#015 - CRISPR: One of the Biggest Science Breakthroughs of the Decade /w Joram Schwartzmann

Show Notes

Episode Contents

In this episode I talk to Joram Schwartzmann and cover some of the following topics:

  • What CRISPR is - explained in simple terms,
  • Why it’s considered to be one of the biggest scientific breakthroughs in the last decade and why it’s such a powerful tool,
  • How CRISPR actually works and in what areas it can be applied to, along with limitations,
  • How far we are from curing cancer, HIV/AIDS and other terrible deceases,
  • Discuss some of the ethical concerns that many scientists have around CRISPR and how far we humans should really go when applying this technology,
  • and so much more.


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Episode Transcript - Click to Expand

Note: This transcript of the episode was machine-generated and has not been edited for correctness. It’s provided for your convenience when searching. Please excuse any errors.


Guest (Joram Schwartzmann) 00:00:00 It’s crazy how much quicker basic research became because of CRISPR, and that’s why I’m genuinely excited about CRISPR for basic research. It’s this incredible tool and suddenly they can not cut the DNA, but change a single letter of the DNA or they can change something on the epigenetic code. It’s pretty crazy what we can do with this, and I’m sure it’s crazy what we will be able to do with this. It’s a milestone method that will influence research for years to come.

Host (David C. Luna) 00:01:05 Welcome back to another episode of the Innovational Cretinous podcast. In this episode, we’ll be talking about CRISPR. CRISPR is considered one of the biggest and most important science stories of the past decade and will probably remain one of the biggest science stories for the foreseeable future. So if at this point you’re getting really hungry for some crispy fried chicken. Well, you’re going to be really disappointed if you haven’t heard of CRISPR yet. The short explanation goes something like this. So in the past decade, scientists have figured out how to exploit essentially a trick in the immune system of bacteria to edit genes in other organisms such as plants, mice and even humans. So with CRISPR, we humans can now make these edits quickly and cheaply. And here comes the kicker in days rather than weeks or months. And this technique has worked on every organism it’s been tried on. So we’re talking about a very powerful new tool in the arsenal to control which genes get expressed in plants, animals and even humans, or the ability to delete undesirable traits and potentially add desirable traits with more precision than ever before. So far, scientists have used it to reduce the severity of genetic deafness in mice, suggesting it could one day be used to treat the same type of hearing loss in humans. They’ve created mushrooms that don’t round easily and edited bone marrow cells in mice to treat sickle cell anemia. In the future, CRISPR might help us to develop drought tolerant crops and even create powerful new antibiotics. CRISPR could also one day even allow us to wipe out an entire population of malaria, spreading mosquitoes or say, resurrect once extinct species like, say, the Tyrannosaurus Rex. If we want this, it could revolutionize everything from medicine to agriculture, as technology, as I mentioned, is often called CRISPR Arcus nine. But we’ll try to stick with CRISPR throughout the episode just to make it much easier to follow. So with covid-19 at our doorsteps, this is the perfect time to get acquainted with this powerful new gene editing technology CRISPR. My guest today is Yoram Schwartzmann. Yoram is a plant biologist that turned his passion science communication into his calling. He has also worked in the research department of the Max Planck Institute in Molecular Plant Physiology in Potsdam, Germany, a government funded science communication agency and is now communicating research in engineering and computational sciences at the world out in Berlin. He’s also the winner of the 2017 science lab and in his spare time he also hosts a weekly podcast called Plants and Pipettes, where he and his co-host talk about molecular biology. So in this episode, we’ll cover some of the following topics. What CRISPR is explained in very simple terms, why it’s considered to be one of the biggest scientific breakthroughs in the last decade and why it’s such a powerful tool, how CRISPR actually works and in what areas it can be applied, along with some of its limitations, how far we are from curing cancer, HIV and other terrible diseases.

Host (David C. Luna) 00:04:21 Discuss some of the ethical concerns that many scientists have around CRISPR and how far we humans should really go when applying this technology. Without further ado, let’s go meet Yoram.

Host (David C. Luna) 00:04:37 Welcome to the podcast, Yolla. Yeah, hi. So do you want to introduce yourself to the listeners before we start?

Guest (Joram Schwartzmann) 00:04:44 My name is you. I’m Schwartzmann. I’m a science communicator. And I used to work in research. I was doing plant research. I worked on tobacco as a model organism and was investigating the photosynthesis there. And through that, I switched then to science communication in one of the big projects that I started after.

Guest (Joram Schwartzmann) 00:05:03 My active research career was all about CRISPR and that ties in. I guess that’s the reason why you contacted me, that I did a lot of science communication for a bit over a year on the topic of CRISPR and trying to explain what it is, why it’s exciting, what are the potential like risks or things we have to be aware of, mostly in context of plants, but also in context of society and also other fields where CRISPR is applicable. And now I’m still working on science communication a little bit further away from plants, but I have plants still in my heart. I’m still doing a blog and podcast about plants, and so I’m still attached to the field of plants, although now I’m more going in the direction of engineering and technical application and computer science and so on my communication work. But today, I think it’s all about CRISPR, what we’re talking about.

Host (David C. Luna) 00:05:55 So most people probably haven’t heard of CRISPR. Do you want to explain in very simple terms what CRISPR is and what the abbreviation stands for?

Guest (Joram Schwartzmann) 00:06:06 Yeah, CRISPR, depending on the way you look at it, can be many things. It can be a tool for genetic manipulation. It can be just a combination of a protein and a molecule called a guide. RNA nucleic acid combined with a protein is a way you can look at it or you can look at it as an immune system of bacteria that they use against viruses. All of these things are true. And depending on from which angle you come, you see these different aspects of it. The name CRISPR stands for clustered regularly interspersed short palindromic repeats. And this is one of these acronyms that actually tells us already quite a bit about what we’re dealing with here. If we go from the back, then we have to repeat. That means we have sequences and in this case, it’s DNA sequences that are repeated. They are found very often in the genome. They’re palindromic, which means that they can be read from front to end and end to front in the same way. Like the classic example is the name now A and A can be read both ways. And this, of course, is like more complicated palindromes. But these sequences in a DNA that can be read left, right and right or left, and they spell out the same, they are short. I didn’t look up how short they are, but they’re usually much shorter than one hundred base pairs. I think they’re even much shorter than a couple dozen nucleic acid letters of the genetic code. Interspace or irregularly interspace means that there is like a spacer in between these repeats and clustered means that you find all of these things in a big cluster together in the DNA. So you have a cluster where you find these short palindromic repeats, then a little of space between, then another repeat and you find a lot of them behind each other. And this is a very particular structure when you look at DNA and that’s how researchers got interested in it and actually found it because they saw this very atypical structure in the DNA. It’s not something that you usually see. And they found that in bacteria. And then they tried to figure out what’s going on here. And then they realized that this these CRISPR regions, this CRISPR is very important in the defense of the immune system of bacteria against particularly viruses.

Host (David C. Luna) 00:08:10 All right. So we have quite a lot to unpack here. For one, now I understand why scientists came up with a very nice and compact abbreviation, CRISPR, so we mortals can pronounce it. And the other aspect is in this kind of surprised me during my research is where I found out that bacteria can actually get infected by viruses. Now, the first question that comes to mind is how is that possible? And I would assume that the reverse would not be possible, because I know viruses tend to be much smaller than bacteria.

Guest (Joram Schwartzmann) 00:08:42 Yeah. And I think the size is already the main critical factor in this case. And bacteria and viruses, they are depending on the size of the bacterium and a particular virus, but they are in the range of a ratio of one to 100 to one to a thousand in terms of size of a virus is a thousand times smaller than the bacterium. And therefore, you can already imagine that a bacterium has a much harder time to infect and get into the body of a virus because it’s so much smaller. Like we can’t as humans, we can’t infect a bacterium because it’s smaller than we are. And that’s a very simple physical explanation for why that is the case. The other thing is that viruses stay off of molecules, often proteins, together with DNA that are on steroids. There are proteins and DNA punch together, but they are not alive. They can’t replicate themselves. So they need always a host system. Where they can inject their own genetic information into them, replicate them, and then burst out and continue to do what they do. That’s why viruses aren’t just like weird like gray area, like they’re not really a life, but they’re still a biological system that replicates with the help of another biologic system. And as bacteria are proper living things, they replicate themselves. They don’t need a host to replicate. If you don’t look at like parasites or some like specific bacteria that have a very particular lifecycle, but usually they are sort of self-contained units and that’s why they can’t really infect the viruses. But viruses can take them as a host to get replicated and spread, spread and get a larger number. And I think phages. So Phaedrus are the particular type of virus that can attack bacteria, particularly a type of virus that found associated with bacteria. I would say, again, like I’m a plant scientist, also have a couple of viruses that can attack them. But the very famous ones are the twin phages that can attach to bacteria. And they have to like Éliane, like structure with the head and the stem and these feet that grab onto the bacterium and inject their DNA in there. And then it gets activated. And the bacterium does pretty much only the thing that the virus wants and then bursts open and releases more of the virus. That’s why bacteria have a very strong interest in doing something against that. Right. Like for bacteria, for an individual bacterium or a bacterial colony. It’s a bad thing if viruses infect them because then they spread and it can very easily go from cell to cell replicate even more like every time they are amplified, they create like a few viruses only have to attach to a bacterium or technically just one. And then hundreds of thousands of new virus particles are made and spread. So if you imagine a bacterial colony that can be very quickly overrun by these viruses and killed, and that’s why bacteria had to evolve in a way that they can deal with that. And CRISPR is one of the ways that they evolved with CRISPR. They pretty much took the DNA that was injected by the virus and chopped a little pieces, integrated into their own DNA and used that as a recognition sequence. So the next time a virus would inject its DNA, they would have a matching set already in their own in the bacterial DNA that they could use to recognize the virus DNA. And it could ring the alarms and say, look, there’s a virus we attacked and then they could activate specific enzymes that would then degrade the foreign DNA and the virus could not be active. So it would inject its DNA. The DNA would be degraded and that’s it. And a bacterium continues to live and do its thing. And that’s essentially the role of CRISPR in bacteria in this relationship between bacteria and viruses.

Host (David C. Luna) 00:12:07 So essentially, we could say, to sum it up for the listeners in very simple terms, that CRISPR is a genetic engineering tool that we stole from the bacteria and then hijacked it for our purposes. And the bacteria has this defense mechanism for which we’re using CRISPR now and integrates little spacers in between the DNA essentially, or RNA for the bacteria, I believe. And these spacers is what I understood from you, are essentially like a vaccination card or a database of past infections, is that correct?

Guest (Joram Schwartzmann) 00:12:44 Yeah, yeah. You could say it’s a databased, a CRISPR regions like these repeated regions, they store pretty much all of the foreign DNA that they’ve counted, and that’s mostly viral DNA they catalog where they recognize foreign DNA in the concepts. It’s similar to our immune system where we identify a pathogen, something that’s making us sick. Then our immune system stores that information and can recall it later and then react quicker. And we don’t get a similar vaccination. If you really look at the biology data, systems work quite differently in detail. But if you just look at them from a concept level, they’re very comparable.

Host (David C. Luna) 00:13:26 If these spaces are essentially a vaccination card or a database of past infections, which the bacteria has encountered, could we then say collect a bunch of people that are immune against various diseases, add them all up into a history, into, say, one giant DNA sequence and inject that into people so that they would be immune against these thousands of diseases like, say, into one giant mega vaccination, if you will, with something like that be possible with CRISPR.

Guest (Joram Schwartzmann) 00:13:59 The thing is that our immune system is not like the bacterial immune system in that. And we don’t use DNA detection mechanism if are infected with a foreign pathogen for the virus, usually not the DNA that’s recognized from the virus, but its outer shell. So the proteins or the fuels that make up the outer shell and these are then detected by the immune system through a very different process. So we could not at all create a bacterial immune system in humans by just injecting sort of a database of DNA sequences of known pathogens because we lack. The CRISPR system, like we don’t have it internally in our genome, that could then take that information and foreign DNA from viruses, for example. No, that would not be possible in humans with CRISPR if it were only that easy.

Guest (Joram Schwartzmann) 00:14:47 Yeah, unfortunately, it’s not that easy. It would be very nice if that could work. So genome engineering isn’t new. It’s been around for the 1970s. So what makes CRISPR so special and how does it compare to see other genome editing tools?

Guest (Joram Schwartzmann) 00:15:04 We have to look a little bit into the history and also into what we can actually do or could do since the 70s. And one of the first things that we were able to do was just transferring chunks of DNA, be it. And that could be any DNA had to have some like physical limitations in terms of size. And Ammon’s had to be there. But overall, you could say can take a gene from anywhere from the organism that we are working with or from another organisms. And that would then be a transgene, if we bring it from a different organism and then we could introduce that into the genome model organism. The thing is that when we do that, in most cases, the integration of our genes that we introduce will be in a random location somewhere in the genome and want to make whatever is encoded on that gene for introducing.

Guest (Joram Schwartzmann) 00:15:52 It’s usually fine, like we can have bad luck and hit part of the genome. That’s very important. And then we introduce our foreign gene in there and then it breaks something and then the whole organism suffers as sick or dies. The chances are fairly in our favor that we just hit an area where it doesn’t really matter if we add a little chunk of DNA there and then it’s made and then and we’re happy. And that’s classic transgene methodology. And this is something that in certain steps has been around since the 70s, especially what was hyped in the 90s when we had this first hype of gene technologies. That was exactly that introduction of transgenes, be it in humans and animal systems and plants for agriculture and plant breeding. All of that was just the idea that we take a foreign gene that encodes something interesting, for example, a resistance against a certain chemical that’s in plant breeding. Very interesting. And so, for example, the resistance against a herbicide, we can just take the gene that’s responsible for that, put that into the plant genome and integrate somewhere at random. Then we just have to make sure that it’s in a place where it’s safe. And then the plant makes on top of everything that the plant anyway does. It also makes our new gene product that is classical gene technology, the thing that it’s always relies on transgenes. It doesn’t really make sense to integrate a gene that he already has, again, in the organism cases that can be useful, but that doesn’t really help much sort of gives the organism an ability that it already has. So why bother? Why invest the time and money into this? So you take something from a different organism and then you end up with all of these questions of ethics and biosafety. Is it OK if we take a gene that’s isolated in a bacterium and put it in a plant? Is that OK or not? And many found that this is not OK.

Guest (Joram Schwartzmann) 00:17:40 This is not something that they want to have as consumers, and that’s why it is transgene technologies. They are usually not very much liked by the public, at least in Western Europe and the United States and in some other countries, other places in the world that have less of these ethical problems with that. But just keep in mind, transgene technologies are the classic approach. And now CRISPR comes along and Christmas actually CRISPR Casani and we didn’t really talk about cost nine yet, but just I want to say it once and then afterwards we can just talk about CRISPR because it’s easier. But usually the system of CRISPR part and a protein part, it’s called Casani and together they work literature. You will always hear CRISPR Casani. But today we’re just going to talk about CRISPR.

Guest (Joram Schwartzmann) 00:18:21 So when CRISPR came along, the very exciting thing about this is that it’s not a tool to integrate DNA. It’s a tool to cut DNA at a very specific location and then have to sell repair to cut. That was done. And while is repairing the cut, it has a tendency to make a mistake. And when it makes a mistake, it creates a point mutation in this very spot. And this point mutation is then able to change the area of the DNA where the mutation is. And that can be anything that can be often destructive change. So you can destroy a specific gene where, you know, if that gene is not there, then my organism performs better or in basic research. I just want to figure out what happens when we break that gene. But it can mean that we change a promoter sequence, sort of a regulatory sequence that controls how much of a gene is made and we can increase its activity or decrease its activity with CRISPR that depending on the location where we introduce that cut change in small and big ways locally with mutations, the DNA and to end result, just that it’s just a gene with a mutation and point. Mutations happen all the time in nature whenever you go from one generation to the next generation. You have just randomly a couple hundred to a couple thousand point mutations all over the genome, and that means that when we use CRISPR, we end up with a result that if you hold it side by side to a naturally mutated gene, you can’t tell the difference between the two because it didn’t introduce anything foreign. You didn’t introduce anything that wasn’t there before. You made a small point mutation after the fact. You can’t really say that we did something. So it’s a system very close to what’s happening naturally without any sort of coincidence, and that we can exactly pinpoint a location where the activity happens and we know that it just happens at its location genome. So we we don’t have the problem that we have a random insertion and we we produce anything foreign. So both of the defining characteristic of classical gene technologies don’t apply to CRISPR gene technologies.

Host (David C. Luna) 00:20:26 All right. If I tried to sum this up for the listeners with an analogy, back in the 1970s and 90s, we had fairly rudimentary tools that were more like, say, a shotgun. So we would go out, try to hit the target, and then just sprayed with a bunch of lead bullets and see if we hit the target. And now we basically have CRISPR, which is very precise, where we would go in with, say, a sniper rifle and locate the targets and hit the target exactly where we wanted to. And with the sniper rifle, we could exactly target the gene section that we wanted to. And then the body would realize itself, healing properties, repair that damage and then rebuild that gene, ideally in the exact location that we targeted. Is that generally a correct way to sum that up?

Guest (Joram Schwartzmann) 00:21:20 Exactly. The shotgun analogy is something that’s often used other people you like to use to with a scalpel for CRISPR Technologies, because you have these very precise cuts. You just rip out chunks that I quite like to visualize.

Guest (Joram Schwartzmann) 00:21:32 The whole thing is that if you imagine you have a book that’s the whole genome, classical or gene technologies would mean that you introduce a paragraph somewhere in the book and sometimes the paragraph makes sense there. It’s good and it’s useful for sort of the performance of the whole book and any successful transgene inserted or inserted your whole paragraph. But you can tell that this paragraph wasn’t written by the original author of the book. It was taken from a different book with CRISPR. It’s more about like a word processor and you have to control F command for search and then you can replace and then you search of a specific sentence. And in the book that only you can only find once in the book and then delete one letter in the sentence and you can change a word from one word to another word. And I don’t have a good example of a word or two words in mind that are just one letter apart. But I think our listeners can do that in their heads. So you can simply change an individual word by removing just one letter or maybe two letters. It’s very small edits.

Guest (Joram Schwartzmann) 00:22:33 And then you close the book and then when somebody else picks up the book and goes through all the pages, they don’t know, is that like a typo, like they always happen when books are printed or is that something that somebody put a deliberately in there? And that’s a difference between classical approaches that you can very easily trace to blunt. I don’t want to do injustice to the people who use classic gene technologies. There’s still a lot of skill, a lot of knowledge about what they’re doing. But compared to CRISPR, CRISPR is much more precise and has much smaller effects on the genetic code level, the effects of the changes of the genetic code, that can be fairly big. But if you just look at all the letters in the DNA, the changes are really small in simple terms.

Host (David C. Luna) 00:23:14 How does the whole process work? Let’s say we have one gene and there’s a certain area that interests us what it does because we’re not sure. So take us through the process of how that whole thing works in very simple terms.

Guest (Joram Schwartzmann) 00:23:29 Yeah, so let’s say we have an unknown origin of unknown function, that’s usually what we start with in research. We picked up that this part of the DNA test gene might be interesting. First of all, we need two things to start our CRISPR experiment. We need to know the sequence of the gene of unknown function that we’re interested in. And it’s very useful if we also know the entire genome sequence. And today we are genomes available for many different species, fana for all species. But for the sake of this example, let’s say we work and something close to my heart, as is Arabidopsis, that is the most common model plant in plant research. And let’s say we have an unknown gene gene of unknown function there and we know the entire genome already. It’s one of the first genomes that we’re sequenced. So we know already all of the other letters of the DNA. Then we can use computational tool. There’s a couple of them around now and we can select a region where we want to have to cut. And then the tool automatically searches for the best cutting side because there are some limitations. And for the CRISPR system, you can’t exactly every single letter you can within a region select a site where you’re cutting because it follows some physical constraints. So this computer algorithm picks the perfect location for the highest chance of having successful CRISPR editing. Then you pick that sequence. It creates for you the sequence for the guide RNA, which is the actual homing system that recognizes the target. And then you can just order that you send out to a company. They create the RNA. And just as a little reminder, DNA is what we find in a genome. RNA is sort of the work copy. The DNA is translated into RNA. RNA is then made into proteins. So RNA is the active copy. That’s when everything is activated. RNA is made and has a ton of other functions in the cell as well. And one of the functions can be also work as a guide RNA and that combined DNA. So we send that to the company they send us depending on how much money we pay within a week or within three months, they send us the RNA back in a little tube and then we just mix that together with an enzyme can do that either by integrating gene forecasting in with classic tools into Arabidopsis, into our model organism, or what’s even fancier. What many people use nowadays is we just take the protein and ofter just the enzyme and mix that together with the guide RNA that we just got from our company. And then we introduce that together directly into a cell, for example, with micro injection. You might have seen that from like fancy videos, for example, for in vitro fertilization, where researchers say, look into a microscope and they see a single cell and then a half a tiny needle that’s smaller than the cell they poke to cell and then they can inject something in there. I’ve seen that in action. It’s crazy because you see the needle and it vanishes into nothing, because at one point it becomes smaller than the what you can see with the naked eye. So they poke into to sell. They inject something in this case to inject a guide RNA and Casani an enzyme. Then in the cell, the guide RNA finds to target that we picked before on the computer in the genome sort of alerts the casini enzyme, the kazmin enzyme and binds there as well. And together they become active. They cut the DNA at the chosen site and then they go away again, because once the DNA is cut, the whole binding is removed and they just float around and eventually they get degraded from the cellular machinery. So in the end, they’re gone. But now we have a DNA that has a cut. And whenever the DNA breaks, that can happen naturally as well to cell tries to repair that break. And it takes that takes another strand of the same information because that hangs around in multiple copies in the cell lines. These two, then another enzyme comes and tries to repair the break. Most of the time that works perfectly. And in the end, you have two parts that don’t look any different. The CRISPR system can come again and just cut again. And it does that so often until there is a mistake made by the repair machinery, which it also does like in a it has a certain chance to do that. I don’t know if it’s in the range of one percent of all cases have a mistake, doesn’t, and it makes a mistake. And suddenly the sequence has changed the CRISPR system now combined anymore because now the sequence is different and now it can’t buy it anymore. But it also doesn’t have to anymore. It’s done its job then we already done with the whole system. Then we can take our individual cell. We can make sure that from this one cell we get the full organism again in Arabidopsis. You do that through cell culture. You can do that with stem cells. You can do that in all kinds of organisms. You can just create from a single cell again, full organism, then the change in your genetic sequence. And if you do that with the way where you micro inject your CRISPR into directly into the cell, you have no trace of it. In the end, you just have to one point of mutation that you introduced, you don’t have anything else lurking around, leaving a trace. And so you can’t really tell this this organism now, apart from an organism that just by chance has the same mutation. Yeah. So that’s. I hope in simple enough words, hard work, so you decide what you want to cut your order, your material, you do your experiment, and that’s really by now. Today, the methods are so advanced that it’s really a week worth of experimenting or sometimes just a few days. So it’s really fast penetrate your your cells and then you’re done. So very quick turnaround from time, from time your materials arrived from the company. That’s usually the bottleneck. You can be done in a week or two and you have your desired mutation.

Host (David C. Luna) 00:28:56 So how long would this whole process take before we had CRISPR?

Guest (Joram Schwartzmann) 00:29:00 Oh, in many organisms, you wouldn’t be able to do anything like that in a directed manner. So what you would do then instead is that you trade a ton of random point mutations and you can do that, for example, by changing UV light at the organism or specific chemicals. And I would just go with a certain probability they would make breaks in the DNA and then the cell would repair them and make mistakes with again, with a certain probability. And in the end, you can choose by the amount of exposure or concentration of the chemical, how many mutations you get, but you get a ton of mutations and then you screen for the ones that have a mutation in a place where you want to have your mutation. You can imagine that’s a numbers game. If you have a genome that’s a certain size that you need to have a certain amount of random mutations in there and amount of repetitions that you can then find by chance the one mutation that you’re looking for. And that’s what we’ve been doing in classical breeding quite a lot.

Host (David C. Luna) 00:29:55 So could I kind of sum this up with an analogy? So let’s say I would have a nut and I wanted it to determine what type of nut it was known and walnut hazelnut and I would take a hammer are very crude method that I have before CRISPR and then try to hit the nut, cracking it open, but not completely destroying it.

Guest (Joram Schwartzmann) 00:30:14 So with that being aptly the correct way to describe that, it’s so we don’t really try to figure out what kind of nut we have. We might try to change the nut in a certain way. An image that I used in the past is if you imagine you have a canvas in front of you and you want to color in a very specific spot there you which is a color at your canvas by your your paint brush against the canvas.

Guest (Joram Schwartzmann) 00:30:37 And I would splatter droplets all over the canvas in random locations and at a couple of times on different canvases that are all identical to the one where you have to spot your color exactly where you want it to be, all of the other color around it, where you don’t want it to be, all the other random splatters. And then you take more of your identical canvases and you do something. It’s called Back Crossing, where you cut your canvas in half, your painted one and your unpainted one, and then you recombine them and then you have half is painted, half unpainted. And then you take the new combination where the color is still where you want it to be. Do you still have half of the canvas with random splatters? And then you do that again and you cut in a different way and half of it and dilute out all of the other random hits that you have. So you only keep the one in the spot where you want to have it. And this is a process that takes a very long because you always have to go through a next generation. And depending on the organism that you work with, it can be a couple of days to a couple of years. Yeah. You dilute out all of the random things that you hit that you didn’t want to hit because you might have broken something else. And it’s impossible to tell if you just do random mutagenesis is the word that’s used for that. If you just randomly introduced mutations, it’s really hard to say that your organism is still perfectly fine, even if one thing do you want to hit and yet you have ten thousand other hits somewhere else that you can’t see right now. So that’s the main issue with it. It’s still very random and you hit lots of things that you don’t want to hit and then you have to take great put in a lot of energy to fix that. And with crossing change that and so long that you only have your desired mutation left and remove all of the undesired mutations make sense.

Host (David C. Luna) 00:32:16 So could we use CRISPR on any organism?

Guest (Joram Schwartzmann) 00:32:20 Yeah, technically that’s not a problem because the way the DNA repair works is very conserved on an evolutionary scale.

Guest (Joram Schwartzmann) 00:32:29 That means something that works on the DNA level will be very similar in plants, will be very similar in fungi. In many bacteria. You’ll find similarities where these basic systems work. So from that part of the biology, it’s fine. But when it comes to actual application, we come back to the thing that I said when we talked about the example. You need to know the sequence of your target and you should know the sequence of your genome, because you always have to check that you when you select your sequence that you don’t hit something else that you don’t want to hit that has a similar sequence in the DNA. I know. Or you might maybe know that genes can exist and duplicate or very similar genes can exist within a genome. And if you just want to hit one of them, you have to make sure that you take a part of the gene that’s very unique to that one copy so you don’t hit anything else. And to know about anything else, you need to know about genome. And as I said, we know about many genomes, but by far not about genome. So if you pick a random desert, a plant. If you find a weird frog in the jungle, you won’t be able to immediately take it to the lab and perform CRISPR on it. You first have to sequence in animals. It’s fairly easy to sequence it. It just costs a little bit of money and plants. The genomes are often very complicated and very large, so it sometimes takes researchers years and years of bioinformatics work to find a structure in the genome. You can’t easily just throw it on a machine like in the movies, and then 30 seconds later, it gives you the entire genetic sequence of it takes five, sometimes 10 years. We have some things like tobacco that we’ve been working on for 20 years to create a functioning genome of it. And we still don’t have like a very good working model for it. We know all of the letters, but we don’t exactly know in which to puzzle together. It’s very complicated. But yeah, but if we have these two things, if we know the gene and if we know the genome around it, we can use crisp on it.

Host (David C. Luna) 00:34:24 OK, so those people that were hoping to create the perfect girlfriend or boyfriend out of the lab are going to be pretty disappointed then.

Guest (Joram Schwartzmann) 00:34:34 Yeah, it’s not that easy. And even with CRISPR, it’s still a numbers game, right? It’s still in biology. You rarely, almost never have 100 percent predictable outcome. So if you imagine how you would want to create your perfect partner or just a perfect human to have a lot of cells that you introduce a change to and with CRISPR, with complex things, I don’t know, a personality trait, if that’s even genetic, actually is often not linked to a single gene or a single mutation. So you imagine you have to introduce 200 different mutations and each mutation has a chance of working. And then you stack up all of these probabilities and you come up with a fairly low probability that all of them work together. So that means to be sure that you will have one embryo in the end that works. You need, I don’t know, a couple of hundred of embryos or maybe a couple thousand of embryos that you have to all to mutations like introduce CRISPR to them, half CRISPR to try to do 200 different mutations and then analyze them, see if all of them worked the way you want them to work, and then select the embryo. So it becomes just from that point of view, very hard to do anything with as a model organism like human, where the amount of material you have is very limited beyond extract or embryos from a single couple. First of all, for ethical reasons, I would really want to stress that I’m really aware of the ethical problems around human medical research regarding CRISPR, and that’s why I want to stress that I’m not condoning it. And I think as a society, we should be very careful and critical about this. And so what I’m describing right now is purely from a technical or research point of view, it’s very hard to do. It need a lot of embryos in mouse. There’s much less of a problem to get a lot of mouse embryos or implants. It’s even less of a problem because you can just use to seeds and or use clonal reproduction and you can create thousands, tens of thousands of plants. Every time we saw seeds on a field, we create a new generation like a next generation. That’s a couple of 10000 plants. And if we take that and do sort of statistical experiments on them that have a low probability, if you have 10000 plants, chances are that you will still find one that has all of the things that you want to have in them. But get 10000 mice or 10000 human embryos with the same probability as close to impossible. So making your own super human with CRISPR still not very feasible, apart from being ethically absolutely wrong. And I would not recommend doing that anyway. But if the ethics don’t stop you, the technicalities of it will be OK.

Host (David C. Luna) 00:37:07 So let’s leave the ethics out for just a moment. We’ll get to that part for sure, present from someone that knows nothing about the topic. But it has got me thinking, why can’t we just sequence all the genomes that we have in our body or take them? Maybe simpler approach to sequencing everything in the embryo from which we derive later on and try to understand all the genomes, the interdependencies and the relationship between those genomes, because after all, we have all the compute power that we ever want. So why not just process that whole pull genome or other genomes in our body and then try to understand the whole source code?

Guest (Joram Schwartzmann) 00:37:50 The sequencing is not really a problem anymore. It used to be very expensive at the Human Genome Project was such a massive, big deal because it costs millions of dollars to assemble the very first human genome because that’s where more and more expensive computing power was reduced to what we have today. So by now, depending on where you get it and how you do it, it costs like a thousand dollars or something to get a full human genome. So that’s in terms of research money. That’s almost nothing like a centrifuge costs more than getting the sequence data of a human. That’s not a problem getting all of the letters identified and the order to. And figuring out how they relate to physical or to properties, and we call that phenotypes basic, comparatively basic things like hair color or eye color or size more complex, the traits and size is already a complex trait. It’s not defined by a single gene by but by a couple of genes, but to things like personality, intelligence, where we don’t even know how much of our intelligence is genetic and how much of it is shaped by our upbringing is things that are so much more complicated than a single A to be a relationship between a gene and a phenotype. That makes it incredibly complicated to just figure out what is the role of all of these genes. And also many of these genes, they are not on or off and that defines their activity. But it’s the fine tuning of them. If we think about like our brain chemistry, if we have certain neurotransmitters that are just produced a little bit too much, like they’re not completely overproduced and they’re not completely absent, they’re just like 20 percent more than what the average human has that can already lead to things like depression or other like neuro diseases, where we have a very complex sort of outcome of it. Like a depression is not a it’s not a very clear diagnosis. It’s not a rash where you can very clearly see it. But it’s it’s more complex than that. And that’s just on our brain chemistry. And we have some so much of that. We have that in all our organs throughout our system. We have these gradual differences that are defined in our genetic code by the fact that in some humans are certain genes, 10 percent more active or 10 percent less active. And these things, if you all stacked and on top of each other, they become this multidimensional, very complicated network. People are still like, we don’t we are we haven’t understood it yet. And we also still pretty far away from fully understanding. We are uncovering more and more relationships and correlations and can figure out like if this cluster of genes has a certain change in their expression profiles, that means this cluster of genes, they all are 10 percent more active than on average. That can lead to people who are more willing to take risks. But then that doesn’t mean that all of the genes and there have this direct are at risk. But the whole class, we just as good as naming sort of the group, we acknowledge that a couple of them might not be true and a couple of them might not be in there that are actually responsible for this trait. So it’s just biology is just so very complicated and that’s just talking about the genetic information. And there’s a whole field of epigenetics that’s on top of that. That’s something that’s a very young research field where we’re only uncovering what these effects are. So taking, even if we know exactly all of the sequences are a human of human DNA of any organism. We can’t predict with certainty outcome of that organism will be. There’s also something it’s very hard to do technically, like you could imagine, OK, we just create an artificial genome and then we put it into an empty shell that has all of the machinery there to activate the genome and then become an organism. And then we just look what the organism looks like. And then we do this with like small changes. And over time we figure out what’s going on. But this is fantastic biology and people are doing this. But it’s insanely complicated. Just, for example, for the fact that getting along intact piece of DNA without breaking into a cell, it’s just very hard to manipulate because when you have a long stretch of DNA, it’s essentially a very long molecular string and that breaks and that has a very weird viscosity. You can’t really manipulate the liquids where you have to DNA. And so just from that standpoint, again, it becomes very hard to do sort of an experiment. It is very easy to describe on paper. It’s very hard to do that in the biological reality.

Host (David C. Luna) 00:42:15 So we try to simplify. This is like having human life being written in source code, but we don’t know what the programing language was used for the code. So we don’t understand what the objects are, what parts of the code or maybe scripts. But some of them are committed also. So we don’t know which parts don’t do anything. And then also the user interacts also dynamically changing the code. So that would be like our social environment, changing the gene expression, for instance. Could that be proper analogy to explain why that’s so complicated to understand?

Host (David C. Luna) 00:42:53 Yeah, it’s like a very complex programing language. It has like multiple layers and we don’t know all of the commands is there might be hidden commands. And there there are two very complicated things, but we don’t know them yet. We have all of the letters along, but they’re written in the language. We don’t speak any random combination of letters could be a controlled sequence or could mean nothing and figuring out where the control sequences are and then figuring out what they do and then following that through the multiple layers that are in my program code is very complicated. And I’m not enough of a programmer to know if that’s, for example, the same as like assembler code to me, the. Sounds like you just have a few zeros and ones that are going into the process and all of them, but then going back from all the zero zeros and ones to a functional programing code, that is understandable. What’s going on to me seems like an equally impossible thing, but maybe that’s possible in it. But in biology, it’s not.

Host (David C. Luna) 00:43:46 How far are we along from, say, curing certain diseases, cancer or Parkinson’s or even HIV AIDS?

Guest (Joram Schwartzmann) 00:43:55 I’m a plant scientist. I want to mention that here on the podcast. I can’t really say things about the scope of where we are, but I looked up a little bit. What are these diseases and what’s going on there? And to go through them quickly as cancer is a very complex disease where you don’t have a single type of cancer, you probably know that you have like skin cancer and bone marrow cancer and lung cancer and all of these cancers, they work differently on a biological scale. Usually like the simple form is there is a cell type that multiplies uncontrolled forms a tumor, and that tumor presses on something that’s important to you and then you die. That’s a very basic understanding of cancer. But how these different cell types start to multiply rapidly and uncontrollably is very different when it happens, the bone marrow or when it happens in the skin cell. And that’s why we can treat things like skin cancer much more easily than we can treat bone marrow cancer. I can’t really say when can we defeat cancer, because probably with time we will become better at treating many different types of cancer. But I can imagine that it’s possible that there’s just some types where we can’t treat it, really certain brain cancers, certain other organ cancers where we can’t treat them like, well, forever. It will be in a place where anything that we do in this area will do more harm than good and we will kill the patient.

Guest (Joram Schwartzmann) 00:45:14 So, yeah, that could be, I guess that in the next decade or two we will see definitely in cancer treatment. But I wouldn’t wait for a complete cure of cancer. In reality, the next thing is HIV. HIV is a virus that has a very complicated or very complex infection pattern. The main thing you have to know about HIV is that it can shield itself with additional shell that like it’s human. And therefore, our immune system can’t tell HIV virus particles apart from anything else in the body. And so they can’t distinguish them. And so they can’t specifically attack HIV. And that’s why it’s so hard to cure that. And we’re very hard to develop any cure for that, because anything that we develop, any drug, any sort of immune treatments, if we would imagine we boost our own immune system in a certain way, maybe with CRISPR, maybe with something else, we still have to come around the problem that HIV cells look like body cells or HIV particles. It’s not a cell. It’s a virus particle. They look like body cells. So if we can’t overcome this problem, we won’t be able to cure it. We can cure the effects of it already. Now, people with HIV, they can live long and healthy lives. They just have to take certain drugs all the time. They already know you can say in rich countries you could survive it very well. We still we can’t be sure that it’s completely dead. We can completely eradicate it. And then finally, Parkinson is a very complicated brain disease. And when I looked at Abbottabad, we don’t know the cause yet. And if we don’t know the cause, we can’t really develop a treatment. We can imagine that maybe in the next decade or two or three we will figure out what’s going on and we figure out it’s genetic. Then we could imagine using CRISPR to change the genes of embryos before they are implanted into the mother and change the genes that are responsible for Parkinson’s in a way that Parkinson’s can’t develop anymore. But that’s completely sci fi. That’s right. Now, that’s not based in any reality because we don’t know what Parkinson’s and there are some diseases that we can that we can cure genetic diseases. We can imagine figuring out where the problem lies and then designing CRISPR therapy to change that. But we can only change that in an embryo. So if you are an adult human and you have a genetic disease that affects, for example, your neurons across your body, so from from your brain, through your spine, down to your feet, all neural network connections have a problem. And that’s genetic. Right now, we don’t have a method to bring the CRISPR system into all of the cells that are affected. We can only bring it into the embryo so that we change it when it’s only a couple of cells big and then all of the cells are changed and then cure is transmitted during the growth of the embryo into the entire system. So in this specific case, so if we know it’s a genetic disease and we can do a CRISPR therapy in the embryo, then we can cure the genetic disease.

Host (David C. Luna) 00:47:57 All right. So we’re not Prometheus yet? No. So essentially, we need much more work that we have to put in to understand these very complex diseases such as CRISPR, also currently being used for vaccination development, say, for the covid-19 virus.

Guest (Joram Schwartzmann) 00:48:14 I can imagine that it’s used in a basic research leading up to it. So when you are studying the pathogen, so the bacterium or the virus and you want to introduce small mutations there to see how it behaves and want to study its. Which are the points of attack for your vaccine? The I think it’s use vaccine development itself is then still done in a biological system and chicken embryos and chicken eggs, where the system is actually quite simple. You infect the chicken egg with your pathogen, then the pathogen replicates in the chicken and the chicken immune system then fights the pathogen. And then in the end, you take your chicken embryo that has been infected for four weeks and then you extract the antibodies that the chicken made. You clean up the antibodies. You mix that with some stabilizes and then you have a human vaccine and that usually takes about one egg per dosage of vaccine. But this entire system is completely devoid of genetic engineering. Essentially, in a simplified way, you take the pathogen that makes you sick. You inject it into the egg, you let the chicken make the antibodies, you take the antibodies from the chicken, you put the antibodies in a human and and helps the immune system. Although I should say you extract the antibodies from a chicken. But most vaccinations, they are not antibody vaccinations, but they are the pathogen is injected and then you train your own immune system. So you take the antibody from the chicken and you can use that as antibody therapy for your dosage. But you can also take a weakened form of the pathogen, inject that into humans and the human immune system takes care of it.

Guest (Joram Schwartzmann) 00:49:48 And for the weakening of your pathogen, you could use something like CRISPR. You could knock out the genes. So destroy the genes that make the pathogen very dangerous. So it’s only able to replicate. And it looks like a dangerous thing, but it doesn’t actually have its weapon anymore. You break the sword that it has to attack you, but you leave its whole arm and everything there and you send it into the human body. And then when it tries to attack anything, it can’t because it doesn’t have a weapon. But it still looks exactly like the evil invader. So your immune system can identify it, learn from it, but is at no risk of actually being stabbed because there’s no sword there anymore. So it’s you could use CRISPR. But again, for example, for Crovitz, it is a viral disease and viral vaccination research is still a little bit different. And you don’t really inject active virus into the body. So I don’t know how much you would use, how much use CRISPR would be for nation development.

Host (David C. Luna) 00:50:45 In case of covid, we talked about what’s possible with CRISPR, but what are some areas where you say this is completely hyped or where we still have a lot of limitations in certain areas, or what are just some hyped topics that are being propagated by the public where you’re just scratching your head and like, yeah, that’s never going to happen.

Guest (Joram Schwartzmann) 00:51:06 I think whenever it comes to sort of the pick and choose building blocks ideas where just, say, a crop plant or a hearing or an animal, we say, OK, yeah, we want to cow that has no horns, that gives us 400 liters of milk every day. And it also makes perfect meat for a steak pie, a lot of food, and it doesn’t drink any water. So it’s really cheap and upkeep these things. They are all individually so complex to to and the combination of them. We just don’t have the knowledge for that. So we can’t create just a perfect crop. We can’t it will create a human super soldier or anything like that. Any of these sci fi stories that come up when you think about genetic engineering, where people get scared and get afraid that spirited people will just creates evil beings, these things that are just not possible for just for the basic reasons that we don’t even understand enough to create these traits and probably still take us decades to get any anywhere near this sort of understanding of biological systems. So I think that is the sci fi aspect of it, where I think that people have have still the wrong idea. Yeah, because it’s something that’s very attractive in movies and something that’s very easy to tell, fear mongering stories in articles about technology. But apart from that, we have some limitations in the technology that we can only do the things that we know already something about. We have come a very long way with research, but there’s still this massive ocean of things that we don’t fully understand and where we still have every year we have breakthrough science articles show something completely new that uncover a process that we haven’t understood before. And there’s no end in sight. It’s not that we are at 90 percent done. And so we have figured everything out for the foreseeable future. Probably like my children and probably my children’s children will still have enough research to do in biology to figure things out, to understand how everything’s connected. CRISPR adheres to the same limitations. So we can’t do anything in CRISPR that we don’t understand yet how it works. I think that’s the limitations of the technology and what people think is possible with it.

Host (David C. Luna) 00:53:14 Yeah, this really reminds me of the iPhone moment where Steve Jobs introduced copy and paste to the iPhone and it was like, this is going to be a major revolution and we’re all like, OK, that copy paste, that’s really helpful. So we can cut and paste now. And we’re all imagining this this beautiful world where we can use this copy and paste this tool and generate with this feature the next Shakespeare seems very similar to that.

Guest (Joram Schwartzmann) 00:53:45 Yeah. And as I said before, we just don’t know what even makes the next Shakespeare. Even if you would have good DNA samples of Shakespeare or any other person of history that we deem to be extraordinary, we would still not be able I mean, we could clone this person, we could recreate the person, but we could not understand all of the complex underlying gene relationships that we could take the genius like the literary genius of a Shakespeare and put that into any other human. It’s just not something that has such a simple relationship. It’s probably a thousand different genes that are very slightly tuned perfectly to come up with this literary mindset of somebody like Shakespeare to keep it in that example, the specific upbringing that he might have had. So even if we create these a clone office and bring it up in our modern world, it might not end up writing like amazing literature because, yeah, we don’t even know how much of that is genetic.

Host (David C. Luna) 00:54:43 So there’s one big topic we haven’t talked about yet, which is ethics. And I believe every scientist should be aware of the ethical dilemmas, but using certain technologies within their field. Now, I personally believe that nature is still so complex that we still haven’t really understood the basics. Even though we think we’re so wise and have come so far. We should be very careful with things like gene modified food as we don’t really know what some of these long term effects are. Not to talk about decades. I’m talking about maybe 100 or 200 years. This argument kind of also follows recent studies showing that CRISPR edited genes can inadvertently trigger cancer. That’s why many scientists currently argue that experience in humans are premature. The risks and uncertainty around CRISPR modifications are extremely high. But at the same time, I really don’t want to limit innovation. After all, an innovation consultant then and know that we have to try and experiment a lot to find breakthroughs. This is the one side of the argument and it’s a libertarian one. So with any technology, it’s not a question whether it gets applied, but rather who will have access to it. And there’s also this tendency in technology become cheaper and essentially democratizing technology. And this is also the stance that the bio hacking community has or is taking. And I believe sometime in 2018, a scientist in China reported that he had created the world’s first human babies with ed genes or a pair of twin girls that were resistant to HIV. So essentially, when we let the Pandora out of the box, there’s actually no going back. So this is basically a long winded way to basically ask. In some ways we’re playing God. Another way is this technique is a scientific miracle. So what’s your take on this discussion? How far should we really take it?

Guest (Joram Schwartzmann) 00:56:42 I personally divide this question into two parts in humans. I have a very strong stance of saying I think it’s unethical to do this to use CRISPR technologies in human. And I thought the risks far outweigh any potential benefit.

Guest (Joram Schwartzmann) 00:56:57 As I said, back to school for gene therapy is fairly limited. Once we start. We have already information, for example, of about certain correlation between mutations and breast cancer, for example. So it would be not a big technical problem to create the CRISPR therapy that just avoid some of the mutations that are linked to a higher risk of breast cancer. And then we could do that and we could create a lot of girls that have a reduced chance of getting breast cancer. And you can make a case that’s a net benefit. That’s a good thing. The problem is that we then end up we can’t possibly make this technology available to everyone because this is it still requires embryonic manipulation that’s very costly, labor intensive, and also far away from the way we usually like to have babies, which is having intercourse and then having a baby with no doctor required, with no puncture of the ovaries where the cells are removed and then mixed with sperm. So they develop as two embryos in a petri dish. This is something that people do who either have money and a certain interest in having these genetic modifications or like couples who want to go through in vitro fertilization because that’s their only chance at getting a child. So the people who have access to this technology is a fairly. All number of people, but the changes that are done then these changes are genetic changes, that means all of their offspring carry start and that will lead to essentially genetically, objectively superior people, because then you have people who have, for example, a lower risk at certain cancers. Their kids have a chance of having also risk at lower costs because they inherit the mutations from their parents. If you imagine you have to in vitro babies that have both been modified to have less cancer risk and then later in life they meet and they have kids, their kids will also have a reduced chance of cancer as only the socioeconomic favored people. Some rich people will have access to this. You will create a rich class that is genetically better. They have a reduced chance of getting sick. And once we figure out more links of disease to genes, you can extend the list. It will then not be only cancers, and they will also have a reduced risk of getting certain other genetic diseases and so on, while the rest of the population, they are still being hit by all of these diseases. And this is a very dystopian reality to me, because that means you will have people who will be genetically better. And that’s not even touching on many of the effects of what happens when we figure out how we can do skin color or eye color or hair color. Will we then get a lot of people who follow their own stereotypes and introduce that into the genes of their babies? And even if they themselves have a darker skin tone, they just modify their babies to the point that they have light skin and blond hair. And so suddenly you have also like a physically different looking rich class that’s less prone to disease. And I find that very dystopian. To be fair, these are things that are still a little bit further away on the horizon, but technically they are within reach. And that’s why I think in humans, I don’t really see how much good can come of it starts developing these sort of therapies. They will be accessible to people, even if we start with the purist goals in mind. Once we have established solid working methods, people will use them for less than nice things. That’s why I think this is an area where I personally would not want to see a lot of research being done or publicly funded because it’s still everything is so expensive and complicated that if we leave it in the hands of just a few private companies, it will still be decades away until it will work reliably. But if we put a lot of public money on it and probably institutes a worldwide joint research course, you can imagine how much quicker everything will happen. So that’s why I am personally in favor of a call on human CRISPR research for diagnosis by for treatment purposes. The second part of my answer is in plant breeding. I see much less of a problem because in plant breeding we don’t have the ethical problem of removing failed attempts and we are already doing for centuries genetic modification and genetic selection. Something is conceivable in humans that we would just like grow 10000 humans, pick the best performing 10 and then use them for the next generation. Eugenics, essentially, this is something that we do constantly in plant breeding, and we’ve done that for thousands of years since we first started to breed wheat and use weed as a crop. We started to modify the original grasses by selecting them and without understanding what’s going on, we were selecting for certain genes and for certain genetic information. And we’ve done that until today, where now we have very good knowledge about the genome and we’re still selecting and manipulating it and just getting better at the tools that we’re using. And CRISPR is a great addition there, because with CRISPR we can stop it or avoid the very long and costly process of randomly inserting mutations and then selecting the ones that we like and then crossing seven, 10 times to sort of dilute out all of the unwanted we have. We can just directly introduce to one mutation that we know from basic research is beneficial to our crops. And I see much less of an ethical problem there because from our yeah. Millennia of breeding, we don’t really introduce a lot of harm to the environment and to the ecosystem or the harm that we introduce. It doesn’t come from the genetic selection of our crops. It comes from the way we do the farming. It comes from our tractors, from the diesel engines, from the way we use land, and that from the way we modified the wheat to grow on the land.

Guest (Joram Schwartzmann) 01:02:31 And therefore, I think something that’s very much discussed in the European Union, the ethics of using genome editing and crop research or in crop development there much on the stand off saying we understand the system good enough, that we can be sure that it’s definitely less risky than the methods that we used before. And therefore, I don’t see any issue with using genome edited crops. It’s a completely different set up from the human set up because doing genetic selection anyway all the time in breeding research, I believe.

Host (David C. Luna) 01:03:02 Also Jennifer Garner, one of the scientists that found the CRISPR technique, asked for a moratorium on any clinical trials involving humans so we could discuss the implications. And risks of this technique now, personally, I’m not so sure we humans are really good at keeping the genie in the bottle, which is too curious in a negative way. With any technology, it’s cheaper and we humans tend to find ways to make things much cheaper and we can maybe prolong this process. But we’ve seen this already in our history where we found and understood nuclear energy and then used it for atomic bombs and now Munser out. Everyone wants one and hopefully we won’t use it in that way again. Another example is when we used fish or whale oil for our lighting and then we switched to fossil fuel. It’s really hard to switch from fossil fuel because it’s in plastic cosmetics and everything. And once you get hooked onto that, well, it’s really hard to get off that drug. And the implications of editing our genes are now much more dire. And I’m not so positive on us humans. We tend to let the Pandora out of the out of the box. And once she’s out, I don’t think she’s willing to go back in. Let’s put it that way.

Guest (Joram Schwartzmann) 01:04:20 Yeah, absolutely. I am also if I’m I worry about this movie about CRISPR, but talks to, I think, Jennifer Garner and Emmanuelle Charpentier, who was the second woman they worked on developing the method. They are both in the movie, but also a lot of Silicon Valley researchers who want to build products based on Crispi and humans. And they’re very lax approach to it. And they’re very much they’re very much driven, at least in the things they say in the movie, about this need to innovate and this idea that innovation is inherently good. These are things and these are people who worry me because, as you said, if we have it out of the box, we can’t put it back in. And genetic modification always has implications for our future generations. It’s not something we can take back like you could imagine a world where we just say we ban fossil like burning fossil fuel and we could stop that. And then with some, like transition period, it would be gone. But any gene that is changed in a human if we don’t kill the human or stop it from breeding or reproducing, which both are highly unethical and morally wrong, we can’t stop that modification from continuing to live on.

Guest (Joram Schwartzmann) 01:05:34 And therefore it has much higher risks and is much harder to control than any other technology. Right. Like we could if like with nuclear energy, we have the problem of the decay. So this is something we will also stick around for a long time, the nuclear waste. But still, if we would shut down the plants and deactivate the bombs, then the radioactive matter would still be there, but the things would immediately cease to exist. Well, we can’t do anything like that with change, genetic information that’s in the reproducing system out there.

Guest (Joram Schwartzmann) 01:06:09 But I’m pretty sure we won’t solve this dilemma.

Host (David C. Luna) 01:06:11 But to wrap up this episode, is there anything or something that I didn’t touch on or forgot to ask you that I should have mentioned this one positive thing that I want to say about CRISPR, apart from the fact that I’m actually I talked a lot about the risks and the challenges and especially in humans, I find that we need to be very careful. But CRISPR for basic research is an amazing tool. And I say that with all honesty, it’s amazing what we can do with it. Now, when I was working in the lab, it was before CRISPR became widely available. It was pretty much when I left the lab that my my fellow researchers who stayed, they started using CRISPR in the lab. And it’s it’s crazy how much quicker basic research became because of CRISPR studying Knock-Out. So breaking down genes and looking at what’s happening is a standard method in basic research. You can do that there because it’s just research, not letting anything out into the environment so you can break and play around with anything and figure out how they work. That’s that’s how we do research. And before that we used to rely on very slow and precise and labor intensive methods to knock out genes and sometimes would just not be possible. And that was CRISPR. We have at our fingertips any mutation that we need and therefore we can do research so much quicker. And on top of that, we will see a huge spike now in methods developed based off. If we look at PCR, which is something that was invented in the 80s, it’s a method to replicate DNA. If you just look at a basic math method, it’s fairly simple and has one task. It makes you put in a little bit of DNA and you get a lot of the same DNA out of it. And that’s that’s important for for research. Then you can if you have a lot of DNA, it’s easier to analyze it. So that in itself is pretty important. And I was doing so many PCR reactions in my lab, but on top of a PCR, people build new methods and modern sequencing is based on PCR. Without PCR, we wouldn’t be able to decipher genomes and CRISPR will. A similar tool for the future, we will see something that we can’t imagine yet, we will see new methods emerging that use CRISPR as one part of several steps to create new methods that will allow us to do all kinds of things that we can’t imagine yet. The same how PCR enabled a lot of different analytical and and research methods without which we wouldn’t be where we are today. And that’s why I’m genuinely excited about CRISPR for basic research. It’s just it’s just an incredible tool. And people change to Casani an enzyme for a different enzyme and suddenly they can not cut the DNA, but change a single letter of the DNA or they can change something on the epigenetic code or they can attach a marker to that specific area so they can have like little light shining from where the thing binds on the DNA and they can learn stuff from that. So it’s pretty crazy what we can do with this. And I’m sure it’s crazy what we will be able to do with this. And I think I would like to end on this this note of excitement for the method to sort of counter the very worrisome tales of human research with CRISPR is that it’s a milestone method that will influence research for years to come.

Host (David C. Luna) 01:09:29 All right. So if people want to get in touch with you, what’s the best way of doing so they can reach me on Twitter?

Guest (Joram Schwartzmann) 01:09:35 I’m at science. You meeting in German and English. However, I feel you can always joke to me there and talk to me. I’m very happy to also discuss further questions and so on. If you want to know more about plant science, because I touch plants quite a bit in this episode together from Antiguan and we are running the block plants and pipettes dot com where we plant research. We try to break it down into simple words that even biologists can understand plant biologists. So it’s sometimes hard to avoid all of the jargon, but we try so you can check that out on plants and pipettes, dot com. And there’s also a podcast where we present current research from the world of plants. It’s sometimes about CRISPR, but often it’s not about CRISPR. I wrote about CRISPR and I will send you the links and you can put them in the show notes. So if you want to have a look at them, they are linked with this episode where little about the regulatory question of CRISPR and crops and plants in the European Union. I think two years ago by now, there was a very controversial ruling by the European Court of Justice. And I talk a little bit about that. That goes too far for this episode. You can read that if you follow the links.

Host (David C. Luna) 01:10:37 Perfect. I’ll make sure to include all those links in the channels. Thanks again, Your Honor, for being on the podcast and taking the time to explain CRISPR to the listeners.

Guest (Joram Schwartzmann) 01:10:47 Yeah, it was a pleasure. I am very happy that you have me on the podcast and I hope I could explain something in understandable words. And I hope all your listeners will learn something from it and take something home.

Host (David C. Luna) 01:10:58 Oh, right. That wraps up another episode. Now it’s time to summarize and give you some additional insights and some of my thoughts on the topic. So as you’re probably already aware, by the end of this episode, CRISPR is not only a scientific breakthrough, but also a very powerful tool for anything from agriculture to medicine. I also recommend you watch the trailer to the documentary Human Nature that I’ve included in the show notes if you’re interested in this topic. But as with any technology or major breakthrough, we still need to explore the limits and potential side effects of CRISPR. In particular, society needs to discuss all the ethical considerations at play here. For example, if we edited a human DNA, future generations wouldn’t be able to opt out. This is something you are mentioned in the episode, so genetic changes might be too difficult to undo. And sometimes the genie can’t be put back into his bottle. Just think of the discovery of nuclear power, which led to one of the most horrific weapons we humans have created. This challenge, though, isn’t new by any means. The Swiss writer Friedly Diplomat wrote about this very dilemma in esoteric drama the physicists, where one of the protagonists convinces the other two that the scientific knowledge he has gained or uncovered is too dangerous to be made public. Mankind cannot be trusted with such power. So all three men make the self sacrificing decisions to stay in the asylum to protect the world. And as most things in life, there is no good or bad can use a kitchen knife to make yourself a sandwich or go out and kill someone. And so the technology itself is not to blame, but how we as a society use any given tool. But, hey, I’m not going to act like I know the answer, but instead try to provide you with some insights into this dilemma by one of my favorite modern philosophers, Alan Watts. And I’m going to quote a short paragraph from him, which goes something like this. And so life is a system or now you see it, now you don’t. And these two aspects always go together. For example, sound is not pure sound. It is a rapid ultra. A nation of sound and silence, and that is simply the way things are. Only you must remember that the crest and the trough of a wave are inseparable. Nobody ever saw crests without troughs or troughs without crests, just as you do not encounter in life people with France, but no backs, just as you do not encounter a coin that has heads but no tails. And although the heads and the tails, the fronts and the backs, the positive and negatives are different, they are at the same time one and one has to get used to fundamentally to the notion that different things can be inseparable and that what is explicitly to at the same time can be implicitly one if you forget that very funny things happen and if therefore we forget that black and white are inseparable and the existence is constituted equivalently by being and not being, then we get scared and we have to play a game called Oh, Black might win. And once we get into the fear that black the negative side might win, we are compelled to play the game. But white must win and from their start, all our troubles.


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This podcast looks at innovators and companies that are changing the game and how they took their initial idea and created a game-changing product or service, while giving you unique perspectives and insights you’ve probably haven’t heard elsewhere.

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They also share lessons they’ve learned along the way to effectively accelerate, incubate and scale innovations within small, medium and large enterprises, all while separating hype from reality and replacing bullshit bingo with common sense.

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