 He's likable science. I'm Jay Fidel. It's a given Monday. No, it's not. Yes, it is. Tuesday. Monday was July 4th when we had to do everything we could to be patriotic and to save our democracy and so forth. Now it's Tuesday, the day after. We have Ethan Allen on likable science, our chief scientist. And we're talking about CRISPR today. We've talked about CRISPR before, but we're going to talk about it again. And CRISPR has taken us, and Ethan has been studying some of the literature that's come out, to what amounts to science fiction. CRISPR is now 10 years old. It seems like longer than. And CRISPR has gone miles and miles. And the probabilities, the possibilities are enormous going forward. And so we're going to take a snapshot of where we are 10 years later and see what the horizon is. So CRISPR has many new and remarkable uses. And Ethan's going to help us understand what they are today. Hi, Ethan. Hey, Jay. How's it going? Not bad. Well, considering that the world is coming apart, it's not bad. True. Right. Well, the volume part of the scenes, everything's fine. So CRISPR has been involved in a number of things. And you sent me a number of articles, and one of them talked about, gee, infectious diseases, T-cell, sickle cell, tomatoes, heart failure, stargum. That was very interesting about stargum. Can you trip down some of those lanes and help us understand the remarkable things that are happening? Let me add, happening all over the world. This is not a science and a research project limited to the United States. There are scientists everywhere who are working on these CRISPR solutions. Right. So it's really remarkable if you think it was just 10 years ago when the first paper got published outlining the basic technique of using what we now call CRISPR. And it didn't really make much of a hit when it first came out. Only a relatively small number of scientists recognized what an incredibly powerful tool was just had been laid in their hands. Now you can buy CRISPR kits online. And yeah, anyone can set it up in their garage to basically do genetic editing. And so, yeah, it's been used tremendously widely. I mean, in essence, the technique involves you have an enzyme that searches for and grabs any piece of DNA that you have coded for and then can do anything with that DNA, can chop a little chunk out of it and insert a little piece into it, can do both of those, can chop some out and put some more in and do almost anything like that. Truly remarkable. Relatively straightforward now, you do not need a lot of technical expertise to do it. You don't need a lot of money, doesn't require a lot of expensive equipment, a really remarkably robust technology. That was only 10 years ago, it was invented. And as you say, now it's used for many, many things. Most of which are for the good so far. Arguably, there are three children who are inadvertent subjects of a CRISPR experiment. They are thought now toddlers in China, whose genes were edited, basically without their informed consent. They weren't even, they were but a single cell when it was done to them. So, but let me, let me, you know, or something you said really made me think of, you know, Bill Gates and, and Apple and all that, all those garage guys in our in our lifetime where they started working on the ambitious project in their garages next to next to the basketball hoop and, and the bike between the cars parked in the garage and made themselves into zillionaires, developing new technology and information technology. But if you say that you can do this in your garage, if anybody can do it anywhere, that is something that, you know, that's sort of like the open architecture of the Apple phone. You know, what they did in the Apple phone is created an open architecture so anybody could get involved, anybody could make an app and look what happened. It went so far beyond the phone or any phone that we have a new world all in the space of what, in less than 20 years. And so this is all the same. This is people anywhere. They don't have to have a PhD in biochemistry. They can, you know, read a book go online, read an article or two and fully know what they can do this and, and they can change the world with a little creativity. They can, they can change the world and that is so, you know, can you take a minute, Ethan and just tell us how CRISPR works sort of as a refresher course. Sure. So I think a good example and you mentioned it was sickle cell anemia. So there's a disease which because of a genetic defect, your red blood cells are not soft flexible donuts, but rather can be elongated and stiff. And that causes them to block in capillaries and causes all kinds of problems. Little ruptures of blood vessels, all kinds of different things, a lot of pain. But it turns out that all of us also, as well as having producing adult hemoglobin, which that is, we all produced one point fetal hemoglobin, produced a slightly different hemoglobin molecule when we were very young, before we were born. And there's a switch that basically turned that off. Sometimes around the time you got born, basically your fetal hemoglobin switched off basically. But the cells still have that memory basically in them. So what somebody did when they saw these people with sickle cell, they said, look, let's just go in and turn their fetal hemoglobin back on because that those cells are not impacted by the sickling disease. Fetal hemoglobin is not susceptible to that basically. And so these people now as adults produce fetal hemoglobin, which probably is not quite as good as the regular adult hemoglobin, but it's a whole lot better than sickle cells. And they basically now can take up enough oxygen that have their blood circulates better. They still have sickle cell, but it does not cause them nearly as much in the way of problems. And it's because somebody just went in and essentially found a little section of DNA that turned off a switch basically turned off a gene and flipped it. So it turned it back on. And so these people now as adults produce this fetal hemoglobin and it works just fine. Well, so, okay, I changed his cell. I get in there with CRISPR. And in a minute, I'm going to ask you what the difference between CRISPR and GMO is. I will ask you that and whether that should concern us. And so now I've changed one cell and now the whole individual is now in better shape. His blood is in better shape. What for the rest of his life? Now, how exactly do you do that? How do you roll that out? How do you deploy it from one cell to a whole life and maybe the progeny of his life? Well, in this case, basically, in the case of the sickle cell, they basically pull bone marrow where all your red blood cells are produced, they pull the bone marrow out, altered a whole bunch of bone marrow cells, not just one or two cells, but millions and billions of those cells pump that bone marrow now altered back into the person. And now that bone marrow produces fetal hemoglobin. So they're fine. And that's basically the only difference it made for them is it changed their blood cells, because that was really the only thing they altered. You have to do that again and again? They basically don't, because once you've changed those bone marrow cells, genetically, you've turned that switch back on, they just keep producing new red blood cells. And if they split and become two cells instead of one, both those cells now produce fetal hemoglobin. So because they've inherited, they've now got that change million now. So there's millions of people, millions of people, mostly African American or African, you know, who have sickle cell anemia. And it's a real problem for the minute. It's definitely, it's, it's, it prevails in that race in the world. Does this mean that, that, that it is going to be a problem solved? How far advanced are we in, in propagating this technology? It's, it's come along. It's, it's being used. There are various different types of sickle cell anemia. It's not exactly just one disease. And this has been tried on one form of it. And it works pretty well on that form. There are probably some bugs still to be worked out. As you say, there's a lot of people who have it, but potentially this is a great solution that will be amenable and affordable to, to essentially a huge number of people who suffer from, from this. One of the articles that you sent me was in the New York Times was about leukemia, which is also a tremendous problem. It's a killer. And is, is the process that sickle, that CRISPR uses to solve sickle cell anemia the same as the process used to dissolve deficiencies in the blood for anemia? Yes, actually it's very similar for all the cancers basically, except what they do there is they look for a sequence of, of DNA that their cancer cells have that normal cells don't have. They essentially send, send the CRISPR out looking for that. It finds all those cells, finds this particular set of DNA that essentially tells the cells to sort of keep, keep dividing, keep dividing, keep dividing, you know, make more and more and more and more and it turns that off, basically clicks that switch off in this case. And so the cells don't divide basically in the cancer cells and live their life and they die instead of, instead of dividing and continuing to cause large tumors and sprout new tumors elsewhere. So again, very powerful because it, it has great down, sort of downstream effects single from even getting into a single cell. It alters the progeny forever basically. Yeah, but one is cancer, but a study of tumors and different organs in the body who are, which are in which the cells are growing out of control. Right. And, and thus CRISPR could do the same thing even in the garage on, you know, dealing with those various kinds of cells and those various organs. So it, it sounds to me like we're in the threshold of solving cancer with CRISPR, no? It's certainly going to be a more and more powerful tool, yes. And CRISPR is being refined all the time. It's gone through several changes already. It's gotten more precise. I mean, the problem with it is it, it looks for a particular sequence of DNA. And which is, as you know, made up of four different bases has an alphabet as it were four letters. And so it just, it looks for a long string of those particular letters in a particular order finds that latches on and does something to it. So you cut some of it out or add something in or does both of those things. And the problem is just like if you were look under word processor and search for a string of three letters, like A and D, that would find every example of the word and in your manuscript, right? But it would also find hand and mandarin and handy, right? It would find a lot of other things too. Similarly, CRISPR sometimes finds another sequence that you don't really intend it to because it's not on same gene you wanted to change. It's in some other part of our DNA. And it locks onto that and does the same thing because it's reading the same sequence. And so this is what they don't really know, for instance, with these three little girls in China. Well, yes, they're very likely more or less immune or highly resistant HIV infection. This may have other effects on them. There may be places where this CRISPR has turned on or turned off some promoter some promoter process for some other gene. So it might, for instance, affect the way calcium sets up in your bones or the color of your hair or something like this basically, it could have some completely unrelated seemingly unrelated effect simply because it happened to have within another gene or section of DNA exactly that same sequence. This is a big problem. I'm reminded of keyword searches and information technology. If I'm searching for A&D and I don't have a refined way of searching, I'll find hand and various other words that are the wrong target. But if I say, look, look for a space and then A&D and another space after that, then I'm going to be much more refined and I won't find hand. I'll find and always. And so it sounds to me as a problem of logic and of using maybe additional techniques and tools that are just coming about now to find only the A&Ds and therefore to avoid bizarre results. And I agree with you that we could have very bizarre results if we start changing the cell, the genetics technology of the wrong thing. God knows what can happen literally. God knows what can happen. And you can do terrible, terrible damage to an individual or maybe more than one person. Right. And so CRISPR can search for strands of DNA of hundreds of bases long, thousands of bases long. And if we had hundreds or thousands of letters that you put in a particular sequence, you're going to find that string that may have been written in one novel back in the 1800s. You Google that string and you're going to find that one novel because for 500 characters in a row that probably hasn't been written at more than once. The problem is that DNA only has four letters and it's alphabet. Right. And so just like in Hawaiian, the words are very long, basically the words in DNA language are very long. And so those sequences, even though they're much longer than three or four bases, may reoccur in other places like places where we don't even think about them because we tend to focus on just a little part of our genome that codes that are genes that are coding for particular protein. There's a vast majority of our genome of our DNA is what used to be called a junk DNA and people thought it didn't do anything. It turns out it's a very important stuff instead. It does a lot. It works with the genes, promoting their activity or depressing their activity or modifying their activity in some way. And that's where the problem comes. You don't always know what's, you know, where else that sequence has occurred. So actually, Ethan, if I took off a few days and I worked in my garage and I came back to you and I called you next weekend and I said, hey, I found out it's more than four letters. Those four letters have various other letters and it's actually eight letters or 20 letters or some other number of letters and you can distinguish an A from an A minus or an A plus or, you know, an AA or an AB or what have you. And it's not as simple as we thought. How surprised would you be? I would be quite frankly shocked. I mean, DNA has been well established to have basically the spiral that are alphabet for decades and decades. Now, there are people building synthetic DNA. Let's let you different alphabet now. But that's a whole different show there, Jay. Okay. Well, I'm not going back to my garage on that one. But let me ask you the question. I promised I would ask you what's the difference between CRISPR and GMOs and should we be concerned if there is a similarity? I guess I would say that the CRISPR technology allows you to do one particular form of genetic modification of organisms. People sort of treat GMOs like it's this big, scary thing. But realistically, organisms have been trading genes for a long time. Sweet potatoes that we all know and like are basically a GMO. They're a natural GMO that some few thousand years ago, a couple of different plants inadvertently exchanged genes, probably through some bacterium or some virus, pulled some out of one and stuck it into another plant. And that gave the sweet potato its particular characteristics that we so much like. That can happen. Not terribly common, but it can happen. Generally, I mean, there's no real problem in terms of GMO for food. You know, we'll eat it, we'll digest it. Where those genes came from doesn't really matter. Some of the genes came from one plant, some came from another. Some genes came from a plant, some genes came from a fish. It really doesn't matter. In your digestive system, they're all digested away. It's not like that genetic change is going to impact your genetic change in any way. So I'm not deeply concerned about that particular aspect of GMO. You remember the boys from Brazil, right? Right. You changed the fetus, and now you have a whole generation. You have a new person, a new human being, a new species, which you have designed, a designer species. Okay, this can be pretty scary if it's the boys from Brazil where they made them all like a pathological Hitler. So isn't that a possibility here? Well, that's why in a sense, I think that having these three girls in China is really, while it's problematical, it should not have been done. I think the guy behaved very unethically in creating them. In a sense, it's a good thing. It's better than somebody having produced hundreds of embryos that were enhanced in some special way, right? Now, at least these people are identified. They can be watched very carefully as they grow up. Their health can be monitored. We can see if there are other changes. It looks from the people who have reviewed the scientists' original work. It looks like they do have other changes than were intended. Looks like there were some other snips made that weren't necessarily intended to be. We don't really know yet. Nothing really odd has happened with them yet. Nothing odd has shown up particularly. But we don't know. Will they be more susceptible to some other cancer? Will they be immune to some other disease too? We don't know. So it's a good thing. In a sense, we have this very small population of three people to sort of, that they are guinea pigs, if you will, willingly or unwillingly, certainly without their consent. It is said really without much parental consent either. This happened better than a whole army of supermen you have to deal with, right? Well, I saw a movie on Netflix last night, which actually covered this topic. It was the serendipitous that I would see it in the night before our discussion. But it was about some firm that was doing some kind of high-tech gene modification, using drugs maybe. And they wanted to make American soldiers impervious to various risks. And instead they wound up giving them brain cancer by accident. And I suppose that was an accident. It was a great movie, by the way. That was an accident. But if you can imagine, really say about these movies, if you can imagine it, well, soon enough, you can do it. And if you can do it, then you can undermine the species. You can undermine the country, the race. You can undermine any selected group of people based on their existing DNA. And you can do terrible things to them intentionally. And are we at risk for that, Ethan? Well, I mean, you can do this technology. You can create genetically modified people that have now been done, basically. It's going to take a while. It's going to take 20 years before they're all adults. So we'll certainly have some time to get used to this idea, presumably before they're able to do too much. And you can do with the boys from Brazil. In other words, you can get into the fetus and have this carried on through the generations, but it's inherited, right? Yes. In theory, if you found enough moms, basically, to carry the fetuses, you could, in theory, go through and do a larger number of these. The scientific community as a whole is basically, as agreed, this technology, while it's great, it's not ready for prime time in terms of human editing. Great, let's use it to improve plant stocks. Great, let's use it against cancer. Great, let's use it for diagnostic tools. They've recently, for instance, found a wonderful use of CRISPR to test for the presence of the SARS COVID virus, basically. So instead of having to buy a $600,000 machine and bring along a technician and really use the machine and run it and do these lab tests that take several hours to run, you essentially can have a little specially coded tube that somebody spits into and in a few minutes, you know whether or not they've got COVID. That's got to be coming down the pike. It's got to be because the stakes are so high and continuing. But it's about the same token, couldn't you do CRISPR to change the genetic code of A, people, so that they could resist it, do better job at resisting and being immune to it. And B, couldn't you change the genetic code of the virus itself to neutralize it around the world? Yes, you could. You could change the code of the virus. Indeed, this is now a problem. I was recently reading an article that basically sort of said that basically all technologies are so-called dual-use technology. They can be used for good or they can be used for ill. And yes, you could take indeed a few years ago some folks took basically a rather pathogenic harmful virus and made it airborne transmissible, which had not been before. And they recognized this was, you know, shall we put this out in literature so anyone can now take the pathogenic virus and make it more transmissible? Yeah, in the garage. Right, it raises serious questions that the community of science along with ethicists, political leaders, everyone are still debating is how freely do you share information like that? You know, there's a great deal to be said for open sharing of information, but there are some dangers with it. And those questions are not by any means settled. Oh, no, and you know, you mentioned that it can be for good or for evil. And the responsible scientists have agreed not to use it for evil. But may I say this, not all scientists or for that matter all politicians, I'm thinking of Vladimir Putin, for example, if this came into his hands, I don't think he would he would restrain himself. And you know, the bottom line is that there are scientists out there who don't believe in being responsible, and who would affirm it and politicians who would affirmatively use this kind of technology to hurt other people. So this is a big problem. And you know, in the world that we live in today, you can be sure there are those who would use it for terrible purposes. But let me let me go to the one thing I want to leave our viewers with a sort of a sense of optimism here. And I read to you before a list of the infectious diseases and things and it includes the T cells and sickle cell anemia, tomatoes, better quality, better tasting tomatoes, dealing with heart failure and dealing with sorghum, my personal favorite is sorghum. But I wanted to ask you what your personal favorite was and how it worked and what it can do for humanity. Well, I like the nice neat example of they now produce tomatoes that crank out vitamin D like there's no tomorrow. And that's not such a big thing. We don't vitamin D shortage is not like a critical health problem in the world. But if you could take a widely grown substance and modify it so it produces a more vitamin A as was done years ago without CRISPR for so called golden rice and got rid of vitamin A or help help address vitamin A deficiency, which was a big problem, a wide scale problem in a lot of various Asia by essentially putting a vitamin A precursor into your rice. Then you have a tremendous ability to help humanity. And so, you know, I like that. I thought that was a nice example in the tomato, not not itself a big thing, but just a pretty, a pretty picture of a nice way to use CRISPR. And the woman, I think Martin was her name who developed that tomato. She was really very kooky looking in the photograph. And again, that goes back to your point about the garage. Anybody can do it. If she can do it, we can all do it. It's funny that you you select tomatoes and I select sorghum. And these are both foods. And you know, there's a certain concern in the world today that because of climate change, geopolitics, what have you, active Vladimir Putin, we have a food shortage in the world. And we need to feed people so they don't starve, especially in developing countries where they are starving right now. And maybe CRISPR can help feed the world. It can help make crops stronger, better, safer, more nutritious. This is very optimistic, isn't it? Yes, deep resistant, all these different things. You can find genes that confer these qualities and start packing them on in. And again, it's not going to really alter the food value per se, but it's going to make the plant tougher, better able to withstand harsh environmental conditions, maybe more fruitful. You know, so I think I think it's got tremendous power in that line. As they say, sorghum is a grain widely used in parts of Asia and Africa. Lot of people eat sorghum and products made from it. And if you can make sorghum with a stronger root system, deeper root system, so it can better survive periods of lack of rain, you're doing a good thing. It's also feeds animals and the animals feed us. So, you know, it's interesting that the need for and the use of CRISPR changes as the world changes. You know, I wouldn't have been so worried about developing countries and people starving a few years ago. I guess it was happening in some places, but it's much more of a threat now. Therefore, CRISPR is more important now to save people from starving. And the same goes with certain diseases. They were not of all that much concern or that we didn't even know about them or worry about them a few years ago. Now they emerge. And so we turn to CRISPR and we see if CRISPR can help us to save us from these diseases. So it's like watching the great challenges, the great threats to humanity and rolling out CRISPR to help deal with them. Its uses will change as they are changing now. Absolutely. Absolutely. But it's shown in the 10 years of its existence. Tremendous promise. It's already been put some very good uses and some questionable uses. But it's very clear. It has great value, potential value to aid humans in a lot of different ways. Yeah, I want to get some from my eyes. I want my eyes to have better vision. I'd like to be a little taller, a little skinnier. I know I can do this. Who knows where it'll take us? But one thing is clear, Ethan. It's not over. 10 years is only the very beginning. Absolutely. And we should all live so long, but you and me, we should continue this discussion on a regular basis to see how it's doing because it is so sexy to be able to have this kind of technology. It is. And this is just like the Model T, the Model T stage with CRISPR. And it's going to bloom into a lot of different forms now. Yeah. And some people, just like in information technology, are going to get very, very rich. Oh, yes. This is the rush. Thank you. Thank you, Ethan. Ethan Allen, our Chief Scientist here at Think Tech, discussing CRISPR yet again. And we will again. Thank you so much. Aloha. Aloha. Thank you so much for watching Think Tech Hawaii. If you like what we do, please like us and click the subscribe button on YouTube and the follow button on Vimeo. You can also follow us on Facebook, Instagram, Twitter, and LinkedIn, and donate to us at ThinkTechHawaii.com. Mahalo.