Ep.1: CRISPR & A Hot Bath

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Episode Agenda w/ Time Stamps:

• 00:24 - Banter: Final Fantasy 7, parenthood, kidney stones, Pedialyte popsicles, Schitt's Creek, Middleditch & Schwartz
• 06:54 - Academic Deep Dive: CRISPR, genome sequencing, and the history and future of gene editing.
• 38:30 - Final Inquiry: Do we cook ourselves when we take hot baths?

Credits:

• Cover Art Photo: Mosby Lake - follow this dog on instagram at regular_mo.
• Cover Art Font: Paper Cuts 2 by Empire of Dust (Daniel Werneck) is Public Domain.
• Intro Music: Shortened version of “Sweat Time” by Loyalty Freak Music is licensed under a CC0 1.0 Universal License.
• Outro Music: Shortened version of “Alethia” by Nihilore is licensed under a Creative Commons Attribution 4.0 License.

Transcript

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Ep.1 - Yondercast: CRISPR & A Hot Bath

Ian: [00:00:00] Hello everybody and welcome to Yondercast, a show where three science teachers and sometimes other people do their best to answer your questions. My name is Ian Lake, and this week I'm joined by my good friend Patrick Leitch, 

Patrick: [00:00:15] yo, 

Ian: [00:00:17] and my mediocre friend Joshua Baltzell . 

Josh: [00:00:22] Hey 

Ian: [00:00:24] guys, how you doing? 

Patrick: [00:00:27] I'm doing fantastic.

I just one hundred percented final fantasy seven so I'm riding a good high here. 

Ian: [00:00:32] Huh? How long did that take you? 

Patrick: [00:00:36] Just shy of 90 hours. 

Ian: [00:00:38] 90 hours. And you've done that over the last, I think two weeks, right? 

Patrick: [00:00:44] Three at about 5:00 AM three at about 10:00 PM with the little one. Just takes a little time.

Dedication. 

Ian: [00:00:51] Yeah. Speaking of the little one, Patrick, you recently became a father. 

Patrick: [00:00:55] Yes. Round two baby girl. 

Ian: [00:00:57] Well, congratulations. Well, I guess you are already a father. Yeah. Cause you already have one. So in that case, no congratulations. Perfect. 

Patrick: [00:01:05] Send it. It's okay. 

Ian: [00:01:07] In fact, shame on you.

Actually, you know that we are recording this a day after, mother's day. So you're going to have to extend a congratulations to your wife for us. 

Patrick: [00:01:20] I will. I will. I'm sure she will very much appreciate that. 

Ian: [00:01:24] Are you guys going to like congratulate me since it's mother's day or was mother's day yesterday?

Josh: [00:01:32] Happy mother's day, Ian. 

Ian: [00:01:33] Cause I just see just because I also pushed something out of my body recently. Oh. 

Josh: [00:01:39] Oh. The kidney stone.

Ian: [00:01:43] Yes. I'm talking about my kidney stone. 

Patrick: [00:01:46] I had concerns. How many pounds and ounces it was. She was like, she was like eight pounds, six ounces. So I'm, I'm kind of expecting along something on the same lines.

Ian: [00:01:58] No, no, no. It was four millimeters. Gotcha. I don't have a mass for you. 

Josh: [00:02:04] Did you keep it? 

Ian: [00:02:06] Yeah, I have it. Doctors got to look at it and tell me what it is. You know so much space. It doesn't 

Josh: [00:02:12] take up on your fridge.

Ian: [00:02:13] I didn't put it on my fridge. I have it in a little plastic baggie in my drawer.

Everybody that I have told about it has told me that, having a kidney stone is the closest that a man can come to experiencing labor pains. So I don't know if I'm very far off in expecting congratulations for mother's day, to be honest with you. In fact, I feel a little bit jaded because. I did not get the beautiful pregnancy experience that I feel like I should have gotten for having gone through that pain.

Josh: [00:02:47] You didn't get to do the photo shoot and 

Ian: [00:02:50] yeah nobody threw me a kidney shower. I didn't get a single gift, a card, anything. 

Patrick: [00:02:57] Well, I did have a friend during labor tell his wifei t looks like she's having a spa treatment. 

Ian: [00:03:01] So wait, the baby was having a spot treatment like was covered in guacamole or something.

Patrick: [00:03:09] So she was vomiting during labor and they put a nice cold towel on her forehead and my buddy decided to have the gall to say, it looks like you're having a spot treatment. That's a big oops. Mistakes were made. Is that good? Is that kinda how it happened with you as well? Nice little cold towel over the forehead when this was all going on.

Ian: [00:03:32] No man, I got  pretty poor care. Honestly. I went to urgent care and, I mean, the whole medical system is really, overwhelmed and urgent care is, is kind of taking the place of, clinics and things like that. But, no, they, they gave me a bottle of water and I sat in a, waiting lounge for like two and a half hours in the worst pain of my life.

And then they brought me back into a room and they gave me a Popsicle. And then I sat there for over another hour, 

Patrick: [00:03:58] desirable flavor? 

Ian: [00:03:59] And when finally came in, it was a Pedialyte Popsicle. It was super gross.

 I think they only gave it to me because I was, so gray and sweaty and shaky that they were like, this guy needs some electrolytes. 

Josh: [00:04:13] Thoughtful. 

Ian: [00:04:15] Yeah, but not, not like a doctor. He just needs a Popsicle.

 But there's probably better things that we can talk about than my Pedialyte popsicles that I got. Have you guys seen anything interesting coming up in the news or in your lives,  been watching anything interesting lately? 

Josh: [00:04:34] We just started watching Schitt's Creek. 

Ian: [00:04:36] Oh, it's so good. 

Josh: [00:04:37] Yeah. I've been binge watching it for the past three or four days. I made it all the way to season five 

Ian: [00:04:44] in three days,  

Josh: [00:04:45] in more like a week. 

Ian: [00:04:47] Okay. Okay. 

Josh: [00:04:48] It's still, it's been bad. 

Ian: [00:04:51] It has become one of my favorite shows, you know, right up there. It kind of, it kinda captures like. A similar vibe to The Office or Parks and Recreation, especially the later seasons where they sort of, they don't ratchet down the humor, but they ratchet up the kind of emotional component and the interactions between the characters and the feel-goodiness that's behind each episode, it's just like kind of feels good to watch. 

Josh: [00:05:16] It might just be because it's Eugene Levy, but it reminds me of Best in Show and like Spinal Tap, that kind of humor 

Patrick: [00:05:23] out of a similar cast too. 

Josh: [00:05:25] Yeah. 

Ian: [00:05:26] I think a lot of those people have their roots, their comedy roots in improv.

In fact, I think the reason that those movies have like a pretty. Signature like style is because a fair amount of it was improved. I mean, they had an idea for a scene, but not  perfect memorize lines or things like that. 

Patrick: [00:05:44] Well, Catherine O'Hara is like comedy gold of improv with what she says.

Josh: [00:05:48] Oh, she's hilarious. 

Ian: [00:05:50] Yeah, she's great. Some of some of the things that she says are my favorite lines of the show. Speaking of, improv, I watched the, Middleditch and Schwartz specials on Netflix, which for our listeners, they're definitely for a mature audience. but they're pretty great.

They're pretty hilarious. And,  believe it's a pretty groundbreaking thing because it's improv comedy. And while there's, you know, like a million standup comedy specials all over the internet and on every single streaming platform. There's not a lot of improv comedy specials, so I'm hoping that it paves the way us seeing a lot more of that kind of stuff because love improv comedy personally.

Josh: [00:06:29] Well, it's such a hard skill. Anytime people can do something like that, it amazes me. 

Ian: [00:06:36] It's really impressive. It's really hard. tried it a couple of times and it's, it's really difficult.

Patrick: [00:06:42] Those two are really good together. Like me and my wife were watching it and it was really funny. We laughed almost the entire time. Even the super obscure stuff. 

Ian: [00:06:50] Yeah. They have great chemistry as a duo. Well, gosh, Hey, should we get to our listener question for the week? Yeah, let's do it.

Awesome. So one of our listeners, Andrew, made a request. he asked that we address CRISPR gene editing on the show. And, I immediately, when I saw that question was like, absolutely, I want to do this because I have a little bit of experience with CRISPR. I utilized CRISPR as a tool in a lab when I was in college, lab that I was doing research in.

And so, it's something that I, have a little bit of background in and that I want to know a lot more on. So, before I jump into an explanation of what CRISPR is, I want you guys to explain it. Oh no, I like 30 seconds. 

Josh: [00:07:33] well, I know that it cuts genes. So that you can put genes into other things.

I think. 

Ian: [00:07:40] All right, Patrick, what you got? 

Patrick: [00:07:42] The only crisper I know is in my fridge and it keeps my fruit nice and yummy. I also have scissors that cut jeans, so I feel like I'm pretty close to an expert already. Well, one of us is closer, but, 

Ian: [00:07:58] I have to ask Patrick, do you cut all of your jeans?

Patrick: [00:08:02] I do like a nice pair of Jean shorts. 

Ian: [00:08:06] much are we talking about here? 

Patrick: [00:08:10] That's not even a question. I feel like 

Ian: [00:08:12] the whole thing.

 All right. Well, Josh, you were closer. 

Josh: [00:08:20] I 

Ian: [00:08:22] a lot. Those are you win. 

Josh: [00:08:23] I don't lose points for getting it wrong, right? This isn't like jeopardy. 

Ian: [00:08:26] No, no. And the points don't matter.  But, Josh, you have one point and Patrick, you have zero points. Ah, 

Josh: [00:08:33] there you go. 

Ian: [00:08:33] so Josh, you were right. CRISPR is basically a tool for cutting genes.

And that has. become foundational skill or a foundational tool for genetic modification. And basically. Everything we're trying to do in genetics right now. which is why you often hear, about CRISPR all over the news. And people are always talking about it and people are always talking about how it could be used for various things because, it's basically a tool for altering genetics.

And since genetics is  the foundational layer of the organization of life, if we can manipulate that, we can like do anything cool. So I want to do a little, a little bit of a history lesson right now and kind of like lead up to, when CRISPR was discovered and,  why it's such a big deal.

So do you guys know when DNA was discovered? 

Josh: [00:09:24] Oh, I have a guess. okay. So Jeff Goldbloom played either Watson or Crick in that movie, and that came out in like 1980. 

Ian: [00:09:36] So Jeff Goldbloom discovered DNA in 1980 

Josh: [00:09:39] yeah. Jeff Goldbloom discovered DNA 1980 that 

Patrick: [00:09:44] Jeff Goldbloom. Nice. 

Ian: [00:09:46] What were you gonna say though? 

Josh: [00:09:48] My guess is like 1960.

That's so wrong. 

Patrick: [00:09:54] I was going to say 47 

Ian: [00:09:59] okay. Patrick is closer. So Patrick has one point now you guys are tied.  so DNA was first, I guess isolated. It was identified in 1860  we didn't know really what it was, but that was really the first time looking back on it, that someone kind of.

Looked at DNA as an thing and was like, Hey, this is something unique. and it was a Swiss chemist, I think, if I'm pronouncing it right. His name is Friedrich Meischer. And, he discovered it basically by accident. he was washing, the cells and the contents off of pus covered bandages that he got from a local surgeon.

He was interested in isolating something else that was in the cells. But he ended up finding this thing that he was like, Hey, this is, this is something that we don't know about. And that thing ended up being DNA. but it was a long time before we really figured out what it was.

 the turning point was Watson and Crick, which is what you were talking about, Josh. in 1953 is when they published their paper, and that's when they discovered that DNA had a double helix structure. 

Now I want to point out that the Watson and Crick article should have been the Watson and Crick and Franklin article because Rosalind Franklin's x-ray diffraction data was vital to Watson and Crick putting together the pieces of the puzzle and solving the double helix structure of DNA. And she was. Not given the credit for her contributions that she should have been given. And this is a problem that has recurred over and over again throughout the history of science, especially with regards to female scientists and scientists of color. But that could be its own entire topic for an entire podcast and, and should be, hopefully we have a chance to do that at some point.

But moving

so that was kind of like beginning of our, true understanding of DNA. And so, through the 1960s and the 1970s, we were really just trying to build off of that and really understand, what was going on with DNA.

And there's a lot that could be said there about, how even in the 1970s, we had ways of manipulating and changing genes, but they were really, really non-controlled. It was things like bombarding organisms with, radiation to just cause random mutations. That's how we would change DNA or, the very first gene therapies where it was trying to insert specific sequences of DNA into organisms, was done using viruses. So they basically hijacked. Yeah. They hijacked viruses. And the way the viruses work, is that they inject their DNA into cells, and then that DNA gets inserted into the, actual DNA of that cell and basically hijacks the cell and makes it a virus factory. So it's just producing tons of viruses and so many viruses until usually the cell can have just bursts, like explodes from all the viruses inside, and then those viruses go on to infect other cells. So the first way that we manipulate a DNA was by. Hijacking that viral system and putting the DNA that we wanted to insert into organisms, into viruses, so that they would go and find cells and inject that DNA and that DNA would get added to the genome of that organism.

so we were doing that as early as like the 1970s we were inserting genes into stuff. But the problem with that is that it was super nonspecific. Like the virus would just insert the gene somewhere. And we had no control over where. So it may have gone in the middle of like another gene, right? Or it may have gone somewhere in front of  another section of DNA that made it so that the gene didn't actually get expressed.

 there's all sorts of things going on with promoter and repressor regions and stuff in DNA. So it wasn't perfect by any means. But that's where the whole thing started, with gene therapy and us trying to control what genes and organism has. And then in the 1980s it was 1987 there was a scientist who was trying to isolate a particular gene from a bacteria.

You know, in the 1980s we didn't have CRISPR. So we didn't have a way of cutting DNA exactly where we want. So he ended up isolating the gene, but with some extra DNA on one end of it and that DNA had this interesting quality to it.

there were these repeating segments, so there was like a section of DNA, and then there'd be another unique section of DNA, and then after that there'd be a repeat of the first section of DNA and then another unique segment, and then a repeat of the same signature sequence. And so he was kind of like, huh, that's interesting.

We should look into that. And that ended up being the real discovery. I don't really know what happened with the other gene that he was interested in. 

Josh: [00:14:40] We don't care about that anymore, 

Ian: [00:14:42] honestly. I mean, I'm sure, it led to some, knowledge, but that sequence of DNA, that was, those repeats and those unique sequences in between the repeats.

that was the first CRISPR sequence that was identified and CRISPR stands for clustered regularly. Interspaced short palindromic repeats. It stands 

Josh: [00:15:02] for something that's kind of a duh, but I just never thought about that. It stood for anything. 

Ian: [00:15:08] Yeah, it's, C. R. I. S. P. R, so there's no E.  it's an acronym.

Patrick: [00:15:13] That's what separates it from what's in my fridge.

Ian: [00:15:15] So, yeah, it basically is these, clustered repeating DNA segments. So after looking into that, what they discovered is that, remember, this is in a bacteria. So these repeating segments of DNA were in between all of these unique segments of DNA and the unique segments of DNA did not belong to the bacteria.

They were actually viral DNA. And what they figured out is that that bacteria when it had been infected by a virus and the virus had inserted its DNA into the cell, the bacteria had cut out a portion of the viruses DNA and inserted it into its own genome. And it basically just added it to the list of viruses that infected it so far.

 what that enabled it to do is that if it ever got infected by that same virus again, it would use these little segments of DNA that were in its genome to program these special proteins to go out and cut and deactivate the viral DNA. 

Josh: [00:16:19] This is almost like a natural vaccine.

Ian: [00:16:21] it's completely an immune response thing that is 

Josh: [00:16:24] so weird 

Ian: [00:16:25] it's not an immune response like ours, right? We have an antibody based immune response. Generally this is a DNA based immune response, but it basically does the same thing.  these little sequences provide immunity to the viruses.

And so this was a huge discovery. And, the  sequences of those repeating pieces of DNA, those were called CRISPR sequences. And the proteins are called CAS proteins, which are CRISPR associated proteins. And so you'll often hear the CRISPR CAS system in reference to CRISPR.

 and that's what it's talking about, is it's talking about the connection between these DNA sequences and the proteins. So the development of this understanding, you know, started in 1987 but we really didn't fully understand it until the early two thousands and then in 2012 was really the breakthrough.

at that point, this whole system had sort of been re-engineered for gene modification. So various groups of scientists, made some modifications and basically engineered. The cas protein so that they could, Oh my gosh, my dog 

Josh: [00:17:37] loving it. 

Ian: [00:17:39] He's got a lot to say about this too. Hey, Mosby Mosby come here.

Josh: [00:17:45] This one of our special guests, 

Ian: [00:17:48] our first special guest 

Josh: [00:17:50] expert opinion. Conversation is going to be a little bit ruff. 

Ian: [00:17:54] Oh man. Wow. So essentially in 2012 we re-engineered these, proteins so that we could program them to do whatever we want. We can create any sequence of DNA we want and put it in a engineered cas protein as a guide, and that protein will go and cut DNA as it's instructed to by that, DNA, or actually an RNA, set of instructions that we put into that protein. And that's, basically it. So essentially we just programmed these proteins to cut DNA at a specific sequence.

Josh: [00:18:34] That's far simpler than I ever imagined. I never bothered to look into it because it sounded so complex. But that, that's really straightforward.  

Ian: [00:18:43] that's the whole thing about it, right? the best technologies are super simple ones. and that's why it's such a phenomenon is because it was obviously a complicated process to get to the understanding.

But the idea behind it and the usage of it is really simple. It's literally just a set of genetic scissors. 

Josh: [00:19:04] So how long? Serious question. How long until I can perform photosynthesis? 

Ian: [00:19:11] I need 

Josh: [00:19:11] a number. I need a number. 

Ian: [00:19:15] No comment. No comment. I'm not going to put myself in the catalogs of history as making a claim.

No idea how to make. But the idea that you have there, is potentially not as ridiculous as you think it is. I mean, the photosynthesis is not, process that is part of our evolutionary history. And so I don't know if that's something that, could easily be translated into a human, but, the idea of Manipulating and controlling, humans and their traits, especially when we're talking about traits that already are in the human genome. that's already happening. 

Josh: [00:19:49] I feel like that's where it gets a little bit dicey. Especially, I mean, as a parent, it's kind of interesting to think that if you knew going into having a kid that they could potentially have a serious health defect that you could potentially treat, which would be kind of interesting.

But at the same time, that gets into the whole eugenics idea of controlling what people are before they even are, I guess really fully developed people. 

Ian: [00:20:13] Right. I mean that that is the biggest ethical dilemma. With regards to, CRISPR and these gene editing technologies, the biggest concern is exactly what you just shared.

And some people even think that, altering human genetics and, you know, messing with natural order. And I mean, even when it comes to like altering,  our foods and things like that, some people think that it just shouldn't be done and we should just not. Not use CRISPR and not do gene editing technologies.

But the problem is that when a technology exists, people will use it. And so there's really  no going back, right? There is no way to eliminate CRISPR from our abilities at this point. And so genetic modification is here, and I think it's. I think it's here to stay. I don't think it's going to go anywhere.

so the question is where do we draw the boundaries? And that's something that is constantly being discussed and is not, a solid thing. Because like you said, it seems like if we have the technology to potentially alter a child in the embryo stage to remove or fix a genetic.

Disease. It almost seems like we have an ethical obligation to do that. Right? But at the same time, the scary thing about CRISPR is that, you could even make changes to germline cells. You could even make changes to the cells that are going to produce reproductive cells down the line. So you're not necessarily just changing an individual.

You could potentially be changing that individual and all of their descendants. Forever. And that's a big responsibility, right?  what if you're trying to fix a disease, but you end up creating another problem that 

Josh: [00:21:56] lasts forever. The butterfly effect sort of thing. 

Ian: [00:21:59] Exactly. Exactly. And then there's the whole question of the slippery slope of like, well, if we're changing genes to fix diseases or fix problems, and we live in a capitalist society where, money is what drives everything, what's, to stop, A person from paying a little extra to not just fix the disease gene, but also, replace a gene that's going to make it so that their offspring is a little bit taller or alter that gene with regards to hair growth so that they don't go bald or something for me. So it's a really interesting ethical dilemma when you're talking about humans. 

The place where CRISPR is  being used in mostly unarguably favorable ways is with regards to other species and with regards to medicine. And so I've got some really cool examples to share with you guys because, since CRISPR is basically just a tool to cut DNA, but also just identify DNA. there are companies such as Mammoth Biosciences that are working on disease identification kits utilizing CRISPR.

Josh: [00:23:07] So they identify if you're sick?

Ian: [00:23:10] Yeah. They identify if  a virus is present in your system. 

Josh: [00:23:13] Oh, that's cool. 

Ian: [00:23:14] They're working on one for the Coronavirus right now. Actually, and it's probably going to be a thing soon pretty good thing. The goal for that is not to edit the genes. The goal is simply to identify if the genes are there.

And so what these kits do is you can, and they can be done at home. That's really the interesting thing is they don't have to be done in a lab. You can take a sample of a person. I don't know if it's their saliva or their blood. It probably depends on the, diseases that you're checking for. And you just add this CRISPR system, these CAS proteins that have been programmed to look for a specific DNA target.

And if they find the DNA target, they cut it. And that causes a change in the cas protein so  that the cat protein starts cutting these other little pieces of genetic material that were inserted along with the cast proteins. And when those things get cut, they alter a molecule that actually produces  a visible color in the sample.

Patrick: [00:24:14] Oh, 

Josh: [00:24:14] science is awesome. 

Ian: [00:24:16] It's incredible. and then they're talking about, even making these kits that test for multiple things. And what you would do is  they would have an app and you would take a picture of your sample and the app would look at that picture and analyze it with an algorithm and detect what colors are there and therefore what diseases are present.

Josh: [00:24:37] In a hundred years, going to the ER is going to be opening up your ER app and like taking a picture of your tongue 

Ian: [00:24:45] so I thought that was really cool. And the reason that this is such a big deal right now is because. This whole gene editing revolution is happening at a time where there's also a genome sequencing revolution, right?

Like the human genome process was what? I think it started in the early nineties like 1991 or something like that. And they finished, and I believe it was 2003 so it took them about 13 years sequence the first human genome.

Josh: [00:25:13] Which is not very long. 

Ian: [00:25:15] No. I mean, in the history of science,  a breakthrough that big,  13 years is not that long and it cost about $2.7 billion.

Now, I just looked it up yesterday.  you can pay a company right now like Veritas is one of the companies. There's multiples. you can go on veritas.com and you can pay them $599 and they will sequence your whole genome for you. 

Patrick: [00:25:37] Ooh, I don't know how I feel about that. 

Ian: [00:25:39] and you'll have the results in like 12 to 16 weeks, but really that's just because of a backlog though.

The process only takes them a couple of days. Now, 

Josh: [00:25:46] do they print it out and send it to you in like a mailed report, 

Ian: [00:25:50] like 

Josh: [00:25:51] 300 gigantic textbooks? 

Ian: [00:25:55] They've got some cool stats that they, say that like, and human genome has almost six and a half billion. No, six and a half trillion? Six and a half billion basis.

And so that would be like 4,200 books. Like 

Josh: [00:26:11] I 

Ian: [00:26:12] low-balled it.

Josh: [00:26:15] Send you 

Patrick: [00:26:15] a recording where they read all the letters and it's like seven hours long. 

Ian: [00:26:21] But   that's another thing to keep in mind is that the fact that we can edit genes is like. That's super cool, right? But the fact that we can know everything about the genetic makeup of an organism and we can edit genes together, those two things are really what's going to just like push this into basically gene editing being everyday science.

Patrick: [00:26:43] You feel that it's almost like that old conundrum. Like you get a book and it tells you how you're going to die. Would you read it. Don't you feel like getting your gene sequence that could potentially have answers of how you could potentially develop a disease or a condition? Would you want to know that the guy like, yeah, 

Josh: [00:27:05] cause I'd open the book and it would be like, no diseases, but probably something really stupid.

Ian: [00:27:10] I agree. I mean I at this point like. I'm a hopeless case, right? Like so, so I don't want to know, but I guess another question is if you were having a baby and you could get your baby's entire genome sequenced and identify all of those places where we know that those genes could cause a problem, and then you could use something like CRISPR to fix those problems, would you want to read that book?

Patrick: [00:27:40] I could see that. Cause we definitely did some genetic testing with both of ours just because we didn't know our history. So obviously if you go to the hospital, they ask you about your family's medical history and you don't really know. Right. But your DNA could be almost be like a, like you were saying, textbook of your family history and where you've come from and the things you've inherited along the way.

So maybe not necessarily more of a future. Impact, but a past impact. But I could see that, cause we definitely did it with both of our kids, just so we could know, just like we'd like to know if there's going to be a potential problem down the line that we might have to deal with her, all that sort of stuff.

Josh: [00:28:19] So I guess I could see her, especially for kids. For myself. I don't know. I feel about that. 

Ian: [00:28:26] Yeah, and I mean, CRISPR is an interesting technology because it's mostly thought of as a way to, you know, edit genes in embryos and at at the early stages of development and things like that. But it also has the potential to be utilized for large scale genetic manipulation.

I mean, there's already quite a few examples of. Diseases being treated like in adults in fully, fully formed and fully developed humans. CRISPR being used to treat diseases by going in and just changing a ton of the DNA and a ton of that person's cells. 

Patrick: [00:29:02] Hmm. 

Josh: [00:29:03] Wow. 

Ian: [00:29:04] So that they start expressing a gene that's going to make up for whatever, you know, loss of function they have that's causing them a problem, or that's going to alter the gene that's causing the issue or something like that. So even though we're kind of talking now about like manipulating babies manipulating embryos, and I said I was a lost cause,  I don't know if that's actually true.

You know, it might be possible to make genetic modifications to fully grown organisms. 

Josh: [00:29:30] Well, considering what you mentioned about 13 years. To map the genome 13 years from now, hopefully we're all still alive. I guarantee that we're going to see things that we couldn't have imagined right now. 

Patrick: [00:29:45] Well, think about it like how old the iPhone is.  when I was in high school, like the iPhone was barely out. Now almost every single person has one. It's changed the way we live our lives daily. 

imagine what's going to happen in the next 10 or so years. Even with something as influential as something like this. Mind blowing, 

Ian: [00:30:03] it is mind blowing.

And, another thing that I want to point out as well, is that, CRISPR is not the only gene editing. I guess platform tool. It's not the only gene editing tool that we have. there's other things that, that are used as well. I mean, like I said, viruses were used for early gene therapies, and so that is still a tool that is available.

There's also some other things that have been discovered that do things similar to CRISPR. This technology called TALENS, T. A. L. E. N. S. Transcription activator like effector nucleuses. These things basically do the same thing that CRISPR does, and in many ways, they are actually more specific and more controlled than CRISPR, but they take longer to develop and they're usually more expensive.

So it's kind of like, it's just a different tool. There's also these things. This is my favorite zinc finger nucleases,

Josh: [00:30:58] That's my supervillain name, 

Patrick: [00:31:00] silver surfer. But evil 

Ian: [00:31:04] so zinc finger nucleuses are another tool that you can do other things with, like pick your nose, that you can't do with CRISPR. 

Patrick: [00:31:15] And do it with your friends either, 

Ian: [00:31:18] but I just wanted to point that out that it's not like there's just this one magical protein.

There's this whole world of these things that are still being discovered. There's also over 90 I think there's 93 or something different cas proteins that have been discovered. And so another thing that's going to just propel this technology, is just understanding All the different tools that are available and  when they're useful for what specific things. so I think, that growth and improvement in these technologies inevitable.  there's still so much more to understand that, going to get better. We haven't reached the ceiling 

Patrick: [00:31:52] exciting and scary all at the same time.

Ian: [00:31:54] Absolutely. Do you want to hear some exciting and scary applications that they've used in the worlds of food production. 

Josh: [00:32:01] Yes. 

Ian: [00:32:02] Okay. So, so far  we've talked a lot about humans, but we've also used CRISPR in pets, like dogs. There's a lot of discussion about pure bred dogs are known for having these genetic issues that plague different species or different breeds, I guess.

And so there's talk about using CRISPR or gene editing to fix those. So that, Oh, that's good. Yeah. Yeah. So that, you know, certain breeds aren't prone to certain types of cancer or, or hip problems or things like that. There are allergen free foods, so things like wheat that don't, it's a wheat plant, but doesn't produce gluten that 

Josh: [00:32:40] then how does the, how is the wheat wheat then?

Ian: [00:32:44] It's gluten-free wheat  along the same lines. Decaf coffee beans. 

Patrick: [00:32:50] Oh. 

Josh: [00:32:51] Well then what's the point? 

 Patrick: [00:32:53] I don't know. What's more pointless? Wheatless wheat or coffeeless coffee. Water, less water. 

Ian: [00:33:02] So those are some examples of like removing function from things. But we can also add function. So with CRISPR, you can cut things out of the genome.

you can turn things off in the genome, but you can also insert things into the genome. And that could be something from the same species or from a different species. Cause every species has the same genetic, you know, system DNA. So, there is, a group of people who are working on making spicy tomatoes.

Patrick: [00:33:30] The Carolina Reaper, Roma. 

Ian: [00:33:33] Exactly. Exactly. And the reason that they think that this is actually reasonable thing to do is because growing hot peppers, which is, you know, where we get  spiciness they're actually not the easiest thing to grow. And so if you could make a tomato that produces capsaicin that produces some of those proteins that are responsible for spiciness, then you can extract that.

And you can use that as like. Essence of spiciness. 

Josh: [00:33:59] I am not okay with spicy ketchup . 

Ian: [00:34:02] We're also, we're also using this technology to, enhance species like the boy faster race horses.

Or like more nutritious fish. there's examples of using, this technology to alter the algae and yeast used in biofuel production. 

Josh: [00:34:22] Oh, cool. 

Ian: [00:34:23] and that's a really cool one because they basically have used CRISPR to alter the algae that produced the lipids that are broken down for, or I guess utilized to make biodiesel.

And they've made these bacteria twice as effective at producing those lipids. So you can get twice as much of the raw biofuel ingredients from the same amount of algae. And then they've also genetically modified the yeast that are involved in the process of taking those raw ingredients and making them into actual biodiesel.

And they've made those yeast more robust so that they're better at doing their work. So. So that's like a cool enhancement, but then you get into like enhancing other species, like making faster race horses and you're kind of like, wait a second. Is that okay? 

Patrick: [00:35:07] Yeah. That just sounds like cheating the whole race horsing ideology. That doesn't always resonate with me either. So I don't know if we need to make them faster or you make them slower and have horse walking, 

that's 

a safer alternative. That going to be like a new cadence to their Gallup. The speed walk. 

Do you imagine a huge, like Clydesdale or thoroughbred doing the speed walking groove, the hip side to side in the hands.

Ian: [00:35:37] Is The horse carrying two and a half pound dumbbells while they're doing this? 

Patrick: [00:35:42] On each of their hooves. And a Fanny pack with a bunch of water bottles. 

Josh: [00:35:45] Now 

Patrick: [00:35:48] we got something here. 

Ian: [00:35:49] yeah, I think that we've really, hit the most important aspect of this CRISPR conversation.

Patrick: [00:35:57] I do like it kinda came full circle that you can use CRISPR items in your CRISPR. Like I can see myself putting really spicy tomatoes in my fridge. CRISPR. 

Josh: [00:36:06] How do you turn off someone else's microphone?

Ian: [00:36:12] So  there's a million more examples, but I really just want to share one more with you guys that I think is kind of mind blowing. They are using CRISPR and other gene editing technologies to try to bring back extinct species. 

Patrick: [00:36:24] Oh boy. Now we've gone back full circle to Jeff Goldbloom. Life will find a way. 

Josh: [00:36:30] Everything in life leads to Jeff Goldbloom.

Patrick: [00:36:33] It's like a better seven degrees of Kevin bacon. 

Ian: [00:36:36] I hope Jeff Goldblum hears this episode

Josh: [00:36:40] He's a national treasure. 

Ian: [00:36:43] So these people at Harvard are working on bringing back the wooly mammoth. 

Josh: [00:36:47] There's a trilogy of movies about why this is a bad idea.

Patrick: [00:36:52] harry Potter? 

Josh: [00:36:53] Yes. 

Ian: [00:36:56] So what do you guys think about CRISPR and gene editing? Are you in favor of it? Are you against it? Where do you stand? 

Josh: [00:37:06] I'm absolutely in favor of it. I, I think that there are so many things that could be done with this type of technology. And. Just thinking about all of the diseases that we have to deal with on a regular basis.

I can see that there's definitely some downsides, but I think that this is something that we should really be focusing on as a society. 

Patrick: [00:37:27] I agree. I think there's just, I mean, there's still a lot of unknown variables and everything else in terms of what people will do with it. I think it's hard because you want to put regulation on something, but at the same time, when you regulate things, people go around it and use it for devious ways.

And you think about all people who make great discoveries sometimes do bad things with them, especially in the sciences. So it's one of those things that I'm super torn on cause I can see all the positives of it, but I can also see so many negatives.

And I'm not saying, I can see the future. But you're just kind of worried sometimes with what you think people could do with it, with this. if it were to be used in a devious way. So obviously I love it, but at the same time. With reservations. 

Ian: [00:38:05] I'm right there with you.

That's where we're at with it. You know, it's here, it's here to stay. I think that it could definitely be utilized for some scary purposes, and it could, change the world in really scary ways, but at the same time, I mean it is a new level of, control. That we have as a species and as a society and we can do a lot of good with it.

So

I have another important question for you guys that I think is important as that other question. this is another listener question. Are you ready for this? 

Josh: [00:38:39] Oh yeah, 

Patrick: [00:38:40] I'm ready.

Ian: [00:38:41] All right. So another one of our listeners asked us, do we cook ourselves a little bit every time we take a hot bath?

Josh: [00:38:54] Okay, well suddenly now bat sounds gross cause it's like human soup. 

Patrick: [00:39:00] Well it depends. Like are you putting something in the bath? Like if you do like a bubble bath and you're putting stuff in it, is that just like flavoring?

Josh: [00:39:10] I mean, I have a mango bath bomb that I've used so. 

Patrick: [00:39:15] There it is. 

I'm on board with saying that it is. 

Ian: [00:39:19] I am absolutely with you. I think it is. 

Josh: [00:39:24] You heard it here first. Baths are cooking yourself 

Ian: [00:39:27] and the water that you get when you take a bath is you broth. 

Josh: [00:39:34] You broth

Patrick: [00:39:40] how would you market that? Like just letter you broth or like Y O U or like EWE

Ian: [00:39:47] it would be one word. It would be U B, R, O F. UBROF, 

Josh: [00:39:53] UBROF 

Patrick: [00:39:55] that'd be the new brah h like brah. 

Ian: [00:39:59] P. H? Yeah. B. R. A. H. P. H. Options. Okay. So if we're going to say that baths are cooking yourself, if you swim in the ocean, are you brining yourself?

Patrick: [00:40:13] Definitely are. 

Josh: [00:40:14] Oh yeah,

Patrick: [00:40:15] for sure. 

Ian: [00:40:16] All right. I think I'm going to say that that is it for this episode of yonder cast. Thank you all so much for listening and if you have a question you'd like us to answer on the show, just fill out the survey that is linked in our show notes, and if that doesn't work or you want to contact us for some other reason just shoot us an email at yondercast@gmail.com thanks everybody. We'll see you next.

You guys should say something too. 

Josh: [00:40:44] I was gonna say do we say bye too? Bye everybody. 

Patrick: [00:40:49] Bye guys.