#73 Biohacking: From Sci-Fi to Reality

Yagnesh Ladumor [0:00] hacking is cool.

Biren Dave [0:03] Like where people try to like work in teams to find solutions to problems

Melissa Galati [0:08] We're recording, guys.

Stephania Assimopoulos [0:09] Oh.

Melissa Galati [0:11] So...

Stephania Assimopoulos [0:12] just saying

Biren Dave [0:14] Our team sat down for over an hour trying to organize and define the scope of today's episode, we recorded the whole thing. Don't worry, we won't make you listen to our entire discussion, just the highlights. We started by trying to define biohacking. In the end, we turn to the one true source.

Melissa Galati [0:31] What does Wikipedia say about biohacking, Stephania?

Stephania Assimopoulos [0:33] Um, well basically, it says that biohacking may refer to do-it-yourself biology, biotechnological social movement in which individuals and small organizations study biology using the same methods as traditional research institutions, otherwise known as Grindr. Related terms: nutrigenomics, quantified self-experimentation in medicine.

Yagnesh Ladumor [0:58] We settled with the most succinct and widely used definition of biohacking. We defined it as experiments often on the self that take place outside of traditional lab spaces.

Biren Dave [1:08] The open access nature of biohacking is something that really distinguishes it from how science has traditionally been done. A lot of these biohackers, for example, the Open Insulin project, which aims to mass produce recombinant insulin to treat diabetes, they plan on spreading their protocols and methods to anyone worldwide who also wants to follow the same method to treat, I guess, themselves or someone they know. And I think one positive aspect that the biohacking community has in their cultures is this openness and this willingness to share with others, which I think is a good thing.

Yagnesh Ladumor [1:41] The goal of many biohackers, particularly those with some scientific training, involves altering genetic code in a specific way. CRISPR technology has allowed these individuals to make genetic edits outside of traditional lab environments in a way that wasn't possible before.

Melissa Galati [1:56] So maybe for people who don't know what CRISPR is, does somebody want to throughout a definition?

Yagnesh Ladumor [2:01] Sure. So CRISPR stands for clustered regularly interspaced short palindromic repeats,

Melissa Galati [2:08] which, for most people, means basically nothing...

Yagnesh Ladumor [2:12] CRISPR works, but it's basically a bacterial immune system that allows bacteria to cut the DNA of viruses, and viruses are just, I'm simplifying here, but they are genetic information encoding proteins, right? So to deal with viruses, you have to come up with ways to destroy the genetic information, and this is one of the ways that bacteria have come up with to do so.

Stephania Assimopoulos [2:38] Which is more or less what we focused on in this episode, mostly the genetic part of biohacking. In which case, more of the ethics come up, and some of our guests touched on that. But yes, definitely as a scientific community, we should talk about the ethics and also the feasibility of each of these forms of biohacking.

Melissa Galati [2:59] So it's been I guess almost two years now, since his initial announcement, but Dr. He Jianqui had announced that he had successfully edited, CRISPR edited several embryos, three embryos, I guess, well, two were, two were implanted, to have mutations in the CCR-5 gene, which is associated with resistance to HIV. And, this is a huge issue in China; I think 0.1% of the population has HIV or is living with HIV. And, so this is this was clearly a huge issue. But, what people are essentially saying is this was the wrong gene to target. So, we don't know what sort of off targets these kids have. We don't know if they're actually HIV resistant, which is kind of sad, because that was the whole idea of the experiment. We don't know any of the health information actually of the babies, but we know that a set of twins were born, and shortly after, a third baby was born. And that's pretty much all of the information that we've gathered.

Yagnesh Ladumor [3:58] Well, another thing I think that is important to keep in mind is that what you're doing with this particular edit is not just changing the direction of human evolution, you're also imposing an external selective factor for HIV. If CCR-5 does confer resistance to HIV, you're increasing the population that has this disease and increasing the selective pressure on the virus to adapt to it. Even if this works, you're not making sure that these babies don't get HIV.

Melissa Galati [4:30] Yeah, but I don't want to be like, I feel like we're being totally negative towards biohacking and gene editing. It's obviously really cool, and there's a reason that we wanted to do an episode on it.

Nathan Chan [4:39] One of the things I picked up from Josiah's interview was the fact that if this technology has been developed by other countries like China, like Russia, it might be the case that we never have the time to actually answer these ethical questions. This technology might move faster than any of us can catch on. It's more than, I think, just ethics. It's also, there's an element of practicality here somewhere. So I mean, that's, there's also things I think we can't predict in terms of the potential benefits. But also, I don't think we're very good at predicting the potential negative effects, either. It might even be premature to, you know, start having these conversations without even seeing some of these effects actually play out, because a lot of these conversations are, at the end of the day, theoretical. It's not like there are 100 million people who are CRISPR babies, right?

Melissa Galati [5:33] As you can probably tell, we had a long, long conversation both on and off the record about all things biohacking. But to wrap it up, we asked everyone if we would ever attempt to biohack ourselves.

Biren Dave [5:44] I think unless if I found myself in very dire straits, I don't see myself ever self-experimenting, at least on the genetic level. I think there's just a level of safety there that, that would be hard for me to replicate in my kitchen or in my garage. And I guess that concern is just too great for me to even attempt to do that type of self-experimentation.

Yagnesh Ladumor [6:04] I'll just echo Biren's sentiment in that when it's relating to medicine, especially in Canada, we're fortunate enough to have socialized health care. So, I would definitely go to the professionals. Certain things are better off in a controlled, laboratory setting, and medicine is definitely one of those. But, talking about that, I think it is important to realize that some people might not have access to this and that we talked about Open Insulin earlier. And it's, it's necessary because some people, due to their socio economic status, are prevented from accessing these life saving drugs. So, there is a need for this. But in our situation, I don't think that's very relevant.

Nathan Chan [6:51] I think I would do biohacking on myself, not... and, well, obviously in particular, for anything that was health related, you know, If I had diabetes, I'd be looking into it. At the same time, a part of me supports the idea of biohacking and self-experimentation only because there is an argument to be made about bodily autonomy and the right to do things to my own body that I consent to. And, you know, as long as I'm not advertising it to other people, or you know, telling other people or encouraging other people to do this, especially if they don't have the expertise or knowledge to do it, then I don't really see a problem. You know, it's my, it's my body. And, I think I am allowed to do what I want to do it, especially for health reasons.

Yagnesh Ladumor [7:40] Biohacking or bio-engineering, whatever you call it, it's in the mainstream consciousness more than ever before. With recent advancement in the CRISPR field, such as prime editing, allowing for more precise edits with fewer off target effects. It's expected to play an even bigger role in our lives in the future. And so, it's important to talk about the ethics of it and to understand the utility of the technology outside of a research setting.

Biren Dave [8:04] As you'll soon hear, our guests on today's episode had diverse perspectives on the biohacking movement and what the future of DIY biology might look like. This is Biren.

Yagnesh Ladumor [8:13] This is Yagnesh.

Melissa Galati [8:14] And this is Melissa. Welcome to Episode 73 of Raw Talk.

Melissa Galati [8:31] We started out by talking with one of the most notorious biohackers around Dr. Josiah Zayner. You might know him as the guy that live streamed his self experimentation with CRISPR, aiming to increase his muscle growth. He also runs a company called the Odin which provides resources, kits and reagents to biohack in your garage school or college lab.

Dr. Josiah Zayner [8:51] I guess I didn't have the traditional growing-up scientists life or childhood or anything like that. I think the first scientist I met was probably when I was in college or something. Otherwise, I had no idea what a scientist was or what a scientist did.

Melissa Galati [9:10] During your undergraduate degree?

Dr. Josiah Zayner [9:12] Yeah, during my undergraduate degree. And so, like, I don't really know what inspired me to be a scientist. I, I think it might just be my fascination with, like, I'm a reductionist at heart, and so just like reducing things down, you know.

Melissa Galati [9:28] Like simplifying them.

Dr. Josiah Zayner [9:30] Yeah, trying to understand them from first principle, or something like that. Yeah, it got me into science, and I just kept pursuing it. I got my PhD at the University of Chicago, then I moved on and spent two years at NASA where it was pretty cool and interesting. But uh, you know, these, academia, the government, it just didn't feed my itch. And, I realized that, like, all the cool things that we really want weren't happening. Everything that we were told that should happen or we should be working towards wasn't, and that kind of disappointed me, because everything was like 20 years away. It's like, yeah, we did this experiment with CRISPR, but people won't be able to, you know, experience it for 20 years or something. You're just like, "wait, what?" Like, how does that make any sense? Either it didn't have anything to do with the thing we'll see in 20 years, or there's something else holding it back from being used in the world. I wanted to start using stuff, and so I decided to branch out on my own and start a company. I run a company called the ODIN, and we teach people how to do genetic engineering in their homes.

Melissa Galati [10:46] You've said before in interviews that you don't like titles, but you call yourself a biohacker. Can you describe that for people? What does it mean?

Dr. Josiah Zayner [10:54] Yeah, you know, it's like, I guess the terminology people are starting to use nowadays is genetic biohacker, because, like you said, there's a lot of different descriptions of what a biohacker is.

Melissa Galati [11:06] Like, people are used to saying it to hack your diet, hack your exercise, etc, right? It's not necessarily...

Dr. Josiah Zayner [11:12] You know, it doesn't really bother me too much whatever people can describe it however they want. To me, it's just somebody who's trying to do interesting and unique stuff. Generally, that happens to be people outside of traditional environments, you know, like academia or big industry, big pharma. But, it could, it could mean anybody, anybody who's trying to do a unique, clever thing. I think that's a good definition.

Melissa Galati [11:40] At the beginning of this episode, we told you that biohacking can encompass an almost dizzying range of pursuits, and there are a number of reasons for why individuals engage in biohacking. While many are motivated by the potential to feel healthier, reach peak performance, or simply be part of a growing community. Josiah expressed another reason for why he's turned to biohacking: frustration. As you might have guessed from his abrupt departure from NASA, Josiah became quickly disenchanted with the slow and often elitist nature of academia.

Dr. Josiah Zayner [12:10] So, I think that, like, forever, there's been all this knowledge that's been locked up in academia, especially science, right? You have to pay to get access to some of it through paywalls, but a lot of it is also just, like, it's entrenched, like, you learn how to do this thing by being in the lab that teaches it, right? There's no, like, documents or guides online that teach you how to do certain things, which is crazy, right? If you want to do certain experiments, hands-on experiments, let's say with animals or with, you know, cells and cell culture, mammalian or human cell culture, like, there's not a lot of description on how to do these things, not a lot of guides and information about the actual hands-on aspect of it. And, that's crazy that it is all just stuck in this environment, you know, academia and big industry. And, I think that, like, giving that knowledge to people can only be beneficial, because with it, if this technology is sufficiently powerful like everybody says, if it can do all the things that scientists believe it can do, then these people who have access to it will also be able to do those things, right? What if the scientific population of the world, like, doubled or tripled or 10X? That'd be a bad thing? You know, I just can't see it that way. I can't, even if people contribute barely anything, like, I can't imagine it's a bad thing that people have access to this knowledge.

Melissa Galati [13:44] So what are the positive things that have come out of biohacking in general?

Dr. Josiah Zayner [13:49] Yeah, no. The big thing for us is just education, right? You know, sometimes people look at it like, like what have people created or something; has anybody created, like, a new drug, like, engineered a new crop, or something like that. And I think those are unfair goals or, or things like that, right? I think those are unfair things, standards to set these people to when, like, just a few years ago, there was nothing, absolutely nothing, right? People could do absolutely nothing, like yeah, sure, you might be able to find some materials here and there and put some stuff together, but there was no way to learn this stuff. Pretty much if you didn't, you didn't know what you were doing. And now, you know we have classes teaching people how to do human cell culture at home without CO2 incubators without anything, and people are successful at it, right? There are so many people that we've worked with, who, in the US, don't, don't even have, like, high school diplomas. And across the world, we've sent out kits to Nepal, Sudan, Ethiopia for free donating the supplies to people. I don't know what they're going to do, what's going to happen in the future in years time; maybe people don't create anything, maybe they just get educated and learn. But like, that would be the greatest thing ever. If society all knew what DNA was, knew what genetic engineering was, knew how to do all these things, like, I think that's a big win on its own, the biggest one, because it's just like, people, you know, we get so many messages like, "Oh my gosh, I didn't think I'd ever be able to like learn how to do this or experienced this in my lifetime, and this is like so cool that I could learn how to do genetic engineering," and it's just like, that's awesome and amazing.

Melissa Galati [15:44] While much of Josiah's motivation lies in empowering and educating the public, we had to wonder. Has he ever regretted any of his biohacking decisions?

Melissa Galati [15:52] So you don't have any, you have no regrets about, you know, publicly injecting yourself with CRISPR and/or your microbiome transplant? There's no regret of having done it or made it so, your journey, so public?

Dr. Josiah Zayner [16:04] Well, what was really hard, Melissa, is that, like, I start to get a lot of people paying attention to me.

Melissa Galati [16:11] Sure.

Dr. Josiah Zayner [16:12] It's even harder for me nowadays, because you don't realize, I don't realize how many people are paying attention to the things I say and do. And then, when I do stuff, it becomes a lot more controversial than I anticipated or gets a lot more attention or something that, than I anticipated, because, like, I never viewed myself as somebody whom, like, people would pay attention to or want to pay attention to at all, because it's just never my goal and things like this. And so, these things that I do, I don't regret doing them themselves, but like, the effect that it can sometimes have is not the intended effect I would want, and that can just be like anger, hatred, or people doing stupid stuff, whatever the negative consequences of these things. It affects me, also, you know, because, like, I don't want my actions to have, you know, negative outcomes. And I've learned, you know, sometimes you've gotta live with the fact that like, you can't protect everybody and you can't be perfect and you can't always have the best answer. So, I just try to be myself and try to do whatever I would do regardless of anybody who's watching.

Melissa Galati [17:31] Even though Josiah expressed some regrets about the publicity surrounding his biohacking endeavors, he still believes they were net positive in principle. We asked him to talk about some of the highs and lows he experienced performing his own microbiome transplant, as chronicled in the New York Times op doc "Gut Hack".

Dr. Josiah Zayner [17:48] I never intended for that to be filmed or anything like that. Somebody asked me what projects, what stuff I was working on, and I mentioned it, and then somehow people were just like, "Oh, you know, we should do some, you know, writing articles, story on it." And, this is before anybody's written any articles really on me or done anything. And, I was just like, "okay, whatever." For that, all the experiments, most of all the stuff I've worked on, all the little art cool things I did, like, they're pretty much free from judgment from the outside, cuz there was nobody watching me, really. And the effort that went into this experiment and just, like, how much it took for me, you know, taking the antibiotics that really sucks and it does do a number on your body no matter who you are, what you do, um, the whole experiment in general and then being scrutinized with the camera and journalists and all this stuff, it was, like, such an emotional and physical investment. It's like one of those instances where, if you play sports or something, where you're just so beat up, and with your just last gasp of effort, you try to do something, and it works. And you're just like, "holy fxxx, oh my god, it works. All that effort and all that, that shit I went through, it actually work." Like I did not expect that at all.

Melissa Galati [19:16] What is sort of like the danger with maintaining the status quo with these technologies? So like only using them in regulated spaces like academia like, is there a specific danger that we're kind of hiding them from the rest of the world?

Dr. Josiah Zayner [19:30] Yeah, I think the first thing is just like the people who control them will be the people in power and get to decide everything, right? God forbid that somebody creates a drug or medicine that can only treat a specific group of people or can only help a specific group of people, and they get to decide when it's released or how much they charge for it and stuff like that. Like that starts to get really sickening, and there are stuff like that, you know? Like, recently, this, this treatment, gene therapy that cost a million dollars, Novartis I think, they said that, like, "there are people who can't afford this treatment, and so what we're going to do is we're going to do a lottery every year for 100 people who get to receive this gene therapy treatment and who can't afford it." And you're like, "that sounds great that you're giving it to 100 people, but like, what about the hundreds or thousands more who don't get it?" That's literally the craziness of our medical system that, like, people are going to suffer and die, because they just can't afford this treatment. And there's nothing we can do about it like nothing. Instead, we hold a lottery, a lottery, like, your life comes down to a lottery. Holy shit.

Melissa Galati [20:48] Yeah

Dr. Josiah Zayner [20:48] that is crazy.

Melissa Galati [20:50] And that brings me to my next question. When we make these technologies commercially available, you know, I think people think designer babies, Gattaca, the eugenics movement reborn or, or at the very least, that people will be misinformed or misled by services pretending to give something that they can't actually deliver. But what, what would your response be to that? Specifically I want to talk about the arrest of He Jiankui, and, and your recent STAT news opinion piece.

Dr. Josiah Zayner [21:18] You know, this stuff is always very inflammatory. People love to, like, associate genetic modification with Nazi eugenics. Not eugenics in general, because, you know, those can be two different things. But like, Nazi style eugenics, forcing people to have certain character traits and then forcing it on, like, a state or governmental level, which I think is very different from, like, people wanting to have certain traits. That, I think, is up to each person, and it's up to their own self-expression. It's body autonomy to me. I mean, what about parents who get IVF and, you know, have a pre-implantation genetic diagnosis to, like, choose whether their child has, has a disease or not? You know, like, where do we draw the line on this? To some people, it's after genetic diagnosis and before gene editing. But if you couldn't tell the difference, if I could gene edit you and you couldn't tell the difference between whether it occurred naturally or genetically, you know, through genetic engineering, like, what then? Like, is that, what's the difference, really, besides some ethical argument?

Melissa Galati [22:35] Sure. Well, I think, just to comment on the the Chinese babies that were CRISPR edited, I think some people actually think, you know, gene editing could, in theory, be wonderful for mitochondrial diseases and, you know, diseases like cystic fibrosis where we can actually cure these people, but it might have been better if he had tried for one of those, like, single gene diseases or mitochondrial diseases, but the argument is, we don't actually know if, you know, these babies were, are actually protected against HIV. They certainly weren't really at risk for HIV to begin with. So, it's not like you're protecting them. You're not intervening in sort of an unmet medical need. We should be removing the red tape, but this was the wrong step forward. So, what would your response be to that?

Dr. Josiah Zayner [23:24] Maybe, but like, tetanus isn't an unmet medical need, right? We get tetanus vaccines. Tetanus is not a communicable disease. It's caused by a bacteria that can be treated with antibiotics. Before the tetanus vaccine came out in the US, there was around 580 people a year who got tetanus. 580 people a year who got tetanus, and it can be treated with an antibiotic. I'm not saying government forced to get a tetanus vaccine, but, you know, we pretty much are, you know, something like that. Yeah, yeah. There's like something like 90% coverage in the US. There's no heard immunity or anything like that with tetanus. Our chances of getting tetanus nowadays, it's a soil bacteria, are like practically insignificant and can be treated with antibiotics. So it's like, according to the CDC, there's about a one in 100,000 chance you'll receive some type of neuropathy from the tetanus vaccine. Is that a, a risk that we're willing to take with our children, with ourselves, with anybody? We say yes, right? To me, it's like, what's the difference between the HIV thing, if we considered it a vaccine, right? About 0.1% of the Chinese population has HIV. That's, that's pretty significant. That's, that's around 1.5 million people, right? 1.5 million. So you know, like, who knows. Sure, like, HIV is not a scary thing, and we should not, you know, stigmatize it at all. There are plenty of ways to prevent HIV without gene editing or anything like that, just as there's plenty of ways to prevent tetanus. But like, if you look at it like that, I don't get the difference. To me, it comes down mostly to an ethical argument, the whole gene edited babies thing. Not really a, you know, like risking lives or anything, risking children or making decisions for children. It's more of, like, an ethical argument. And that's what, where it bugs me.

Melissa Galati [25:29] Yeah, I think, well, I think people, their thought is, and this is, was also sort of my thought process, it's a permanent change, and it affects not only these kids, but, in theory, their kids and future generations, and you've made that choice. And we don't necessarily know the context in which informed consent was given or, like, how much knowledge the parents would have had on, on HIV, and, like, the specific gene that was mutated and what the specific mutation was. So to make a choice that will affect that many, like, that many generations to follow is considered irresponsible.

Dr. Josiah Zayner [26:06] You know, like, there's so many of these arguments, and but they're all hypothetical. And yeah, we need to be cautious, and whatever level of caution you think is appropriate, I get that. That's, that's an argument people could have. But, everything is, like, all these hypothetical things, what if, what if, what if. And, it's like, #1, we don't know really anything. We are approaching it from the standpoint that, like, all the effects from this will just be strictly negative. And, you know, I don't know, you know, don't, don't put me in and say like, "I'm going to argue that they're all going to be positive," or you know, that things positive will come up. But, what if we approached it from the point of view of that, like, it is positive that like one of these babies was treated, has no side effects, and they're resistant to HIV. Then what? Again, then, it just becomes, comes down to an ethical argument, right? Or, you know, trying to figure out if consent was given properly or something like that. And, that's where bugs me, because, like, the only thing, I think, between viewing this in a positive or negative light is just if you think the results will be positive or negative. You think the results will be negative, then you're probably going to hate this guy. If you think the results would be positive, then you're probably not going to hate this guy.

Yagnesh Ladumor [27:31] As you can imagine, Josiah has gotten quite a bit of pushback for his opinion piece in STAT news, defending Chinese scientist He Jiankui, particularly from the academic community. If you stick around, you'll hear more from our interview with a bioethicist on this topic later. But there are also people who sort of see his point. We spoke with self-proclaimed genomic futurist Andrew Hassel, founder of Human Genomics, a start-up that does virus engineering, and co-lead of Genome Project-Write, successor to the Human Genome Project, that aims to actually write large genomes, like the human genome, from scratch. As someone who exists on the forefront of genomics and thinks about its future, we had him weigh in on the ethics behind gene editing in embryos.

Andrew Hessel [28:15] So, what we saw with the gene edited babies was, was complicated, because people were a little shocked. This was, they weren't prepared for it. That was, that was kind of, it was just kind of, you know, it appeared without a lot of warning. And, and frankly, it was a very poorly deviced project. But, I want to be clear. If the scientists had, had used CRISPR not to do an enhancement to make HIV resistant babies, but instead, he had worked with infertile couples to bring a baby into the world that wouldn't otherwise have been born, it would have been the IVF, you know, the modern version of IVF. That was the, that was such an obvious mistake in the choice of the project that I can only think he was just poorly advised, because I would have told him that, in two minutes, "hey, if you're going to go in and try and push the envelope, go and do something where there is a moral force behind." You're bringing a person into the world that wouldn't, didn't have a chance to be born. You're helping parents who, you know, the most powerful thing you can do in life is, is have children, and you're helping them. And so even the corners were cut, he would ultimately be forgiven, because that was what history taught us around the idea.

Melissa Galati [29:45] Yeah, yeah. And that's that was exactly what we said as well. Like, it was a step forward, but it was perhaps the wrong step forward in a sense. It's, because you, like, as you've said before, even IVF was controversial back in like the 70s, correct? So, that's changed the lives of so many people.

Andrew Hessel [30:04] I have two kids that that are, you know, born from IVF, so, like, I have great respect for the technology. But, the, you know, that, so that was a waste. I also agree with Josiah's essay that it's a waste to put the scientist in jail even as flawed as his work was. He did humanity a service by taking what had been a theoretical discussion and making it very pragmatic, and now people are thinking about, well, how do you do this in a safe and responsible and transparent way with proper regulatory oversight? And, and I think that's done humanity a service. We won't figure all this out; there will always be edge cases, there will be, there will be other problems. But right now, CRISPR is an amazingly powerful tool for helping people, and, and I believe that over the next decade, as we start to move into whole genome engineering, we're only going to be able to do this type of modification or design of completely new things at a faster and faster pace more accurately, more robust. So, again, it will offend some people just because they think we're playing God, but in my view, it is just another technology that humanity has to, you know, to master. And, it's the only technology that, that is provably sustainable and compatible with life. So, I think it's, I really believe that bio-technologies, in general, help us find a or create a new balance with nature that, you know, that really makes, starts to repair some of the damage that we've done with early, with earlier technologies.

Melissa Galati [32:06] Do you think there would have been so much pushback if he had released the findings in a scientific paper as opposed to a YouTube video?

Andrew Hessel [32:14] Hard to say. Like, like, everyone's so reactionary today. Someone says something, and tweets are, like, we all have our little puppets to stand on today, and there's so much noise in any type of communication. At the end of the day, you just have to kind of choose things that you think are important and valuable. Turn the volume down on people that are, are negative, and, and see, you know, and kind of work with the positive. And, I'm not too worried about... Like, accidents can happen. I get it, you know, like that, I like to say, look, the, in terms of existential risk, we still got tens of thousands of nuclear weapons. I don't really worry about life all that much. You know, I think that's the threat. I think, in terms of causing harm to others, you can do it with computers, you know, much easier than you do with biology today. So, I think we've got a window here, you know, to kind of get, you know, get up to speed. And, I think there will be some sort of sensitizing events at some point where someone will use these technologies in a way, either nefariously or by accident, to do something that sensitizes the world that we have to start thinking about things. And it's not, it's not gene editing things; that's not going to change the world. I think, I think it's going to be something, can be some other biological, perhaps with a virus. I don't know. But, but I want us to start thinking and preparing for something like that, because it's pretty predictable. It's going to happen. When we, when we started networking computers, the scientists didn't even really think about, "oh, we need kind of an immune system for computer networks," but then, there was a sensitizing incident with the Morris worm, and if you don't know what that is, go and Google it and read about it, but, that was kind of a error that set off a chain of events that ultimately crippled the nation's internet, and, it was an honest mistake. And, and that kind of seeded more and more awareness that, yeah, we kind of have to have, you know, if you have a, you need a digital immune system and then antivirus software, blah, blah, blah, you know, start rising. So I think, I think there's an opportunity to completely rethink biological security and create a whole new ecosystem and industry that is a lot better. And I think it turns into what we would recognize today as just better public health, and public and healthcare, and environmental stewardship. That's what it would look like if you built that type of system. I think, in general, it's not so much an ethical issue. I think it's how do we get everyone in the world more comfortable with these technologies just as they've become more comfortable with computer technologies, and cell technologies, and AI, and robots, and whatever else. I think, I think we just have to recognize biology is a technology. And you know, it should be, you know, used appropriately.

Stephania Assimopoulos [35:29] We talked to Josiah Zayner, and he was, he's also one of those people that are talking about taking all of these technologies and bringing them to, to consumers, to bring them to outside of the lab, outside of institutions, and making it accessible, of course, expressing some frustration that the rate of that is happening really slowly. Where do you think we are in terms of that, because I've heard you speak previously on how the rate of this, that, this technology is advancing really fast. Do you think that that is something that is possible? Or, or it's sort of dreaming that we can actually, anybody can do it? Is there a middle ground? Or can we actually get to that?

Andrew Hessel [36:11] Oh, well, let me, let me just say I'm completely aligned with Josiah in that the bio... I don't like the term biohacker. Every scientist working in life science is a biohacker; they are taking something that exists already, and they're dissecting it, whether it's physically, or molecularly, or computationally that they're, they're taking it apart and trying to figure out how it works and then, and then manipulating the systems. No one's got the blueprints. In a sense, every scientist working in life science can be called a biohacker. I don't like that term, because it comes with some edgy negative connotations. I like bio-engineering.

Yagnesh Ladumor [36:56] Specifically, what Andrew likes is synthetic biology. A relatively new area of science that uses the principles of engineering to design new or redesign existing biological systems. Most of you probably know about the successes of the Human Genome Project, a multi billion dollar initiative to sequence the first human genome. The Human Genome Project was completed nearly 20 years ago, and now, we've dramatically improved technologies to read DNA faster at a much lower cost, from several billion dollars to now just a couple hundred dollars per genome. More amazingly, we can not only read our DNA, we can edit it using tools like CRISPR. And now, we can actually write the code of life, too, using synthetic biology. Andrew explains how we can write code using all the A's, T's, C's, and G's, compile it, turn a digital DNA into physical DNA, and load that code into cells or cell free systems to see if it's running properly. We can then go through iterations of debugging until we reach our biological design goals.

Andrew Hessel [37:57] I want to be able to robustly design and build a biological system. And, whether it's a single protein, or a nucleic acid string, or a virus, or a cell, or an organism, or a tissue, it doesn't matter. I'm kind of application agnostic. But, I'd like to be able to go and bio-engineer. And, here's what I know from working in other areas of engineering. It requires tools. And, that means, for me, it all starts with the software tools to make the design. And now, and you can go a little upstream from that where you can say, well, you have to have a design intention. I want to build a bridge, I want to make a cell do this, whatever. But, you, but then, you need a tool set. A building is easy compared to a cell. So I want CAD software for cells. I want, I want it to be like Google Earth but for a cell. I want it to be that powerful. I want to be able to design code for that cell simulator and have a pretty good idea of how it's going to run in that model cell before I ever go and build it. But to get there, we're going to have to do a few iterations between genotype and phenotype at the cellular level to really train that system, because bio physics compared to the physics you would do for a building or car, like biophysics is magic. Like, how and, how a single protein folds or an enzyme works can be mind boggling. So, I know we have to go and do a little bit of, you know, more work on the model, but, but that process of sitting down at software designing, compiling your code DNA synthesis, getting it into a cell or cell-free system, and doing the test and measurement, I want to see that entire process as be completely digital and no lab tools required for any, for, so I want my daughter who's like five to be able to go up, and I want to be able to teach her own software very easily to be able to make a bacterium glow. But, I don't think she needs to actually handle that bacterium to do it. So, all of the backend, you know, DNA synthesis, and boot up, and testing, I want to see on an automated platform. Josiah is much more hands-on and wants to teach people the experience of doing lab work and get them, you know, feeling, and tasting, and, and really building a community around it. And, and that's hard, because you need a place to do it. You need the reagents and supplies, which is his business. He's doing pretty well with that. But, you also have to train, and you have to engage. He's just got a very different way of dealing with, with his community and supporting his community. He's done a great job. But, I want to see, I want to see that community grow even faster and in a more synchronized way. And, I think that's done through a digital platform. Another thing that I absolutely think is going to happen is we're going to have more biological engineers, whether they are 10 year olds, they're learning how to start coding, you know, bacterial metabolism to, to just the diversity of various professionals coming into the world, very much like software engineer. I think we're going to have, you know, biological engineers like that. And, more of those biological engineers, then we have PhD scientists in, you know, in the next five to 10 years. I think this community is just going to explode, and not everyone is going to go and try and cure cancer or completely reprogram, you know, E. coli, but, to me, the outputs of a lot of bioengineers being empowered with a digital system, ultimately, you end up getting something like a biological App Store. If you go into the App Store, there are, there are so many apps that, you know, you don't even know where to start. But, you know, they, it's kind of a, it's kind of a primordial soup of software. And the best stuff kind of, you know, people find out about it, and they start to use it. I think something like that is going to happen in, in biological engineering. And, it will be bottom-up with people that may not have a lot of training, just someone comes along and says "oh," and they can look through past projects that iGem where they can take a course with Josiah or they can just have an idea that they want to try. And, if they can write a little bit of biological code with the right software tool, and it's going to get easier and easier to do this type of work with better software. And, if, if compiling that genetic code is inexpensive. Again, I tell people today, "look, if you have to pay 10 cents a base pair, like you do it many DNA synthesis places like 10 cents a bit. If you pay 10 cents a character every time you type, no one would tweet, because it would be 14 bucks." Right? So that's kind of the limiting step in playing with synthetic biology. It's not the software tool, it's access to synthesis at, you know, at a playful price. So, because, you know, so you write a gene of 1000 base pairs to code, you know, it's still going to cost you 100 bucks to boot up that gene. Right? So that's okay. There's ways to do it cheaper if you have... But, but still, that's just, that's a lot. And then, if you actually, that doesn't get you the results of running that code in a cell yet, so then, you have more overheads. But, when all of that is integrated, and it might cost $1, then suddenly people get to play, and particularly if that, if that system doesn't involve you doing those manipulations in your garage or your bedroom or your kitchen at home, now it's being done in a robotic laboratory that is essentially properly equipped for dealing with, you know, living organism, potentially infectious and living organisms, now you can really start to get the creative juices going. So, I think we are entering an age of explosive bio-engineering and and exploration of the possibilities of cellular systems.

Yagnesh Ladumor [44:34] Andrew is inherently optimistic about the future of genetic engineering and synthetic biology. But as these tools become cheaper and more accessible, does that mean we have to think more carefully about the ethics surrounding their use?

Andrew Hessel [44:47] Well, I should say a couple things One: I'm not an ethicist, and I have no ethical training, and if anything, I probably... so so ...

Melissa Galati [44:57] Push the boundaries

Andrew Hessel [45:00] Yeah, well, I just want to say that at the beginning, because they're, in general, I believe that ethics are dynamic. And, it's not a, like, I think, I think your ethical framework largely is part and parcel of the environment that you're in. And, and you might, you know, for example, you might be completely against GMOs, but, if you were starving you, you would shift your opinion, you would soften a little bit. So, you know, you might be really against animal research, but then you might need a drug to treat your cancer that's been tested on animals. Like, I think it's really hard to get people to agree on an ethical position, because they're so personal. You might find clusters around a mean, but, but I think it's, I think they're really something very individual, and most people think that their ethical constructs are ethical.

Biren Dave [45:54] Advancements in genomic technologies and their applications in medicine and biohacking are inherently ethically charged. We spoke to Dr. Michael Szego, an associate professor in the School of Public Health at the University of Toronto. He specializes in clinical- and research-related bioethics with an interest in genetics. To learn more about what his role entails, we asked him to describe what his day-to-day work looks like.

Dr. Michael Szego [46:17] Each day is different, which is one of the reasons why I really like this job. So I do clinical work. So I work in a downtown academic teaching hospital. And, so whenever there's an ethical issue that may come up on a unit, lots of end of life issues, some beginning of life issues, which I was actually just dealing with now, transitions of care, elder abuse. So, those are all sort of some themes that sort of, was sort of percolate up and then trigger an ethics consult, and then, I would get a page and get involved. That's kind of the clinical side. So, that's maybe the sexier side of what I do. The other things that I do would be policy development. So, often when I'm working on a clinical case, I may look at the hospital policy and sort of see what the policy has to say.

Biren Dave [46:58] Michael also deals with issues related to research ethics.

Dr. Michael Szego [47:01] So, I think at its core, research ethics is about ensuring that the research protocols that are, that are done, keep people as safe as possible. So really, what we look at is, we want to make sure we're maximizing benefits, minimizing the risk, and of course, making sure that patients are able to provide informed consent prior to initiation of a study in most cases. So there are examples of research studies where there will be a waiver of consent, but again, as an REB, there needs to be special justification for why that would be necessary.

Biren Dave [47:34] Although Michael isn't an expert on biohacking or DIY science, we felt that he would be able to offer valuable insight into the ethics of such practices.

Dr. Michael Szego [47:43] So, so I'm not an expert in biohacking. So I will, I will put that on the table right away, although I'm familiar with the term, and I'm sort of familiar a little bit with, with, with, the landscape. So, I guess what would concern me the most, and maybe this is just because I've, I'm sort of heavily involved in regulated science like being a part of an REB, but I guess what worries me is that people might be doing things without really knowing what the risks are, righ?. And, they're not doing it in a regulated environment. They're basically conducting science on themselves in their basement. And, there isn't sort of that, there isn't any oversight. And, one could argue from a libertarian perspective that if they wanted to do that to themselves, you know, that's fine. But, I am so used to a regulated environment where we, again, we try and mitigate risk the best we can. We do things in a very stepwise fashion where, you know, if we're doing a, we're doing a clinical trial, there's always going to be a phase one where we gonna look for what is the kind of the safe dose to give, and that's a very small number of patients, and then, there's the phase two, then there. So, things happen in a very slow but regulated way, and biohacking seems like it's exactly the opposite.

Biren Dave [48:51] Right. And that's your main concern with it is people tinkering without knowing what they're doing with consequences that might be serious in some cases.

Dr. Michael Szego [48:58] And other circumstances where they might be doing harm to other people as well, right? So right, and it's not just about themselves. So, I'm thinking about if they're playing around with viruses or other implications to the health of other people, right? And then, so my concern would get elevated if, you know, I think people can do what they want on themselves, when it starts to affect other people, I think, is when I would have an even elevated level of concern.

Biren Dave [49:22] Can you ever imagine any scenario where you would consider the use of biohacking or self-experimentation to be ethical?

Dr. Michael Szego [49:28] I mean, I think it would, again, it would depend on whether anybody else could be harmed. I think that would be an important question that I would want to know and what was the risk profile of whatever the person was doing. So, if it was something relatively innocuous, then I think it really does, it does sort of hinge on what the risk to the individual are and how well informed is that individual about what they're doing. So, it's not that it happens to take place in the person's home and not in a hospital environment that just makes me uncomfortable, because it's very different. But, I guess I could imagine a scenario of something was, you know, perfectly safe and the fact that somebody is doing it to themselves and they're not harming anybody else, I think that would be their right to do.

Biren Dave [50:07] Since all of our guests weighed in on the CRISPR babies incident, we thought you'd like to hear bioethicist's take on it. We asked Michael, if it would ever be ethically permissible to genetically manipulate a human embryo or fetus and what the implications of this gene editing incident would mean for the future of human gene editing.

Dr. Michael Szego [50:24] So one scenario I could think of is imagine that you had a baby, or if you had a fetus with a genetic condition that would be lethal. So you know, the fetus would die in utero. And this was sort of one, this was a last ditch experiment that you could think of, or I wouldn't even say it would be an experiment, but it would be, the intent would be clinical to try and save the life of the baby, then I think, again, I'm, this is all kind of made up, but that would be sort of a set of scenarios where I could imagine one making an ethical argument. In this case, they were changing one of the receptors to HIV to confer resistance to HIV infection. So, these children would have been born perfectly healthy without CRISPR. They, it was basically just a proof of concept. And so, scientists took perfectly healthy embryos and altered one of the receptors for HIV. And again, you know, we don't know what the off target effects could be. We don't know what the long-term effects would be on the health of these children. So, I think it really was, you know, reckless use of science and, in many ways, could take a good technology and, like, you talked about the event that happened in gene therapy, this could be the same thing with CRISPR where everyone all of a sudden looks this technology remembers what happens in China and says, you know, we shouldn't be doing it, we shouldn't be touching it. And I think that would be too bad. I think there is a lot of promise with CRISPR. It just needs to be done in the right way.

Yagnesh Ladumor [51:44] Biohacking takes the science outside of its normal academic and industrial confines and places it into the hands of innovators, entrepreneurs, and pretty much anyone else who has an interest in it. While this sort of DIY science has exciting implications for how society may one day deal with innovation, drug costs, scientific literacy, and the food industry, we must temper our optimism by acknowledging and grappling with some of the ethical challenges that biohacking poses. We tried to keep an open mind while putting together this episode and not be swayed by preconceptions. We gained some new perspective on biohacking from our guests, and we hope you did as well. If you're interested in learning more, we've linked some additional resources recommended by our guests in the episode show notes. You can also let us know what you thought by commenting on our latest Facebook, Twitter and Instagram posts at Raw Talk Podcast.

Biren Dave [52:30] This episode was hosted by myself Biren Dave, Yagnesh Ladumor, and Melissa Galati. Nathan Chan, Stephania Assimopoulos, and Tsukiko Miyata helped conduct the interviews, develop content, and share their opinions during the roundtable sessions. Melissa Galati was the executive editor. Photography was done by Nathan Chan, and Kat An was our audio engineer. A very special thank you to our guests Dr. Josiah Zayner, Andrew Hessel, and Dr. Michael Szego for speaking to us and sharing their insights. And of course, thank you for listening. Be sure to check out our next episode in two weeks where we discussed pandemics.

Melissa Galati [53:05] Raw Talk Podcast is a student presentation of the Institute of Medical Science and the Faculty of Medicine at the University of Toronto. The opinions expressed on the show are not necessarily those of the IMS, the Faculty of Medicine, or the university. To learn more about the show, visit our website rawtalkpodcast.com and stay up to date by following us on Twitter, Instagram and Facebook. Support the show by using the affiliate link on our website when you shop on Amazon. Also, don't forget to subscribe on iTunes, Spotify, or wherever else you listen to podcasts and rate us five stars. Until next time, keep it raw.