DIY Human Crispr

Josiah Zayner



People are starting to roll in. If you didn't get this guide, or you don't want this guide, the answer is to look it up on your smartphone. I see you right there-- you're not fooling me, hah. Sorry, I'm just teasing of course.

You can find the guide online: .. otherwise you can just follow along.

This workshop is going to be a little different from the rest of the conference. I am pretty boring myself, so I have to spice it up a little bit by seducing you with some free human CRISPR DNA and some scotch. But I want to make this kind of like a conversation. So like, if you have a question or a problem, please let me know if you think I'm stupid just yell a little bit. I'm not perfect, at all.

Unfortunately, I'm not going to tell you all the othe rtalks you probably heard that I'm going to save the world and/or I'm innovating beyond anything you've seen before. I'm not. I don't know if that's disappointing, or exciting.

My name is Josiah Zayner. I run a company called The Odin. We are a maybe the only consumer synthetic biology genetic engineering company. What we try to do is, we try to get genetic engineering into the hands of consumers to let them do basically whatever they want with it. It scares some people. It does. To me, there are a lot more scary things. Clowns, number one. ((laughter))

No, but seriously. To me, the scary things really are-- people not having access to human gene therapy technology. It's crazy to have a technology that can be so innovative and there's so few companies talking about having a consumer actually using it. Every talk you heard today at Synthetic Biology 5.0, ... oh it's Anthony, come on in. People will let you in, if not, we'll figure something out.

Today, many of the talks you probably heard besides Taxa-- people aren't putting this technology into the hands of people. Think about all the great technologies in the world. None of them have flourished without consumers having access to them. Consumers are one of the major driving forces in innovation and in research, development and everything. It's crazy to see how synthetic biology and genetic engineering has missed this. They want to create stuff for other companies. I am sure you heard talks about stuff you'll see in 2-5 years. It's a lie really... they told me 2 years, 2 years ago.

But, my whole goal and purpose is to make this technology accessible now. Basically, no matter what it takes. Feel free to come in, I might be able to give you my chair actually, I could stand to part with some of these chairs ((literally lifts chair)). Am I going to have to stand up now? That's a little disappointing.

Anyway... you probably have all heard of CRISPR. Probably. I assume so. And, CRISPR-- it's so funny, because when I started learning about CRISPR, it was one of those things you hear about on the internet all these journalists wrwiting about "oh man we're going to have these quantum invisibility cloaks in 20 years" and "we're going to have these quantum computers coming out in 10 years, it will change the world" and I was always like, well what the fuck? 10 years, 20 years? I'm never going to use this stuff. You know 10-20 years is a lie. I want these technologies that people always talk about; I want to be able to use it, to learn how to use it. I want to give other people that information so that they can use it.

If this technology, this information, is just in the hand of a few people and nobody else is using it, then it can't have the power that it really needs to have. As much as I want to make fun of academia and call it all bullshit, genetic engineering is one of the most powerful technologies that we know about. It blows my mind when I think about it because this is the first time in human history where we are no longer slaves to our genomes. The genes that you were born with, you don't have to keep them throughout your entire life.

The genes that your children have? They don't have to have just the genes from you. Whether you agree or disagree, or whatever you want to say, the fact that the possibility exists, is right there. So that's kind of what I want to talk about today.

This is going to be I guess I'm just going to wing it because my laptop-- my USB-C connector couldn't connect to theirs. So I'm going to talk about how this all works and if you didn't see up here, I provided for everybody a sample of DNA-- just a plasmid. This plasmid contains the cas9 protein, the guide RNA that literally if you basically took this DNA and put it on your skin, with low efficiency it would change the genetic material of your cells. If you added a little bit of chemical like PEI, it would change a lot more cells if you injected that. Probably less than 5% of the cells it came into contact with. I want you to take these samples freely. Stick it into some bacteria, grow it up, replicate it, inject yourself, whatever.

What this plasmid does is that it modifies the myostatin gene. I don't know if you've seen those jacked dogs that they have in the media with CRISPR. There's a knock-out of the myostatin gene and it makes those dogs really ripped. There have been studies that show that myostatin knockouts cause you to have more muscles and more strength. It's not just hollywood. You actually get stronger. It's pretty cool. Feel free to take those samples on your way out, or if you're desperate you could take the package right now I guess.

The main thing I want to talk about is not just how simple genetic engineering is, or how simple CRISPR is.... because I have a PhD, and the amount of effort I've put into figuring this out, and into writing this guide, it's taken some effort. But the crazy thing is that all this money dumped into CRISPR over the past feww years.... that's not the cool thing. The cool thing is that there's this infrastructure that has built up. Infrastructure is what makes things. As a company, as a CEO, as someone who works in business-- infrastructure is what makes things. My cell phone 10 years ago, to write an app or use an app, that was an alarm clock or something. I had to download an alarm clock, because the one on my cell phone was supe rannoying and creeps me out or something, so I had to get one that doesn't scare me or traumatize me like those alarm clocks in movies. I didn't have to write new software, I just went to an app store and got it on my phone. The infrastructure for that has been built so that you can download apps. You don't have to know how to program apps, to downloa apps. I think there should be an app store for genetic engineering. Why can't people use this technology, without knowing completely how every atom works? Why not build up the infrastructure where you can genetically edit something just based on the idea of what you want? You want to make your muscles big. Alright. Maybe that scares some people, I don't know. To me, that sounds awesome. It completely changes the way we think about our genome, our genetics, who we are as individuals, who we are as a species. If our genes can change, then almost at will, at a species, are we still Homo sapiens? If I modify my genetics, am I the same as you, if it doesn't go through the normal rounds of sexual transmission?

So... I don't exactly know how much time we have. We have about 15 minutes. But there's two points I want to get across in this guide. The first point is that, well, maybe three points. The first is that, contrary to popular belief, CRISPR doesn't actually edit the genome. Maybe you didn't know that. Maybe you didn't think about it too much. Actually, what this CRISPR-cas9 system does is that it damages your genome. It's crazy to think about. You want a dCas9 cytidine deaminase, really. It uses the same thing used in TALENs and ZFNs. It cuts your genome, and that's it. It cuts your DNA. It doesn't modify any bases, it doesn't change anything. Right? But then what happens is that most cells, they have machiner that repairs these cuts. When it repairs those cuts, that's when you can trick the cell into modifying the genome in certain ways. So basically the CRISPR-cas9 system is just this simplest way to destroy your genome that we know of so far.

The second point I want to bring up-- and I really like these numbers and lists, I don't know why-- the only thing that you really need to know about CRISPR is about this guide RNA. This boggled my mind for a while. I don't know if you have heard of gRNA. Maybe you have heard of sgRNA or tracer RNAs, crRNAs, or all these things. You're just as confused as anybody ever was because this whole CRISPR thing is so many acronyms. You can take a protospacer, or spacer, and then there's a PAM, and then you take this and you put it in your gRNA, or into your crRNA, and the crRNA has to bind this tracer RNA if it's there... and you're just like, what the fuck? Can we simplify this? What do we have to do? If I want to modify myself with CRISPR, what do I need to know? What's the one thing you need to know? There's only 20 bases that you need to figur eout. These 20 bases are in the guide RNA or crRNA that help the cas9 enzyme find the place in your genome that it wants to cut. Those 20 bases are basically the only thing that you need to know if you want to genetically modify yourself with CRISPR.

What are those 20 bases, and what do you want them to be? That's the big question. What do you want to do? If you had the chance to do gene therapy, what would you do? What would you genetically modify about yourself?

The really cool thing is that, you don't need to search far to figure out what these 20 bases are. Look at step 3 in the guide. I like steps and lists. They are awesome. There are actually websites out there that have this search infrastructure already built. You can type in the name of a gene, or the name you think a gene should be named. These sites will predict the best guide RNAs or the best 20 base pairs to use, so that cas9 enzyme can cut in your genome at this exact place. Literally, you don't have to do anything. Right? You have to go in, type in the name of the gene, you press enter, and you could modify yourself with CRISPR, alright? That's what this DNA basically is. This DNA, if you think about it, in the bag here, it took me about 5 minutes to make. It happened so fast, I had to go back and verify the information a bunch of times. I didn't think that I could create DNA that could modify my own genetics with CRISPR, in 5 minutes. But that's what happened. If that doesn't blow your mind, then I don't really know what would.

So what's holding us back? What's stopping us from doing this? I don't know. To me, I don't really know what's stopping us. I think about it a lot. I have this really, bad tooth. What would happen if I could change that? When you think about it, people are born with things that they have no decision over. And then everyone else says, ah you know what, fuck you, I'm athletic and 6 feet tall and good looking... even just the genetic lottery, you lost, that's why you're ugly and short and whatever. Right? But it's the truth. We just tell people that they lost the genetic lottery and they have to suffer through it. How does that make any sense? How does it make sense that we use the most terrible genetic engineering system of all time, fucking sex right, you don't know what's going on in your offspring when you have sex. That's why we do genetic tests and we pay thousands of dollars to have genetic tests when you have children. You still don't know everything. Veritas and other companies are opening up full genome sequencing for the fetus, but you don't know what's going on otherwise. That type of genetic engineering is okay, but for some reason being thoughtful about it is not okay? That's messed up.

So... I guess in conclusion, literally, if you wanted to, and I'm not recommending this, this DNA right here in this bag, you put it on your skin and basically it would transfect some of your cells and the CRISPR system would actually work, modify some of those myostatin genes in your genome, at very low efficiency. Not going to modify many cells. But that's all it takes.

We have 5 minutes left, maybe. Maybe we can stretch it out if you guys want some scotch. What's stopping us? I don't know. To me, it's like, what's stopping us from all putting this into our shot glasses and making ourselves jacked right now? Yeah.

Yeah, there's off-target activity. Yes. But people are afraid of-- there's off-target activity of... look, people are complaining about this but if you breathe in the atmosphere, it's modifying your genome. If you smoke a cigarette, you're modifying your genome. You could even grow your own extra organ, a tumor, right? That's from cigarettes. I think it's more about, what are you comfortable with? The sun and UV light is modifying your genome when you're outside. Nobody complains about those off-target effects. So what are you comfortable with? I don't know.

Q: What's holding you back?

A: Not much. Are you suggesting I haven't tried it?

Q: ...

A: Alright, let's do it. What we have here is some DNA mixed with PIE which is a poly cationic polymer, which surrounds DNA and helps it enter cells. This is a syringe. ((loading up new syringe)) This will modify my muscle genes to give me bigger muscles. ((checking syringe)) Doesn't actually hurt that much. Hurts a lot more going in. Alright, there we go. ((applause))

I don't know why people don't try it. I'll let you know how it works. Yeah, the number of cells that it will modify will be quite small. You'll probably have to do a bunch of injections over a period of time to see any effect. In the literature, with gene experiments in mice, it's injections per week for months. But considering the drugs we take over time, that's not something that's completely crazy in terms of timeline. Doesn't even have to be CRISPR-- to have an injection that is DNA.. You drink alcohol all the time, I don't know, just replace it with an injection I guess.

((28min 52sec))

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