 Think Tech Away, Civil Engagement Lives Here. Likeable science with Ethan Allen, and I'm the guest host, and he's the host guest. You can switch those around, whichever way you want. And we're talking about a subject this Friday that we've talked about before, a couple of occasions, which is CRISPR. And CRISPR was in the paper a couple of days ago, a few days ago, with a Chinese scientist who went public on a discovery that, well, a biological action that he could recreate a human being using CRISPR. And then immediately the hailstorm started, because there's big ethical questions in that. So tell us what happened, actually. Well, again, all this is just sort of reports that we hear. Not too much of it has been absolutely confirmed yet, but apparently this Chinese scientist, last name of Hay, helped this woman taking, took her embryos and edited two of the, one of the genes for HIV resistance, because apparently the father of these embryos was HIV positive. And so he edited this gene to make the embryos more resistant to getting HIV. Well, that all sounds pretty positive. Yeah, all right. You can sort of see his motivation for doing that in that sense. However, basically CRISPR, which stands for Clustered Regular Interspersed Short Palindromic Repeats. No, that's going to be on the final exam. I hope you caught that. It's still a very experimental technique, right? I mean, CRISPR is basically it's a little molecular machinery they found in bacteria and archaea that they basically used to defend themselves. They would snatch little bits of the DNA from viruses that were hacking them and then use it to fight the virus. Oh, interesting, like a vaccination almost, at the DNA level. Right, they sort of pick it up, copy it, and then they combine it with something called a CAS9, which is a protein which can go and CAS-9, which is just CRISPR associated protein 9. And it basically can snip that stuff out. And that was the basis of sort of this whole technique because this allows you to essentially snip DNA and then you can simply insert other bits where you snipped. Can I drill down right there? Sure. How do you snip your little tiny scissors? How do you snip out from the virus and put it somewhere else? How do you change things that small? Well, more or less, I mean, it's molecular scissors, if you will. There are molecules have the right receptors to latch on to things at the right point and literally have them bond to that molecule instead of this molecule and then pull it away. And it's now snipped out. So it's not a chemical thing, it's a physical thing. I'm able to go into- At that level, chemistry and physics are pretty much the same thing. Oh, thank you for that. Yeah, I see what you mean, yeah. And the other thing is, no, OK, now you've done that. And you've created like one cell maybe or a handful of cells, I suppose. But primarily one cell, which has different characteristics. And it happens to be a human cell and it happens to be better equipped to deal with HIV. How do you make that into a person? How do you take the one cell and do anything with it? Well, that is, they did this with very early stage embryos, which are only a few cells anyhow. And so they changed the genes within those few cells. And that has changed up permanently. If these girls grow up, become women, have kids of their own, their kids will have this modified HIV receptor. Permanent change in the DNA in a gene line. Not just in the one cell, but in all the cells that come off that cell. Exactly. And we have never had anything where a sort of human-edited change in a gene has been put into a situation where it can be passed along from generation to generation. Although we've been doing DNA changes on people, we've been doing stem cell treatments actually in doctors' offices. Isn't this the same thing? It is similar, but different. It's the same in, yes, they use CRISPR in treating cancer or whatever. But treating it, putting it into embryos, permanently altering their DNA that they will then pass along to their offspring is a very different thing than just treating somebody going in after their cancer cells and getting screwing around with all their cancer cells. Yeah. God reminds me of the boys from Brazil with Gregory Peck. Yeah, exactly. This is, thousands of Hitler's is what they created, yeah. And this is what people are upset about. This technology really is not really ready for prime time. OK, so what is the problem? Is it imperfect? It doesn't work, right? Or is it the ethical consideration? Well, there's both. One, yes, it's still being worked on in CRISPR. There's actually a lot of forms of CRISPRing and associated CAS proteins. Multiple ones that work slightly differently, have slightly different characteristics. People are still playing with these, figuring them out. You know, again, you don't know exactly necessarily that it's only going to cut exactly the piece you want. You believe that, but. So you're saying that on the scientific side, forget the ethical for a moment, that we're still learning how to do this. Exactly. But what's the downside? I mean, is this going to be the creature from the Black Lagoon or what? What are we worried about here on the, in order to do science, you have to have trial and error, don't you? To some extent, yes. And the general opinion in this is there should be a lot more trials done on non-human animals before running this one on people, because it does have this potential to change the germ lines of people, to really alter them in ways that we do not really fully understand. But that could happen with an animal, too. I mean, how can you control it? You could have a creature from the Black Lagoon that's an animal, too. Right. But I mean, if your mice, your line of mice gets all weird and funky, you can just sort of exterminate your mice. Make them go away. Yeah, right, and they're probably gone. Not so easy with a human being. Yeah, exactly. They start developing a second head or whatever. You still, like, you can't really just say, let's get rid of them. So there's the possibility of real tragedy here, by developing a human being that would be a sort of pathetic biological result. And we'd all suffer knowing that happened. Right, and so this is why the Chinese government has condemned this guy. The scientific societies have condemned him. People feel it's going to... For one, this technology has tremendous potential to be used and to be used very well to take care of cure a lot of diseases that are currently attractable, and they worry that this sort of bad press that's resulting in this is going to set the whole thing back. Either it's going to be draconian regulation against it, or it's going to get a very bad name and will be associated with sort of sloppy science. So now you're getting into the ethics. Right. What is the ethical conversation about this sort of thing? And this isn't the first time we've had this kind of conversation, either. But what's the conversation about CRISPR changing human DNA? Well, it has sort of unparalleled capacity to change the germline, to change the reproductive cells, basically, and therefore to make permanent alterations in the human genome, as it were. And that's sort of a scary thing. You don't want to go into that really like, let's just do this and see what happens, right? It could be a worse case analysis. What could happen? A side effect could be, for instance, that the offspring all develop nasty, untreatable cancers when they're three or four years old. And in that case, maybe it doesn't get carried very far. Maybe they develop a Huntington's-type disease, so it doesn't show up until they're 40 years old. And then they develop nasty cancers. And meanwhile, they've now passed it on to their kids who are then going to develop these nasty cancers when they're 40 years old. So, take the one cell, and then you have one person. And then you have that person have offspring with other people. And then this could be a dominant trait in the way it works. And then all of a sudden, lots of people are logarithmically expanding. And maybe it could cover all of humanity over time if you... Yeah, now you're getting into the worst case. I'm giving you the worst case. Gene drivers, yeah, which is a sort of related bit, a sort of different kind of thing. So just as easy as making a person resistant to HIV, you could make them into a guaranteed psychopath. And well, like the boys from Brazil, right? Not quite. I mean, this was a somewhat controlled thing. And the genes that control our psychological of being are not well understood and not that cleanly identified yet. So it's because we don't know what will happen that gives us the ethical concern about this. That's in large part right. There's still a lot of unknowns about it. OK, so just for a moment, can we look back at ethics and science? You were telling me before the show about a conference that happened some decades ago relating to that that actually had a positive effect on controlling science that could get out of control. Right. So if you remember back in the early 1970s, the recombinant DNA became a big thing. And they were just learning how to start pulling genes out of one organism and sticking them into another organism in a pretty crude way. And that was really frightening because some of you thought, yeah, what happens if I start sticking human genes into tomatoes or vice versa? You have these weird hybrid organisms. And they called a conference in Asilomar, California. And it was actually a different conference because it didn't just involve the scientists. It involved legal scholars, theologians, ethicists, all kinds of different people from very different walks of life as well as the scientists who were doing the work. And they basically incorporated everyone's feedback, listened to all their concerns, and came up with a set of guidelines on how to deal with this. And again, they recognized then as we should recognize. Now, the technology, you know, once you've led a technology out of the bottle, like the genie out of the bottle, you can't stuff it back in. There's just no way it's going to go back in. It's out there, particularly something like CRISPR now. CRISPR is very easy to do. It's a cookbook technology now, basically. So you don't really even have to be much of a scientist to use it if you get the right stuff. You have to practice your technique. But anyhow, so what Asilomar showed us was that, yes, you can bring, if you bring the right groups together, and that's more than just a scientist. Scientists have good insights, but sometimes don't see the whole picture. Yeah, they don't see the big picture. They're limited into science. That's the nature of what they do. Right. And so what hopes that sometimes this maybe a wake-up call will do the same kind of thing again and bring, convene a group or multiple groups around the world to think about and try to set up guidelines or how we deal with CRISPR. But what were the guidelines back when? They were basically, they agreed not to do certain kinds of things. They wouldn't do this recombinant technology on people. And you simply would not do it on people. You wouldn't try to make people with recombinant. What is recombinant technique? That was, again, it was crudely pulling out genes from one organism and sticking them in another organism. They basically said, you can play around with their plants all you want and this. And they even actually put strong limits on that. And they sort of said, you've got to report what you do very clearly. It should all come to some central repository. People should have a chance to weigh in on it before you proceed too far along with it. We should have an open discussion if you're doing something, say, messing around with corn plants or wheat plants or rice plants. That has potential to spread around the world. We're talking about more than just ordinary human being people. Right, yeah. We're talking about agriculture in the world. Right. And so they agree back then, these kind of issues had to be dealt with up front. And you can't just sort of let people run a muck and do this. So how do you stop that? Well, yeah. That was, the results were basically a sort of self-regulation by the industry, by the enterprise. Recombinant DNA technology was pretty complicated at that point. And you couldn't just do it willy-nilly. You had to be a pretty sophisticated scientist to do it. So the community who could do it was relatively constrained. So that self-regulation sort of worked. They did, really. They made it all sort of sad, yeah. This is very sensible stuff. OK, but here we are how many years later, decades later. And a couple of things have happened. One is I'm sure it's easier to do that technology. And two is it's easier to propagate that technology to everywhere in the world. Because they're a PhD in biochemistry and what have you that live in every country that are trained, many of them in the US. And it's so easy to be acquainted with and implement that technology now and read about it and learn about it wherever you are. Oh, CRISPR has commercialized. I mean, they sell kits. Many multiple companies sell CRISPR Cas9 kits. And just, you know, you can just buy them anywhere and start doing your experiments yourself. And so, yeah. Talking about it out of the bottle, boy. Yeah, talking about it out of the bottle, right. And so it may require, and some groups are suggesting, yeah, so we should certainly have at least a national conversation, if not a global conversation or a series of national conversations, international conversations about this. And think very hard about what we want the technology to do, what we really don't want it to do, and how we can sort of maximize its chance of being used for good and minimize its chance for being used for ill. And whether that involves a legal system, in Britain they did that. They looked at some of this technology when people began being able to move mitochondria from one cell to another. And they made strict laws that actually allowed in Britain the classic, the three-parent baby now, right, who has sperm from a donor, the egg from the mom, and mitochondria from another woman, because mom's mitochondria were sort of screwed up. And we don't actually allow that in the US. That was actually set up by a legal process in Britain that came up. When we come back after this break, Ethan, I'm going to talk about sanctions. That is, you know, the hard end of those laws and what they mean and how well they would work, are working, and how they might affect this going forward. Pretty scary. OK, take a minute off, everybody. Deep breath. Deal with your fears. Come back in one minute, and we'll go further with this discussion on CRISPR and people. Aloha. I'm Marcia Joyner, inviting you to come visit with us on Cannabis Chronicles, a 10,000-year artisty where we explore and examine the plant that the muse has given us. And stay with us as we explore all of the facets of this planet on Wednesdays at noon. Please join us. Aloha. My name is Mark Shklav. I am the host of Think Tech Hawaii's Law Across the Sea. Law Across the Sea is on Think Tech Hawaii every other Monday at 11 a.m. Please join me, where my guests talk about law topics and ideas and music and Hawai'iana all across the sea from Hawaii and back again. Aloha. I'm Jay Fidel of Think Tech here on Likeable Science with its principal host, Ethan Allen, who is a scientist. He's our chief scientist here at Think Tech. And we're talking about CRISPR and how it has affected and could affect the development of human people. This is really kind of scary. I hope you're over the primary fear in the first part of our show, because now we're going to discuss other things. So one thing is, gee, how do you deal with this in the scientific community? So you have statutes, they're different in different countries. They may be different in different states. Who knows? This is really not settled. And furthermore, you have sanctions. It makes it a crime, I guess, and outlaws it somehow. And then what is the sanction? You go to jail, what happens? You pay a fine, what happens? The stakes are so high on this. The risks are so high that it's not clear that a given sanction will actually work. And furthermore, it's really hard to find what somebody is doing in the back end of his laboratory. So how does it work now? How is it going to work in the future? So right now, I mean, there aren't really rules, regulations, guidelines, beyond some very basic stuff that's set up. Nobody sat down 10 or 15 years ago when Christopher first was being developed and said, oh my god, let's set up a set of policies on how to deal with this. No, that never happened. So there aren't any real regulations. The Chinese Minister for Science and Technology wrote a rather scathing statement about Hay's work. And basically, I'm guessing the Chinese government will impose some sanctions on him as they see fit. We have to talk about the Chinese scientists involved in the Chinese government's reaction. But I'm just very curious as to how this would work in a sort of industrial sense. So I come to you. And I say, my family, we have a predilection to a weakness, vulnerability to HIV or any number of other diseases, Ethan. We'd like you to go in the back room of your laboratory and create a new fidel that is resistant to these bad things because we don't want our children to be dying at an early age or have a bad life. So we want you to make a super fidel. And we're going to give you for this because we have the bucks. We're going to give you $100 million, Ethan. You're going to be worried about the statute and the sanctions. You'd be worried about being turned out ethically. Well, I mean, scientists do care about the approval or disapproval of their colleagues, certainly. But it's funny, you mentioned that. At Harvard right now, they are proceeding with experiments using CRISPR on sperm. It turns out, for instance, that Alzheimer's, which is a devastating, ugly disease to get right, particularly when it strikes early. And there is a particular genetic variant, a gene called apoE, which if you have a particular form of this gene, you have massively increased odds on developing Alzheimer's early. So Harvard scientists are now working on designing sperm and going into sperm and altering this apoE gene. And really, all it takes is it's intranets. It's literally one little base molecule out and subsets another base molecule in. And it turns it from a variant that promotes Alzheimer's to a variant that almost certainly prevents it. And so it's, and they're working on this. So to make a better line of people, basically. And nobody's really coming down on Harvard about doing this because they're only doing it on sperm. And it's really no difference. Sperm, per se, are never going to do anything, right? It's the same thing, isn't it? But yes, you can see within vitro technology, of course, all the sperm could. But again, I suspect the Harvard researchers are not going to go and sell those sperms to a sperm bank and let them be used. That would probably cause a good deal of controversy and besmirch Harvard's by name, right? Yeah, but it's not limited to Harvard. For one thing, I want to say that you think about sperm, in vitro virtualization, IVF, was invented right here, right here in Hawaii, in the University of Hawaii, Manoa, by a guy named Ryozu Yanagimachi. We covered that years ago. And he was active in many genetic change kinds of experiments. And he had a lot of interesting outcomes. He was world famous. And one of the things he did for which he was never compensated, for which the university was never compensated, for which Hawaii was never compensated, is he developed IVF, which is used all over the world, all over the world. So my question to you, and recently, what is it? The Vika virus has been resolved. I think it's here. Yeah, we're going to have a show about that not too far away. Hawaii Biotech has been working on it. So I think there's the possibility. And we have brilliant researchers at the medical school, cancer research centers, crossover, over this molecular biology. Is it possible that Hawaii could participate in CRISPR? Are we participating in CRISPR? I'm sure there are researchers here in Hawaii doing that. I don't know the details on that. I've not followed who's doing what now. But the technology is around and available. I'd be absolutely blown away if no one was doing it here. That should certainly be part of it. I mean, it is. It's a technology of tremendous potential. Because it's a little easier, in some sense, to say we're going to edit your genes, then we're going to actually pull genes from a different organism and stick them into you. That seems heavier shift, right, rather than just saying, hey, we're going to go in and fix this gene and make it slightly different. Because your genes have all these variants by themselves anyhow. So all we're doing is mimicking nature, in that sense. But it is a process you don't want to play with lightly. Well, I'd like to just throw the two possibilities out at you. Number one is this isn't living into Harvard. There are a lot of schools in this country, medical schools and research facilities of one kind or another, that have access to the same technology, the CRISPR technology. And likewise, there are schools all over the world, say China, that have access to this and scientists that are interested in making a name for themselves, but also helping the human race. So the likelihood is that the gene is not going to stay at Harvard, or the school the guy was working out in China. It's going to be Hither and Yang. OK, the other thing is that this technology is not static. It's going to change. And a third thing is that the ethics are not static either. Because when the technology goes forward, the ethics will have to follow, don't you think? To some extent, yes. And everyone agrees it's OK to use it to fight diseases, to help cure people of incurable conditions and all that. The question becomes, suppose, A, I want to have a kid with blue eyes instead of brown eyes. Is that an OK use of it? I want my kid to be six feet two instead of five, 11. Is that OK? Are you allowed to sort of engineer for desired traits? Yeah, if I can afford it, if I can afford it, and then the price is an issue going forward, assuming this passes the ethical test at some point, then I can create, I hate to use this term, but a master race. I can create, if I have the money, I can create a master race of people who have advantages over everyone else. Super smart, super strong, super resistant to disease. You name it. That's, and this is exactly why this is today or yesterday or 10 years ago is the time that we should be talking about this and figuring out how to best regulate this technology, how to keep everything open and transparent and be sure that as it moves along and advances, that we're all aware of what's being done, that people have a chance to question it before it gets too widespread or some gene variant spreads across the world. We don't want to do that. Yeah, it's not climate change in a sense, because you have to have a global collaboration to deal with this. And you have to have a global body that has some authority. And you have to have rules and statutes embodying ethical concepts that are going to be accepted around the world and sanctions that will work around the world. And that's very tricky, because different cultures have very different views about, for instance, sort of abnormal people. And some cultures have a great deal of sympathy for these people and embrace them. Other cultures basically shun them, think of them as less than fully human. And how are those cultures going to get together and come up with a common set of guidelines? It's going to be a very tricky thing to do. Yeah, so this guy, I'm going to read his name. This one who did this, Hei Jiangui, Chinese scientist. He did this, and he thought it was a good thing. And he went public with it. And then China's vice minister for science and technology, Xu Nanping, made a statement only a few days ago to criticize him. You want to give that as the quote of the day, this is a quote of the day on what that scientist had done. So the Chinese minister said, the genetically edited infant incident reported by the media blatantly violated China's relevant laws and regulations. It's also violated the ethical bottom line that the academic community adheres to. It is shocking and unacceptable. I wouldn't want to be that scientist right now, because this is telegraphing terrible things that are going to happen to him in terms of prosecution by the Chinese government. I think I'm going to tolerate this for world opinion purpose. He was in Hong Kong for his, when he delivered this news, and if I were him, I would be on a fast boat out of Hong Kong. Stay in Hong Kong. Get out of there. Well, so the question is whether there'll be other scientists who are drawn or magnet-style to this kind of technology. This was a comment in one of the articles I was reading. Hei may have been the first scientist to create CRISPR babies, but he certainly won't be the last. And you can bet your bottom dollar on that. The technology is just so readily available now, and there's so many people who could use it. And the potential for making a name for yourself, for making money, for doing something dramatically good is so tremendous that other people are bound to do it. Ethics are going to have to change. I suspect this is just the first of what are going to be a whole series of incidents that are going to pop up here and there until some sort of firestorm emerges where we really start building the regulations that we need. What I hear you saying, though, is that it's not just this one guy right now. There are others right now. As we sit, as we speak, we're doing the same thing. And they're faced with the issue of getting criticized or prosecuted the way Hei Jing-Pu, Jan Kui, is going to be punished when they get him. But in different countries, different results. And so there are probably a lot of people who actually, who are working on it, and I know this sounds strange, but reading about this, learning about this, they may be attracted to work on it now. Sure. Absolutely. And there may be people who now realize, like, I'd like to work on it. I'd better go quiet, go underground, find some rich sponsor who wants me to improve his germline, her germline, basically. So they can be the founders of a master race or whatever, and they'll support me while I work out the bugs out of the technique. And you just do it quietly and figure these people will, the payoff will come down the road. You'll be famous 20 years from now. So yeah, I think it's almost inevitable at this point that people are going to be doing what he did in various places. But that's one of the concerns, is that his actions, in some sense, will drive some of this work underground and make it harder to see. And part of the issue and part of the beauty of Islam are was it produced transparency, and everyone became very open about what they were doing. That was part of the deal was, hey, we all want to share this. We all want to know what's going on. Stakes are higher now, though, somehow, way higher. And I'm going to offer one other really interesting thought and possibility here at the end of our show. And that is, I can make my line stronger, taller, smarter, more resistant to disease. And ready, are you ready? With the ability to live longer. It's the fountain of youth. Oh, potentially, yeah. And for money, I can buy crisper technology to make my line live longer. That's indeed, yeah. No reason, no reason. There are people working on it today. I would bet my bottom dollar that are people working on just that problem. Wow. Well, as usual, Ethan, we've opened up a can of worms. And they're not going to go back in that can. Thank you so much for this discussion. I enjoyed it, Jay. Always fun. Aloha.