Podcast appearances and mentions of jacob korn

John1. Youngtee - Love will save the day2. Lovebirds - The Night3. Crazy P - Burning4. Maceo Plex - Can't leave you5. Moulinex - Don't you feel (Crackazat mix)6. Ben Watt - Lone Cat7. Dj Dealer ft. Insta Day - My all (Hideo Kobayashi instrumental)8. Sinc, Daniel Sanchez - New Day9. Art of Tones - Queue de Cochon 10. Jacob Korn, San Soda - The Music11. Mateo & Matos - Want U tonight (Ian Pooley remix)12. The Layabouts ft. Portia Monique - Bring me Joy (Director's Cut Remix)13. Carlos Varga - Deep Expressions14. Elise - Poseidon (At one Remix)15. Two for Soul ft. Chelsea Como - I want you (Montana & Stewart Remix)16. Typeni - Is it love (Neal Conway & DJ Spen Afro Latin remix)17. Rhemi ft. Hanlei - The Real Thing (Our Sh**!) (Main Mix)18. Ross Couch - Still on my mind19. Stirling Void - It's alright (Eric Kupper remix)

This is the Tenth episode of - The Global Boom Clap - The monthly podcast from Synapson! Available on all platforms: https://podlink.to/GlobalBoomClap Follow the boom clap playlist https://open.spotify.com/playlist/6LgGAdfAbuhYYm6AHsHu6T?si=b0dec95c3f254ab6 Tracklist Bonga - Mona Ki Ngi Xica (Synapson Remix 2021) Africa Ni Leo - Synapson Remix (Mastering 2021) Jacob Korn, Good Guy Mikesh, Filburt - Philipp Dolphia Axel Boman - Hello Mr Raoul K, Laolu - Sene Kela (Mr Raoul K - Laolu Version) Climax Orchestra - Nte Tan Da (Synapson Remix) (Extended Mix) Maajo - Maajo Al Zanders - Long Gone Al Zanders - I Don-t Want You To Judge (Original Mix) Follow Synapson: www.instagram.com/synapson/

On International Holocaust Remembrance Day, we hear how brothers David and Jacob Korn survived the Holocaust as children.

RawrGroove #006 featuring: Konstantin Sibold, Buben, Nhan Solo, Dennis Ferrer, Sabb, Forrest, Round Skin, Jacob Korn, Leo Wolfel, Made By Pete, Paolo Barbato, Valentina Black, David Hasert, Marina Martensson rawrgroove.com

RawrGroove #006 featuring: Konstantin Sibold, Buben, Nhan Solo, Dennis Ferrer, Sabb, Forrest, Round Skin, Jacob Korn, Leo Wolfel, Made By Pete, Paolo Barbato, Valentina Black, David Hasert, Marina Martensson rawrgroove.com

Host Lisa Kiefer interviews Innovative Genomics Initiative lab member and UC Berkeley post-doc Mark DeWitt, PhD., about the perils and promise of the CRISPR-Cas9 gene editing technology.TRANSCRIPTSpeaker 1:You're listening to method to the madness at my weekly public affairs show, k a l x Berkeley Celebrating Bay area innovators. I'm your host, Lisa Kiefer, and today I'm going to be interviewing biophysicist Mark Dewitt. We'll be talking about gene editing, both Fitz promise and itch perils [00:00:30] as well as his work here at the innovative genomics initiative lab at the La coshing center for Genomic Engineering on the UC Berkeley campus. Welcome to the program, Mark. Thanks for having me. Speaker 2:You're a biophysicist a postdoc researcher at the innovative genomics initiative here on the UC Berkeley campus at the La cashing center for Genomic Engineering, and you're doing some exciting work on many [00:01:00] things and we're going to get into what you're doing. But before we do that, I want to talk about the golden age of gene editing and talk about some of the fundamental parts of that so that our listeners who are not scientists or biophysicists can understand what we're talking about. Here's UC Berkeley's very own professor Jennifer Doudna a few years ago with my colleague Emmanuel sharp on ta. I invented a new technology for editing genomes. It's called CRISPR cas nine the CRISPR technology [00:01:30] allows scientists to make changes to the DNA in cells that could allow us to cure genetic disease. The CRISPR technology came about through a basic research project that was aimed at discovering how bacteria fight viral infections. Speaker 2:Bacteria have to deal with viruses in their environment and we can think about a viral infection like a ticking time bomb. A bacterium has only a few minutes to diffuse the bomb before it gets destroyed. So many bacteria have in their cells [00:02:00] and adaptive immune system called CRISPR that allows them to detect viral DNA and destroy it. Part of the CRISPR system is a protein called cas nine that's able to seek out and cut and eventually degrade a viral DNA in a specific way, and it was through our research to understand the activity of this protein cas nine that we realize that we could harness its function as a genetic engineering technology, a way for scientists [00:02:30] to delete or insert specific bits of DNA into cells with incredible precision. The CRISPR technology has already been used to change the DNA in the cells of mice and monkeys. Other organisms as well. Chinese scientists showed recently that they could even use the CRISPR technology to change genes in human embryos and scientists in Philadelphia showed they could use CRISPR to remove the DNA of an integrated HIV virus Speaker 3:from [00:03:00] infected human cells. Okay. Mark, let's get a little bit more into this gene editing. Speaker 4:You can imagine that our genome is essentially like a document that has 3 billion letters. Those were the different bases in the DNA that makes up our genome, right? A 20,000 genes, 3 billion characters, which I think is about a million pages. This is an, if it was an award document, I think that would be about three gigabytes of data. Right? So is this one really long document and gene editing is quite simply the ability to edit that [00:03:30] document. Speaker 3:It's like a cut and paste system, right? And a global global positioning system. Speaker 4:Yeah. What Dean editing lets you do is you can now go into this document and before all we could do is really read it. We could just know what was in it. But now with, with gene editing, we have the whole edit menu, right? So we can go to a location within the genome, we can cut out a sequence that we want to remove and then we can paste in a new sequence. So for example, if you have a, uh, a gene, uh, with a disease causing mutation in it, you [00:04:00] can cut that disease causing mutation out and then paste in a healthy gene. Speaker 3:Right. Okay. So it's, it's Kinda two parts, right? You know, you've got the, the CRISPR. Okay. And that stands for clustered regularly interspaced short palindromic repeats. Yeah, Speaker 4:it's a pretty, it's quite a mouthful. Basically what happens is that the bacteria would store this array of short sequences. That's the CRISPR array. And the sequences would match the sequences of the invading virus viral DNA, Speaker 3:so [00:04:30] that if it ever came again, it would recognize it. Speaker 4:Yeah. If the virus ever came back, it'd be like, oh, I know you. And then it would end the way that it recognizes the invading that DNA from its own DNA is because of, it's in this CRISPR array, it gets put onto the cas nine nucleus and the nucleus goes to the finding invading DNA and chops it up, but it won't chop up your own DNA because you don't have any of that sequence. You provide a guide, you have the cast nine nucleus and then you provide a guide, which is like a little RNA guide. It's an RNA guide. Yeah, we do it. We do it with RNA. Other [00:05:00] people can use RNA that's transcribed inside the cell. We actually provide the RNA outside the cell and put it right on the cas nine so RNA as a sequence, just like DNA. The sequence of the RNA can match a piece of DNA somewhere in the genome. So when you provide the guide and the CAS nine at the same time they get together and they go find the part of the genome that matches the sequence of the guide. So the guy guide has literally a guide Speaker 3:so you can program the guide to tell it where to go. Speaker 4:Exactly. So it's very, very easy to, to construct different SDR [00:05:30] and Aes, different guide rns to direct casts down to different places and in fact that's a major advantage of CRISPR cas nine technology over other gene editing technologies where they're not so easily repurposed to go after different targets. We've been doing gene editing for I think about 10 years in the old days, you know? Yeah. You'd have to do a lot approach in engineering. You have to synthesize a lot of different constructs, you know, different plasmids to continue to make different reagents, send them into cells and then pick the best one. It takes a lot of work, maybe a whole team of people, right? If you're working at a company that have like a whole team of people that do just [00:06:00] protein engineering, whereas mcast nine if I want to make a cas nine reagent that targets anywhere in the genome, I essentially order, I can order a template to make the RNA by typing it into the computer. A company sends it to me a day later. I can make you know, 10 different targets, hundreds of targets, right? People have done thousands or hundreds of thousands at once and then take that, make the RNA in my lab, mixed that with the protein in the night and introduce it into cells and generally almost all the cells get at it or they at least get the cut. The turnaround is, I mean I have my undergrads [00:06:30] doing it. I have visiting students doing it. I do it all the time. Speaker 3:What kind of oversight can anybody like? I can recreate the polio virus. Speaker 4:I can't just order a huge chunk of DNA that is big enough to encode an entire virus, Speaker 3:but are there other regulations on who can order what? Speaker 4:There are for sequences that contain toxins or infectious particles Speaker 3:like the polio or something like that, the whole polio virus. Speaker 4:And you're not allowed to order those synthetically. Or if you are, you have, you have to demonstrate that you have the qualifications [00:07:00] to work with that kind of genetic material. But you know, in our case we're going after genomes that are already there. So it's like your genome doesn't have any, you know, infectious particles in it. It has nothing contained in what we order that actually causes a disease. Okay. We're just going after disease genes that are already there. Okay. So in some senses it's actually much safer because there's no information that we're providing to the cells that could cause a disease unless we, you know, really want it to. Whereas for example, uh, the older version of gene therapy was to do viral delivery of [00:07:30] genes. And so since you're working with viruses, there's always risk of side effects. Even though the viruses are essentially de weaponized, there's still issues of where it puts the DNA, whether it could evolve into a different type of virus, these kinds of things. Speaker 3:Okay. You know who Hank Greely is at? Stanford law school. Oh, that sounds fun. Okay. He Dura, he's the director of the center for law and bio-sciences down there and he calls a the CRISPR cas nine the model t of bio-science. Hmm. Speaker 4:I guess what he's thinking is the model t was not the first car [00:08:00] or even the first car to be manufactured and just as that CRISPR cas nine is not the first gene editing technology. We've had it for some time, but it is the, it is the most robust and it's the easiest to work with. It's the one that everybody is out getting and trying and using. I mean not people that, not just people that specialize in gene in genomics or genetics, but really everybody. Yeah, and that sense it is the model t. It's the first one. It's the first version of this technology that everyone can use. What is the goal of it? Right off the bat, it is completely changed [00:08:30] the way that we do basic research. So, as I mentioned, it's very easy to work with now even if you're not a specialist in gene editing, but you have a, you know, a favorite gene that you like to, you want to characterize, you can target and manipulate that gene in human cells with such ease that you don't have to be a specialist and you can target many, many, many, many, many targets at once. Speaker 3:And so you in, in other words, like a goal of eradicating a certain that's heritable Speaker 4:[inaudible] well, so first is this used in basic research and then the other [00:09:00] potential application for CRISPR cas nine gene editing, early gene editing in general. And this is indeed already sort of underway, is m for gene therapy. As I mentioned, you know, you could have a genetic disease and then in some part of your body and then we can synthesize and inject reagents that will correct that mutation, fix the broken gene. And instead of, in the past we've been able to introduce genes into tissues, but only we can't fix a broken gene. Now we can actually go to the broken gene and replace it with healthy [00:09:30] sequence. Speaker 3:Okay, mark, let's break away for a minute and tell our audience they're listening to method to the madness here on k a l x Berkeley. Mark Dewitt is a postdoc over at the innovative genomics initiative at La caching center for Genomic engineering here at UC Berkeley. It sounds like you can do it one of two ways. You can go in and and fix an individual's broken chain system, or you can go in and correct it in embryonically and then it affects generations [00:10:00] later down the road Speaker 4:potentially. That's called germline editing and that's where you're editing the human germline. So that means that you create a heritable mutation in an embryo or probably a a fertilized embryo. Once you create that mutation or once you make that change, you know that that embryo will be implanted into a mother. She'll, uh, the baby will grow up, they'll have that change and then that, that kid will pass on that, that change to their kids. Most therapeutic applications of gene editing aren't really focused on that. Instead, [00:10:30] we're really focused on, and at the IGI we're only focused on, you know, editing healthy adults or sorry, adult patients. So it's just about the individual. And so in that case, when we make the edit, it's not transmitted to their progeny. So if you have a disease of your, so for example, I studied sickle cell disease, if I correct the sickle cell mutation inside your bone marrow, your bone marrow will be corrected and it'll be fixed, but your germline, your eggs or your sperm will not. Speaker 3:And we don't want it to be right because didn't it arise out of a resistance [00:11:00] to malaria thousands of years ago? To me, that's the issue of going after a germline. You don't know. That Speaker 4:raises the possibility that there could be unintended consequences of introducing things of introducing genetic alterations into the human germline. And that's absolutely true. And that's one reason why I think that, especially at this stage, it is just way too premature to undergo that kind of undertake that kind of research. The other issue is that it cuts at the place. You tell it to almost all the time, but sometimes it cuts other places. [00:11:30] That's called off target cutting. So it's not on your target, it's somewhere else. It's off your target. What's the success rate? Usually though the frequency of off target cutting is, it depends on the application. It's usually on the order of 1% or less. So it's too bad. Yeah. But if you have 4 trillion cells, a substantial number of cells in a gene edited individual. So if one of those off target cuts causes a nasty side effect, like for example, it knocks out a gene that's supposed to protect [00:12:00] yourselves from cancer, but then you could, all it takes is one cell to be edited to be edited in that manner. This unintended manner to cause the cancer. Speaker 3:Weren't you in a paper recently? I think nature biotechnology where you guys came up with a bubble technique that avoids cutting. Speaker 4:Yes. So one way to avoid off target cutting is to just don't cut it all. What we found in that paper was is that if you use a a cast nine that doesn't cut it simply can't cut it all. It still creates a structure, DNA protein structure that is accessible to the [00:12:30] replacement sequence you're trying to provide. It's not nearly efficient enough to really drive the kinds of levels of editing that would be relevant. You can think of it as DNA has two strands, the famous double helix. What we found is as the task then goes and pries open those two strands and clamps really hard on one of the strands, but then the other strand is essentially released and is free and so if you provide a sequence of DNA that binds to that strand, it will get incorporated. Now you've opened it up, you can stick stuff onto it. The advantage [00:13:00] of that technique is that you get no, is that since there's no cutting, the chances of off target activity are vastly reduced. Speaker 3:Are you primarily working on sickle cell? Speaker 4:So sickle cell disease is a disease of your red blood cells and you know, we've known about the genetics and the molecular basis of the disease. For almost 70 years. I mean it's one of the oldest, it's the oldest genetic disease that we know about and it was the first genetic disease to truly be characterized. I mean right around the time we discovered the structure of DNA, [00:13:30] we were already figuring out how sickle cell, Speaker 3:right and it's a defect in only one gene, which is very different from a lot of other diseases. Speaker 4:Exactly. So we call that monogenetic versus poly genetic. It's a moto genetic disease and that it has exactly one cause and in fact that's all the way down to the molecular level. There is a single letter or a single base pair change in your genome that causes the disease. And so that change is in this gene called Hemoglobin Beta, which is one of the two proteins that make up hemoglobin, which is what makes your red blood cells red. [00:14:00] It's what carries oxygen, you know, from your lungs to the rest of your tissues. It's all going through this hemoglobin protein, hemoglobin protein that has this sickle cell mutation will aggregate inside the south, will form these long, these big clumps inside your red blood cells. And these clumps cause the cells to become deformed and adopt that, that this characteristic sickle cell. Yeah. It's more like a crescent moon. Speaker 4:I mean we're not farmers anymore. So I figured, yeah, we should update the language, but I sip like a crescent moon or a sickle. The sickle RBCs [00:14:30] well, first off, they're not as effective at carrying oxygen. So you have anemia, but also they can clog blood vessels and like your capillaries, they won't fit in your capillaries very well and that can damage the capillaries and also can lead to these crises where your blood vessels get clogged. So it causes that increased risk of stroke and pulmonary hypertension and also the damage to your blood vessels can cause organ failure. So it's a progressive disease in the sense that individuals in, in countries with developed health systems like the United States, their symptoms aren't very [00:15:00] severe and they're very manageable for the first few years of life. But then as they get older and older and older, um, increasingly severe symptoms will manifest. Speaker 4:And ultimately it leads to something like a 25 to 30 year detriment in lifespan. And it's an inherited disease, inherited disease, and we have two copies of every gene, right? Individuals that have one copy of this, of this mutation. So they have a mutated gene and the healthy gene are called carriers and they also have this clinical presentation is called from sickle cell trait and individuals with sickle cell trait [00:15:30] are generally healthy and also have some resistance to malaria. And that's how the, that's how this mutation is maintained in the populations in, in populations and malarial regions to Subsaharan Africa and southern India where the mutation first arose. The United States is not a malarial country, but of course we have a large minority of African Americans whose genetic heritage is from Subsaharan Africa from these regions. And that's why sickle cell disease, which is when you have both of your genes have the mutation in America is found [00:16:00] almost entirely in the African American population. Speaker 4:So about a hundred thousand Americans, again, almost all African American had the disease in the country as a whole and I think 10,000 in California. So it's actually quite a lot of people close. Are you to a cure? I'd like to think we're pretty close. We, we, we haven't moved towards the clinic yet. I'm hoping that one of us will be able to start trials within the next two or three years. But there are other strategies for treating sickle cell disease that are more indirect, that are already in clinical trials using gene editing. [00:16:30] How are those different from what you're doing or our approach at IGI is to directly correct the mutation so we know exactly where the mutation is and we've known it for 70 years. But as I mentioned, just because you know where something is in the word document doesn't mean you could fix it until now. Speaker 4:What our approach is is to make a cut at the mutation and then supply replacement sequence. The replacement sequence is a short piece of DNA. So in order to cause a lasting alteration to your, to the genetics of your blood cells, we actually have to edit your bone marrow cells. [00:17:00] So we take bone marrow cells from patients that have sickle cell disease and then we, this is all in the labs. So we're working this Albridge called ex Vivo or in the lab we cut at the [inaudible] at the mutated region using cas nine and then we supply a short piece of DNA that has the corrected sequence in it. So it just doesn't have any grow. Yeah. And so that will get incorporated in some fraction of the cells. We generally get about 20 to 30% in view in vitro. Then you let the cells grow, then we just analyze them. Speaker 4:So we'll differentiate them into red blood cells and see if they still have sickling [00:17:30] properties. We'll look at their, their gene expression, um, viability, all sorts of, you know, in vitro and points. The other thing we do is that we will edit the cells and inject them into a mouse carrier where the cells will live for months and months and months and then take the cells out of the mouse four months later to see if they still have enough editing to cure the disease. And so none of this goes back into people. Now, the way it would eventually work, if you actually were doing this in a clinical setting, is that you would take a fraction of a patient of a sickle patients bone marrow. You would correct [00:18:00] it using the same exact technique that we're using, but at a much, much larger scale, like we're doing a hundred thousand to a million cells. Speaker 4:You'd be doing more like a billion cells. You would correct the cells, culture them for a day or two in an incubator and then pull them back together and reinfuse them into the patient. Now meanwhile, you would be ablating the patient's bone marrow are using chemotherapy. You can't avoid that. No. What we're hoping is is that if the editing is efficient enough, you don't have to completely ablate the bone marrow, so you don't, you can use a lighter course of chemotherapy, [00:18:30] but you still have to use a certain amount of chemotherapy to get rid of all the remaining uncorrected bone marrow that we just don't have the ability to, to correct that many cells at once. It's just the scale is not practical. So most, um, applications for now for gene editing or gene therapy in general, whether using viruses or, or CRISPR, cas nine or anything else, uh, they generally do this chemotherapy step. Speaker 4:There are many, many groups working on noninvasive methods to do gene editing. So one is to inject a virus that contains [00:19:00] all the stuff you need to make the edit into straight into the compartment that you're trying to treat. So in this case, it would be the, you inject the reagent into the bone marrow, which is painful, but it's a lot better than chemotherapy. Right? Virus is sort of nature's oldest nanoparticle. It's very good at finding cells and putting stuff inside of them. I think we can do better. We can engineer synthetic particles that can do all the same things. They can find the target cell, in this case, a bone marrow stem cell, the cell that leads to all of your other blood cells and they can find them. [00:19:30] And then they can inject all the reagents into that cell specifically and they'll go in and make the edit while the bone marrow cells are still inside your bones. Speaker 4:Um, and that's called Invivo gene editing and that's still very, very much in the early stages. But you know, whether using a viral technique or a nanoparticle technique, you know, from what I've seen in the literature, it's probably only a matter of time. It could be 20 years, it could be 30 years, but you know, it's only a matter of fact. Well, I mean in medical biomedical terms, that's pretty short. You know, when you read the articles, I mean this stuff is all [00:20:00] over the media now and it just sounds so exciting. Like in a couple of years, everything's going to be, these technologies take a very, very, very long time to perfect and try and then get through FDA approval and so on and so forth. A lot of that is just that it takes a lot of time to iron out all of the kinks and biotech. Speaker 4:But what about in other countries won't develop countries? They still don't, they still don't exactly move very quickly. First off, it's hard to prove efficacy. Sometimes it's hard to show that your treatment is actually being effective and you need to try [00:20:30] it. On a whole bunch of people in a whole bunch of different settings and for a whole bunch of reasons and that's just never not going to be really expensive to get the numbers you need to show that something's effective, whether you're the FDA, FDA or anybody else. It's a very expensive process. Getting enough statistical power to do that. You're still talking or thousands of people that you have to test it on and the process is lengthy and expensive. But you know, in my opinion, I think that's all well and good that we have that level of oversight, but it doesn't mean that things take years to really come to fruition and maybe maybe gene editing [00:21:00] might be a little quicker. Speaker 4:There's a lot of very specific problems associated with viral techniques that hopefully we won't have for our approach. I wouldn't be surprised if it took another five or 10 years to really get all the, get all the kinks ironed out. So down the road, what are some of the goals of this research? Monogenetic diseases like sickle cell. The second goal is poly genetic diseases. So this is sort of more of a pie in the sky idea here. We're just beginning to uncover that there are significant genetic contributions to non genetic diseases [00:21:30] to the chances of coming down with a non genetic disease. And I'm speaking specifically about Parkinson's and Alzheimer's. And so we found that there are certain mutations that we're not exactly sure why the sudden mutations that appear to increase your susceptibility to the disease or decrease your subset susceptibility to the disease. Speaker 4:And so that provides a handle for researchers to determine whether or not there is a sort of silver bullet genetic solution to actually curing this disease so that the [00:22:00] patients with these mutations or individuals with these mutations have almost no chance of getting Alzheimer's. Does that mean if I take a person who is, um, coming down with or starting to show signs of Alzheimer's or is at a high risk of Alzheimer's and I introduce this mutation into their, you know, into their tissues, you know, would that cure the disease? Would that essentially short circuit? Would that beat out whatever factors are making them get the disease by providing a different mutation entirely. How do you make that mutation in cells? Well, you should use gene [00:22:30] editing and then make the mutation and then see if all things being equal, that mutation alone can confer resistance to the Alzheimer's phenotype. Speaker 4:That'd be pretty exciting. It is very exciting. So I really think that, I guess as a gene editor or as a hammer looking for a nail, there are a lot more nails, especially in America, developed health system that are non genetic diseases. Are you from California? No, I'm from Boston. Where did you go undergrad? Um, I went to Undergrad at this small liberal arts college [00:23:00] in Portland called Reed College. It's, it's a, it's a fascinating place. Some enormous percentage of Reed college graduates go on to get PhDs. And so after I finished at Reed, I was there for a couple of years and he came down here to get my phd and I stayed on for my postdoc. Now my phd was in something completely different than what I do biophysics. And specifically I studied, um, these proteins that carry materials around your cells called motor proteins. My entire phd was, you imagine a bunch of white dots [00:23:30] on a computer screen moving across the screen, like in a straight line. Speaker 4:That's what I did. I looked at these dots and looked at how fast they're moving. And so I did that for about seven years. And then I just, you know, went to this seminar here, actually the first rewriting genome seminar. It was a, it was a seminar organized by Jennifer Doudna and it had all of the top investigators in gene editing at the time. So I went to the seminar. I was just blown away. I was like, this is so cool. This is just the coolest thing ever. Right? Like I have to do this. I emailed Jennifer, who [00:24:00] is in my building, my old building, Stanley Hall up the hill from here. I'd heard that she was trying to set up this, this organization, this, um, initiative to explore the applications of CRISPR cas nine, whereas her lab is focused on the, the core technology itself, making the technology better. Speaker 4:We would be taking those kinds of innovations and the innovations of others and using it to find applications. Right. And so I was more interested in that, partly strategically thinking, you know, we're going to get past the developing the technology [00:24:30] part pretty soon, but we're going to be exploring applications for hopefully the rest of our careers. So, you know, I thought that was a good decision for a lot of reasons. And so I talked to Jennifer and she said, oh yeah, like yeah, I'm doing it. We need postdocs. She could put me in touch with Jacob Korn, who's the director of IGI who hadn't formally joined yet. Speaker 2:And IGI is again Speaker 4:the innovative genomics initiative. The research lab is about 15 people. It's going to get a little bit bigger and then, but as you had just lots of other stuff, IGI also does some outreach. [00:25:00] The most inefficient thing we've done yet is we host a workshop. So we invite scientists from all around the community, ideally scientists that don't work in the field of gene editing, but want to try it out. Not just scientists or doctors, but also, you know, policymakers. And Speaker 2:there is a reason to make sure that it stays in the right hands. Yes there is. Does anything scare you about it at all? I mean, you're right in the heart of it, Speaker 4:you know, you think of bad actors and things like that. Although again, whether we're happy about it [00:25:30] or not, humanity has invented a whole host of really dangerous bad things from nuclear weapons to infectious agents to chemical weapons, weapons of mass destruction. And you know, we're all still here. It's, I guess what I mean. Should there be any controls on the use of the technology for research compared to other technologies like I don't think so. Should we be very careful about, well, what if someone wanted to do something not so good with this method that I'm outlining in publishing in a paper, [00:26:00] right? I mean, yes, we should. And that's exactly why we, I think should be very careful about germline editing. And again, that's why at IGI we're really focused on more traditional therapeutic editing. Speaker 2:Yeah, you're lucky that Jennifer is a big part of that because you know, she is a vocal person about the ethics involved. Here's a short segment from a Ted talk that she gave recently. Together with my colleagues, I've called for a global conversation about the technology that I co-invented so that we can consider all of the ethical [00:26:30] and societal implications. Imagine that we could try to engineer humans that have enhanced properties such as stronger bones or less susceptibility to cardiovascular disease, good eye color, or not to be taller designer humans, if you will. Right now, the genetic information to understand what types of genes would give rise to these traits are mostly not known, but it's important to know that the CRISPR technology gives us a tool to make such [00:27:00] changes. Once that knowledge becomes available, this raises a number of ethical questions that we have to to carefully consider. Speaker 2:This is why I and my colleagues have called for a global pause in any clinical application of the CRISPR technology in human embryos to give us time to really consider all of the, the various implications of of doing so. This is no longer science fiction, genome engineered animals and plants are happening right now. And this puts in front of all of us [00:27:30] a huge responsibility to consider carefully both the unintended consequences as well as the intended impacts of a scientific breakthrough. So mark, what would you like to see happen in this space in the near future? Speaker 4:Suddenly, I'm thinking about a lot lately is that this idea of personalized gene editing. You can imagine a world in which you go into the doctor, they sequence your genome, they see if there's anything that needs fixing [00:28:00] and then they put it in order for the reagent that can be synthesized custom to whatever specifications. So it can go into whatever Oregon you want, whatever cell type you want and program any genetic change you want based on your own genetic sequence. You then go into the doctor's office and they put something into your arm and they infuse you with that reagent and then it starts to make the change. It's certainly our approach with sickle cell, you know, points in that direction. The reasons that we're using are simple. They're easily customizable. [00:28:30] Um, you don't have to have a lot of it on hand. You can produce it in a factory instead of having to grow it from cell culture. Speaker 4:I imagine that future, this far off future in which we have sort of live in this almost Saifai type world where you know, you can make any genetic manipulation you want or your doctor candidly, you know, in the doctor's office, no surgery, no surgery, no nothing. Well then I think about, so what am I doing today that's going to nudge the, the rock a little bit further up the hill in that direction? Where do I want things to be in 20 years and what can I do [00:29:00] to go there? We'll see how I do, right? I mean, I'm still just a postdoc, but I think it really, really helps to think about like what's the La crazy, crazy far off like vision for what you're doing? Like how, how could it totally change the world? And it's important to think about that when you're at the lab bench. Speaker 4:You know, whether you're in a classroom lab at bio one a or whether you're in my research lab, what am I doing to bring that out? That longterm vision. It's so easy to lose track [00:29:30] of where you're going in the day to day, especially as a scientist, because as researchers we have, our head is filled with innumerable minutiae of our day to day experiments that just all we ever think about, and sometimes you need to step back and be like, what am I really doing? That's a characteristic, certainly of the most successful entrepreneurs and probably the most successful scientists as well. Speaker 3:Well, mark, you've helped us understand some very complicated ideas. I've been talking with Mark Dewitt. He is a biophysicist and a lab member of the innovative genomics [00:30:00] initiative here on campus at Lee Kushing center for Genomic Engineering. Thanks again for being on this program and talking about a very difficult and complex subject of gene editing. Thanks for having me. You've been listening to method to the madness. We'll be back again in two weeks is the same. I'm Speaker 1:telling you. 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1. Denney - On & On (Monday Club remix) 2. The Korvids - Beach Coma (BlueAzure Remix) 3. DE GRAAL - Liedown (Original Mix) 4. Saccao, West.K, Liz Kretschmer - Dont Call Me (Original Mix) 5. Hector Couto - 1993 (Original Mix) 6. Borshulyak - White Flakes 7. Tatsama - Wanderlust (Soledrifter Remix) 8. Several Definitions feat. Kimono - Wanted To (Original Mix) 9. Moonbootica - June (Etienne de Crecy Remix) 10. Domestic Science, Aumcraft - Sentimental Planet (Aumcraft Dive Remix) 11. Mathew Anderson - We Hurt Each Other (Original Mix) 12. Jacob Korn, San Soda - The Music (Original Mix) 13. Riccicomoto Feat. Elimar - Get Ready (Klartraum Remix) 14. Putzlicht - Precious (David Dorad Remix) 15. Madmotormiquel - Sad Reindeers (Mario Aureo & Manuel Moreno Remix) 16. Danny Tape, Jay Patterson - Lets Run Away (Feat. Sky) (Jay Patterson Remix) 17. Planet Funk - Chase The Sun (A.Kraft Nu Disco Remix)

1. Denney - On & On (Monday Club remix) 2. The Korvids - Beach Coma (BlueAzure Remix) 3. DE GRAAL - Liedown (Original Mix) 4. Saccao, West.K, Liz Kretschmer - Dont Call Me (Original Mix) 5. Hector Couto - 1993 (Original Mix) 6. Borshulyak - White Flakes 7. Tatsama - Wanderlust (Soledrifter Remix) 8. Several Definitions feat. Kimono - Wanted To (Original Mix) 9. Moonbootica - June (Etienne de Crecy Remix) 10. Domestic Science, Aumcraft - Sentimental Planet (Aumcraft Dive Remix) 11. Mathew Anderson - We Hurt Each Other (Original Mix) 12. Jacob Korn, San Soda - The Music (Original Mix) 13. Riccicomoto Feat. Elimar - Get Ready (Klartraum Remix) 14. Putzlicht - Precious (David Dorad Remix) 15. Madmotormiquel - Sad Reindeers (Mario Aureo & Manuel Moreno Remix) 16. Danny Tape, Jay Patterson - Lets Run Away (Feat. Sky) (Jay Patterson Remix) 17. Planet Funk - Chase The Sun (A.Kraft Nu Disco Remix)

#DHC014 - Mixed By Dj Mojonti Tracklist Artist - Title - Label 01. HNNY - Kitigai (Original Mix) - Studio Barnhus 02. Joel Alter - Unsung Heroes (Original mix) - Uncanny Valley 03. Jacob Korn, San Soda - The Music - Uncanny Valley 04. Kerri Chandler - Turn Off The Lights (Who's Afraid Of The Dark)(Original Mix) - Kaoz Theory 05. Till von Sein Feat. Russoul - It's All In The Spirit (Tanner Ross Remix) - Suol 06. DJ Fresh Ft Kora Calendar-Cherrie (Rocco Deep Down Instrumental) - Big Dawg Productions 07. Derrick Flair - The Transition (Original Mix) - Deep Obsession Recordings 08. DJ Angelo, Foremost Poets - 100 Years (DJ Angelo Original) - NuLu Electronic 09. Ost & Kjex, Jens Carelius - Easy (Lehar & Musumeci Remix) - Diynamic 10. The Groovers - Heres To You Mr Robinson (Original Mix) - Razor-N-Tape Records

As many have noticed Uncanny Valley celebrated its 5th birthday this past summer. On this occasion Philipp invited lots of UV artist into the coloRadio studio and asked them if they would play their favourite Uncanny Valley tune and talk a bit about it (Jacob Korn, Scherbe, Sneaker, Carl Suspect, Albrecht Wassersleben, Conrad Kaden, Sandrow M, Cuthead and special guest Max). The result is a pretty decent mix and (if you speak German) also fun and interesting to listen to. Tracklist Thomas Fröhlich - Get US Jacob Korn + Kelli Hand - Dance Away One Day In Metropia - Night Train CVBox - Blinking Lights Kryptic Universe - A Light In The Box DMX Krew - Astro Logical Jacob Stoy - Gegenwart C-Beams - Beaming City Sneaker - You Think, You Think Scherbe - Jardin Du Midi Break SL - Atlantic Ocean Road Projektname Unbekannt - Dresden, den 15.5.2015 Credit 00 - Red Wine Kornhead - Sur la Plage Sandrow M - Gonna Make Cuthead - Maputo Jam Steve Kasper - Helms Klamm Joel Alter - Mecca UV Funk is a radio show which is broadcasted every third Friday from 9:30 pm to 11:00 pm on Dresden based community radio station coloRadio. The show is hosted by https://soundcloud.com/philipp-demankowski. It's all about stories, interviews and tracks out of the world of Cosmic Electronic Music. The show was aired on 18th September 2015 Check: http://www.uncannyvalley.de/category/radio/

The next mix is penned by our good friend Eva Rose, co-founder of the label @Rose-Records which - surprise - was named after her. In her own words: "Piano is the devil- in a different kind of interpretation! This mix is an homage to Leipzig, Amsterdam and all those sweaty party nights, lying in the arms of beloved people, occupying the front rows of the dance floor. (Beware of emotional music…only suitable for people who can tolerate a little piano in their lives ;) )" KANNMIX 3 - Eva Rose (Piano Ist Der Teufel) - 72 min 1.Frivolous - One Fine Solstice 2.Frank Ocean - Swim Good 3.The Band - Stage Fright 4.J Dilla - U-Love 5.Jaques Renault - Piano's on the Beach 6.Axel Boman - Fantastic Piano 7.Hauschka - Radar 8.Baths - Overseas 9.Chilly Gonzales - Siren Song 10.Pawas - Piano Rain (feat. Matthias Keul) 11.Jacob Korn & San Soda - Punta del Este 12.LeSale - Before the Night 13.Mille & Hirsch - Change 14.P'tahh - Your Soul On Mine 15.Night Works - I Tried so Hard 16.The Cinematic Orchestra - That Home PS: Big love goes out to @m-ono, without whom this would never have added up to a coherent file but would rather have stayed a Spotify playlist until the end of time. Credits (Pic): Miami Müller + Kat Lanoe www.kann-records.com

enjoy some brandnew music ! ! ! feat tracks and remixes by: Cass., Jacob Stoy, Thorne Miller, Byron Stngili, Urban Absolutes & Paskal, Tension, Chymera, Jacob Korn, Auntie Flo, Microphunk & HouseRiders, Matthias Vogt, Napoleons, Deeperholic, Jesus Gonsev, Marcus Worgull, Frank Wiedemann

In this episode Jacob Korn's debut on Mild Pitch will be celebrated with a proper liveset by himself and another mix by our host Simon Hildebrandt. Playlist: Tim Schumacher - Somaman Theo Parrish - Lost Keys - Music Is... Smallpeople - Black Ice - Smallville Lawrence - Oolong High - Pampa Langenberg - I'll Be Late - Mild Pitch Jacob Korn - IT - Mild Pitch Jacob Korn - From A Distant Point Of View - Left Of The Dial Jacob Korn - Supakrank - Dolly Jacob Korn - Selene - Running Back Jacob Korn - Sand - Dolly Artwork Photography by: Lukas Faller / www.lukasfaller.de

With tracks from Richard Rodwell, Dionne, Solomun, Rainer Truby, Adultnapper, DJ T., Runaway, Jacob Korn & Kelli Hand, San Soda, Art Department, David August, Portable, Rick Wade, Lauer, OOFT, Black Van, Om Unit, Hardfloor, Maceo Plex, No Regular Play and Soul Clap Edits. Contact: dj@ribeaud.ch.

With tracks from Christian Prommer, A Mountain Of One, Archie Bronson Outfit, LCD Soundsystem, Soundsystem, Ytre Rymden Dansskola, Chilly, Donnacha Costello, Nufrequency, Jacob Korn, Mano Le Tough, Roberto Auser & Alden Tyrell, Boom Clap Bachelors, OOFT, In Flagranti Feat. Natalie Smash, Late Nite Tuff Guy, Chopstick & Johnjon Feat. Fritz Kalbrenner, San Soda. Contact: dj@ribeaud.ch.

Download: http://www.uncannyvalley.de/wp-content/uploads/2010/07/Unkoenig%20Willy%20auf%20der%20Suche%20nach%20einem%20Hofmusikanten.mp3 Aufgenommen im coloRadio-Studio zu Dresden - www.coloradio.org Sprecher: Stefan Menzel, Carl-Johannes Schulze, Lydia Mojzis, Robert Arnold, Thomas Fröhlich, Sebastian Lohse und Jacob Korn. Plot: Thamash Kestawitz und Lydia Mojzis Postproduktion: Stefan Menzel Musik: Break SL - Low Light, Jacob Korn - Slamduck, Thomas Fröhlich - Get US, Cuthead - Unacceptable Mustache Styles

Mix session - 54 min. / Electro.1 / Entropy (original mix) - Etienne Jaumet2 / Fighter (original mix) - Mark E3 / Whatyagonnado (original mix) - Jacob Korn4 / Was Better In 88 - DJ Ringardos5 / Chocolate Shop (original mix) - Black Bird6 / Iridium (Superpitcher remix) - Lullabies In The Dark7 / Venus (Pepe Bradocks, Saucy Precog remix) - Cheek8 / Eurodans (riginal mix) - Todd Terje9 / Space Fortress - Altair Nouveau10 / Detoured - Morgan Geist11 / Breath Me (original mix) - Smash Tv12 / Voce Seconda (Haruomi Hosono remix) - Ennio Morricone