How to Get Into Ketosis Fast
The low-carb, high-fat keto diet has been shown to improve body composition and increase endurance performance. But getting into ketosis is difficu...
Updated August 30, 2018
It's just so much more complex than I ever imagined, so much more complex. It's fun. It's fun manipulating biology.
The idea of manipulating this fundamental building block of life has teased humanity, but what happens when we actually have that power?
Dr. Josiah Zayner, who holds a PhD in Molecular Biophysics and previously worked with NASA on engineering bacteria to terraform Mars, is drawn to exploring applications of genetic engineering in humans.
Josiah has performed multiple self-experiments, one being an attempt to genetically engineer the color of his skin. He's the first person ever to attempt altering his DNA by injecting himself with CRISPR-Cas9.
People who do it all the time and understand the chance of dying and stuff like that, to them it's not such a big deal because their level of knowledge on the subject is in depth. That's the way I try to approach things. The reason I do these experiments, I think mainly stems from just innate curiosity. I don't know where it necessarily comes from, but I'm just curious about everything.
Geoff: Hey friends, welcome to this week's episode of the H.V.M.N. podcast. It's been a while since we've had a biohacker on the show. I invited my friend Dr. Josiah Zayner to join us today. Josiah holds a PhD in molecular biophysics and was previously employed with NASA, the engineer of bacteria at the terraform Mars. He has a very impressive list of biohacking experiments. He's sterilizing them, replaces entire microbiome through a fecal transplant, attempted to genetically engineer the color of the skin, and was known as the first person to do a direct gene editing experiment with CRISPR-Cas9. He's also a recent father. Congratulations to him and his partner.
In today's episode, we discuss the nuances of genetic engineering, increasing one's creativity and divergent thinking by reading atypical books and explore the biohacking space can mature and evolve alongside regulatory agencies like the FDA. This is a fun one. I'm excited for you guys to tune in. As always, please send my producer Zhill and I feedback at firstname.lastname@example.org. iTune reviews are always appreciated. Remember, you'll score a free Sprint Mini in the process. Okay, let's get started. Josiah, thanks for coming out in the program.
Josiah: Yeah, no problem.
Geoff: It's been a while since we last hang out. I know this is a long time coming because we've been on a couple different panels and conference together. We actually had a false start with our first try of the podcast.
Josiah: Yeah, I think it was going to be almost ... We tried two times. This is our third, but hey, third time's a charm.
Geoff: Third time's a charm. This is going to be awesome. Where should we start?
Josiah: One thing I want to start with, so I recently started ... It's only been a month, but I recently started going out on a keto-type diet, trying to lose some weight just ...
Geoff: And your experience so far?
Josiah: It's interesting because the first two weeks or something like that, you feel like you're dying.
Geoff: Keto flu, keto adaptation period.
Josiah: Then after that, your stomach shrinks and you start losing weight. It's crazy. Now, the portion sizes I eat are smaller just because I get full faster. Yeah, it seems to be working out great.
Geoff: What are the metrics? What are you measuring? Measuring mainly weight?
Josiah: Yeah, measuring ...
Geoff: Are you measuring bloods?
Josiah: No, no, no, nothing on blood or anything like that right now. No, mainly just weight and just my body, how I feel, general stuff, energy, sleep. The other thing is sleep. I couldn't tell if it was a keto or not, because I have a hard time sleeping anyway. Some people say it's hard to sleep sometimes when you're ...
Josiah: ... eating just a high protein, no carb diet.
Geoff: Yeah, what are you eating when you're eating keto?
Josiah: Just high protein, no carb, right?
Geoff: I think that subtleties there would be that keto is described as mainly fat actually.
Josiah: Oh, fat ...
Geoff: 89% of fat.
Josiah: No, no, no, I don't do ...
Geoff: As low carb as possible and moderate protein.
Josiah: No, I don't do so much fat ... I mean, I was.
Geoff: It's almost a low carb like Atkins style diet.
Josiah: Atkins, yeah.
Geoff: Atkins will be basically aisled a bit in fat protein. It's mainly a carb restricted diet.
Josiah: I don't know how much fat I do.
Geoff: What are you eating? Are you eating fatty steaks, pork?
Geoff: Are you trying to add a lot of ...
Josiah: Chicken, steaks, bacon and eggs, stuff like that. I probably had bacon and eggs everyday for the past month for breakfast, sometimes for lunch also.
Geoff: Okay. Bacon is fairly fatty. I would probably guess that you're closer to maybe a 50-50 fat protein ...
Josiah: Yeah, probably something like that.
Geoff: ... with very restricted carb. You're probably getting a ketosis. It wouldn't be necessarily a strict keto diet, but you're definitely carb restricting, which I think is half the benefit of eating keto.
Josiah: Yeah, I think it's a huge benefit. I don't know. The other thing, I remember ... Maybe I told you this a while ago. I used to wake up hungry in the middle of the night. I'll wake up in the middle of the night and I would just be so hungry. I would have to eat something. I couldn't sleep. I was so hungry and then that went away, which is really weird. I don't know why.
Geoff: Well, one of the ...
Josiah: Even my microbiome or something is starting to change or ...
Geoff: That's actually a common result, is that fats are more satiating. Fats and proteins are more satiating than carbs. Actually, it affects ghrelin more potently than carbohydrate.
Josiah: Okay, so it's just keeping me full for a long ...
Geoff: Yeah, it's keeping you full longer, that's probably what it seemed.
Josiah: The thing is, sometimes I don't feel full. I guess my body is full, just that ...
Geoff: Well, I think if you just realize from ... As you know, I do a lot of fasting. You just realize your body is never truly hungry. You're just mentally poor.
Josiah: Yeah, totally.
Geoff: What I realize when I was doing a seven-day fast was that your mind literally misses a dopamine hit of yummy stuff in your belly. You almost realize the difference between hungry ...
Josiah: Well, yeah. Sometimes I do get hungry. Sometimes I do get ...
Geoff: ... and then you're looking for ...
Josiah: Yeah, I know.
Geoff: Yeah, I think there's probably something to that if you're very carb heavy. As you know, you spike insulin, you have a blood sugar spike and you crash, and then you want to eat, makes you fill up like lipids.
Josiah: Yeah, I eat lots of pastas, lots of rice. It was like ...
Geoff: Probably just cycling.
Josiah: Pretty heavy carbs.
Geoff: Glucose crashing and spiking.
Josiah: Yeah, it was pretty heavy carbs. I think it probably affected me a lot more.
Geoff: You actually do look more lean.
Josiah: I don't know, only four or five pounds or something but still ...
Geoff: You just feel better.
Josiah: Yeah. Well, the thing is my weight ... It's like you immediately start to feel like ... I don't know, the weight is rearranging or something. My pant size starts to get looser and looser.
Geoff: Cool. Yeah, keep us updated on the experiment here.
Josiah: Yeah, I will. I think I'm going to keep it going for a while because it's like ... Pssshhhhh! You can have cheat days every once in a while. I have some pasta or something like that. It's not like I really miss anything. Like I said, the first two weeks are just hard. Because you're just like, "Oh man, I miss carbs so bad. I want some carbs." After that, your body just adapts to it. It's really cool.
Geoff: Yeah. If you can stick to it for a while, it will be cool to hear because I think just for me personally, it's pretty hard to maintain that infinitum. I mean, it's just like ...
Josiah: No. Well, no, no.
Geoff: ... it's hard to deal when you're eating out like it's ...
Josiah: Totally, totally. Well, no, no, no. I have Fridays cheat day where I can have carbs or something like that, but in general try to keep every other day really low.
Josiah: It's like I get that little break. Even if I'm like, "Oh my gosh! I can't ... "
Geoff: To keeping you relatively sane.
Josiah: Yeah, yeah, yeah, keep you sane. I think that's a good ... Because I think a lot of times with these diets and stuff when you're trying to lose weight, you just go really hard and it's hard on your body. Then, you're just like, "Oh man, I don't want to keep doing that. I can't keep doing that," instead of just trying to find a way to adapt your lifestyle to something.
Geoff: Yeah. I think that's a realistic look. I think that's something that we discussed on our community like fasting ...
Josiah: What about these drinks that you got? I was thinking about keto drinks. I don't know anything about the weight loss and stuff like that, but does that help with dieting at all?
Geoff: We showed in November of '17, so last year, that this drink, the ketone necessary actually suppresses ghrelin.
Josiah: Like makes you have no appetite?
Geoff: It reduces appetite, so it actually reduces subjective appetite. We didn't actually study if that actually transited to weight loss. That would be a natural extension of the study.
Josiah: Yeah, yeah, yeah, totally.
Geoff: The root mechanism is that we believe that beta hydroxybutyrate, the main ketone body, essentially suppresses ghrelin.
Josiah: Yeah, but I think ...
Geoff: The kind of reverse explains what ketogenic diets are more satiating.
Josiah: Here's the thing, and you think about it like even if you're a professional dieter, you or something ...
Geoff: I would not say I'm a professional dieter.
Josiah: I know, I know. I'm teasing. I'm teasing.
Geoff: Maybe I should describe you as a professional poopietor, and we can talk about that experience in a little bit.
Josiah: What I mean is like we think a lot about food all the time, everybody, even somebody who's got a hold on their diet and food like you probably do. I imagine that's like if there's anybody who has control of their diet and the things they put in their body is somebody like you.
Josiah: You still think about food all the time. I don't even know how many minutes a day, but it's probably a good portion, planning meals, eating meals. It's like how do we remove that from our consciousness or public consciousness? I think about that with my work in genetic engineering like, what happens if we could genetically modify somebody so that they never had to try to lose weight or think about what they eat or anything like that? Like their metabolism, let's say, was perfect. With this genetic engineering, would that change society in ways more than just like people are more attractive and healthy. Our mindset, we wouldn't have to think about food so much.
Geoff: That's an interesting scenario. 100% I think if you just free up 20% of proactivity time, that's pretty massive in terms of proactivity or GDP. You just focus more brain power and neurons towards intellectual work than your animal instincts. I think appetite make sense from evolutionary perspective, just our core reptilian brains is like hunting and stuff.
Josiah: What happens if you get rid of your appetite, would you?
Geoff: No, I wouldn't.
Geoff: That might be just due to the fact that I feel like I have good discipline around it and good understanding around it, and maybe I'm scared of the side effects of just removing like a core instinct. Would you remove sexual desire, for example? That reminds me of like ... A lot of people think about sex all the time and for just as important reason as eating about food all the time. It's like how to pass on and survive and your genetic material. The very core of all ...
Josiah: Well, you could still enjoy it but you never get really hungry.
Geoff: Yeah. Or if get never like have to think about ... If you're just lonely ...
Josiah: It could just be like, "Oh, I got some time now. I'll eat some food or something."
Geoff: Right, which I think just altering such a core part of the human experiences ...
Josiah: Would make us not human anymore, are you ...
Geoff: No. I do not worry about that. I think it's just like ...
Josiah: Wait, are you afraid you're not a human?
Geoff: No. I think there's a lot of side effects to think about before you just remove a core drive. To me, it's like as impactful as removing like sexual drive.
Geoff: Would you remove sexual drive? I think it's a very similar argument. Like not having any appetite is similar to like, okay. If you're just in a shape didn't want to have sex and didn't have desire for that, that would give you proactivity, that would save you lot of energy.
Josiah: I think that would be more harmful to my sexual partners than me because they'll be like, "Damn, you never want to have sex or anything like that?" You're like, "Yeah, well, I can just decide." As a person if I was single and didn't have anything, I don't know. Sometimes sexual cravings do get in the way of just wanting to get stuff done, be a normal human being.
Geoff: Yeah, exactly. I would have to think about if I would want to remove my own sexual drive ...
Josiah: Are you ...
Geoff: ... in the same way like I would have to think about if I want to remove appetite.
Josiah: What happens if you could evolve beyond what you are now? Would you be into that? Going to the stuff ...
Geoff: Like a transhumanism, like if ...
Josiah: Not transhumanism. That stuff is a little weird. I don't know. I'm just saying genetically. Are you against, say, all genetic modifications of yourself? Say, what happens if you could get genetically modified safely and everything? There's no side effects or anything like that and it would make you say ... I don't know, perform better as an athlete.
Geoff: Yeah, that is a lot more interesting to me. Obviously, the caveats of like, I'm not going to get cancer, I'm not going to like ... It's fucking up.
Josiah: I just want to know, you're not against ...
Geoff: No, no, there's no ethical, moral, religious, the qualms around manipulating biological material. To me, I think there's interesting side effects to think about in terms of appetite to me. It's again like, do I want to remove my sexual drive?
Josiah: I got a question here, just interesting.
Geoff: Maybe not, maybe.
Josiah: Maybe you have ...
Geoff: Our sexual partners would be like, "Ah. Are you trying to tell us you're asexual here?"
Josiah: That would be the biggest problem. Your girlfriend just being like, "Ugh." I have a question, and maybe too deep. I think about this a lot, people who do stuff that you do. Why do you do what you do? Maybe people don't ask you that question enough or maybe they do, but it is something I'm interested. Why do you what you do? Because it seems like ... Even talking to you, I think you've mentioned some stuff for that. It's hard to like you do all these different experiments.
Geoff: Sure, yeah.
Josiah: You push your body to limit and peak all the time. Why do you do all this stuff? I'm interested.
Geoff: Yeah, okay. I'm curious to hear your answer around a lot of the biohacking and genetic engineering that you do with your stuff as well. I can start. I think self-reflection and self-understanding is probably one of the most underrated things. I think a lot of people are not very self-aware. I don't think people think about improving themselves. I think if one is on the path of analyzing themselves, then one is just open to the fact that there's areas that you want to improve or areas that you want to edit of yourself. I think my drive towards improving my habits, my lifestyle is that ...
Josiah: Does it focus mainly ...
Geoff: It's like maximizing my enjoyment and my time and my capacity on this planet.
Josiah: Does it focus mostly on the physical side? Or do you also do a lot of stuff on mental or just like, "Oh man." Sometimes I work a lot on mental stuff way more than physical. They'll be like, "Oh man, sometimes I get angry too much about something like this. I'm going to try to fix that so I don't get ... "
Geoff: Yeah, I think mental is probably less spoken about because it's less obvious. I would say mental is more important to me than physical.
Geoff: Yeah, I think I care about physical in the sense that I care about living longer and being healthier. We are physical beings. Our hardware is important for our software or cognition to actually work. I'm not trying to be a super athlete. I know I'm never going to be a super athlete, but I care about improving the machinery of my biology so I can have more stamina, more endurance, better cardiovascular health. That's my interest in performance. I know other people in our community or other colleagues are really targeting very fast marathon times went breakable records. I think there definitely people that are trying to just be the best of a physical specimen. I think for me, it's mainly physical and the longevity side. What's important I think especially for both our work is being sharp cognitively.
Josiah: Yeah, I guess a lot of your products do have ... Or you started as cognitive.
Geoff: That's where it started, is you cared about the cognition first but that's the only thing that's very interesting from us as humans. I think one thing that I thought about a lot in terms of just cognitive health that is somewhat applicable for everyone is that the inputs into our brain are so important in the sense that I think most of us are seeing the same information sources. All of us are on Twitter, Facebook. We get the same ... I don't know, CNN or Fox News alerts. To me, that's making the same neuron pathways firing for everyone. At the end of way that I want to counter that was I wanted to read information sources or books that were very different from what everyone else's reading so I could be more creative. That's the core thesis.
Josiah: Yeah, for sure.
Geoff: I want to read like off the path books, read other things, and try to just populate my brain with other ideas.
Josiah: It's like the one thing that I figured ... Well, maybe I haven't figured out but the one thing I've figured out in running my company and doing science and all these things is that when everybody thinks the same way and there isn't a good reason, think the opposite. When everybody's doing something a certain way and there's not a good reason, see what happens when you do the opposite. It's led to so many interesting outcomes because people tend to just do stuff because of dogma or because that's the way it's always been or that's the easiest way to do this thing. That usually doesn't lead to interesting things.
When you break off from that, like you said, start to experience different things than people normally experienced. That's why online, I try to brought in my online community. I purposely try to keep myself out of an echo chamber and will follow or seek out people who are just completely different from me, totally completely different. These people are smart. That's a thing that people would say. Like somebody who believes vaccines cause autism, they can site you scientific papers that are published that back up the things that they're saying. Just like people who say vaccines don't cause autism.
It's really interesting especially from the idea that people think the other side is stupid or whatever, because they're not. These different ideas, if you can just understand them and comprehend them, I think not only does it lead to way more love and understanding among people. It also leads to completely interesting creative ideas because you can hold two contradictory ideas in your brain at the same time and see what comes out of that. Most people can't. Most people can't do that.
Geoff: I think that's hitting some core truth. I think people can extract logical steps. It's like their actions might be different. Okay, fine. What assumptions that they're making that are different that leads them to that very opposite conclusion? I'm curious to spin the mic back to you. What makes you do your experimentation? I know that you think diet is interesting or hardcore. Some of your exploits around your microbiome or genetic engineering. That I would say is even more hardcore than anything that I'm doing, which is like ...
Josiah: See? No, that stuff is the ...
Geoff: That's just something that you just ... It's only to only put in.
Josiah: That stuff is 90% mental, and then 10% experiment. Whereas yours is probably ... I don't know, 50% experiment, or 60% experiment, and 40% devising the experiment.
Josiah: It takes a lot more out of you to do your stuff physically because you have to do it. Whereas me, it's like all the work is beforehand and then the end is just injecting yourself. Obviously, some stuff is a bit hard and takes more. I think if you understand it on a certain level, it's like people who skydive. I would never skydive. I just don't even think it's a good idea at all, I'm not into it. I don't see ...
Geoff: I haven't tried it, but I'd be open to it. I hear you.
Josiah: I see no positive outcome for myself.
Geoff: You get terrified.
Geoff: You might have a 0.001% chance of dying.
Josiah: Yeah. People who do it all the time and understand the chance of dying and stuff like that, to them it's not such a big deal because their level of knowledge on the subject is in depth. That's the way I try to approach things. The reason I do these experiments, I think mainly stems from just innate curiosity. I don't know where it necessarily comes from, but I'm just curious about everything, curious about people, curious about ... Sometimes I'll go on Facebook, just some random person I don't even know, not like a famous CEO or anybody like that. Just a person who was at Walmart and a town you never heard of in New Mexico, and just redo the profile because there is such an interesting person because there's something so different and unique about them.
Finding that unique thing is so hard in this world because there's so much ... Like we just talked about, so much sameness everywhere. We all have the same point of view. We all read the same stuff. We all see the same movies. I think that leads to a lot of just same thinking. The curiosity drives me to explore new things and think differently and find new things.
Geoff: You could explore infinite things but obviously you've explored a lot of how you can genetically engineer ...
Josiah: Yeah, so exploring.
Geoff: ... democratize these technologies, so like ...
Josiah: Yeah. I've explored a lot with biology and genetic engineering.
Geoff: How did that curiosity focused?
Josiah: It's interesting because I started out in computers. When I was 18 or 19, I got a job at motor. You start out in computers also, didn't you?
Geoff: Yeah. I have a computer science degree from Stanford.
Josiah: Yeah, yeah. I work at Motorola when I was 18, doing some computer networking stuff.
Geoff: Like high school intern? I mean, that's pretty young.
Josiah: No. I'm old. This is back during right before the dotcom bubble burst where they're just like, "Oh man, everybody gets jobs, everybody gets money." Dotcom bubble burst is crazy. I was 18 and they just hired me on. It is a full time network engineer.
Geoff: Holy shit.
Josiah: Yeah, it was crazy. Then, dotcom bubble burst and they laid off 100,000 people.
Geoff: Oh shit.
Josiah: Of course, I had the least seniority. I was the youngest. They're just like, "You're going." It was that ability to control thing or build things with computers like programming or building networks or something like that. Build things on this fundamental level that always fascinated me. That's how I got into genetic engineering and biology is manipulating things on some fundamental level. I wanted to be able to do that. Now, I know how limited all this stuff is even though I still can with genetic engineering manipulate stuff. It's just so much more complex than I ever imagined, so much more complex. It's fun. It's fun manipulating biology. Yeah, I think it's really a curiosity thing.
I think if I couldn't do biology or biological engineering or genetic engineering or anything like that, I think I would find something else. One thing I'm really fascinated with right now is I know this sounds stupid and silly, and probably off topic. Documentaries and filmmaking and stuff like that, I don't know why I'm just really gotten into it lately.
Geoff: I don't think it's that off base in the sense that perhaps you're sensing something that I think we're sensing at H.V.M.N. is that a lot of our work is just storytelling and educating people.
Josiah: It is the truth, storytelling.
Geoff: I think to them be that's like where that interest comes from where ... I think your work with democratizing, getting genetic engineering to people, that side of biohacking is very much as educating people. I've seen ...
Geoff: I mean, we've been to a lot of conference together. I've seen you just talk about the mission of the ODIN, getting these tools out there, educating people that it's not something that you need a PhD and academic center.
Geoff: Although you have a PhD and you have an academic background, but you can ... Just like how computer programming or computer hacking was democratized. You can't just code something when you're 12.
Josiah: Oh man.
Geoff: I love to see a future where you can do biological engineering when you're 12 too.
Josiah: Yeah. I love the whole storytelling thing. Again, into that like, oh man, it's just was so fascinating. It's been so fascinating to me for just a while now, just how to tell good stories to people. Because if you look at social media and everybody uses social media, everybody's trying to tell a story, everybody, even if you're not trying to tell a story like the post you make are trying to tell a story about who you are or whatever you're trying to promote or whatever. Maybe you're a funny person. You have these funny Facebook posts all the time or a meme person. You share memes. Or maybe you're a science person. You share lots of science articles or whatever. It's telling this story about you. We don't think too much about that that we're creating a story. I've just thought so much about that how to tell the good story, how to be that person, that character in the story, and make that ... It's so fascinating.
Geoff: I would say that you are in a sense of ... Storytelling are playing that role. I think just that mantra people that aren't aware of.
Josiah: I don't know. They just love me in the media. I think it's because I am that cliché like, "Oh man, he's got crazy hair and he looks crazy, and all this stuff." It's funny because in New York Times I don't know if you heard. Everybody else that they mentioned in the article, they ...
Geoff: They use doctor, right? It was interesting to ...
Josiah: Yeah, PhD. This has been a constant problem. I just had somebody who I was in a documentary for and they're like, "What do you want your bioline to be," or something like that, or "Here's the bioline we're going to use for you." It's just like Josiah Zayner biohacker or something. I was like, "I have a PhD, it's cool to put that." People like to portray me as this real guy who's just doing stuff and all these things. That's cool, whatever, whatever sells the paper or something like that. Sometimes it is a little bit annoying because it's like, "Hey look, I'm not just this rogue crazy guy. I'm also a human being."
Geoff: That's something I wanted to talk about. Why do you ...
Josiah: Do you feel like you're portrayed in the media as somebody like ...
Geoff: I think it evolves a little. I think it has evolved.
Josiah: San Francisco, Silicon Valley, startup guy, stuff like ...
Geoff: Yeah, doing biohacker shit, doing like starving themselves when they're fasting, doing weird ...
Josiah: Exactly, exactly.
Geoff: ... pseudo legitimate things that you consume. In the beginning, I think we leaned into that image to build up momentum.
Geoff: I think that media is using us a little bit to play their character they want to tell.
Geoff: It's like ...
Josiah: We're playing each other.
Geoff: Right? I think it's like, okay, they get a Stanford educated computer science dude talking about applying engineering towards biology and wanting to live forever and live longer and make them feel smarter. Great story, and that's going to sell some paper, to get some clicks. We're going to use that story. I think probably for you, I think, yeah, like the crazy dyed hair where you ...
Josiah: Crazy guy, yeah.
Geoff: You don't seem like an academic. You don't come off as a PhD bionerd.
Josiah: No, so many times it's so funny. There's a computer science conference in Utah and they invited me to give a talk and everything like that. I remember showing up at the conference or arrived at the hotel and there's this other person who's obviously there for the conference. They just have that look. I'm just like, "Do you know where we register or something like that?" He's like, "I think you have me mistaken for somebody else." He's like, "I'm probably not going to what you're going to," or something like that. I'm like, "Are you going to this computer conferencing." He's like, "Oh yeah, I am." I'm like, "Yeah, me too. I'm going to give the talk or something like that." He's like, "Oh." I was like, "Yeah, I have PhD and stuff. They invited me. They paid for every ... " It's just so funny, because people don't see me like that, which is sad. It's also just the way the world works to a certain extent.
Geoff: I think you enjoy it. I think you enjoy it.
Josiah: To a certain extent, I do. Yeah. To a certain extent, I do. It's that whole trying to ... Like we talk about in the beginning, be different or doing different things.
Geoff: Do you think you could do your mission better if you played more by the book?
Josiah: Probably. I think a lot. Here's this ...
Geoff: Why don't do that? I'm actually curious. I would say that for ...
Josiah: I have a little ...
Geoff: I myself, I think we are becoming more serious as we have more and more momentum and more and more serious [crosstalk 00:31:02].
Josiah: I have cleaned up a bit. I try not to curse as much anymore and all these other things. I remember story. This was two years ago when I was trying to get the company off the ground. I got an interview at Y Combinator.
Geoff: Okay. That's the most prestigious startup incubator.
Josiah: Yeah, probably anywhere. I show up and I show up just absolutely looking like I'm homeless. At that time, I had more piercings and my hair was probably blue or something. I walked in and I just like with some engineer ... At the time, we're working on engineering brewing yeast to be able make a product for people where they could genetically engineer brewing yeast to do different things. One of them was Glow. I just brought in these plates of brewing yeast and just tossed them out to everybody and sit down. They were just like, "What the fuck just happened?" They're just looking at me like, "Who is this person who just walk ... "
Geoff: Handing out random petri dishes of sketchy stuff, right?
Josiah: They're just like, "Ahhhh." They don't know even where to start with me. I was just sitting there with a big grin in my face like, "Yeah, I got this." Our company, we ... That's where you're first starting to do well and stuff like that, and make money, and things, we're developing new products. It was just like I was so different I think then what they think a good founder is or anything like that, that like I don't even have a chance. It's true, because we connect with people who are like us.
Geoff: Sure, yeah.
Josiah: When there's people who aren't like us, and this is part of where racism stems from. When there's people who aren't like us, we're fearful of them sometimes. It took me a while to realize that sometimes being different pushes people away. I've tried to find a good balance of being able to be who I want to be, but also not to ...
Geoff: Freak people out like, oh, this guy is some mad scientist genius cooking like [inaudible 00:33:19] on this kitchen.
Josiah: Totally, because there's no reason to do that. It's like the way I look and my image and the way act just started to slowly move more towards the norm, because I don't want to lose opportunities. There are a lot of interesting people that I don't want to scare away or that I want to enjoy, people in general that I want to enjoy. It's a ...
Geoff: I think it is like an aha of interesting journey where I think you gain access a lot of people because you're interesting.
Josiah: No, totally, totally.
Geoff: It's like how do you get, but that's both roles.
Geoff: I think that's something I've realized where people know you for being this crazy genetic engineering guy who's been injecting himself with stuff.
Josiah: On the other hand, it's like ... I get both types of people. People who want to hang out with me because I'm interesting, but also people who don't want to hang out with me because ...
Geoff: Because they're like, well, this guy is crazy.
Josiah: Yeah. It's like finding that balance that's really good. It's starting to work now. As I become more towards more people reach out to me, more people want to spend time with me and hang out with me and be around me. I think I have a good balance now.
Geoff: This is my impression given where your product and your technologies going towards. Some of it like a lot of the focus perhaps earlier was like, I guess more in an experimentation on yourself.
Josiah: Yeah, totally.
Geoff: Like total place in microbiome or trying to genetically engineer your own muscle. Now, you're moving towards genetically engineering other things.
Josiah: Yeah, animals and stuff like that. That's going to ...
Geoff: Is that partly progression? Like telling people to, hey, we should all just inject ourselves with CRISPR?
Josiah: Well, here's the thing, Geoff. You know what, I came to the realization. When I was working on genetically modifying myself or doing these experiments with the bacteria, my microbiome, to help with my gut health ...
Geoff: This is when you ate someone else's poop.
Josiah: It's somebody's poop.
Geoff: They got to close that poop eating reference.
Josiah: Hey, just someone to be like weird reference. I realize that this doesn't scale. Every single person can't do genetic engineer, learn how to do it, and inject themselves with something they know what it is and they're doing it properly. Every person can't find somebody who's a healthy donor of poop to help modify their gut microbiome so that they become healthy. That was a huge realization to me. It's that like ...
Geoff: On a business perspective or like a storytelling perspective?
Josiah: No, just from a human perspective. Let's say your product, the bottles or whatever your products, and your packing them by hand. You're doing it all by yourself. You're like, "Oh man, how are we going to get this to a million people?"
Geoff: They can do it.
Josiah: I think this is going to help people how do we get it to many people like you can. Every single person who uses these needs to know how it works with genetic engineering, they need to know how to purify it. They need to know how to make it well. They need to know how to inject it properly. They need to know all this stuff. This is not going to scale. Everybody doesn't have the time to learn all these things. How do we make stuff that scales? Because the FDA wants to shut down or regulate the stuff pretty heavily. How do we develop a system that scales but can also be somewhat safe or something like that, safer than just somebody doing some random drugs, random injections?
That's really what I've been trying to focus on and understand because it's like, I don't want to change the world necessarily or anything like that. I wouldn't mind reaching a large number of people. The only to reach people is to make things accessible, make things easier, make things more safe, make things ...
Geoff: FDA compliant and all that stuff.
Josiah: Exactly. Or if not FDA compliant, just some way that they can't target you. We were trying to figure that out. If we want human genetic engineering to be a thing, cosmetic or just non-health related human genetic engineering, how do we get this stuff into the hands of people? How do we teach people about this stuff?
Geoff: As a layman, help our audience here, what is the current status quo for genetic engineering? Can you, at a high level, describe the steps that you mention like purification in ... Can we just go to the genetic engineering biohacker guide 101?
Josiah: The hardest thing ...
Geoff: What are the steps? What are the things that you need?
Josiah: Like I was saying, it's like if you're trying to devise a whole new supplement or whatever, enhancement, I don't know what you call them because not all know tropics. What do you guys call them though?
Geoff: Some are supplements, some are foods.
Josiah: Yeah, food supplements. We're trying to design something new. That's when you get the scientists or people like, "That's the hardest part." It's like if you want to genetically engineer yourself and understand what you're trying to genetically engineer, the hardest part is figuring out the DNA sequences to put in your body or put in yourselves, and things like that. After that, I don't want to say easy but relatively easy. Nowadays, you can order the DNA online or something like that. You can have somebody do the purification and everything, and then basically just inject it in yourself. The hardest part is the design part. It's like programming.
What you need is an app store for DNA in some way to show that it works, some way to test it. The way to test it, the prototyping system has to be living because you can't really test and see if this DNA is going to make your muscles grow on something that doesn't have muscles. Like bacteria and yeast and all these single-celled organism are out, you need animals, you need animal model. You need one that's easy to work with, not illegal to work with. It isn't regulated or anything like that. We came upon frogs. A lot of people probably don't know or think about is that human DNA or the DNA that you used to genetically modify yourself also works in frogs.
Josiah: Despite their DNA being different, all the elements in a lot of the proteins are similar enough that ...
Geoff: What was the muscle growing, I guess, sequencing you are injecting yourself?
Josiah: I'll get to that in one sec. If you want to do and experiment a prototype, a gene therapy on yourself, from the time you order the DNA until the time you get results from, say, frogs or bunch of frogs, probably two months, maybe three months, but two months. You're talking frogs are so easy to keep, so easy to use, everything like that. Take zero effort. They're so inexpensive. That is great. When I attempted to genetically modify myself, I was trying to ... This gene myostatin, which controls muscle growth. Well, what you can do is, and we recently got the DNA to test this, take this gene that inhibits this myostatin gene.
It's called follistatin and make yourselves or your body produce lots of it through a gene therapy. Well, yeah, too often you could test this on yourself without knowing if it works, which there should be no reason that you have to test stuff on yourself unsafely. I hate to test stuff on animals. Usually with these gene therapies, you're not harming them. Usually when you're given these gene therapies, their muscles might grow but they're not dying. They're not getting cancer. You're giving them anesthetics. They really don't feel anything. All they're doing is getting bigger muscles. It's an amazing opportunity to learn how a gene therapy works, test it and see if it works, provide people platforms.
They want to test other stuff to see if that works and just spread this stuff around. I think it's amazing because think about if anybody could genetically ... or knew how to genetically modify animals. It sounds just crazy and wacky. You essentially are an animal.
Geoff: We are animals.
Josiah: If you could do it with a frog, you can apply the same principles to yourself. Whether that's a correct way to do it or not the correct way to do it, I think it's moving towards a reasonable path.
Geoff: That will be interesting to compare with academia. It sounds like it's the same techniques, right?
Josiah: Exactly so.
Geoff: What you're saying is that you can do the ...
Josiah: Probably the safer.
Geoff: ... same things in an academic context. I guess you skipped like that in the IRB, the Ethics Review Committee, you skip the publication stuff. You have the animal model. You can order the same genetic ... I guess the gene therapy to a same DNA sequences and just do it yourself.
Josiah: It's all the same. Yeah, it's all the same. You should see the research that goes on with animals by academics. I'm not harshing them or anything, but they're pretty brutal. Their protocols and techniques are not developed to make sure the animal doesn't get hurt or be kind to the animal or things like that. You could help develop these things. Also, a lot of the work they do is with mice. The reason that scientists chose mice because they're like, "What animal can we experiment on that nobody will be against?" They're like, "Dogs, that's out. Cats, no. Horses, no." They're like, "People hate rats. Let's do rats and mice. Let's experiment on them. Nobody will be against it." They do. They're not really the greatest organism. They're really hard to keep.
Geoff: Do you think frogs are actually a better model?
Josiah: Well, man, if you want to get into the DNA and immune systems and stuff like that and the fact that they're cold-blooded instead of warm-blooded, there are some differences definitely. If you're talking about scale, here's the thing, if you wanted to do an experiment on 100 mice, it would be epic, pretty epic experiment.
Geoff: I visited labs. One of my friends, Zumi, does a lot of rat experiments. It sounds like you literally have hundreds of rat cages and feeding them.
Josiah: Rats could be big, that big. You got to house hundreds of those.
Geoff: That's pretty big rat, yeah.
Josiah: You think about frogs that are this big, they don't require much upkeep at all. You feed them some crickets or something like that and that's it. They survive just fine, just normal whatever temperatures. You can house hundreds easily. I'm not saying you should and a cage like this big.
Geoff: Yeah. I guess the argument is that like, okay, rat model is going to be closer to humans because of they're mammals.
Josiah: Here's the thing that people don't know. It's like when you are trying to get FDA approval with mice and stuff like that, you can't use normal mice.
Geoff: Yeah. They're all genetically ...
Josiah: They're genetically modified to be humanized, because mice are such a terrible representation of humans. They actually have to put a bunch of human genes and stuff in the mice to make it more like humans, to make them ...
Geoff: Better human models, sure.
Josiah: Yeah. It's like, oh, I get it but if we're just looking at things purely on a genetic level, purely like can I make this muscle grow bigger. The difference between mice and frogs is virtually negligible.
Geoff: A difference ... Okay.
Josiah: You're not going to get any better results from a mouse than you would from a frog. The first product we're going to release is using this IGF-1 gene therapy. I'm sure you heard IGF-1 insulin, growth factor 1.
Josiah: It's a gene that just causes growth. In humans during puberty, it's expressed a lot. It causes growth hormone to be made in the body. It causes you to grow and go through puberty.
Geoff: On the flip side, it's also implicating cancer.
Josiah: Yes, that's a really ... We could go into a whole discussion. I try to figure out because there's a lot of things that are associated with cancer, but do they actually cause cancer?
Josiah: That's a whole mess and stuff like that. This is the first experiment we did with these animals, because we thought it would be really simple. They give cows growth hormones, so they get more meat and stuff like that compared to the cows that don't have growth hormone even though they eat the same amount. We thought, let's just do the same experiment. Let's inject some of these frogs with this gene therapy.
Geoff: That increases IGF-1 production.
Josiah: Yeah. It makes a lot of IGF-1. If it works, the frogs will get bigger than the ones who didn't. It totally worked.
Josiah: We got some frogs that just grew almost two fold. Compared to the other frogs, they're like, whoa! There's this one frog we call sick boy because he just got so big. He got so big.
Geoff: That's really awesome. He just grew fuck ...
Josiah: We grew ...
Geoff: ... huge ass frogs.
Josiah: We did a huge experiment on a bunch of frogs like 20 something frogs just to see what happen.
Josiah: It worked phenomenally.
Geoff: Can you help describe some of the steps like this is what we productize. What are the steps? Help me visualize what you did.
Josiah: It's not too complicated, because you're generally getting everything handed to you. You're getting the DNA mixed with this solution to inject it with. We just got the whole kit. Basically, what you do is you take the frog, anesthetize it. You just put it in this solution. Funny, you can actually anesthetize frogs with 5% alcohol, vodka, or something.
Geoff: Get drunk.
Josiah: They will get drunk and they'll pass out. This is old school. Normally, we use this other molecule called benzocaine, knocks him out. You just take a syringe and you inject it in the muscle or you inject it in the body.
Geoff: This DNA sequence what, blocks inhibitor for IGF-1 or just ...
Josiah: No. This is actually just IGF-1. It's actually human IGF-1.
Geoff: It's like a gene that makes IGF-1?
Josiah: Yeah, it's a gene that just makes more IGF-1, human IGF-1.
Geoff: I guess, what's the vector that bind it into the ...
Josiah: The DNA, when you inject it, there are some chemicals mixed in it. The DNA just goes inside the cell. The cells think it's its own DNA ...
Geoff: And just starts replicating.
Josiah: ... and just starts using it. They make a bunch of this IGF-1 and then the frogs make a bunch of growth hormone and [crosstalk 00:48:05].
Geoff: It's not like you'd only use CRISPR or anything to just splice it in.
Josiah: No, no, no. This is super simple.
Geoff: This is just like IGF-1 DNA material.
Geoff: It gets absorbed into the cell membrane.
Josiah: Putting in a bunch of extra IGF-1 copies in the cells.
Geoff: That works.
Josiah: Yeah, that works. It's basically just an injection. That's it. This is what gene therapies are. Most modern gene therapies are basically just an injection.
Geoff: I didn't notice that conceptually simple. You literally just like jam and extra DNA sequences and the body's protein synthesis machinery just popping them out.
Josiah: Totally, exactly, yeah. It's an interesting form of hacking like trick the cell into thinking this DNA as its own by putting in certain DNA sequences in there. It thinks it's its own. It's like, "Hey, I found this new piece of DNA." Reads it and he's like, "It looks correct, I'm just going to use it." Doesn't ask any questions, it just uses it.
Geoff: Interesting. Help me, this is ... I'm actually interested, how does that differ from the big hoop around CRISPR-Cas9?
Josiah: CRISPR ...
Geoff: Could this embeds it into the sequence or replaced ...
Josiah: There's a lot of hype about editing genome engineering. Normally, as an adult, you probably aren't going to want to edit your genes. There are a few cases in which you'd want to. You don't need permanent modifications. If you inject some DNA into yourself, it causes a spike in growth hormone over a period of time.
Geoff: It's probably what you want.
Josiah: Then, it goes away. That's exactly what you want. Or if you're a doping athlete, call me. No, I'm joking. You can inject the gene into your body, causes your muscles to grow or something causes your body to grow. Then, it just goes away. You can't even detect it. The thing is, is that normal people might already have this. Normal people, athletes, some athletes might have DNA sequences that causes over expression of follistatin, or IGF-1, or VEGF, or EPO, or something like that naturally in their body. They're already at a competitive advantage. It's interesting to think that you could just temporarily adding genes to your body and cells that help you compete.
Geoff: Right. I guess the biggest difference is like editing your existing DNA, which is a permanent change. It's a big question around how do you make all yourselves how this ...
Josiah: Yeah, it's so hard to get it to work. It's just not efficient because it's 1% efficient. If I try to edit myself, it's like 1% or less efficient.
Geoff: I see.
Josiah: If you try to add DNA, it's highly ... You're talking 20%, 30%, sometimes more efficient. The DNA is getting into so many cells.
Geoff: Make sense.
Josiah: It works pretty robustly. In adults, obviously, it's a little bit more difficult than somebody who's growing. In adolescent, [crosstalk 00:50:57].
Geoff: I guess there's also recent news where there's more side effects. Basically, it's CRISPR ...
Josiah: Would be like gene editing, yeah, yeah.
Geoff: It's basically missing targets.
Josiah: As far as we know with just injecting DNA or something like that ...
Geoff: That is the most efficient actual way.
Josiah: The safest ...
Geoff: ... and to the old school way.
Josiah: The safest way ... Yeah, the old school way, the safest, most efficient way to do gene therapy.
Geoff: I guess why is that so much hyped on CRISPR then?
Josiah: As a scientific tool, it's really amazing, right, because I can edit … or like as a tool for plants or something like that, I can edit a plant when it's a seed or embryo. Then, the plants has those traits for forever. Or like for cattle and livestock, I can engineer a cattle to have more meat and then all its offspring also does.
Josiah: Whereas on adults, generally, we have our body plan mostly there, so we don't really want to edit …
Geoff: You can make arguments like something like sickle cell anemia …
Josiah: No, totally.
Geoff: These are genetic disease. Then, there's application there, right?
Josiah: Totally, yes.
Josiah: No, I'm not saying that there's not any application, I'm saying for the majority of cases that people want to genetically modify themselves.
Josiah: That wouldn't be the one of choice, right?
Josiah: It would be more like if you wanted to genetically modify your embryo so that it didn't have a disease that you were susceptible to or something like that, then you'd want to use CRISPR.
Josiah: As an adult, you'd want to use this other gene therapy technique which is just basically injecting DNA. It doesn't have a lot of hype just because it's nothing exciting. It's basically just literally injecting DNA. A lot of clinical trials use this. A lot of science experiments use this so it's totally legit. It's like something people have used and done. With our stuff, we show it can work.
Geoff: Yeah. It's an exciting therapeutics, existing drugs. These are basically injecting DNA sequences.
Josiah: There's none that's approved, so there's only actually one gene therapy that is approved.
Josiah: It actually uses a virus to get the DNA and it's for a congenital form of blindness. There's no gene therapies approved that use this technique but there's only one gene therapy approved in the US in general so I don't think that's like … a lot of people use viruses to get genes into their cells, because viruses help the genes get in much better.
The viruses don't replicate, they have all the stuff taken out to replicate. They just infect cells. Viruses probably infect at a rate much, much higher than just injecting DNA. You're probably talking, I don't know, 50, 60, 75% infection rate, getting the DNA in the cells.
The problem with virus is your body develops immunity to them.
Geoff: Okay. Antibodies that kill them.
Josiah: If you get a viral gene therapy, the chances that you can get another one and it will actually work are not high. They actually screen people going into clinical trials to see if they have the antibodies of these viruses, because they know if those people have the antibodies, sometimes you have them naturally.
Josiah: Then, they won't allow you in the clinical trial.
Geoff: I see. There's limited set of viral vectors that have their different antigens.
Josiah: Theoretically, you could try to always make a new one or something like that. DNA can be immunogenic but generally, it's not. There's generally not antibodies that will …
Geoff: Attack DNA, sure.
Josiah: Yeah. Right. You can imagine why because our bodies have …
Geoff: It will kill itself right.
Josiah: Yeah. A lot of viruses are RNA based viruses so our bodies rather attack RNA than DNA or something. It's not immunogenic, it works great or it works okay, good enough that you could do multiple injections or something and probably still work.
Geoff: It's not my wheelhouse but I'm surprised there's only one FDA approved genetic therapy. It just seem like there's been in the news being discussed …
Josiah: Oh man, there's thousands and thousands, you know what?
Geoff: In some trials, like this gene therapy works. I'm just surprised there's only one. There's only one gene therapy …
Josiah: If you want to talk about how the FDA works, it's my new mission, it's like bring down the FDA. Or figure out a way around them.
Josiah: The FDA works like this. Their job is to make drugs that can help the most amount of people by hurting the least amount of people and make companies money, right? If doesn't fit those three things, it doesn't matter, right?
Geoff: Okay. The first two points are legit, right.
Josiah: The people making the drugs are companies, right?
Josiah: They're investing in research and development. If they don't make money off these drugs, they're not going to invest money in it.
Josiah: There has to be a system where it helps them make money.
Josiah: The problem is that most common diseases or common things or things like that are very profitable because I don't get any special benefit from the FDA, right. If you have a rare disease that you're targeting or a first-in-class drug, which means there's no other treatments for that disease, you get fast track, so it takes less time, less research.
Geoff: Yeah, the Orphan Drug Act, yup.
Josiah: If you do get it approved eventually, you get a fast track voucher that you can sell in a secondary market or keep for yourself and those are worth like $150 million just to sell.
Geoff: You can sell these vouches too?
Josiah: Yes. You can sell these vouchers to other companies to fast track their drugs.
Geoff: You get a fast track pass on your molecule. You're like, "Yeah, I want to sell this for a different molecule," they'll transfer?
Josiah: You just get a fast track …
Geoff: It's a weird government …
Josiah: I think there's requirements on it. It's really weird.
Josiah: You have to understand that companies who are trying to get drugs approved, they're trying to make money, right?
Josiah: Obviously, they're trying to help you but their first goal is to make money.
Geoff: Okay. It makes sense.
Josiah: If you're targeting something that makes the most money, it's generally not something that's like sickle cell anemia, right, because that's just going to be … there's such larger people with sickle cell anemia.
Josiah: Your clinical trial size have to be massive.
Josiah: To find effect sometimes with massive clinical trials can be hard because there can be so many confounding factors that you're not looking at, so many things that you're not taking into account. All these money you spend in this drug. Then, at the end, if it gets approved or it doesn't get approved or whatever, what are you going to do?
These gene therapies that have been approved, they're trying to charge a million dollars.
Geoff: Right. Is the eye conjunctivitis thing a million dollars?
Josiah: Yeah. It's a million dollars for the gene therapy because it's the only way that they could theoretically make money. If you were to go buy this from a company, the virus and the gene will probably cost you like $5,000.
Geoff: Yeah. Does insurance pay for that? Is this gene therapy actually being sold? I'm actually curious.
Josiah: Yeah, no, no. I think one person has got, I think, insurance companies and hospitals are trying to find ways to make this available to people because it's just like so ridiculously outside the norm. You can imagine like if you had this blindness and somebody is like, "It will cost you a million dollars to get it fixed." You'd be like, "Oh no …"
Geoff: How do I do this? Yeah.
Josiah: How do I get a million dollars?
Josiah: The system is incentivized for people who are trying to make money. In a sense, incentivize for people trying to help people. That's unfortunate. That's why gene therapies have such a hard time because everybody is targeting really rare diseases and a lot of times, hard to find patients.
Geoff: Right. What you're saying is like the trial process of going through phase one, phase two, phase three is really, really high, it's super expensive. By the fact that these genetic therapies tend to target rare diseases that the market opportunity just doesn't exist, like the economics don't work out.
Josiah: Totally. If there's one thing people in Silicon Valley should be thinking about disrupting it should be the FDA because it's just like the most inefficient process known to human being.
Josiah: You're talking about getting medicines to people.
Geoff: Yeah. I know, it's an interesting conversation. Let's dive into it a little bit. Because I know I've had a lot of conversations with you know Balaji Srinivasan?
Geoff: He was somewhat rumored to be Trump's FDA commissioner. He's looking at it. It's his story to tell, but he has this similar questions around like how do you make that system better?
Josiah: Yeah, well here's …
Geoff: How do we have like a fair conversation? Because I think on the other side of the coin, I think, a lot of people listening are probably like, okay, FDA, their job is to make sure it's safe. They're there to be good regulators. I think that's very good intent. I think FDA wants to help people stay safe and not have people give bullshit drugs and hurt people.
Josiah: Totally. Here's the thing is that like say, I make a drug that can cure two people but kills the other eight that take it, right?
Josiah: That means the individual outcomes are crazy good, right? If I can get those two people cured … if I can get the drug to those people or find those two people …
Geoff: Out of the 10?
Josiah: … out of the 10 and get them cured, that would be awesome.
Josiah: The problem is the FDA doesn't work based on individual outcomes, right?
Josiah: Because the whole way the clinical trials are set up …
Geoff: It's population medicine, right.
Josiah: Exactly. It's population medicine it's not individual outcome medicine.
Josiah: What we need is a system that allows individual outcome medicine, because it sounds stupid but like people do crazy things. Sometimes they get grapefruit seeds to try to cure their cancer.
Josiah: If somebody were to tell me, "It's impossible to cure cancer with grapefruit seeds." I would say, "That's crazy." There's probably somebody in existence out there who has a cancer that can be cured with grapefruit seeds. We don't understand the metabolism of their body or the cancer or what chemicals are all in there and how they're acting and …
Geoff: It's unlikely but there's a non-zero probability …
Josiah: There's a non-zero probability for sure. I'm not advocating anybody ever to try to use grapefruit seeds to cure cancer, anything like that. I'm just saying, exactly, there's a non-zero probability, we can't rule it out.
Josiah: It's like, how do we move science and medicine towards individual outcomes in a way from population based medicine? Because how do we try to strive for these individual outcomes versus when somebody has lung cancer, we just say, "It's untreatable, you're just going to die in a few years. Sorry, here's some chemo."
Geoff: Right. No, I think that's where you're arguing is the strongest. There are a ton of diseases where the standard of care is you're fucked.
Geoff: It's like, okay, it's like people are kind of screwed with the status quo let them try anything that they want, right?
Josiah: I agree. They're trying to make movements towards this. They recently approved right to try which means that drugs that are in phase one clinical trial, patients can get access to them or try to get access to them now through laws. It helps protect companies with liability and things like that.
Josiah: Which is interesting because you think of a model where you just try to get a bunch of drugs into phase one to sell them to people to help them get treatments, to work around the FDA. That would be a good company idea, right?
Geoff: Yeah. It kind of, right? I think the intent is good.
Josiah: Here's an interesting thing. Here comes my point. There's a drug that was recently approved that's composed primarily of cannabidiol, all right, CBD for seizures. It was approved obviously in places where CBD is not legal like here in California …
Geoff: It's legal now.
Josiah: Yeah, it's legal here in California.
Josiah: Other places where it's not legal, it costs $70,000 a year. I did a calculation to see like how much would it cost if you just purchased it on the weed shop?
Josiah: It was like $3,000.
Josiah: You're just like, basically, this is illegal but it's also could be like an FDA approved drug for seizures. It's really strange. In some states, it's legal and you could get it way cheaper.
Geoff: I think that's definitely a kink in the system. I think that the path for marijuana being legalized is going to happen. I think it's inevitable. I mean, who knows? Jeff Sessions, this current AG, is pretty anti-marijuana.
Josiah: Yeah. What about your dealings and what do you think about the FDA or you just hope to never have to deal with them? Is that your goal?
Geoff: No, no, no. I mean, I think we're lucky in the sense that we make foods and or supplements, our ketone ester is a food. We deal with FDA in terms of like submitting the data around safety to make this, like regulate as generally regarded as safe. Folks out there might have seen the Impossible burger.
Geoff: They went through a whole thing to make sure that the soy heme was GRA … or keto ester GRAS. We got that approved in 2015 actually.
Josiah: Oh really? Wow. Awesome.
Josiah: I didn't even know that. How cool.
Geoff: Yeah. A lot of credit to our partners at Oxford University for doing a lot of that heavy duty lifting there. That's the extent in terms of making a food. In terms of therapeutics, that's something that we're interested in. I think, if you look at the literature on ketones and ketosis, other interesting implications towards neurological conditions, obviously, a lot exciting data on diabetes, metabolic syndrome control, reducing glycemic index.
I think, obviously, when we go into medicines or making medical claims, that's kind of different beast. Yeah. How do you fast track some of these things where if they are just super safe, if this is a food and there's a …
Josiah: There's no way you can really fast track anything. That's the problem.
Josiah: I think the best thing to do is well, you got two options. One is to open up a dialogue with the FDA and just try to get things going and try to fill them out in what they're thinking. They're always going to be in the negative about everything. It's always going to be like, this needs to be approved, that needs to be approved, that needs to be done, this needs to be done.
Like the generally recognized as safe, the ketone ester, you probably didn't have to do that, right? You don't have to do generally recognized as safe. That means that like you'll never run into issues down the road.
Josiah: If there is [crosstalk 01:05:52].
Geoff: With the US Military, they care.
Josiah: Totally. Totally.
Geoff: I think it's like Impossible burger how to do it. I don't think like the big guys would touch it if it's not like not …
Josiah: Totally. Also, if something went wrong and they're like, "We blame it on the ketone esters." They're like, "Give us two years to do the research and prove to you that it's safe." It's kind of not a good situation to be in. It is very, very good.
I think what I would do is find an ex FDA lawyer or a person who work for the FDA, if you want me to put you in contact with this one, I can, and figure out loopholes. There are so many ways to work around their system that open up a lot of opportunities, though some of them are risky, but it opens up opportunities rather than or at the same as going through the whole process of getting something approved.
Geoff: Yeah. Our stance on it is that there's preliminary, a lot of animal work, some early human work on some of these medical conditions that people are just experimenting with. It's like, if this is a food and if you want to use this food to run a faster marathon and that's the claims that we make in terms of athletic performance, great.
If you want to use this on your grandma like we're not trying to check how you …
Josiah: Yeah. The one thing about the FDA, they're slow when it comes to approving something but if you want to just talk with them or just set up a conversation, I've never had problems getting them to respond to emails or anything. That's what I would say, just open up a dialogue with them, it's probably the best thing you can do, because usually, they're happy to talk to you.
Geoff: They're professionals.
Josiah: That's probably what they're all doing is just talking to people instead of approving all the drugs.
Geoff: I think there are interesting arguments around how the drug paces [inaudible 01:07:44] given the FDA hurdles where like penicillin went from like lab to bench or to like hospital site in like two years or something.
Josiah: Yeah. Scott Gottlieb, the current FDA commissioner or whatever has been trying to speed up.
Josiah: I think they have been getting record numbers of approval but it's like ridiculously tiny.
Josiah: It's like yay, we approved like 200 drugs last year or something. They're like, "Wow, it doesn't seem like a lot. For all the different diseases that exists?"
Geoff: Yeah. What is the dream state with what your work is? It sounds like there are, to me, my interpretation is that you're almost arming people with education and knowledge and now you have the frogs and the platform to test some of these genetic therapies. Then, you're not saying, "Hey, go make your own gene therapy," but like you basically …
Josiah: No, I mean, that's all we're trying to push it towards.
Geoff: … given the tools.
Josiah: Here's the thing.
Josiah: Is what I've learned is that like …
Geoff: Can it be like, "Hey, here's the rolling DIY genetic therapy test, you figure it out and …"
Josiah: Probably, yeah, yeah, yeah.
Geoff: If this is going to work for your rare disease …
Josiah: This is probably like …
Geoff: … a master plan.
Josiah: I think when I was 18 I read "The Art of War" by Sun Tzu or whatever but like it's probably something like that like don't attack your enemy head on. If the FDA is like a cosmetic human genetic engineering, it's probably never going to be a thing. Don't try to force it down their throats.
Instead, what you do is you build up a base, you build up ways in which you can go around or like have a community or a population of people who support this technology or who want this technology so that if you ever do have to approach them, then you're like, "Look, 90% of the population in the US is pro this technology. You have to help us make this happen now."
That's kind of what we're going. We're going for the long slow road of educating people, giving people access to technology, the technology. Then, helping them maybe learn how to use it on themselves, maybe, maybe not. I don't know how that's going to work with the FDA and everything.
Then, maybe when people are using this, when it's out there in the wild, when you have this huge base, then it makes your approach so much more easier. We have people …
Geoff: Yeah. That sounds very sensible. I think you're a little bit aggressive. I think that sounds like a very sensible statement, right? It's like, okay, let's educate people …
Geoff: … and let's like work within the system.
Josiah: Maybe work within the system. It's figuring out, I think, if you're not going to work within the system, I used to be like a lot more … if I'm not going to work in the system, I would just burn it all down. Now, I'm more like, we could develop things that are safe, effective and work outside the system perhaps, right, instead of being all anarchic and like burning everything down.
Josiah: We could develop ways that maybe work around the system but also still provide people at scale something that's safe and effective.
Josiah: I think that's going to be what takes down the FDA or something like that, right? When they're like …
Geoff: I would say like let's not take it down necessarily but evolve them, enlighten them.
Josiah: Yeah. Government institutions like that, they don't like evolve. They just die. What I'm talking about is like …
Geoff: I'm actually curious, would that be part of like the goal? Would you want to eliminate the FDA? I would say that, hey, there's definitely some rule for …
Josiah: No, right now, the FDA does its job.
Josiah: If another system came along …
Geoff: Yeah. We saw them evolve the mandate, right? Evolve the FDA's mandate.
Geoff: Your dissolution on that?
Josiah: Yeah. I think you're talking about … it would be like rewriting the constitution, right? It would be like, let's rewrite the … because the FDA and all their regulations and all this thing. I don't know if you ever read, I've delved into a little bit like the Food, Drug and Cosmetics Act and all the regulations and …
Geoff: Yeah, it's a big document.
Josiah: It's just like all these different things and you're just like, it's going to be a beast to knock down. The one thing that would knock it down is if somebody said, "Hey, look, I have this drug. I have this treatment, it's safe, effective and all these people want it and need it. It works. I'm just giving it to them."
Josiah: Nobody dies, everything is safe and it works. Then, everybody's point of view will tend to be like …
Geoff: You'd force the institutional change.
Josiah: Yeah, you force …
Geoff: You're like Uber, you're Airbnb, you're just …
Geoff: All right, this is reality now. The consumers want it. We're just changing it a little bit.
Josiah: You can't do that too early. You can't just be like … and some people have gone … there have been other biohackers now who are trying to just like force it. They're just like, "Here's everything. It's not safe. It's not effective but we're just giving it away and trying to get it sell to people or whatever."
You're just like, "No …"
Geoff: That's messing it up for everyone.
Josiah: That's not going to work, right? You can't just like give people stuff that's not safe and effective but who's going to want to use it?
Josiah: Everybody is going to be like, "This guy suck." No, you need to find something that's just … you have to develop it. It's slow and patient.
Geoff: Yeah. Yeah. People really try to sell genetic [inaudible 01:13:26]. They're like, "Hey, this maybe might work. There might even a chance it will work."
Geoff: They just don't understand their product and they're like …
Josiah: I mean, there are a lot of hoaxsters out there man, right, and everything, right? I think that's a lot of reason that a lot of biohacking has been held back, right?
Josiah: Nothing against those people who drink butter in their coffee or whatever, sell people butter in their coffee. I'm sure it does help some people and stuff like that. We know that biohacking is a little bit more complicated and can be more complicated and more beneficial than just like butter in your coffee, right?
Josiah: That's what we're both trying to do is make it …
Geoff: That's why I'm almost like what are the term of biohacking recently? I think it's just like a weirdly loaded term with like kind of amateur …
Josiah: It really is.
Josiah: Part of me kind of embraces that and part of me …
Geoff: No, not amateur in like the hobbyist way like amateur as like they're just dumb, like stupid stuff.
Josiah: No, I know what you mean. No. Part of me kind of embraces that because it's like you are, how do you say … I don't want to say surprise people but like, you have this advantage that people don't think that you're capable and serious.
It gives you more wiggle room in a lot of different ways because people aren't expecting. If you're just like, "Yes, we're like a drug company, then we're going for this." Oh my gosh, everybody is … the FDA, OSHA, everybody is going to be all over your grill and trying to make sure you're doing everything perfect and everything like this.
I think the stuff you're doing and the kind of stuff we're doing, is kind of trying to develop a new way of doing science, a new way of doing … I don't want to say medicine, but kind of a new way of doing medicine. It's long and it's hard. We're not traditional.
Josiah: We're not.
Josiah: It's like biohacking might not be as the best term, because of the people it's associated with but it's like, what else?
Geoff: Yeah, what is the better terminology?
Josiah: Because we're not biopharma companies.
Josiah: We're not. We're probably not ever biotech companies, right? Just nothing like …
Geoff: I mean, I kind of describe ourselves like a hybrid biotech consumer.
Josiah: Yeah. Right.
Josiah: Exactly, the same, right?
Josiah: Some consumer biotech. Whenever I tell people that, they're like, "What does that mean?"
Geoff: Yeah. Yeah. I guess like biohacking … Yeah. I think you're right in the sense that there is some understanding what biohacking is. I think the way I articulate it, at least to myself, is that just like there was computer hackers …
Geoff: … they evolve them to be computer scientists.
Josiah: You want to know what started out in the beginning? What I see in biohacking? It starts out in the beginning where there's like a bunch of people who don't necessarily have a lot of credibility. They're just like are able to get publicity or hype based just on the fact that people are interested in this new technology.
Over time, eventually, it's the players who have the credibility who went out, right?
Josiah: Just because …
Geoff: It's the products that people want, right?
Geoff: Their stuff works.
Josiah: Exactly. People want stuff that is credible. Eventually, those people who have less credibility or don't have credibility, you'll see that maybe some of them will survive but a lot of them just fall by the wayside and are gone.
Josiah: I just constantly see it especially in biohacking. If you were to ask like who were the names in biohacking 10 years ago or something, nobody even knows those people anymore.
Geoff: Totally turned over.
Josiah: Yeah. Totally turned over and starting to get more and more credible and more and more robust. Yeah, so it's …
Geoff: Yeah, hopefully that continues, right? Hopefully, we'll stick around …
Josiah: Otherwise, you and I, we can really try to popularize this term consumer biotech.
Geoff: That's a sexy term. Yeah. I want to move on to some audience questions before we ran out of time here.
Geoff: Because we actually do have a number of questions that people wanted answered. Let's run through that. Alejandra asks, she read your interview with Atlantic a while ago, and in it you mentioned that you consider yourself a social activist. I think this kind of touches around the storytelling stuff that we were talking about.
"Did you get into biohacking because you believe that this is a way to improve a part of the society?" It's actually a great question.
Geoff: Thanks Alejandra.
Josiah: Totally. That is exactly the reason, right, is because I'm talking about all this … it leads right back all this stuff with the FDA and everything like that. What I saw was that like there is this amazing technologies, biotechnology, molecular biology, genetic engineering and all these stuff that nobody had access to.
I was just like, "If our century or our time is going to be the age of biology," which it seems like. Things are moving towards that. Away from the age of silicon and to the age of biology emerging, silicon with biology …
Geoff: Our tagline is humans are next platform.
Josiah: Yeah, exactly. Then, people should have access to this technology.
Josiah: People should be able to use this technology or learn how to use this technology. That's one of the huge things that inspired me at heart like I am just … social act is like, my company would go, we volunteer at local biotech organizations or whatever. We donate our time. We donate material. We donate all these stuff, because we are not just trying to sell stuff, though obviously, we're trying to make money ever [inaudible 01:19:07].
Josiah: We're also trying to build a community, develop a community, build something that's sustainable. That requires more than just us or more than just a few individuals that requires everybody. I think being a CEO is, in general, just social activism.
Josiah: Right. It doesn't matter what you're doing like you're trying to do the most help with the least harm that you can do.
Geoff: No, I mean that just resonates with me personally I think what we do at H.V.M.N. as well. I think that the highest order of any company is change in culture. If you can change culture, social activism, whatever you want to call it. At some point, you're like, business is dealing with people like [inaudible 01:19:53] people.
If you can change people, that's the highest order that you can influence the world around you. I think that's a great question and great answer.
Geoff: Yeah. Let's talk about it …
Josiah: Yeah, no, no. Like what Alejandra asked, I've done a couple experiments that I've kind of like publicized or like had reporters and documentary crews. This is necessarily not normal for like a science experiment or something. It seems very publicity hounding and it is for sure. I'm not saying it's not.
The idea behind those experiments is to raise awareness. One of the first experiments I did was this experiment to replace the bacteria in my gut in my body because I was suffering from gastrointestinal issues. I found out like a ridiculous number of people do. Some of it is linked back to antibiotic usage because antibiotics, right, they don't target specific bacteria. When you take them, they just wipe out a large portion of bacteria in your gut, which can just be terrible.
A lot of people have issues with their gut after this. One of the major ways to treat this, which is actually outlawed in the United States, it's outlawed, is to do a fecal transplant. That's taking feces from a healthy donor and transplanting it in your own body to help with unresolved gut issues.
Geoff: It's banned? I mean it's explicitly banned?
Josiah: Poop is a scheduled drug in the US. That means that doctors can only prescribe it for the intended indication. The only indication it's allowed to be prescribed for in the US is antibiotic resisting clostridium difficile infections. That's a bacteria that infects the body.
If it's antibiotic resistant, if you can't wipe it out with antibiotics, the other treatment is just to take like 30 grams of healthy donor feces and there's like a ridiculous cure rates, which is 90 … I'm not even joking, it's like 90 something percent. Almost better, if not better than antibiotics.
Josiah: That's the only indication it's approved for. All other gut issues, it's not approved for. It's crazy. Other countries in the UK, you can get treatments, these fecal transplants. A lot of people fly to the UK or some place like that, go to a clinic there and get transplant and come back. Yeah, in the US, it's not approved.
I thought like, "Wow, I think this would be like a great experiment to do scientific experiment." Get all the DNA from my gut which you collect through the feces and sequence it, see what bacteria is in there, do a transplant and sequence my gut after and see if taking the donor poop works. It modifies the bacteria in my gut and see how it helps with the symptoms.
I kept a spreadsheet of all these different things. What I was eating, my weight, my physical activity, my mental aptitude and sexual drive and all these different things and did the DNA sequencing and the DNA sequencing worked. My gut health returned and it's been pretty great. Keto, I say, it's been a little weird, I don't know …
Geoff: It definitely shifts your microbiota …
Josiah: Oh yeah it does. Yeah. Yeah. Yeah. There's been a little adaption period where like … that upsets my stomach or something.
Geoff: Extensive reason, right?
Geoff: It's different feels.
Josiah: Yeah, no. It really helps. I wouldn't say cure because I think cure is a strong word but reduce all the symptoms. I have not have blood in my feces since I did that experiment. Yeah, it was kind of a form of social activism to be like, "Look, it's …"
Geoff: It's kind of like quite a bit of PR, right? Is it the first like …
Josiah: Yeah, it was one of the first big experiments I did that …
Geoff: What caught the attention of the media? It was the first self-transplanted fecal transplant or?
Josiah: No, it wasn't the first one. What it was is it's the first time somebody documented it scientifically and tested to see if it work, see if the symptoms resolved and all these other stuff. It was like one of these first tested on human scientific experiments like this, because it's like usually all …
Geoff: What put you on the map?
Josiah: That was one of the first …
Geoff: Is that the first thing that …
Josiah: It was the first time I was in the press but that was one of … that was probably the big thing because then there was a documentary that was made about … there's a crew that's filming there for the Verge who was writing the article. They got in a huge beef so they just left and decided to just make their own documentary and they did. It was phenomenal. It's like South By Southwest and all these other places.
Geoff: They're taping for Verge and then they're like …
Josiah: It's on the New York Times now and it's on the Atlantic now. A bunch of people picked up the video.
Geoff: It's cool.
Josiah: Yeah. That was kind of like the first big experiment of social activism was to just hey, here's a problem and the same thing with my CRISPR experiment. Here's a problem. A lot of people are suffering from illnesses and diseases.
Josiah: You're saying CRISPR can cure it. Why isn't anybody using CRISPR on themselves? I'm just like I'm going to see how easy it is and do this experiment on myself. That's kind of like my form of social activism, like trying to push medicine forward, trying to cause change in the medical scientific community.
Geoff: Yeah, no, very cool. James Reyes asks, what do you think will be the biggest advancement in genetic engineering the next 10 years?
Josiah: The biggest advancement in genetic engineering, well, I don't think it's going to necessarily be like an advancement like we're going to learn how to do something new and crazy. I think it's just going to be like cosmetic human genetic engineering.
I think that's going to in the next 10 years be something that happens on some sort of scale larger than one or five.
Geoff: Interesting. Like will that be like muscle.
Josiah: Yeah, I think it's going to start off-
Geoff: Like facial features.
Josiah: I think it's going to start off with athletic performance, because it's so easy to measure, it's so easy to use.
Josiah: I think in the next 10 years, probably the next five years, you're going to see hundreds if not thousands of people trying this stuff just because like we talked about, the process is easy. It's just understanding what DNA you need, how to get that DNA, what you need to inject, and how to inject it, and how much, and stuff like that. There's no like …
Geoff: There's no handbook yet.
Josiah: Yeah. That's what we're trying to develop. I think once something like that is developed and out there, yeah, you'll see humans genetically modified. The problem is, is like if it starts getting used in sports it's really hard to detect and you're going to have a lot of gene doping stuff going on. It's going to be interesting. For sure, it's going to really change sports I imagine.
Geoff: Yeah. I mean I think it's something that I think will inevitably have to be discussed. I mean I think it's like a whole another discussion on it. I mean sport is about finding advantages like, that's the definition. If you're just taller than me like Kevin Durant is going to just like, he's unfair because he's taller than me, but also, he's much more skilled than me. It's just like what are the advantages that are okay and not okay.
Geoff: I think it's going to be an issue.
Josiah: Unlike these gene therapies, they go away after some period of time. It'd be just like taking steroid or anything else except like there's no test really for. You could try to find test. Maybe you could try to target oh, this person is elevated, like full statin or IGF1 level.
Geoff: People say there's a genetic passport, like I guess like …. That's not going to matter, right?
Josiah: It's just so hard. It's just like so hard to do. What happens if somebody has normally elevated levels of that stuff, right? It's not just okay. What happens if you have 10 times elevated EPO levels like I do?
Geoff: Yeah. I think that's why it is messed up like in cycling for example [inaudible 01:28:08] working a lot of cyclists. There's like a max limit of EPO or like hematocrit like amount of iron in your blood. It's like 0.5 or something.
Literally every single cyclist has that 0.5. It's like I'm naturally 0.5 and you're naturally 0.4. You like dope up the 0.5. It's not fair like you're catchy. Like people with … A lot of people are asthmatic in cycling not because they maybe actually have asthma but it's a legal like the lung steroids are legal if you have asthma.
To me it's like ugh, okay. Some higher percentage of the cyclists have asthma, like 20%. It's like really like you guys are elite cyclists, you guys all have asthma.
Josiah: That's funny.
Geoff: Some drug use is okay.
Josiah: If you told somebody like, "Look, I just inject this thing into you" and especially right now because they don't even have ways to test it right now. They're not even testing for it. If I can get it in your muscle and not too much in your bloodstream anyway like they won't be able to detect it without taking a biopsy or some things.
Geoff: Yeah, they're not biopsing people.
Josiah: VEGF, this is vascular endothelial growth factor which increases the blood vessel growth in the muscles, angiogenesis. You can imagine increasing angiogenesis your muscles to get more oxygen to them and perform better.
Geoff: Yeah, that's probably going to help.
Josiah: How you detect that? What are you? You have too many veins in your legs, you're excluded or something?
Geoff: Yeah. You can't test that. You like take a snapshot of your leg every month and like oh, this month you have way more blood vessels now like it's a flag.
Josiah: It's just so-
Geoff: I mean it's ridiculous like you can't test it properly.
Geoff: I agree with you. I think there's going to be some reckoning in sport where it's like look, you just can't enforce this stuff. That's my hypothesis.
Josiah: Yeah. They'll ignore it for the longest possible. What's interesting, you know what they do in sports where people are missing limbs and stuff like that. They actually have a point scale. It's really interesting. Like wheelchair basketball and stuff like that. What they do in wheelchair basketball, they have different point scales. If you can only use one hand or you only have one hand you get a certain number of point score. You're like three points. If you can use both hands you're like five points. If you have no hands, you're like one point. You can only have a certain number of points on the court or field at one time. A team can only have in their lineup out in the court like eight points.
Geoff: That's kind of a weird way to judge people but shit, yeah.
Josiah: No it is, but it works. Because like how do you have a team if where everybody can't use their legs but they all have perfect use of their hands.
Geoff: Right, it's weird.
Josiah: They're going to way outcompete another team that doesn't.
Josiah: You can imagine in professional athletics if everybody has their genome sequenced or something like that and they find these mutations or they find this gene doping, let's say.
Geoff: Like we have a certain amount of points of genes or something.
Geoff: It's interesting. You have something like Usain Bolt. It's like that guy's gene is probably just like off the chart like maximize your sprinting.
Josiah: Right, exactly. Exactly.
Geoff: Right. It's not fair. Like LeBron James, he's like an animal.
Josiah: It's not fair at all.
Geoff: Does everyone get to just gene dope all the way to Lebron James' little genes?
Josiah: I don't know, maybe.
Geoff: Yeah. I mean it's just like an open … Yeah, the commissioners in the league and the sports, we'll see how they'll figure that out. I mean I guess people like us will supply them tools to let them do it.
Josiah: You guys go …
Geoff: You guys figure out what you want to do. Well, I mean, before wrapping up here I mean you hinted at the different products you're launching. What are the main things? Where will people find you? Where they can follow your work?
Josiah: Yeah. The company is The Odin. Our website is the-odin.com. If you look at my name, Josiah Zayner. They can find that in social media, Twitter, Facebook, LinkedIn, whatever, I'm there. Find me, send me a message. I usually try to respond to people.
All of our kits right now are centered around genetic engineering and molecular biology, things like that. If you're interested in learning about this technology, go check out our website. Even if you're not, like hey, hit me up if you just want to have a conversation about some of the stuff.
Geoff: Yeah, awesome. Hey, thanks for coming in. I think we should do this more often. I think this will be a fun conversation.
Josiah: There's a lot of content. That's pretty good.
Geoff: I'm sure our audience is going to have more questions for you. Do this again soon.
Josiah: Yeah, no, man, I'm down. Just hit me up. We'll figure it out.
Geoff: Cool. I appreciate it.
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