especially people who are thinking about going into science, to realize that there's world-changing work happening just probably down the street and that it's a lot easier to become a student and to get your hands dirty doing that work then it is to figure out how to become a world famous physician or inventor or something.

Brian: Right.

Quinn: That's fair.

Brian: I love that. You get too focused on that, like you said, the big thing, cure cancer. But really, it's just a bunch of people doing the hard work on the ground. That's how it's going to happen.

Theo Roth: Yeah, yeah, absolutely.

Quinn: Awesome, all right. Like I said, we're going to set up a little context for today's question. I guess it's more of a topic, electrocuting the shit out of cancer. We're going to define that in a little bit. I got some notes here to get everyone – us, our esteemed guest with all the letters coming, our listeners at home, mostly Brian – on the same page. Today might get a little wonky, which is fun, but it is important everybody knows what the hell we're talking about. Theo, please jump in, correct us, hang up, runaway, whatever works. 

Quinn: I should preface this by saying if anyone wants to take a deeper dive on the history of cancer and cancer treatment, I loved "The Emperor of all Maladies." Did you happen to read that, Theo?

Theo Roth: Yeah. I can certainly say that as somebody related to cancer research, that book is probably the best introduction to the field that you can go. Honestly, even graduate students or professors, I think, probably start there rather than digging into primary published articles and literature.

Brian: Oh, wow.

Quinn: That's really cool. It's really impressive. Siddhartha's just such a smart human being. He also wrote "The Gene," which I love, the history of genetics. On a personal note, cancer's a big one for me. My best friend died of cancer about 10 years ago and I actually-

Theo Roth: I'm sorry to hear that.

Quinn: Well, you know, it happens. He wasn't a smoker or anything like that, but esophageal cancer got to him. I cracked that book about 10 times before I could actually get through it, which is something I also talk to my therapist about. But when I did, it was just stupendously enlightening and thought provoking, and really helps you understand, again, what folks like you are working on, how complicated cancer is, but how much progress we've made.

Theo Roth: Yeah, absolutely. And certainly also, is a big indicator of how important it is to have exceptional science writing and science journalism because a book like that can synthesize 50 years of science into something that the popular or the general public can understand. That's a huge win for science in general.

Quinn: Yeah, it makes a difference. I think of that when, I don't know if you've heard of Carlo Rovelli? Rovelli wrote "Seven Brief Lessons on Physics" and has got a new book about time and is such a smart human. It's ridiculous. But just a stunning writer and will just help you. Again, you might not be like, "Shit, I should be a scientist," but it will make you go, "Wow, this is incredible." Thank god someone who's able to really dial this down for me. It's like that incredible college professor you have who's not just smart, but is actually able to explain it and transfer things to his students.

Brian: Yeah, pretty important part of education.

Quinn: Sure.

Brian: Getting people to actually be able to get it.

Quinn: Yeah, yeah, yeah.

Brian: While we're getting into this, guys, since I can ask any question that I want, says Quinn.

Quinn: Any question is putting it out there a little bit, but go ahead.

Brian: Just what is cancer exactly?

Quinn: All right, you know what, Theo, why don't you go ahead and give us the two-sentence description on what cancer is? I feel like a lot of times, it's not lazy, it's the easy way of doing things, but you hear people say, "Let's cure cancer." Give us the two-sentence story on what cancer ... What is happening inside the body and how many variations on cancer there really are?

Theo Roth: Yep, yep. The way that always made sense or makes sense to me now and the way I think about it is we all start off as one cell, the fertilized zygote of your mom's egg and your dad's sperm. That one cell divides a lot and it becomes this 100 and whatever-pound human being that you are, which is made up of – the number bounces around depending on who did the last estimate – but maybe 30 trillion cells.

Brian: Jesus.

Theo Roth: So one cell becomes 30 trillion and it's gotta do that by dividing, so cell division is inherent to the process of life in general. That process, though, has to stop at a certain extent. At a certain point, it no longer makes sense for us to grow bigger; we want to invest more energy, more of our time, and this is the trade-off that was made evolutionary in our deep history, that it makes more sense to stop growing and start investing in reproducing to make another copy of yourself by combining with another person.

Theo Roth: It's still shocking to me after studying science for 10ish years that this all works, but it just comes down to that. We grow by cell division, we replicate, the species propagates by cell division. It has to stop at a certain point. That ability to stop is hard-coded into our genome. There are many pathways, many, many mechanisms by which your body tells the cells, "Okay, we've finished growing. We don't need to divide anymore."

Theo Roth: As an individual cell though, we have to remember that each of our cells doesn't necessarily know that it's a part of a human and my goal is to survive to go have a good weekend and then maybe reproduce someday. The cell just knows that it needs to divide to grow like any living organism. It's these inhibitory pathways that really prevent everything, all of those 30 trillion cells, from all going their own individual way. That's what you gotta prevent.

Theo Roth: The issue with cancer is that, like I said, you have those trillions of cells and if just one of them figures out a way to get around those roadblocks that the body throws up to prevent division, that's enough to lead to a cancer that can eventually kill the entire organism, take all the other trillion cells with it.

Brian: Really, just one out of 30 trillion? That's wild.

Theo Roth: Just one at the start. Yeah, it ends up being a lot more.

Quinn: Right, right.

Brian: Sneaky bastards.

Theo Roth: That's part of the problem, right? There are so many different types of cells in your body and then some of them, like immune cells, they have to keep dividing in order to do their normal function. Other cell types like the lining of your gut is dividing constantly your entire life and that's necessary for a healthy metabolism. But sometimes it goes awry and it can go awry in a lot of different ways because there are so many different cells that it could happen.

Theo Roth: That's where you get to the stage where the scientists, I guess, will say that, "Cancer isn't one disease; it's a thousand. It's a million different diseases," which makes it a little bit harder to cure than, say, finding the cure for a one specific bacteria.

Quinn: Right, right. Yeah, I think that makes a lot of sense. You know, I guess we can get to the more recent accomplishments and discoveries, but we know, I think, the first sort of not cave drawings but evidence of cancer goes back to Egypt, 4 or 5,000 years ago. But obviously, homo sapiens has been kicking around for a few hundred thousand years and variations on the species go back way further than that. Cancer isn't new.

Brian: Yeah, it must be-

Quinn: Cells have been dividing, shit has been going on for a long time. What we've done is we've brought on a shit load of new factors to influence that from smoking, and air pollution, and hormones, fucking bacon, alcohol. We've basically learned, and I feel like every day we discover whether it's diet or genetics or something, everything is a trade-off, right?

Quinn: Microscopes turned to be super helpful for really starting to look at how these things were dividing and what happened instead of just ripping tumors out of the body and saying, "What's that?" But you know, I guess when we talk about the history of treatment, again, getting towards where you are now, is great. We like to cut out tumors. A lot of times it came back, they didn't really understand why or how, but also hygiene was a total fucking nightmare.

Theo Roth: Exactly.

Quinn: If anyone is interested in following up there, I recommend "The Knick," with Clive Owen.

Brian: That show?

Quinn: Yeah, that show, which is terrifying.

Brian: Oh.

Quinn: Be so thankful. Hey, wash your hands. You will never appreciate Purell more than after you watch that show. Anesthesia really made the whole thing a lot better; we're not biting on sticks anymore.

Theo Roth: No, absolutely. And the history of science, the innovations that have cured the most people are often by far the simplest. Hygiene like that, but also a surprising one is one of the interventions that cured the most, saved the most lives in the 20th century was oral rehydration therapy, which was giving people who had diarrhea water that had salt and sugar in it. That cured more lives than probably most antibiotics did.

Brian: What? Wow. When was that happening?

Theo Roth: In the middle of the 20th century started to be realized that children who were dying of diarrheal diseases could be cured with just-

Brian: With salt water.

Theo Roth: Doesn't necessarily taste good, but could save your life.

Quinn: Right. Now I'm a dad and can pop down to CVS and buy a bucket of Pedialyte.

Theo Roth: Right, exactly.

Quinn: And everybody jokes it's great for hangovers, but it's like 50 fucking years ago, everyone was like, "Well, water is going to do it." And 50 years before that, it was like, "Well, sure we can drink dirty water. Why would we boil it?" It's crazy, these super simple things that have made enormous strides. But we have made big strides, right? 

Quinn: Exploratory surgery, which again, understandable, but thank god we've moved away from it, have given away to CT scans and MRIs and PT scans, which are also slightly less invasive. We've gone from more recently radical mastectomies to a much more nuanced and complicated approach to breast cancer surgery. From the default brutality of chemotherapy, which chemotherapy, I've always felt like we're going to look back on in 20, 25 years and say, "Thank god we had that, but at the same time, can you believe that was our best option for so long?" Because it is just so incredibly brutal.

Quinn: The nuclear option to the promise of immunotherapy and hormone therapy and hyper targeting and lasers. Now we're using ultrasound to guide operations instead of, again, exploratory surgery, which is some fucking medical student apple bobbing around in your abdomen. Right?

Theo Roth: You don't want that.

Quinn: Right, no, not fun. So the question is what impact now, going forward, can things like CRISPR have on cancer treatments, right?

Theo Roth: Mm-hmm (affirmative).

Quinn: What is CRISPR?

Brian: CRISPR. Yeah, does everybody know what CRISPR is? I feel like I have-

Quinn: Are you asking for everybody else?

Brian: I have a general understanding.

Quinn: You know what?

Brian: It seems like magic.

Quinn: Well, I'm going to give my incredibly simplistic answer and then we're going to let Theo spend the next hour talk about it.

Brian: Got it.

Quinn: But it's gene editing with very tiny scissors. We can grow better, theoretically, we can grow better rice with it, we can cut out disease. It's already very early, but some people, who might be on this podcast, might be putting it to use. All that said, let's talk about electrocuting the shit out of cancer.

Quinn: Theo, what have you done?

Brian: Yeah, what does that mean?

Quinn: What is going on here?

Theo Roth: Yeah. Our work is kind of combining two different recent trends in potential cancer treatments. You highlighted one, gene editing. I'll talk about that one second. But the other one is this trend called immunotherapy. This new area of cancer therapy, although you can go back and if you search through literature and stuff, you can find people who were doing something vaguely similar 100 years ago, as you often can.

Brian: Oh, really?

Theo Roth: It takes a couple interesting stories of people who would inject a tumor with a bacteria and turned out 1 in 10 times-

Quinn: Because why not?

Theo Roth: You know, well, at that time, there wasn't exactly a long life expectancy after just about any type of cancer. The modern understanding of it has really taken off, scientifically, in the last 20 years or so, and then therapeutically, the last 5 to 10 years.

Theo Roth: This is a field based on the fact that ... I mentioned earlier that it only takes one cell out of those trillions of cells that make up our body to become a cancer that could eventually kill you, kill the organism. That's not to say though that the only time cells have that cancerous transformation is when we, in the medical setting, detect a cancer occurring. It's actually much more frequently than that. But your body itself has ways of fighting off and killing those very small tumors before you ever even notice that you had it.

Brian: This is just happening all the time in everybody?

Theo Roth: How often it happens? That's a matter for debate. It certainly happens much more often than the reported prevalence of pancreatic cancer or prostate cancer or breast cancer, things like this.

Quinn: Right.

Theo Roth: One of the main ways that we think that these very small cancers are eliminated before they become a problem is that the immune system, that big system of cells that is constantly floating around the body protecting you from viruses, and bacteria, and making sure that when you fall down and you get a cut that your arm doesn't get inflamed, and infected, and you have to lose a limb, which before the advent of more careful hygiene, that was a very unfortunate but expected outcome.

Brian: Yeah, ugh.

Quinn: Right. And again, that's kind of what I meant about the immunotherapy. It's the same thing. If you go back and look at the difference between World War I and World War II, and penicillin and field surgery, that was the way to cut out the infection is to just lose the fucking leg.

Brian: Yeah, buh-bye.

Quinn: Again, thank god we knew to do that, but also holy shit, that was the best option.

Theo Roth: Yeah, yeah. Immunotherapy, I'm glad you mentioned penicillin. Immunotherapy for cancer brings up the challenge of using similar approaches like developing an antibiotic in cancer. The reasoning is that when you have a bacterial infection, bacteria are very evolutionary distant from humans. They have a lot of biochemistry and metabolism that is different than the way our cells work.

Quinn: Yeah, we've talked about, gotten into bacteria on here and how they've definitely got the upper-hand.

Theo Roth: Yeah. But the key weakness there though is that it's different. It's different from the way our cells work, which means that we can find little chemicals – and we call them antibiotics – that mess with the bacteria but don't mess with our cells. That's why antibiotics can just be pop one pill and then it's done. It's gone and it doesn't have any bad side effects.

Theo Roth: Whereas cancer chemotherapies are so horrendous, so awful, the side effects are horrible because you're trying to kill a cell that looks very similar to the cells in the rest of your body.

Brian: That are fine.

Theo Roth: Yeah, that are fine.

Quinn: That's a pretty high degree of difficulty.

Theo Roth: Yeah, and there's no-

Brian: Is it crazy for someone like you to hear when people have cancer and don't want to go through chemotherapy?

Theo Roth: I mean, having been in the hospital-

Brian: Is that like hippy shit?

Theo Roth: I would say there's grades here. There's a very important, I think, movement now to understand the limits of modern medicine and know when additional treatment is not necessarily going to improve somebody's final days. That's very important, I think, to let people live out the last few days of their lives the way they want to rather than being hooked up to a bunch of machines and stuff in the hospital.

Theo Roth: So in a certain sense, we could have kept somebody alive for another week, but if it means the difference between dying in a hospital or dying at home, then in that case, denying treatment can maybe be the right choice for a patient. That's very different than when, for whatever reason, someone denies treatment that would be curative. And it gets especially into very difficult territory when you're talking about someone denying treatment for a child who has a curative condition. That stuff ends up being the plots of "Law & Order" episodes and stuff.

Quinn: It's so complicated.

Brian: So-

Theo Roth: Please.

Brian: Immunotherapy, I mean it's early days still, but could be an alternative, yeah?

Theo Roth: Yeah. That's, I think, the synthesis I'm trying to bring together is that the immune system is already pretty good at finding and preventing a lot of these tumors that grow and that you never know started growing.

Brian: Right, so is immunotherapy like a harness thing? What is it?

Theo Roth: Yeah.

Brian: Like, I'm a kid.

Theo Roth: The goal is to build on that natural process that already happens inside our body to use our own immune system as a way to cure cancers, especially the types that are difficult to treat by surgery or are difficult to treat with chemotherapeutics right now. There's been some very, very promising early successes.

Brian: Harnessing the power of your own body, that seems genius.

Quinn: Can you literally tell us what is the practical steps of immunotherapy? What are the five steps, like take something out of the body, how do you use it? Just real quick so people understand.

Theo Roth: Yeah. Well, that's step one, yeah. The nice thing about these immune cells is that, again, in work that basic scientists did over the past 30 or 40 years, we've learned how to take immune cells from the blood. So a patient would just, essentially, give a blood draw. We take those immune cells and separate it from the blood or the red blood cells, and we can actually keep them alive and culture them and even expand them, make many, many more copies of them in a dish.

Theo Roth: We do that in the lab all the time. There's more regulated and more standardized ways of doing it for cells that are coming out of and going into a patient, but essentially we can take them out. That means that we have them in front of us and we can do stuff with them. That stuff that we can do-

Brian: Like modify them?

Theo Roth: Yeah, exactly. We can potentially try to make them better than they were before, make our Superman version of the immune cells. We do those modifications. We can expand them, make many more, and they go back into the patient where we hope that they have acquired a new functionality. 

Theo Roth: We talk about that in much more complex terms, but essentially, the new function that we want is that they're going to find the cancer that the patient has and kill it.

Brian: Is it also helpful that they're just replicated, like just that you're putting so much more back in than you took out?

Theo Roth: We think that's probably important. Cancer's can grow quite quickly.

Brian: Right.

Theo Roth: The other thing is that also, a lot of times cancers, they don't just grow in one site. We know this as metastases. They can bud off and seed other sites and that's one of the hallmarks of very late-phase tumors that, again, if there's a cancer in 20 or 30 different sites in the body, that's not something you can treat by surgery. If it's so widespread, the amount of chemotherapy that would be necessary to treat that would also kill the patient.

Theo Roth: We think that these immune cells, by the fact that we can put a lot of them in, they can go search throughout the entire body searching for where the cancer is, and attack it. Like any good scientist, I'll throw a lot of disclaimers on that. That's the goal. There's a lot of stuff sitting between us and that working in a large number of cancers right now.

Quinn: Right. It seems like immunotherapy, and I recognize this is incredibly simplistic, but right now works – and again I know just the word cancer, the word immunotherapy is much broader than I'm proposing – but from what I understand, immunotherapy works very, very well for some people, almost perfectly well; and for a lot of people, it doesn't work; and for some people, it can make them worse. Is that correct?

Theo Roth: That's certainly been seen in certain types of cancer, certain types of approaches. 

Theo Roth: Yeah, well, I think maybe one useful distinction is in this immunotherapy, we're talking about partly because it's what our lab does, but we're talking about taking immune cells out of a patient, modifying them, and putting them back in. We usually call that a cellular immunotherapy because we're dealing with cells that we take out.

Theo Roth: One of the more common approach right now that's being tried in ever more cancers is rather than taking the cells out and modifying them, trying to use the immune cells that are already in the body that are already in the cancer that are maybe responding to it a little bit, but not enough to prevent the cancer from growing, to try to ramp them up without taking them out. That's using-

Brian: So you just find where they are exactly in the body and then put something in?

Theo Roth: Essentially.

Brian: Okay.

Theo Roth: You're putting in ... These therapies, which are again, come under the heading of immunotherapies, involve antibodies against proteins or systems that immune cells use to regulate their actions. The classic analogy we're removing the brake from these immune cells so that they just go on and on and on. Obviously that's bad if you have an autoimmune disease, but if you're dying of cancer, then maybe you'll take an autoimmune disease over knowing that you're going to die.

Quinn: Sure. When I first read about what you guys were working on, I was like, "What?" When did your glow in the dark, electric field shit come into play? It's crazy. What are we talking about? What the hell is going on over there?

Brian: Electrocuting cancer. Yes, I would like to know more please.

Theo Roth: Yeah, it all comes down to this key technical step that we talked about. There's three steps for actually treating someone with these cellular therapies. We take immune cells out, we modify them, and we put them back into the patient.

Quinn: Okay. How long does that process take?

Brian: Five, ten minutes?

Theo Roth: Well, actually modifying the cells can take a very short amount of time.

Brian: Oh, really?

Theo Roth: The thing that takes a lot of time is just growing the cells up because we expand them to get many, many more copies of the cells. That can take one to two weeks or so.

Brian: Is that something that's being worked on specifically? Can that process be sped up also, possibly?

Theo Roth: Yeah, absolutely. This kind of gets down to the key step which is how you actually modify the cells because if you can modify the immune cell to be even better or to be able to make more copies of itself more efficiently in the body, then maybe you don't have to expand it as long outside the body. Then now the patient doesn't have to wait two weeks; they only need to wait a day or a couple days.

Quinn: Wow, that's a game changer.

Theo Roth: The real game changer would be if we could take cells out, modify them, and put them back in on the course of an hour or two. That's something that-

Quinn: I know it's early, but is that theoretically something you guys are reaching for? That would be incredible.

Theo Roth: Certainly, when you think about one of the big barriers to these therapies are their cost and their complexity. That's something that we think about. It's not necessarily something that we're working on right now in the lab, but part of the guiding ethos for our work, which is mainly centered on how do we modify T-cells in an easier, simpler, better way? If we can do it and the process is simpler, then that means that the actual, when we move into clinical therapies, that it can be a shorter process, and hopefully a cheaper one as well.

Brian: What's a T-cell?

Theo Roth: Yeah. We've been saying "immune cells" throughout but there's a lot of different types. One of the main ones and the most important ones though is called a T-cell. The T-cell is classically the cell type that will search for viral infections and try to eliminate any cells that have been infected with a virus.

Brian: Oh, great. All right.

Theo Roth: So you can kind of see, so viral-

Brian: Seems important.

Quinn: Yeah.

Theo Roth: If you don't T-cells, then you end up having a condition called SCID or Severe Combined Immunodeficiency, but more commonly known as the Bubble Boy Syndrome.

Quinn: Right.

Brian: I've heard of that.

Theo Roth: Without these immune cells, you essentially, you're powerless to fight off most infections that have evolved to infect humans.

Brian: Got it.

Theo Roth: But that has an important connection with the cancer side of the things, which is that because T-cells are made to recognize our own cells, but our own cells that aren't healthy, our own cells that have been changed in some way, and the change that they evolve to recognize is a cell that was infected by a virus. But it turns out that they also can recognize cells that have been changed in a very different way, which is cells that have become cancerous.

Quinn: Interesting.

Theo Roth: So the actual systems, the processes that they use are very similar between these two. Obviously there's differences. I can imagine somebody who works in the field listening to me say that and scoffing and writing down the big list of all the differences.

Quinn: They're not here.

Brian: Hopefully they realize that you're just trying to help me.

Quinn: If they want to come on and talk about it, they can come on.

Theo Roth: But yeah, these T-cells, they have this inherent ability to look at our own cells and tell if there's something wrong.

Brian: That's pretty dope.

Theo Roth: That's the backbone for what we want to build on top of them. In the lab, in what we study, and what many other labs study, are ways that this process doesn't work 100% of the time, and there are ways that cancer can get around this process.

Quinn: Fucker.

Theo Roth: Just like there's ways that viruses have evolved to get around the immune system.

Quinn: Right, right.

Theo Roth: Cancers do the same thing on this much more accelerated time scale, which is pretty scary to think about, your own cells evolving inside your body to evade your own immune system.

Brian: Yeah, what the shit man? I thought we were on the same page here.

Quinn: Not cool, man. So what is your guys' big innovation? Explain this to us and why it's such a revolution.

Theo Roth: Well, I'll let time tell whether it's a revolution or not. We're excited about it.

Theo Roth: Like I said, the key steps for these immunotherapies is how do we modify these cells to make them more functional so that when they weren't killing a cancer before, now they are? That step has traditionally been done by actually using a highly modified virus that is able to insert new DNA, insert new functions, into the genome of a T-cell and in that way, give it a new function.

Quinn: I mean, just to be clear, that does sound like the beginning of a really bad zombie movie.

Brian: Yeah!

Quinn: So I'm glad it's gone right so far.

Theo Roth: Well, certainly we think long and hard about the limitations of the ways that we do this engineering, this genetic engineering. Certain movies are more or less accurate when they come to things that actually could happen. The latest gene editing movie, "Rampage," that has a 30-foot crocodile in it?

Brian: Oh yeah.

Theo Roth: That's probably not a likely outcome.

Brian: No?

Theo Roth: The thing that we worry about more is like I said, we're making edits to the genome. We're very concerned and we do a lot of experiments to make sure that, to reassure ourselves, that those modifications that we're making are not going to cause any chance of the cells that we're modifying, themselves becoming a cancer.

Quinn: Yeah, that's not great. What specifically is the modification you guys have done now? What is the advancement?

Theo Roth: Yeah, so I said the main way it has been done traditionally is to infect the cells with a modified virus. Those viruses, they insert their DNA randomly in the genome. I'll take a metaphor that the head of my lab, Alex Marson, has taken to using recently. It's like if you found an error in one paragraph of one page of a book, you can print out a new version of that page and stuff it somewhere in the book, and maybe someone will realize, "Oh, this was the way that paragraph, 100 pages before, was supposed to be."

Theo Roth: What we're going through and doing is, rather than stuffing that page randomly in the book, is going into exactly where the error is, where that typo is, and correcting it on the right page. We think by doing this, that there's one less of a chance of putting the new instructions in in the wrong place and having the chance that potentially those cells themselves, we knocked out a critical gene that suppresses cancerous transformations. That's bad news. So by putting it in a place that we know, we can verify that it's safe. And then also, again, you can take advantage of the context around the site that you're inserting it in.

Theo Roth: Something that we're doing is we're using a patient's own cells, but we're also using a lot of those cells' own instructions that they already have. Like I said earlier, these cells, they have a propensity to attack cancers already. We want to build on top of that. We don't necessarily need to give them an entirely new way of killing a cell or an entirely new way of recognizing a tumor; we just want to enhance the functions that they already have. We think that could be a little bit simpler and a little bit easier to do than coming up with an entire new way to do it and putting in a huge set of new instructions.

Brian: Will this version or does it work much faster?

Theo Roth: Yeah. Getting into the weeds of how we actually do that, the technique that we worked out – and I guess it plays into the title of the podcast – is using these electric fields. A technique called electroporation, which for somebody who took physics in college long ago and has since forgotten most of it, I just kind of know the effects, what happens afterwards, rather than the actual physics.

Quinn: Yeah, it's fine.

Theo Roth: But essentially, we take these T-cells, we put them inside a capacitor, and we discharge the capacitor. For reasons that-

Quinn: Brian just nodded as if he's like, "Oh no, I totally get it now. That makes perfect sense."

Brian: I see a regular plug that you just plug into an outlet-

Quinn: I'm glad you said that. The second you said, "Capacitor," I stopped listening and just thought about "Back to the Future." I'm glad we're all on the same page.

Brian: Right.

Theo Roth: Yeah. Like I said, part of modern science is that it's really, really complex and you can't understand everything. Even in the lab, we know how to use these devices and we know that they work really well. Actually, some of the physical bases of why they work are not necessarily known very well. Even the companies that sell them are kind of a little fuzzy on the exact-

Brian: Whoa!

Theo Roth: Chemistry or the exact physics.

Quinn: Great.

Brian: Wow.

Quinn: It's like all the machine learning that's going on. They're like, "Here's the answer. Don't know how we got there."

Brian: Right.

Theo Roth: Exactly. You don't know how the algorithm did it, but you do know it works.

Quinn: Yeah, enjoy.

Theo Roth: It's like, well, I'll take what works now and then maybe in the future we can figure out exactly why it's working. And again-

Quinn: What is the benefit of the electric field and also why does your stuff glow in the dark?

Theo Roth: We'll get to the glow in the dark in a second. But the benefit of using this electrical process is that just like if, I guess if you remember from physics lab, discharging a capacitor, it's very quick. It's just an instant reaction. That's all the more it takes to modify our cells.

Theo Roth: What this electrical field does is that it temporarily makes the cells very permeable. It means that stuff outside the cell, which normally would not get into the cell-

Brian: Now can.

Theo Roth: Can just float on in for just a very small period of time. What that means is that it's really easy to get stuff into your cell. That stuff that we want to get into the cell are the things that we need to modify those cells' genomes and to give them new anti-cancer functions.

Theo Roth: Rather than going through this big process of making complex viruses and stuff, what we can do is we essentially mix our cells with the protein and a piece of DNA, which are both pretty simple to make, and we put them together inside this little capacitor. You press a button. It shoots. It goes zap! That's all the longer it takes.

Quinn: 88 miles an hour.

Theo Roth: And now you have these modified cells.

Brian: That seems wonderful. What an advancement!

Theo Roth: Well, it is. I can tell you, me personally, I like it for two things. One, because I do these experiments. Anything that makes the experiment that I do go quicker means one, I have more free time, but it also means we can do more experiments more quickly and increase the pace of development of these therapies. We're excited about that.

Theo Roth: I think the second thing is if it's easier for us to do in the lab, then that it means it should be easier, and cheaper, and simpler to do in the clinic as well.

Brian: Right.

Quinn: There's going to be people going, "Well, wait. Does this apply to all cancers?" Who does this treatment apply to? What sort of cancers does this make sense for?

Theo Roth: Yeah, yeah. I think in that case, I live in San Francisco, so it's hard to not start using the buzzwords that the tech employees use, but we think of this more as a platform. These immune cells, these T-cells, they can be made to be specific for many different types of cancers. If we can modify them very quickly, we can modify them in just the right way to attack this type of tumor, say prostate cancer or color cancer. 

Theo Roth: So rather than trying to find a chemotherapy that works against every single type of cancer, if it's really easy and really fast to modify these immune cells, to make them the right type of immune cell for an individual cancer, and that can be an individual type of cancer or potentially under the heading of personalized medicine, and individual patient's tumor. If it's fast enough and easy enough, we can make the immune cells have just the right modifications so that they attack that patient's or that type of tumor.

Quinn: That's the grail a little bit, right? Which is instead of trying seven different things and saying, "Well, this worked on this cancer in this person, but it didn't work on this person with cancer," it's going, "This is this person's type of this cancer and we can now move on these things so quick, that we can act on them in a much more personalized and effective way." Is that kind of what you're aiming for?

Theo Roth: Yeah. No, I think that's exactly the goal. We started by making the process of doing that modification simpler and easier. The next steps for our lab, for many other labs, are figuring out exactly what modifications work with each type of cancer. But we hope that by making the actual modification very simple, then we can go ahead and move forward. There's some cancers that we already know what the types of modifications that we want to make are.

Theo Roth: In our paper, we go through and show how to make T-cells specific for melanomas. We show that, in little mouse models, that these T-cells can attack the melanoma and clear the cancer and so on. Very straightforward stuff that any cancer paper would have, but the key point is that we knew what to do with that cancer because of work that had already been done by some of our collaborators.

Theo Roth: Now, if we can make that type of work go quicker, then maybe we know what to do for other types of cancers sooner. And then we can put it into therapeutic practice for those types of cancers.

Brian: I imagine that you are not doing this with a bunch of humans yet. I want to make sure that everybody who's listening doesn't think that that's happening.

Theo Roth: Oh yeah.

Brian: What's the next step with regards to trials?

Theo Roth: Yeah, yeah. I'll tell you a big disclaimer. The specific types of modifying T-cells that we've done are not in clinical trials yet, because we just published the way to do it this summer. Using modified T-cells that have been modified in other ways, like I said, using viruses and stuff, those are in a variety of clinical trials. Actually, the first FDA approval for a gene modified cellular therapy just came last year for two therapies for two different types of B-cell cancers, or lymphomas.

Theo Roth: These therapies are now starting to hit the clinic. So it's a really exciting time to be working, maybe not a little bit more on the gritty backend of things, and the techniques and the methods that are used to actually make the therapies. It's an exciting time for that.

Theo Roth: For us specifically, the next steps in our lab, we do basic research. We have ideas about how to make this technique even simpler or even easier. We're working on testing those. But at our university and with some collaborators though, now we're starting to do the work to put together an initial clinical trial, testing this either in cancer indication or for a slightly different indication but actually correcting a specific family's mutations that have caused an autoimmune disease in that family. We know the mutation that is causing it, we know that's the reason why, and we know that we can fix that mutation, the exact mutation itself, in their own cells' genomes. We're working towards doing a clinica trial for that family.

Quinn: That's, I mean, I think of a couple of things. I think about how mad my wife gets when I just want to fix things, and she just wants to talk about them, and be heard, and I'm always trying to fix them. But it's generally things like why haven't I made the children's lunches in time for them to get out the door to school? And you're trying to fix a family's genome. It's impressive.

Quinn: I also think about how I've been trying to get Brian to read some important project organization books for a couple years, and he refuses to do so.

Brian: I appreciate that you're trying to help me.

Quinn: Maybe this whole episode is an intervention.

Quinn: All right, so Theo, we're getting a little bit more towards action items. We know the history of everything, we know the context, we know what you do and why it could possibly be so helpful, and where you guys are aiming yourselves in the short-term and the long-term. People are excited about something. Thank god, fuck cancer.

Brian: Fuck it.

Quinn: How much does a project like yours cost? Where does the funding for this specific project come from?

Theo Roth: Yeah. That's a great question. I think it's something that even having been in labs and working in science for eight or nine years now, it's something that a lot of people in science don't really know exactly where the money comes from.

Theo Roth: I can tell you that the single largest source of basic science research, especially health-related research, in the United States is the federal government. The US tax dollars fund the National Institutes of Health. The National Institutes of Health divvy that money up in a meritocratic process. They take proposals. We write, we call them grants. We wrote a proposal about a project that we think would be useful; we have to convince them that this is a good use of American taxpayers' money, and that it's going to potentially have some benefit.

Theo Roth: We write those proposals. The NIH, they convene groups of scientists together. Crucially, these are not federal employees; these are just working scientists. It's an outside review process. They determine which ones, which grants, they think have the most scientific justification, and are presented in the best way, and it looks like the group will actually be able to do the research they set out. And based on that, they recommend a certain portion of those grants for funding.

Theo Roth: I can tell you the funding, the proportion that get funded is a number that scientists watch in eager anticipation. Right now, it's about 20%.

Brian: Whoa.

Theo Roth: One in five proposals that scientists send to the government to say, "This is research that we think is worth doing," and these are big, in-depth proposals. It's not a fun couple of weeks when you're-

Brian: And there must be thousands of them.

Theo Roth: Oh yeah, oh yeah.

Quinn: So where is 20% on the historical barometer of things that are getting funded? Is that average? Is that pretty low? Is that pretty high? You know, with these complete fucking monsters running things.

Theo Roth: Well, it depends on what you look, when you compare it to. 

Theo Roth: This modern system of funding science through federal grants only really came about after World War II. In its modern iteration, it's probably only been around, this system's only been around for 50 or 60 years. Before that, science was primarily funded by individual benefactors. The classic Victorian Era mad scientist who has some nobleman who thinks he's cool and sends him money to do crazy experiments. That's how science went forward for a long time.

Quinn: God, I just want to be that guy so bad.

Brian: Yeah, it'd be cool.

Quinn: Okay. In a slightly broader context, real quick, one of our overarching goals is to help shine a light on where we need to go as a people here, which is obviously coming to press here in a couple months before the midterm elections. You said one of the biggest chunks of funding is coming from tax dollars. Obviously, this isn't your day job, but what, in your view then, are three big actionable questions the rest of us should be asking either of our representatives or the people who are running for office?

Theo Roth: Yeah. Probably the single biggest one is do the people who represent you value the impact of basic science research as a way to help improve all of our lives? 

Theo Roth: There's many classic examples, but the lasers were developed with federal research funding for basic science applications long before we had any idea of all of the amazing uses they would have. Despite how much we complain about our phones and stuff and whatever, but modern technology, a lot of it's based on stuff that was developed in basic science labs. Generally, we think it's quite useful for us and makes our lives better.

Theo Roth: This is actually, especially when it comes to biomedical research, that's actually probably ... It's hard to find areas that the two parties still agree on, to an extent. Basic biomedical research funding is probably one of the few that's left. I think that makes it all the more precious that people on both sides of the political spectrum continue to value this because we don't necessarily want funding for the next cancer drug to become a partisan issue.

Quinn: Yeah. It is impressive. Trump tried to destroy science budgets, from NASA to biomedical, and Congress not only said, "No, fuck that," they actually gave it more. There was an increase, which like you said, it is maybe the last thing we can agree on. So sweet Jesus, let's hold onto it. But also, let's put even more people in office who believe in empirical data and evidence-driven decision making and rational thinking because gosh, if this is what we can do now, imagine if we could increase that even more and provide more specific support.

Theo Roth: Yeah. Like I said, it's not necessarily something that I think a lot of people think through and take pride in, but not saying to make America great again, but America is the leading center of biomedical research in the world. American universities are some of the best in the world. There's lots of good science going on in Europe and in Asia and throughout the world as well, but a lot of the key advancements, like the key therapies for cancer, for infectious diseases, for autoimmunity, they were developed with American tax dollars.

Theo Roth: I certainly, I get my chunk of my paycheck that gets taken out to fund the government, but I think people should take pride in the fact that this is something that we, as a society, decided was worth funding. It's something that your parents and our grandparents funded, and now we're the ones that get to take advantage of those therapies that were developed based on the research that was funded by your grandparents.

Quinn: Right, this stuff doesn't come from nowhere. They might have destroyed the planet, but they did pay for basic science.

Brian: Pretty important.

Theo Roth: Yeah, I think that's something you could take ... If you take pride in that and then try to, for your representatives, you say that, "You know what? This is something that's important. This is a way that we can invest in the future, that we can make our children's lives better than ours by doing basic science research today."

Quinn: Sure.

Brian: Love it.

Quinn: Right, if those were the implications of their funding now, what could you do for your children and their children? Assuming we're not all under water in 25, 30 years.

Brian: Ugh. Well, we have taken so much of your time, Theo, and we really, really appreciate it.

Quinn: Yeah.

Brian: Who do you think we should talk to, besides you? Maybe Marson? Anybody else?

Quinn: Yeah. We're, again, from climate to cancer to clean energy to antibiotics to space, we're trying to, again, have these evergreen conversations about the things that are actually – not sci-fi stuff – but things that are actually affecting people and in the next 10, 20 years. And then again, diving into a specific topic, specific question, and then finding someone who's on the ground doing the work like you.

Quinn: It doesn't have to be electrocuting cancer, it can be anything else.

Theo Roth: Depending on the way you wanted to take things, obviously there are other people in our lab like Alex, the head of our lab, would have more thoughts about the work that we did. There are leaders in the field actually using these immune cells clinically already.

Brian: Oh yeah, that'd be a cool angle to hear.

Quinn: Right.

Theo Roth: The two names that I can say off the top of my head, a guy at the University of Pennsylvania, his name's Carl June, and a guy at Memorial Sloan Kettering in New York. His name's Michel Sadelain.

Theo Roth: A general topic, we didn't really talk a lot about the actual CRISPR/Cas9 genome editing, and that stuff, that's a much larger topic though than making cancer therapies.

Quinn: Right, right.

Theo Roth: Especially when you start talking about making gene modifications for stuff that's going to go back into the environment. That comes in two forms, both genetically modified crops, and all of the controversy around those, also now genetically modified organisms. The main example right now is mosquitoes. We think there's ways that we can actually genetically modify mosquitoes that they will take over ... You can make a version that won't get infected with malaria and-

Brian: Could we make version that doesn't exist because they're a pain the ass?

Theo Roth: Well, there's people that they think can do that too.

Quinn: Yeah, but it is crazy. It's such an incredible backdoor way. Instead of treating malaria, it's like the old Sun Tzu version of what if we just cut it off and kill it from the start?

Theo Roth: Yeah.

Brian: We just read an article about genetically modifying humans so that we can live on Mars one day.

Theo Roth: There you go.

Brian: Shit is going crazy.

Quinn: Yeah, it seems to be a little bit of the moment of, "Oh, why not this?"

Theo Roth: Right, yeah. It kind of gets into a larger of topic of some people think that maybe engineering solutions of the environment are the way to combat climate change, that you're never going to do it on the human side, so we're going to have to make up for our mistakes or whatever. It's kind of a similar thing from the environmental side. I think there's a very healthy conversation going on among scientists about whether that's actually a good idea or not. 

Theo Roth: Now, you actually really do get into the plot lines of disaster movies or zombie movies and stuff where you're talking about, "Oh, we're going to make the super mosquito that can't get infected with malaria," and it turns out you actually just made a mosquito that you can't kill and that can infect even more.

Quinn: I'm pretty sure, and I think we talked about this on a different episode, but I think the beginning of this version of "I Am Legend" was they're like, "Hey, Will Smith is this military doctor and he figured out how to stop AIDS" and then two weeks later they're like, "Ha ha it turned everybody into zombies." Not great. What was the? "Snowpiercer" is the same thing].

Brian: Yep, yep.

Quinn: Earth is getting hot because we shot a bunch of stuff in the air. Bad news, it's snowing everywhere.

Brian: As long as there's no super mosquito that can't be killed, I'm going to be pretty happy. That sounds-

Quinn: That's it, that's your threshold?

Brian: That's just my worst nightmare.

Quinn: All right.

Brian: All right, let's get into, we have a little lighting round of questions that we love to ask everybody.

Theo Roth: Great.

Brian: Except for the first one that's not a lighting round question, but it hangs out in this category anyways.

Quinn: Shut up. I'm too tired. I have so much to do. Theo, when was the first time in your life when you realized you have the power of change or the power to do something meaningful?

Theo Roth: First time I wasn't just taking a test or learning stuff out of a book that a thousand people had learned before was the first time I worked in a lab. It was over the summer after I'd graduated from high school. It takes a while to learn a few techniques and stuff, but pretty quickly, you do an experiment and it's an experiment that no one's ever done before. You're the first person to know the result of it.

Quinn: That's so wild. Brian, what'd you do the summer after high school?

Brian: We are not getting into that.

Quinn: Theo, who is someone specifically in your life that has positively impacted your work in the past six months?

Theo Roth: I don't know if he listens to the podcast, but there's a guy in my lab who's a post-doc. His name's Eric Shifrut. 

Theo Roth: One of the beautiful things about science is that it's this big collaboration among lots and lots of people. Experiments are very complex; you have lots of people working on experiments, but also the ideas are complex and they go across fields. There's this guy, this happens to be a guy in the lab that really, his way of thinking about these experiments really clicks really well with mine and just having that sounding board to say 100 dumb ideas before you get to the one good one is super useful in the lab and in life in general, I guess.

Quinn: Yeah. As a writer, that person is super helpful, who can just be like, "No, that's a terrible idea" and [crosstalk 01:06:28] because that's the only way to get to the good stuff.

Theo Roth: Oh yeah. No, we have a lot more bad ones than good ones. I'll tell you that.

Brian: Hey Theo, how do you consume the news?

Theo Roth: Maybe it's a little bit anachronistic, I try to stay focused on work during the day and stuff, so I stay off-

Quinn: What are you talking about?

Theo Roth: I try to stay off Twitter and social media and stuff as best as anybody can. Doesn't mean that always happens. I actually like the weekly news magazines that are kind of like, "Here's the 50 pages of stuff that we've thought is useful from the past week," and if you read all that, then somebody's said that they think you'll be well-informed with that. I like to read magazines when I get home at night or something like that.

Brian: Nice.

Quinn: It's very civilized.

Brian: Very civilized. All right, if you could Amazon Prime one book to the president of this country, what would it be?

Theo Roth: I'll bet you people have tried that already. I don't know if he'd read it, but there's a classic book that-

Quinn: Don't worry about that as being the prerequisite.

Brian: Yeah.

Theo Roth: There's a classic book about the history and the development of modern molecular science. It's called "The Eighth Day of Creation." It's written by a guy named Horace Judson. It was published in the late '70s. Now it's, what? 40-years-old and so I was like, "Okay, certainly science has moved on," but the process hasn't and the type of people who do science, I don't necessarily ... The people who really enjoy science necessarily hasn't changed or the type of person.

Theo Roth: This was an example, this guy Horace Judson, was an example of a science journalist, he wasn't a scientist himself, who took years to interview all of these practicing scientists and find out how they worked, what their process was, what they thought was interesting, and how they had made these monumental discoveries like the structure of DNA, how DNA encodes for what all of our cells do. The product of this 10 years of work and interviewing, all of the people – Watson and Crick and the big names of molecular biology – he put it altogether in this admittedly quite large book, but that book was something that I read a couple of years back and really reignited my passion for basic research.

Theo Roth: I think, if anybody, you listen to somebody talk about how it was just this idea in their head how DNA was structured and then they spent years figuring out how to actually test that. Then they showed that it was true. Now so much of modern medicine is based off of that single discovery. It's just two guys and, you know, essentially all guys doing the research then unfortunately, just sitting there in a room thinking about it.

Quinn: Yeah, that's so wild.

Theo Roth: But that is how science moves forward. It's like, "Oh, I'd like to sit in a room and think about things all day" and that be a paying job.

Quinn: Oh, Jesus. Wouldn't that be incredible? But it is true. 

Quinn: I mean, honestly, it doesn't matter what you're working on and I'll find some of the specific research on this and put it in the show notes, but there's been so much that's come out that said how important "daydreaming" is and how much of our ideation and creativity comes from the subconscious and unconscious brain, not sitting at a fucking computer and white screen all day because you're inputting things and your unconscious and subconscious are tethered together both so differently and so much less rigidly than it lets you put together these disparate ideas. You can't even take credit for because it is an entirely different process you might not of otherwise come up with.

Quinn: Writing science fiction is very much the same way. It's not the first thing that comes to mind. It's crazy ass shit to come up with when you wake up in the middle of the night.

Theo Roth: Yeah, no. Can't tell you how much of our paper and experiments that I do in general are something that while I can't fall asleep, just randomly thinking about, and suddenly this idea clicks and you're like, "Oh, that's the best idea I've had all month." And then rush to write it down and wake up the next morning and run into the lab and set it up.

Brian: I think I've been daydreaming too much and not working enough so I gotta work out the balance of those things.

Quinn: There's a balance.

Brian: Yeah.

Quinn: Awesome.

Brian: Theo, where can our listeners follow you online?

Theo Roth: I would say there's a lot of good summary emails and stuff for advancements in science. One of my favorites is the "Journal of Nature" has a daily morning briefing email, like a lot of companies have nowadays, that sends out a really nice broad stretch of what are the interesting things happening in the scientific world right now? If you're more interested on the medicine side, there's a new online news service called Stat that has-

Quinn: Oh Stat's great. Love Stat.

Theo Roth: I read through their morning emails every day just to get a sense of what's going on what's outside of my specific field. I think that's a great way to stay in touch with-

Quinn: I'll definitely pull from "Nature" and Stats stuff when we're trying to do our newsletters on a weekly basis to find those real top hits that people should know about. They do really excellent work. The Conversation is another one like that.

Theo Roth: Yeah, absolutely.

Quinn: Yeah, they do great stuff. 

Quinn: Theo, man, we've taken so much of your time but this has been awesome. We really, really appreciate it. We really appreciate all that you're doing, just taking cracks at this thing. You're helping people man, you're saving lives and that's pretty incredible.

Theo Roth: Hey, like I said, it's comforting to think that the work that you do is useful, but I can tell you on a day-to-day basis, the thing that we like about it is we do get the unique privilege to sit around and think about things that we don't know and how to test them. Doing that in a way that is useful is, like I said, it's a great privilege that we're able to have that opportunity as scientists. 

Theo Roth: For people, if anybody's listening thinking about careers, can't recommend basic science anymore than that. You get to come up with ideas about what you want to test, learn something new that no one else has ever known before, and that thing may very well be something that helps patients in the near future.

Brian: Right.

Quinn: Yeah. It's a privilege, but it is absolutely necessary. It is where all of these things come from, and we are thankful for it, man.

Brian: Yeah. Thank you very much.

Quinn: Awesome Theo. Well, we will talk to you soon, brother. Please go get back to work.

Brian: Good luck on all the letters after your name.

Quinn: Yeah, good luck man.

Theo Roth: Yeah, we'll try.

Quinn: Let's us know when you're done.

Theo Roth: That'll be a while. Thank you, thanks for having me on.

Quinn: All right, man. Thanks.

Brian: Thank you.

Quinn: Be good.

Brian: Ciao.

Quinn: Bye.

Theo Roth: Bye.

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 dish washing, or fucking dog walking late at night that much more pleasant. As a reminder, please subscribe to our free email newspaper at ImportantNotImportant.com. It is all the news most vital to our survival as a species.

Brian: And you can follow us all over the internet. You can find us on Twitter @ImportantNotImp.

Quinn: Ugh.

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Quinn: Please.

Brian: You can find the show notes today right in your little podcast player and at our website, ImportantNotImportant.com.

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

Brian: Thanks guys!