Episode 2 Transcript Devaki (D): Hello and welcome to our second episode of Synversations a podcast that explores the depths of synthetic biology from various multi-disciplinary standpoints. I'm Devaki and I will be your host for today and I'm a second year life science student. So Synversations is a five episode long podcast created by the University of Toronto policy and practices division of its iGEM team. iGEM is a student association dedicated to the practice of synthetic biology and dissemination of scientific foundations. In today's episode we'll be exploring how bioethics plays a major role in synthetic biology. Joining us today is Estée and Kat. Estee (E): Hi I'm Estée and I'm a third year student in bioethics and Ethics, Society and Law. Kat (K): Hi I'm Kate and I'm a fifth year student in molecular genetics and immunology. D: And it's no simple terms CRISPR is an innate system that naturally protects bacteria from viruses by using it to store DNA sequence to match and encode any viral DNA. If we give the cell a DNA sequence to repair the damage it will incorporate the new sequence into its own DNA. If these changes are made to the eggs or sperm the nutrients will be passed on to future generations. In this case the offspring have a 50 percent chance of inheriting and you trade how our gene drives defy this rule of inheritance by increasing this rate to nearly 100 percent. The introduced trait will then get passed on to all future generations. This technique works in organisms that reproduce sexually and can make a significant breakthrough in agriculture and disease control. That is putting Stop putting a stop to malaria or increase crop yields. This is incredibly powerful as it can change the course of evolution. OK so why are Gene derived so important today. K: Well I think one of the reasons why Gene drives have become such a topic of discussion is because of certain probably because of the Zika virus outbreak because one of the reasons why has been brought up more. But, other things other major illnesses that can be spread by mosquitoes like Malaria and Dengue and sleeping sickness, I think. E: Yeah, people are really interested and the capacity to cure or get rid of diseases. So, it's becoming more prevalent now as we’re more capable of being able to and in different areas of gene editing and stuff like that. you know getting answers like that. But also we we've been discussing before that it's been around the idea of gene drives have been around for many years. K: There are certain genes that are selfish genes in the sense that like you were saying that generally genes or traits have a 50 50 percent chance of being inherited by the offspring. But there are certain genes that have a slight bias towards being inherited some selfish genes. So those are existed naturally before the advent of Gene drives became something or a tool or technique that we can actually apply to solve problems. And I think another reason why Gene drives have become so prevalent or the thought of using gene drives has become so prevalent is with the advent of the crisper revolution because now we can use the crisper CAS system to engineer Gene drives really efficiently. E: Yeah and basically the idea I guess to back to the question. The idea that we have the capability or comes to being able to cure diseases and get rid of invasive species that harm the ecosystem along with the issues that come with that. K: Countered gene drives basically the idea of resistance emerging to Gene drives. And so what they've also tracked not only is the spread of the gene or the activity of the gene drive within the population but also the emergence of resistance because if you have a fluorescent marker you can just shine a light on your fruit flies and they’ll basically fluoresce red and you'll know if you have it machine drive is working. But also if you monitor them over time the loss of that fluorescent protein would then indicate the emergence of resistance which is something that is also very interesting topic when you're talking about drives is that if you if it works that's great. But then how long will it work. Because you know as you know evolution. We can't really control evolution over long periods of time. We can do Gene drives with short term changes that can be quite drastic. But then over time – E: -Is the idea you are getting at that they can outgrow the gene? K: Yeah. Sort of in the sense that. Yeah like over overpopulation is what might happen is that there might be some sort of pressures selective pressure against the gene drive. And, we can study and try and identify it and then try and change our gene drive. But we can't stop that process of resistance. D: So maybe let's start by looking at the benefits and the harms gene drives can have. So let's start off with the benefits. What do you think can be achieved with the use of gene drives? K: Well I think if we look at like two different types of Gene drives that they have they have a replacement Gene drives where we can basically modify your vector such as a mosquito so that it can no longer carry whatever disease agent you're looking at whether it be like malaria or Zika and then you also have like the suppression Gene drives which basically engineered your vectors so that over a period of time they will eventually die or become extinct. So I mean either one of those that the benefit is that ultimately you can you can possibly prevent people from acquiring the illness that seriously impacts their life. E: Yes. I mean curing diseases illnesses definitely one thing that people can look at as well as also increasing crop yields in some cases. Which is great if you in terms of reducing famine and basically being able to produce better crops and more consistent crops reducing and stopping famine. K: It's interesting because like when I think of it like Gene drives and mosquitoes and gene drives in like agricultural plants somehow, like, the idea has there's different associations that I make with it like certain things. Like the mosquito Gene drive, to me it feels more isolated if is that makes sense. E: How so? K: Like. You’re engineering one. I'm not sure how specific - Generally gene drives like the idea of Gene hopping from one organism to the other. It’s a design consideration you can avoid it to some extent and you can put safeguard mechanisms to make sure that you can drive this isolated system and mosquitoes to some extent at least to me feel like an isolated, they’re part of an ecosystem for sure. But they're more removed whereas I feel like a crop plant - E: You mean it was spread more sporadically? K: Not that it spreads radically but if you make a crop plant. Perhaps grow more efficiently. The idea of like Gene drives for invasive species like you might engineer an invasive species out of a crop plant and that makes sense if you make it grow better. E: I guess I mean it seems like there would probably be similar though. D: What kind of problems you think will face if this happens? K: Like technical or in terms of like implementing? D: Let's start with technical. K: I mean technical I guess we’ve sort of addressed the problem of like the emergence of resistance. In this sense that you can engineer a gene drive, but you cannot ensure that it will be selected for continuously through multiple generations. And as a short term it can spread in the population but then as we have learned life finds a way. E: Is this back to the idea that eventually they outgrow the gene drive? K: Yeah evolved out of it. But I think another problem would be that if you were to engineer a gene drive that would make a species less competitive or less dominant so to speak in a population or maybe to engineer for extinction you'd have that problem of first of all you're removing an organism from an ecosystem that functions as a whole to disrupting a system but also on another level. What would happen once the system tries to mend itself? So how would the system try and reach that equilibrium again. To specifically looking out like mosquitoes the specific mosquito vector that has been used for a husband looked at as a species of aries aegypti mosquito that transmits malaria and Zika more readily. E: I mean it seems that if we eradicate the mosquito altogether then it kind of gets rid of the problem because they wouldn't exist anymore. But there is a problem if other mosquitoes might learn to or begin to take over the role of delivering malaria in like a pretty package. Other harms are- D: -Loss of biodiversity. E: Yeah that, you know the main question is I mean everyone hates mosquitoes or most people do. K: Who likes mosquitos? I want to meet this person and have a very serious conversation with them. E: We don't know what role mosquitoes truly have in the ecosystem and no one-pbviosuyl they are food and we don't know to what extent other species would be able to survive without mosquitoes. So bats eat mosquitoes frogs mosquitoes you know all these different species provide them as food. And I used to think when I was younger ‘oh they can eat so many other things’. We don't know that you know if an entire species is gone and that’s their main source of food, well that can diminish the presence of bats you know or you find it it's the same thing that happens when you introduce a new species into the territory. K: Yeah, it's really hard to predict and I think the Cornell University tried to build a mathematical model to try to understand what would happen and to some extent you can try and model what might happen. But there are just things you can’t account for in that model because there are so many variables. And. Like. D: In nature it's very unpredictable. K: Yeah. So I mean you can try and write like rationally design out what the outcome is. But. At the end of the day you don't really know. E: And there is the whole idea that you want to. I mean that's a risk that you take and you want to think about the fire. Is it worth it. I mean of course we don't want to. Let people continue to get malaria. You don't want those to continue. So is it worth the risk that you could harm the ecosystem greatly potentially. It's hard to say, and, while it seems like or it of course is a horrible thing to keep these diseases around. They're also in some ways a part of nature, so I'm not saying that we should allow people to just say but it's to say that it is in some ways nature communicating what it's trying to do. So mosquitoes transmit diseases and we have evolved to the point where we can-evolution- we have evolved you know. This is our ability, you know, the sheep or gazelle run away from the lion, this is just us attempting to run away from the disease spreading mosquitos. But there is something that is quite unsettling that we can completely control nature in its whole. K: And they and they feel that sort of guilt perhaps. Could that be one of the reasons why people are kind of against the notion? E: Well I mean, this idea that like what right do we have to get rid of this specieces. You know why are we better than this species. This is we're trying to get back on track in terms of the way. So if we are like this is our missionary have to be able to get rid of. Why. Right. To me. Yeah. Do we have. I don't think there's any. There's no natural process. I know that I know you know the way it willingly they just are knowingly getting rid of an entire species like it's a race you know when it's competition. K: I mean other than like things like disease like natural disasters which do just eliminate entire populations which are kind of unpredictable forces of nature so to speak. There are no like I think that this approach is very like it's very planned out. It's very like there's a lot. Yeah there's a lot of thought put into it. And it's let's systematically designing a method in which to get rid of another species would be. We're talking about Gene drives like eradicate species it's very thought out like if we were to put it into a legal system it's like first degree murder. Yeah in the sense that you have the you have the intent and you thought about it's premeditated not to see this necessarily but- E: -but I mean this idea that you can argue. K: I mean you could argue that it is murder if you if you go down that line. E: Well I mean there’s the concern that. Why is it that we should be able to kill an entire species, so that other humans don't get diseases? This is not only get into the whole thing on animal testing but we humans are better which it can be concerning. And the humans are better so we should test on animals and humans are better so everything we do should be OK. We do all these things to animals or other species you know. So, for the safety and security of humans it is difficult sometimes to argue that for mosquitoes because they're not self aware and they don't really have- K: -How do we know they're not so we don't have a question. D: Yeah. E: So I guess we don’t, but are very very instinctual beings. You know they go based off of- they have a goal you know they eat they breed you know . Then I can even imagine if it wasn't a mosquito if it was you know, if it was a certain type of gopher that transmitted diseases. To the same extent that mosquitos did. We draw the lines in different places and I personally have trouble drawing the line, necessarily at different markers. I mean certainly murders because it becomes difficult to. Move. What is the point in which a being is equal to us? We could extend it and some people do extend it to ecosystems. And we have no right to put our own personal welfare above the ecosystem. So you can reasonably argue that ecosystem has as much of a right to exist and you know to survive as we do. And to destroy it completely I mean most of it for but it's not good for us but it’s not good for the animals in it. It troubles me and a lot of other thinkers to what extent we put human lives first is what I'm getting at. But at the same time we don't want Malaria. D: If you look at it from what you mentioned this earlier how if you look at it from an evolutionary look standpoint the basic goals of any kind of species is to survive and reproduce. Anything that prevents us from doing so is something that we need to stop. K: And I think this is sort of like a basic animal need. If we were to go down to our instinctual level is to reproduce and to survive. And anything that starts to get to the way that we as a species will start to try and problem solve to figure out how to how to get around that. E: So yeah it’s a loaded issue. D: It’s a nice discussion to want to talk about. K: What's wrong people get access to the technology? E: Oh yeah. D: So yeah let’s discuss what if it falls into the wrong hands? E: If it’s like accessible? K: It's kind of it's it is and it isn’t in the sense that an article in Science basically that addressed how to work with gene drives safely and their one of their principles was always to have two stringent confinement strategies when you're engineering a gene drive. And also like I'm blabbering on a little bit. But basically it's from like an iGEM team perspective I think there was a lot of drama. There was a lot of press about like a college team potentially engineering a Gene drive but it really wasn't that. E: They were concerned about some college team releasing some large mosquito – K: -Yeah to them it seemed very accessible like a college team but they actually had advisors and actually was monitoring kind of what they were doing from a certain distance and making sure that they weren't doing things that were dangerous. But then we get into like community labs like DIY bio, bio hacker community. D: Yeah what is that? K: So basically to kind of oversimplify it it's people who don't necessarily have a science background or maybe people who don't have institutional access to a lab who would in their community want to get their hands dirty with say biology and synthetic biology and to sort of engineer try to engineer some kinds of applications for their community. So there are little communities like community labs where people can do synthetic biology to some extent and I guess what people were worried about with was that the iGEM teams and Gene drives was if a community college team can do it why can't a community lab, or DIY bio lab can get access to this gene drive. And what happens if they do it and what happens if they get. E: If it becomes more regular presence technology that is you think perhaps it is more likely that people have access to it and are less regulated or more regularly than matter. But maybe it's more available so potentially people more will be going after it. So I can see there being like maybe say if you were to release engineered organisms into the environment like say if he were to engineer Gene drives and mosquitoes and you release those mosquitoes into the world with those mosquitoes have the gene drive or like the engineered sort of genes are out there. E: You need some sort of world agreement and multi-nation agreement that has regulations on them on these technologies that as we’ve seen in the past can be very difficult to regulate. It's very difficult to get nations to agree. K: I think something that was brought up was that even if. Every single nation agrees to some unified policy what happens if one nation decides to go against it. E: Yeah exactly. Because every nation has. A lot of time their own interests and interests but mainly their own interests at heart. You know so as you can see even with the Paris climate which took a very long time to get most nations to agree to it and even now one nation can decide not to participate as well is a very different subject in terms of climate change and Gene drives. If one nation decides “oh I don’t want these regulations or not good for our country” you know the whole safety of these regulations are in place. K: Going back to what you said about nations having their own interest there is also a problem with commercial interests in a way like say maybe engineering some gene drive to cause a certain species to go extinct can help increase the crop yields of some certain company or increase product. Then you can see there being a lot of like conflicts of interest. E: Yeah there is concern when you try and commercialize everything you have every piece of science especially when it comes to the health of people and when you involve money it becomes very tricky. And you know you potentially when you see if there's some way to manufacturers some kind of drug resistant paper you know some kind of like enhanecd drug. I don't know how it would play in- D: -Anti-malarial drug. E: If gene drives played into this commercialization drug manufacturing I don’t know if it would at all. K: Like you mean if we could tie it to with like big pharma. E: Yeah. This might be a big leap and it probably is It's like a big leap but you know and be concerned about commercialization I think. K: We can see other industries with the power game you guys rising to some like equal sort of power status. Yeah. And I think that is one concern that people have and rightly so, is that it gets tricky. E: The more money is involved and the more personal interests play a role. [00:24:49] Well folks that's all for a bioethics episode. This episode was a sneak peek into some of the questions we will be exploring as a team. So keep up with our progress in the upcoming months as we talk to people with various perspectives on the issue and don't forget to check us out on Facebook Instagram Twitter and iGEMToronto.ca. Stay tuned for our next episode as we explore the roles of engineering.