The Melanie Avalon Biohacking Podcast Episode #284 - Zack Abbott

TRANSCRIPT

(Note: This is generated by AI with 98% accuracy. However, any errors may cause unintended changes in meaning.)

Hi friends, welcome back to the show. I am so incredibly excited about the conversation that I am about to have. It is a long time coming. So probably over a year ago or so, I heard a podcast episode, I don't even remember.

Did you go on Dave Asprey's show? I did, yeah. Okay, I think it was his show. And it was about this probiotic which helps you process alcohol, a genetically engineered probiotic. And I was so fascinated for so many reasons.

You guys know that I love drinking my wine. I'm also all about healthy drinking. I'm also all about probiotics. So it was literally everything up my alley. I put it on my list. I was like, I must interview these people.

I think I actually reached out blindly on the website. And then serendipitously after that, a mutual friend just offered to introduce me to Zach who I'm here with today, Zach Abbott, the CEO and co-founder of ZBiotics, that incredible brand that I've been listening to on that show.

So I am so excited about this. I did a deep dive into the science of how these probiotics work and what they do. And I just have so many questions and I'm really excited about the potential for this to really optimize people's lives.

So Zach, thank you so much for being here. Yeah, I'm really excited to chat with you too. Thanks for having me. I'm like really, really excited. I'm a big wine drinker personally. What's your drink of choice?

I like to typically drink beer. My wife and I enjoy drinking cheap champagne. We have fun hunting down drinkable bottles of champagne that are not too expensive and then occasionally cocktails. I have so many questions about all of this.

A little bit about your background for listeners. So you have a PhD in microbiology and immunology from the University of Michigan where you studied bacterial gene regulation in, you're gonna tell me out.

Legionella Nemophila. OK, in that. And you also worked in clinical trial design, as well as researching HIV vaccines and pursuing novel antibiotics in academia and industry. I'm really curious, working in clinical trial design, does that mean that you, what does that mean?

You just like, what does that mean? It was a, yeah, it was a cool job that I, it was my first job after grad school. I was working at a company that basically specialized in designing clinical trials.

So like if a pharma or biotech company came and said like, hey, we want to test out this new drug or this diagnostic or something, we would sort of put the whole study together and design it to make sure that they would get results they could use to kind of apply to the FDA for drug status.

And so it was cool because I really got to see how these companies think about gathering their data and kind of what the steps are for regulatory approval, which was what it wanted to do after grad school was thinking about like, how do you...

how do you really bring scientific advancements to market? That sounds like such an incredible skill set, like a really practical, helpful job to have for all of your goals. I got to see like really, you know, kind of behind the curtain on a broad spectrum of different kinds of companies, small companies and big companies and like broad spectrum, different kinds of drugs and diagnostics.

And so it was just a really cool kind of crash course and seeing how all that happens. Oh, wow. Did you work on any, like, what was your favorite one that you worked on? If you're allowed to, can you talk about it?

As you specific, so I certainly could say like in generalities, I mean, there was a really cool, there was a company that was relatively small and they were working on a very cool new type of painkiller that was just, it was just totally different than everything else that was out there.

And I was just really inspired by what they had developed. So it was really fun to work on that. So, so cool. OK. And then so, so going back to this, what you're doing now, I'm really curious because a lot of times companies come out of people's personal passions or like a health issue or a goal they have personally.

So I'm curious with this technology that you created for Z biotics, did it come out of because I ask you about like what you like to drink in the beginning. Did it come out of that, like wanting to address an issue that are not an issue, but address something with drinking that could be helpful or you discovered this incredible potential technology or was it something else entirely or a blend?

Yeah, it was I guess it was largely the the technology that was really exciting to me, and that's where I started with. I had this idea that we could essentially like make probiotics better or really, honestly, if I'm telling you the real kind of order of operations here, it was really that like I saw probiotics as a way to deliver functional proteins to people.

And so there are these like you basically essentially you have like these proteins or enzymes that can perform all these different functions. And biologically speaking. It's the most common way that a cell of any kind gets things done is by making proteins.

And so there's always amazing things that we can do with them. And so, and honestly, when I was working at that, designing clinical trials for drug companies at that job, at that CRO, they saw a lot of these therapeutic proteins being developed.

But the challenge was that they're very expensive to make, and those proteins are very unstable once you make them. And so these have to be stored in a refrigerator or a freezer. They have to be injected, and they're very, very expensive.

But the thing is that we use microbes to make those proteins already in the drug industry. And so I thought, well, what if we just gave you the microbe and had it make the functional protein or the enzyme directly in your body?

And that just felt like a really simple and powerful idea. And I looked around, and I was surprised to see that while there were other people working on it, it wasn't... there weren't very many. They weren't really working on it in the way that I envisioned it.

And so I thought, wow, there's like an opportunity here to develop something really powerful. And so thinking of taking just essentially safe, addable probiotic bacteria that you already get every day.

And these bacteria are capable of producing thousands of different proteins. And fundamentally, you can kind of think of a protein as just like really like the way in which something executes a function.

So these bacteria are making thousands of proteins. That's really that they're executing thousands of different functions in your body. And for the most part, those functions are for the benefit of the bacteria.

And then sort of like tangentially, they may help you in some way. And so that's sort of like, kind of the foundation of the hypothesis behind probiotics, right? That like, oh, well, we'll eat this safe bacteria.

And then maybe some of these functions it's performing might help me in some way. And so we sort of like the probiotics industry sort of built on that, this idea, like, okay, look, here, these bacteria that we found in the ground are really, realistically, these are bacteria that are the leftovers of the food industry and largely like the dairy industry.

So we see like these lactobacillus and, and bifidobacteria and stuff. And then we say like, okay, look, we know they're safe, and we have tons of them left over. So like eat them, and maybe they'll help you in some way.

And I thought like, well, what if we just engineer them to express a single protein perform a single function that we know, for sure, will be valuable to you, in addition to all the thousands of things it's already doing, just give this one extra thing, just kind of lay that over the top.

And then if you eat that bacteria, then you'll get this, you'll get this guaranteed benefit or this guaranteed function, I felt like it was really was that idea that kind of was the foundation of the heart and see why it was a question of like, okay, cool, like this, I think this idea is powerful.

And I think we could really do it. I think it's feasible. So then okay, what do we what, what function do we give the bacteria? What problem do we try and solve with this? And candidly, you know, the next day effects of drinking.

was not my first thought or my first idea for this. I have a long list of ideas I thought would be really cool, but of course, as somebody who wasn't trained in product design and customer research and things like that, these ideas were very scientific and not all that interesting to consumers probably.

And so as I started to pitch the technology idea and pitch some of the applications, I saw that there wasn't a lot of interest. It was not as much as I thought there should be, because I thought it was just such a cool idea.

But then the first time I pitched the idea of engineering a bacteria that could help you feel better after drinking, it was almost like I was added up to the end of a long list of ideas, and it was almost like a joke.

We could do anything with this. And I just saw people's eyes light up. Can we do that actually? Yeah, they were like, oh, it was like the first time they actually like, like, listen, you know, like, okay, whoa, whoa, tell me all about that.

And I was like, okay, so apparently, that seems to be, you know, you have to think about things that people care about, and they understand and they're interested in. And so that was like a big aha moment for me.

And so I started to like, think about like, well, like, could we actually do this? And like, what would it look like? And it seemed feasible. And, and so I started to kind of pitch that one more. And like, it and just saw that there was just a ton of interest and traction with that.

And I was like, you know what, actually, this makes a lot of sense. If I want to build what would be the world's first ever genetically engineered probiotic of any kind to go to market, it makes sense to build something that people will understand and they're excited about, and that they can actually feel the benefit of and that's sort of like a proof of concept for the tech.

So it's it quickly kind of like leap to the front of my list. And, and so I started kind of like, you know, pitching it more and people were excited. And so then I built that prototype and saw a lot of really, you know, positive effects, it was really affirmed that this was a feasible approach.

And so then it was like, Okay, I think, you know, we should really just we should really commercialize this as kind of the first one. And so when we launched this product, in August of 2019, it was the world's first ever genetically engineered probiotic to go to market, which was really, really exciting and something I was really proud of.

Wow. Okay. Were the other ideas? Were they more like, like, what were some of the other ideas you had, like increased nutrients, or the early ideas I had were, like I say, deeply steeped in sort of like academia and like, so I had these ideas that I thought were like, interesting, biologically, and I think that they are, but like, not something that people understand or care about, like, I was thinking about,

like, reducing, like the ill effects of exposure to radiation, I was thinking about, like, you know, astronauts and people who, you know, you know, or, you know, when you get a CT scan or something like that.

And I think that that's cool. But ultimately, I don't know how much risk mitigation would have happened. And people really didn't understand it wasn't a problem on people's radar. So like, that was like, I was like one of my early like lead candidates that I thought was like really strong.

And then I had a few others kind of like in the same kind of vein of things that I think I think are biological problems that a micro would be really well positioned to help with but weren't really taking into account the customer and people's interests.

Gotcha. Okay. Well, so when you sat down to, you know, actually engineer this ability to help us deal with alcohol. Well, I have so many questions where to go from this. I guess first of all, can we can we go through the process in the body of how it breaks down alcohol so people can understand that?

Yeah, totally. So an important point is that it doesn't break down alcohol. It breaks down the metabolic byproduct of alcohol called acid aldehyde. When you drink, most of the ethanol is absorbed into the bloodstream, right?

And pretty quickly, and it sort of circulates throughout your blood, it has the effects that alcohol has, right? And then it makes its way to the liver, where it's broken down. Thank you. by two enzymes in like two stages.

So the alcohol is processed into acetaldehyde with one enzyme and then a second enzyme converts the acetaldehyde into acetate. And acetate is innocuous. It's essentially vinegar. And at this point, you know, other things happen after that.

But at that point, the molecule has been detoxified from the from the body's perspective. And so that's good. Both of those reactions in the liver happened very efficiently. So very little that intermediate acetaldehyde builds up, which is a good thing because acetaldehyde is highly toxic, much more toxic than alcohol itself.

It's an aldehyde. It's very reactive. And it just basically creates a lot of problems. So the good news is, as I say, the liver is good at that. But what happens is that actually a small amount of alcohol you drink was actually broken down directly in the gut before it can be absorbed into the bloodstream.

And so this isn't really a meaningful amount of alcohol from an intoxication standpoint, which is why we don't really hear a lot about like sort of the gut pathway for alcohol oxidation, but it exists.

And the small amount of alcohol is converted into acetaldehyde, but not subsequently into acetate. So basically, the microbes in your gut are good expressing that first enzyme the same as your liver does, but not very good expressing the second one.

So even though it's only a small amount of alcohol that gets broken down there, it's pretty much all getting converted into acetaldehyde. So the gut ends up being the major source of acetaldehyde in the body.

And we see in the scientific literature that gut acetaldehyde levels can be 10 to 100 times higher than blood acetaldehyde levels, even though only a small amount of alcohol is being processed there.

And then this acetaldehyde is highly soluble. And so even though it initially forms in the gut, it gets absorbed into the bloodstream, it sort of circulates throughout the body, and kind of like wreaks havoc.

And then it makes its way to the liver where it's really efficiently processed. But at that point, it's too late. So kind of the hypothesis here was obvious, right, that we just kind of complete the same reactions happening in the liver, but in the gut.

And so engineering a bacteria to express that second enzyme, the same type of enzyme your liver uses. is sort of complete this two-step reaction to convert acetaldehyde into acetate. So that's what we did.

We built this probiotic and we engineered it to express this enzyme. And we saw that the enzyme, it can express the enzyme at high levels and that enzyme was functional in like gut-simulated conditions.

And so all of that was sort of supportive of the idea that this mechanism of action could be valuable. Okay, so can I repeat that, make sure I'm like following and for listeners? Yeah, yeah, yeah. So, so we have alcohol, it gets converted through one enzyme, which I have notes that it's called alcohol dehydrogenase.

So ADH converts that into acetyl, how do you say it, acetylaldehyde? I should know this. Everybody, yeah, it's acetaldehyde. I'm gonna learn this once and for all, because I say this word a lot, like I talk about this.

Wait, so it's acetaldehyde, wait, say it again? Acetaldehyde. Acetaldehyde, I'm like looking at the word. Okay, into acetaldehyde, which is toxic, a problem. That gets converted through another enzyme, aldehyde dehydrogenase into acetate, which is basically vinegar, which is not toxic.

And that process happens rapidly in the liver, but in the gut, the body does or does not make that second enzyme in the gut, ALDH. It doesn't make very much of it relative to the first enzyme. So then, so you get this sort of like backlog or this pileup of the acetaldehyde, that sort of like intermediate acetaldehyde.

The timing of that, when a person has a drink, and let's say on an empty stomach, because I have questions about how food would affect things, but like on an empty stomach, is it like the gut process happens and then the liver process, or they're happening at the same time, but at different, you know, amounts?

So the empty stomach just means that you're going to absorb alcohol more quickly. If you have food in your stomach, it's going to slow down the absorption. And that's slowing down absorption is a good thing from the perspective of toxification and detoxification.

That being said, in terms of when things are happening and where, they are essentially happening sometimes. If you imagine, basically, that your body is like a tube within a tube, right? Like you have this, you have your gastrointestinal tract from your mouth down to your anus, right?

And as you drink, stuff goes into that tube, and then some of it gets absorbed out of the tube into the bloodstream, and then a small amount of it that doesn't get absorbed right away stays in the tube.

So the stuff that gets absorbed quickly, and that in the case of alcohol is most of the alcohol because it's absorbed pretty quickly, then it's sort of circulating that the body it's making is where the liver it's being broken down.

And then simultaneously, the small amount that hasn't been absorbed is still in the tube in your gastrointestinal tract, and then there, it's being broken down in large part by the microbes in your gut.

So basically, those two things are kind of happening at the same time, but in sort of different locations. Okay, so like, I guess what I'm trying to understand is if, if you had just like a sip of alcohol.

Is it possible that that just all goes to the liver and doesn't even go to the gut or doesn't get processed in the gut at all? I think you should. It's probably, it's so first and foremost, as a disclaimer, I mean, it's going to be that the amount that's processed in each part of the body is going to be somewhat dependent on each person's individual biology.

So there's no kind of like hard and fast rule that being said, in general, I think it's probably most accurate to consider it as like a percentage, like some small percentage. So if you have, you know, let's, let's just for the sake of, of clarity here, like call it like 10%.

So if you take one sip, then you know, 90% of that sip will make it in your bloodstream and 10% will probably get processed in the gut. And then you drink more than, you know, it'll still just be, it'll sort of be like a percentage, I think is probably, it's not, you know, it won't exactly work out that way.

But I think that that's probably the easiest way to think about it. Okay, that totally answers my question. And then So I know like East Asian populations and people, they're known for having facial flushing from a lack of being able to, or from a buildup of that acetaldehyde.

Is that an issue with the buildup in the gut or is that from the liver not having that inside enough? The liver specifically. And so that's really, it's really, that was an interesting observation that actually led me to, one of the things, there were several things, but one of the things that led me to acetaldehyde as an important factor to focus on.

And so yeah, people, there's a mutation, some people have a mutation in their aldehyde dehydrogenase enzyme. And that mutation is common in people of East Asian descent, which is why I see it most of them.

But essentially what happens is yeah, exactly that your, that process described of the liver being really efficient, but the gut not being very efficient, is they actually are inefficient throughout their whole body.

So now the major source of alcohol metabolism, the liver is also bad at breaking down that acetaldehyde. And so you get a lot of acetaldehyde systemically throughout the whole body. And the reason you see the flushing is that one of the effects of acetaldehyde is vasodilation.

So it causes your blood vessels to swell. And so you get a lot, you get this vasodilation of the blood vessels next to your skin. And so they turn red and you get like this hot reaction or those hot feeling, I should say.

And so, and that's like really just sort of like visible, tangible evidence that you're getting exposed to acetaldehyde, but acetaldehyde does a lot of other things as well to your body. That's just kind of one of those symptoms.

Okay, gotcha. So when we have, when we do have those symptoms, and you already said this, but just to clarify, even though it's like a smaller percent coming from the gut is the majority of those symptoms for most people coming from that build up in the gut compared to the liver because the liver is much more efficient.

It's a small percentage of alcohol is being broken down, but the majority of the acetaldehyde is being formed. in the gut. And so the way we feel the next day is largely driven by acetaldehyde specifically.

For people who don't have this mutation that we just discussed, so for people with normal functioning acetyl dehydrogenase enzymes, the gut is the major source of acetaldehyde in the body. And so by dealing with the gut-derived acetaldehyde, we are dealing with the major source of acetaldehyde you're being exposed to, and therefore having a significant impact on the way you feel the next day because of that.

Because there is that lack of adequate enzyme in the gut, and then it gets into the bloodstream, how does it ultimately get broken down? Ultimately, so if without pre-alcohol, without Z-box pre-alcohol, ultimately that acetaldehyde goes to the bloodstream and gets absorbed into your cells and reach out throughout your body.

And then it's ultimately processed by native-aldehyde dehydrogenase enzymes, either in the liver or in your cells. But, you know, kind of after... those aldehydes have had a chance to essentially bind to, I mean, the main mechanisms by which they kind of cause disorders, like aldehydes are really reactive chemicals, they have this like double bonded oxygen that can react with lots of things.

And so it can literally like bind to proteins in your cells. And so essentially deactivate them, which like will gunk up the works, it can bind directly to DNA and RNA. And so it can create DNA or DNA addicts as well.

And these are also going to disrupt how the cell functions. And in many cases that causes like cell death, they're essentially just kind of like pictures like a bull in the China shop, it gets in there and it kind of just like kind of starts disrupting everything and kind of wreaking havoc that often can cause cell death.

And then which sort of triggers like an inflammatory response as you're trying to deal with like, you know, the debris from a cell dying and things like that. And so then the next day, you're essentially like the acid is gone, it's been it's been processed.

And but you're dealing with all of the leftovers, all the broken dishes laying everywhere in your in your China shop, even though the bowl is gone, right? And so then the next day, you're feeling miserable, because you're dealing with all of that debris and that inflammation, among many other things.

But like, that's, that's kind of like one of the core elements of of how acetaldehyde kind of affects the way you feel the next day. Oh, I'm really curious about this. So say we're having a drink with food, and we're taking this, you know, pre alcohol, would that conversion now happen exclusively in the gut?

I know you said stuff goes from the gut to the bloodstream. But that conversion ultimately to acetate essentially vinegar, is that vinegar acetate now in the gut? And would that actually support digestion?

Because I know people will take vinegar vinegar can be helpful for digestion. Yeah, exactly. So acetate is a short chain fatty acid. So people may be heard of if you've kind of tried and target is short chain fatty acid production.

So acetate propionate and butyrate are all short-chain fatty acids and they all can be beneficial. So the short answer is like, yes, like we're creating acetate in a short-chain fatty acid in the gut.

That being said, it's really like not really a lot. I wouldn't emphasize that as sort of a benefit, right? Like the thing about acetaldehyde is kind of like the dose mixed to poison, even though it's the major source of acetaldehyde in the body, a very small amount of acetaldehyde creates a big problem.

It's a very like toxic molecule. And so we're converting a very small amount of acetaldehyde that can cause a big problem into a very small amount of acetate, which is unlikely to create in and of itself the acetate itself create like a large benefit here.

It's more the acetaldehyde reduction. That's kind of like the core benefit. That totally makes sense. Okay. And okay, so when you sat down to do this, just a question in general about using probiotics to, you know, create this enzyme in the body because I talk a lot about the gut microbiome and we hear all the time about different benefits of different probiotics and I think it often can feel very,

well it can feel like there's like a lot of benefits to a probiotic or it can feel vague or it can feel like it affects people differently and it just always feels like a little bit nebulous and how like we just hear all these benefits about probiotics so it doesn't feel very like clear and specific necessarily and so this is the idea of having a probiotic with a very clear specific like goal so my question is how potent is the effect from this probiotic?

Should we even think of it in the way we normally think of probiotics with that benefit or should we see it more as like a supplement that is creating this very specific effect and for example is the probiotic, is it always creating this compound or just in the presence of alcohol?

So I love this question it's spot on it's exactly the kind of reason that I started this company and as a microbiologist I agree with you kind of completely that traditional probiotics as they currently exist they don't really have a good clear hypothesis for what kind of benefit they're supposed to be creating and how they're supposed to create a consistent benefit from person to person right like everybody's microbiome is totally different everybody's biology is different and so the idea that like for instance a lactobacillus which is not typically part of a healthy adult microbiome in any meaningful amount and it's really just kind of something that we know is safe and part of the largely part of the dairy industry in terms of the gut microbiome.

This can go in and uniformly kind of benefit us in some sort of unspecified way around like gut health is not a very strong hypothesis and I don't think there's a lot of data to support that I think the best you can find in the scientific literature is that some probiotics can help some people sometimes and that makes sense right that like you have this everybody has a totally different community of microbes and And so you put a new microbe in there and maybe it's beneficial,

maybe it isn't. And so I was thinking about probiotics in a very different way, which is that, look, we know you can eat them and we know they're safe and they're capable of kind of performing all these functions.

So let's use it as a chassis or a delivery mechanism for the function. And so it's exactly like you said, that we don't really sort of advertise this in a sort of a traditional kind of probiotic gut health lens.

We really think about this, as we try and message this around the idea as like this is a, we're delivering a very specific function. And in this case, that function is the ability to break down acid aldehyde.

And it just so happens that a probiotic is the best way to accomplish that specific function. And so to your question about whether or not it will perform the same for everybody, that's the way it's designed.

And that's sort of where I leveraged my expertise in bacterial gene regulation. So bacteria have thousands of protein encoding genes and... And they don't just express all of them all the time. They turn them on and off in given situations.

So, you know, if they're around food, they'll turn on or upregulate functions that allow them to sort of like extract nutrients and energy from food. If they're sort of in a stress situation, they might upregulate, they might turn down, you know, nutrient acquisition proteins and functions and instead turn up like the ability to run away or to fend themselves or things like that.

And so they sort of like, they're able to regulate their DNA in really cool and interesting ways, which by the way, is like why I fell in love with bacteria. They're these like incredible like biosensors of thousands of different conditions and like constantly changing and fine tweaking what they're doing at any given moment, which is just really cool.

And so I designed our bacteria, our probiotic bacteria, to be able to express the aldehyde dehydrogenase enzyme specifically in the conditions of the gut and totally agnostic to what's going on. Since everybody's microbiome is different, it wasn't dependent on the conditions of each individual's gut.

For instance, like a lot of probiotics try to advertise that they will sort of like seed your gut or sort of join the community and take up residence there as a way of functioning. And we actually actively do not do that because that's a really hard thing to do consistently.

In fact, at this stage, it's impossible. Nobody has designed something that could consistently join everybody's microbial community, nor should they. We just made sure that the bacteria is just passing through your gut and as it's passing through, it is expressing a lot of this enzyme.

You don't have to have drink and alcohol for it to express this enzyme. It will just do it. So we just sort of programmed it to be constitutive, to have it be on all the time in the conditions of the gut.

And so if there's no alcohol around, then there's probably not any or not very much acetaldehyde around. And so then the enzyme, which is very specific to acetaldehyde, just doesn't do anything. But then, of course, if there's any acetaldehyde there, bacteria will be able to kind of break that acetaldehyde.

high down. So that was the idea. And so that obviously, that's that strategy wouldn't work for everything, right? There are certain proteins or enzymes you don't want to have around all the time. But this is one where it's totally fine to do that, because the enzyme just won't do anything if there's not any cell of the high present.

Did you have internal conversations about maybe not even, I mean, I guess people would know if they looked at the ingredients, what it was, but about not even like saying it's a probiotic for that reason.

Yeah, we did. Honestly, like that, there was, I certainly was concerned about the misunderstanding or improper interpretation of, of like, if we calling it a probiotic, and people would be like, Oh, is it and we saw this early on, when we first were pitching kind of like prototypes of the product, and some people were like, Oh, is it like yogurt?

Because they like, that was what they associated with probiotics. And it was like, No, that would be gross. We don't want you to eat yogurt before you drink alcohol, like that's not doesn't go together.

And so we had to do all this. And so we thought about like just like not even sort of like talking about it being a probiotic at all. But what we found was that if we didn't, people were really like, well, what is it?

And they really people really wanted to know what it is and how it works. So we actually found that the strongest way for us to explain the product was to just say that, like, this was a this was a this is a probiotic that we engineer to perform a specific function.

And that was like a really powerful, I think, way for that. People, I think pretty quickly understood the gist of maybe they didn't have like all the scientific details, but like, OK, I get it. Like, I was really surprised to learn first and foremost that even people who regularly take probiotics didn't always know what they were.

They didn't know that they were live bacteria. And so but what they didn't what almost everybody we found knew was that, like, that probiotics were a thing that you that are generally considered like good for you and they're safe.

And so even though I have my own, you know, sort of like opinions and thoughts around like the benefits or lack thereof of traditional probiotics, generally, it was a good way for people to just be like, OK, I'm interested in hearing more.

And so then we would and we really lean into the function and the benefit and the ability to break down acetaldehyde and less into the fact that's probiotic. But we did need to explain that that we needed to start somewhere.

And people were were fine. You know, it was a good kind of entry point to just say like it's a probiotic that we've engineered. Wow. OK. Yeah, this is so, so fascinating. And so you mentioned like people not realizing that probiotics are actually live bacteria.

So is this bacteria shelf stable? Like, how does it act in temperatures? Yeah, that was like a really fun part of the design process was like, OK, well, like, oh, I guess it as a microbiologist, I think it's fun.

I don't know if other people would care as much as I do. Sounds fun to me. Yeah, it was like, like, well, how do we like this is amazing? Bacteria can do everything. They live everywhere, like the most remote and extreme environments in the whole world, right?

Like in the middle of Antarctica at the bottom of the Mariana Trench, like everywhere in the whole on the whole planet will find bacteria. So they're capable of doing so many things. And so it was. okay, what bacteria can we use that will like really be the perfect product, right?

We have this opportunity here to build something that's really great. And so I looked for a bacteria, as I say, one that we knew was safe, that you likely eat every day already. And that was capable of passing through your gut and remaining functional, remaining alive, but doing minimal kind of, like I say, remaining as agnostic as possible to kind of the conditions of your microbiome.

And so I found this in a really common microbe called Bacillus subtilis. B. subtilis is this environmental microbe. It's in, it's a sort of, it's a soil microbe. It's kind of, you know, dirt and water around us all the time.

It's, and because of that, it's everywhere in our food system. It's all over the surface of fresh fruits and vegetables. It's all over your kitchen. It is part of many fermentative food processes. So like coffee and chocolate and kombucha and And notably, it's like kind of the star microbe in a fermented food called natto, which is like fermented soybeans.

And so it's this bacteria that we already eat every day. And what's really cool about it is that it has evolved alongside of essentially all mammals for the last, however many hundreds of millions of years that we've been evolving.

It's evolved to be a soil microbe first and foremost, but one that is happy to pass through our gastrointestinal tract. So it forms this like really resilient spore, which is basically a dormant state where it is incredibly hard to destroy.

And so it can pass your stomach acid totally fine, totally unharmed. And then what happens is that once it gets in through your stomach and into your small intestines, it senses that, you know, the pH is now not so caustic.

It's risen to a more neutral pH and there's all these nutrients around in the gut. And so it actually senses that and then wakes up out or germinates out of the spore form. And then it sort of floats down your gut and it enjoys the environment there and then just passes out the other side back into the soil.

And it already does all that all by itself. So when it's in this dormant spore state, it can like, it's very resilient and it can kind of last indefinitely. They've literally pulled bacillus spores that are tens of thousands of years old from like ice cores or like deep caves and things like that.

And then, and they're just in this dormant spore and then they literally, you just give them nutrients and they will wake up and they're alive. So they can last forever, which is very cool. And so when you think about it from a supply chain perspective, it's like, it's great.

As long as we get them into the, to go into the spore form to sporulate and then we put them into a bottle and we make sure there aren't any nutrients in that bottle to wake them up, they're happy to just sit on your shelf forever.

And they're also happy to pass to your stomach acid without encapsulation and survive just fine. And then they naturally already have the ability to once they get into your intestines, just wake up and start doing their normal functions.

Luckily nature provided all of that. And I was able to just kind of leverage that pre-packaged ability. so that when it woke up, in addition to all the other things it was doing, it would also express an enzyme of interest that I had sort of engineered into it.

What is the signaling in the intestine that makes them wake up? Is it the pH? Yeah, so it's the rise in pH. And then critically, kind of like one of the key signals for it to wake up is that is the presence of amino acids are basically like, you know, small bits of protein.

Wow. Okay. And you have tons of that in your gut, regardless of whether you've recently eaten proteins or not. It's just, it's always, it's always there. Yeah. I'd taken soil-based probiotics in the past.

And so that's my experience with looking into this. I just remember when I was, I was taking one called, I think called prescriptocyst. And I remember there was, I remember this was like a long time ago, like a decade ago, but I remember there was, I was on all the like message boards and there was controversy about the soil-based spore.

Like you're like, I'm getting a lot of like memories of people like arguing about the spores. And why were they arguing? They were, they were like, I'm worried that it was a problem. I know. To be very clear, there is literally not a single shred.

It's not even a controversy or even a debate in any sort of informed microbiological community about any risk-related spore formers. There was a weird sort of pseudoscience health trend around spore-based probiotics.

Like you say, about 10 or 15 years ago, that there was sort of, I think, as with many of these things, somebody who wasn't an expert in the field, did some sort of thought experiment and said, well, if these are really hard to kill and they're really resilient, then they might get stuck in my gut and I could never get rid of them.

And so they're dangerous. But we just know that that's not true. Every human on the planet eats spore-forming bacteria. You could never avoid them. You eat them every day of your life. And they're the most innocuous bacteria on the planet that literally is no case ever of a bacterial infection with bacillus subtilis.

It is like one of the safest bacteria you could possibly be exposed to. There was some sort of a controversy around that in the health community. But these days, as is correct, most, I think, you see actually kind of a counter movement.

There's like a lot of enthusiasm for spore-formers because of the fact that they're so safe and because they can pass to your stomach acid unharmed. You know you're actually reliably getting a good amount of them.

And so people are actually sort of like leaned into spore-formers and actually a lot of companies that are trying to develop bioactive live therapeutic drugs are using spore-formers because they are the ones that we think can be feasibly delivered and still retain activity.

So when you look at people who are developing drugs, for instance, for C. diff infections and things like that, they really focus on the spore-formers because they're just really powerful malic bacteria.

I'm so happy to have this conversation like a decade later because I was like, just, I remember all of that. I remember thinking, well, since this is like a soil-based probiotic, I would literally like open it and dump it on my food because I was like, I want to eat it in the most like natural way.

It's like I'm having dirt on my food. Good times, good times. So your pre-alcohol is in a like a drink form. Why did you choose that, that method? Yeah, it was purely kind of, that was purely a decision of like user experience that the great thing about these bacteria are that as I say, they're very stable.

And essentially, we can manufacture them and then sort of like grow them into a bioreactor and as you with any probiotic, and then you turn them into a powder. And then at that point, we have this powder that really functions like any ingredient, any other powdered ingredients.

And with this first product, we felt like the best user experience was one, like we anticipated people would be drinking this right before their first drink of alcohol. And we sort of anticipated that being a very social behavior, you'd be out with your friends at a bar or at a party, and you could all sort of share this.

I mean, it felt like people were sort of standing in a circle at a bar and all took a pill together, that would feel very weird. And so like thinking about like, well, what was sort of like a social behavior?

And so the liquid shot made a lot more sense. That being said, we wanted to keep it really easy to use and small and portable. So we made the shot as small as possible. So it's like a half ounce. So the bottles are really small, and they're easy to carry with you, they're easy to share, you know, you don't have to drink like a whole glass of water in order to take them or anything.

So the idea of being this just be really simple, really quick, easy, portable, and fun. So I know, because I'm just looking at the ingredients, my audience and I are like really neurotic about ingredients.

And we always get questions. So so it's water, natural flavors, potassium sorbate, sodium chloride, and then that bacillus subtilis ZB1A3 trademark, the natural flavors people are going to want to know.

I know. I if I had to over again, we I didn't know that I didn't know about this concern that the other people had like around natural flavors, I totally get it. It's like a way for, you know, I get that it's not transparent.

And I didn't I know that now. And I wish I'd known that when we formulated it. And I think it's like, we're definitely due for reformulation to fix that. I can share that the natural flavors we use, you know, it's not in any way meant to like sort of like hide anything devious.

They're literally just like extracts, largely citrus, to sort of create a and if you taste the part, you'll see it sort of like has this like sort of like very minimal, like very mild, like kind of like tart citrusy flavor.

And so like, that's really what those natural flavors are meant to kind of like create was just like, just sort of the hint of citrus. But yeah, I'd like to fix that going forward. I did, I did not appreciate or realize that people were really concerned about sort of like natural flavors.

And I understand why there's a lot of stuff out there. And it's not well defined and stuff. So we could do better there. Yeah, it's it's the natural flavors in the food. And then it's the fragrances and cosmetics where it's like, what is actually in that?

Yeah, what is that? And I totally get it. Yeah. So I, you know, a version, you know, I don't know, what version number we're on right now, but like, you know, a version 3.0 or something that that has clearly defined flavor molecules will be will be definitely an improvement.

I'm dying to try it. Is it sweet at all? Or is it more just like citrusy? No, it's not sweet. And like, and like, say the flavor is very mild. It honestly, like naturally doesn't really have any flavor.

And in early, and we thought, great, we'll just leave it like that. And but in early testing, what we found was that people we beta tested it, they were like, like, Oh, that just tastes like water. Is there anything actually in here?

Is it doing anything? Like they needed a flavor to know that there was something in there. We decided we first actually made it like a very complex flavor with like, that we thought was like, you know, for lack of better phrasing, we got a little too cute with it, we tried to like make something that was really unique.

And people like it was very polarizing. And a lot of people hated it. It turns out, we're not like flavor masters. So we just so we went and we just really minimized it. And we just went down to like a really simple, like very, and the whole idea is that it doesn't linger like because like, as you say, like, you know, you enjoy a nice glass of wine, somebody might want to have a nice bourbon or something,

you don't want to have some weird flavor kind of like lingering on your tongue when you're about to drink something that you enjoy the flavor of. So it's like a very mild flavor that does not linger.

It's just like a very slight kind of like tarp. And then it goes away. So when should you take it? And how long does it last? So I take it basically immediately before my first drink, just because that's what I'm thinking about it.

That's very like social opportunity as well. Like I'm usually like, you know, I have a drink with some friends and just take it right then, right before I drink the bacteria will, as part of their natural life cycle, as we talked about before, will pass through your gut in about 18 to 24 hours.

So the whole time they're in there, they're able to express this enzyme continuously. So the bacteria will last for a for about a day. And so essentially, you could take it earlier. But you know, it's like, for instance, let's say, you're heading out to the bar to meet some friends, you could take it at home before you leave.

And even if your strength is not for another hour or two, and that would still be totally fine. Or similarly, let's say you're going out to have brunch with some friends, and you plan to have like a mimosa brunch.

And then later that night, you're going to go meet up with some friends for a holiday party or something like that. And you might have a drink or two there as well that taking one before those bunch of mimosas will still cover you that night as well.

Okay. And so because I have a glass of wine every night, so I could take I could take one every night. Yeah, you can take it every night. Yeah. Okay, awesome. I love that you Okay, so when you were approaching how to communicate the GMOness of all of this, was that how?

What were those internal conversations like? And I love that you you put proudly GMO on your website. So what's happening there? Totally. This is like a core mission of the company. And I feel like in the biohacker community, people are pretty informed and enlightened on this.

So I'm like, always grateful to kind of talk about this that yeah, I mean, when I started this company, I was really frustrated created by the experience of walking through the grocery store and seeing kind of all of the non-GMO butterfly everywhere.

I think that the concern around GMOs started from a very reasonable place. There were certain products that were produced using genetic engineering that I think we have a very reasonable debate over their value versus their risk or danger.

And so in particular, when you think about round-up ready corn and soy. And so people were like, well, look, does this enable us to use too many pesticides? And are we ingesting those pesticides? Are those dangerous?

And so I think that's a very reasonable debate. But then unfortunately, what happened was that the entire technology of genetic engineering sort of got conflated with these products of genetic engineering.

And so then it became the case that because these were the only products people knew about, they just said that all GMOs are bad, which is like. really not like a reasonable or rational conclusion, right?

That like, genetic engineering is a technology and it's used to make products. And then so really, each of these products should be kind of considered in its own right about its safety or lack thereof.

So the analogy I often use is like, like, there's a very reasonable debate to be had over the risks and problems around guns and gun control, right? But we have that argument and nobody's arguing, nobody's like anti metallurgy, like the technology used to make guns, right?

Like we just say like, this application is bad, but right, like a spoon, which is also made with metallurgy is fine and actually a good thing, right? And so the non GMO movement really like kind of got co-opted by a bunch of brands that were looking to profit off like kind of fear mongering.

And so you see brands in the grocery store now that have nothing to do with this topic at all. They don't have any ingredient that has any possibility of being genetically engineered, right? Like, literally, you'll see like, I literally have pictures on my phone of like, non GMO water and non GMO salt, like these are not things that even have genetic material in them, right?

And so these brands are just fanning the flames of fear to try and look like sort of like, you know, green wash their product to make customers think that are like health wash their product to make customers think that this is better than some other water that might be genetically engineered, which is insane, right?

Like there isn't, there is no such thing, right? And even like, you know, wheat, there is no genetically engineered strains of wheat on the market. And and yet you'll see lots of like wheat flour being advertised as non GMO, but all wheat flour is non GMO, right?

And so like, and there's, you know, so I guess I was just really, really frustrated that basically, like this very powerful and valuable technology was sort of being kind of thrown under the bus by these brands that had no idea what they were talking about had nothing to do with the conversation.

And there's a lot of good that can come from genetic engineering as well. Like, you know, to be clear, I'm not I'm not saying that all GMOs are good. I think, as I say, there's some reasonable debate and reasonable concern about around like certain genetically engineered products that are currently on the market.

it. But we also can and are using genetic engineering to accomplish a lot of things that align with those very same people's values around like sustainability and protecting the planet. And a good example of this is, you know, there's a company that engineered microbes to fix nitrogen from the air directly onto the roots of plants and therefore prevent our you don't like over utilization of nitrogen fertilizers,

which are incredibly, ecologically damaging, like 15% of all greenhouse gases are, are produced because of the nitrogen fertilizer industry. And so the idea of taking a micro that's genetically engineered to not to fix nitrogen directly into the roots, like it massively solves this problem of a kind of like over fertilization.

And that's like, you know, a sustain, using genetic engineering for a sustainable practice, right, that like, I think we're aligned with everybody's values and the same people who are like, really concerned about like Roundup ready corn, would be excited by the idea of like, actually, like engineering used in this way, right.

And, and so The idea that we could elevate this conversation above good or bad or is it or isn't it, I think is really, really important. As you face the existential crises that humanity is facing right now, which is like feeding a growing population of people and dealing with climate change and dealing with emerging infectious diseases, genetic engineering is a very important tool in our toolbox.

And if used responsibly and aligned with people's values, I think it is an incredibly powerful opportunity for us to live more sustainably on this planet. That being said, if we throw the baby out with the bathwater here, then we're really asking ourselves to kind of fight these challenges with one arm tie behind our back.

And I think that that's a really risky and dangerous thing. And so when I started Zebatics, I was really passionate about this technology. And I was also really passionate about ideally, hopefully using this as an opportunity to elevate the conversation.

It was a deal breaker for me to work with anybody who didn't like share that, that that this was a core mission of the product was to be open and transparent with everybody about the fact that we use genetic engineering to like have to be prominent and front and center so that everybody was making an informed decision.

I think that was the biggest problem. I are not the biggest, but a big problem I saw with the genetic engineering as it was being used was that part of the reason people were so frustrated was that these companies tried to hide the fact that they were using it.

And they basically lied to people about it. And that made people upset. And they were like, we didn't even get the opportunity to evaluate whether or not this product was safe for us because you didn't even tell us that you're using this technology.

And so understandably, people were upset about that. And so I felt like, as a baseline, like, you know, table stakes move, we needed to be really transparent and let people make an informed decision about whether or not they wanted to try the product.

And then we would explain why we engineered it, how we engineered it. And a lot of people, again, to make an informed decision and hopefully feel comfortable with what we've been doing and why we use it and how it's clearly very different than Roundup Ready Corn, right?

These are two very different. things and just because they use the same technology they shouldn't just be lumped in as the same thing. Probably GMO is kind of like really the kind of a core of who we are and really trying to kind of get people to kind of evolve their thinking into something that's a little bit more nuanced and reasonable as they sort of evaluate genetic engineering because the act of genetic engineering in and of itself all it is is just guiding a genetic change which is the same as just the natural drift mutations that already happened that cross-breeding you know all these things are ways for us to sort of like that are ways that sort of genetics get changed and so as we advance in our understanding and our technology we can be more precise and more guided in that but fundamentally that in and of itself is not created a problem what creates a problem is what you genetically engineer something to do or something to be that theoretically could create a problem like in the case of something that was able to resist glyphosate you know that that theoretically could create a problem and so understandably we should evaluate that more carefully.

Have you seen other companies that are doing this, like the proudly GMO thing? I haven't really. It's one of my kind of like crusades is like I see like a lot of companies that build these incredible products that are beneficial, sustainable, responsible, and then they choose to try to hide that.

And I really strongly, I reached out to these people personally and like say like, I urge you to be transparent about this and like, and give people the opportunity. Like here's the thing we found is that like, there's this sort of like pluralistic ignorance around GMOs.

Like there's this belief that everybody else has a problem with genetic engineering. Like the most common thing I heard when I was doing sort of like the early interviews with people about to get better understanding of what people thought around genetic engineering when I was first getting started.

And the most common thing I heard was like on a phone call, somebody would just be like, well, I don't really care about GMOs, but I think everybody else does. So you probably shouldn't talk about it.

And the sort of like, everybody thinks that everybody else cares. Everybody's saying everybody else. Yeah, right. And that's basically evidence of a really well executed like kind of like smear campaign by a vocal minority that sort of convinced us that like every, like when you walk through the grocery store and you see the non-GMO butterfly where you assume like, oh, well, I guess everybody thinks they're bad and,

or like in the most cases people are like, I don't really know much about it. And this, but I guess I shouldn't like it because it seems like everybody, all these brands are taking such are doing such an effort to kind of like advertise that it's bad.

So I guess, I guess there must be something wrong with it, but I don't really know. And that's the most common thing is I think really for most people it's a lot of like ambivalence. And then there's sort of like this vocal minority that's very strongly opposed.

And then there's obviously there's a small number of people like myself that are enthusiastic about the potential of the technology generally. But there's just kind of like this broad middle. And so what I found was that if we were like this sort of like ambivalent middle that maybe like leans a little towards like, I don't know, maybe it's bad.

I don't know a lot about it. if we just explain what we do, and we're transparent about it, and we explain the benefit, that's the other thing, right? You walk into a grocery store, and you have the choice between non GMO corn or GMO corn, there's no benefit to you to buy the GMO corn, right?

That benefit was for the farmer, it wasn't for you. And so why would you ever choose the GMO corn? You know, I don't know much about it, but I've heard it's like bad for you, it's risky. So I'll take the non GMO, you know, 10 times out of 10.

And, but like, if we say like, Hey, look, here's this bacteria that and we use genetic engineering to create this very direct benefit for you, the bacteria can now break down acid out of high, so you can feel better the day after drinking.

And you wouldn't be able to get this benefit if we didn't if we hadn't genetically engineered it, like this benefit only exists because of genetic engineering. And like, here's how we did it. It's a safe bacteria that expresses an enzyme your body already produces, it's very safe.

And it's just a sort of like a logical progression of kind of the biology that's already happening in your body. You know, people are like, Okay, I'm comfortable with this. I want this benefit. I'm willing to choose this this product.

knowing that it's a GMO. For me, that's a really important first step. People can knowingly choose and rationally evaluate a GMO. I feel like the more we do that, the more people are willing to accept that this technology can be used for good.

Not to say it always will be, but that it can be. And ideally, we'll hold people accountable to using a product responsibly and transparently. Is there still that vocal minority that attacks you? Not really.

Honestly, it's funny. It's great the order of operations. We have this conversation. We get way more people writing in concerned about our natural flavoring than we do about the fact that it's a GMO.

Honestly, it's the fact that we lean into the... As I say, there's this belief that everybody is anti-GMO, but the fact is that most people don't actually care, or they have convictions loosely held.

And so us being transparent about it is enough for people to be able to feel like they are armed. And yeah, we definitely get people who reach out and want to know more. But in most cases, it's from a place of curiosity or trying to learn.

We really don't get a lot of people reaching out with the mindless knee jerk, GMOs are bad, which has been great. And I've reached out to many people in the non-GMO movement, people at some of these organizations and try to foster open conversations about how we can advance the conversation together.

Because my goal here is not to create an adversarial relationship. As I say, it's to get to a place where we're all aligned with what's the real villain or what's the real risk? And what should we be focusing on and how do we move this forward?

Because I think our values are aligned. I think we all want responsible human behaviors in the environment. And I want that as much as anybody does. And a really strong advocate for responsibilities to technology to allow us to reduce our impact on the environment and on the planet.

And I think that genetic engineering when used properly could be a tool to help us with that. And so ideally we kind of are able to create a dialogue and create regulations that are irrationally motivated to create the best outcome as opposed to sort of like a blanket ban, which I think is sort of like one of the objectives.

Speaking to that risk, I was gonna say, I think what most people worry about, but now I'm realizing the irony of that statement. So I don't know how many people worry about this, but I guess what I wonder, I'm curious about, is this idea that you could be engineering it for a certain purpose.

Because earlier you were talking about the problem is what it's being engineered to do, like that's where the problem lies. Is there the possibility of thinking or trying to engineer it for one purpose and some other purpose happens or like goes rogue or, that's like this, you know, fear mongering idea I have in my head.

Yeah, totally. And I think that you put it well, right? I think that that's, that sort of ill defined, like, well, it's alive. So what will happen is like, it's, again, it's sort of like one of these sort of like thought experiments, like that, like, that somebody would do, you know, very reasonably.

But the reality is that, like, we have a, all genetic engineering represents is an increased understanding of how, how biology changes its own DNA, and then basically applying that. So like, for instance, with our with our product, our technology, we use a product to, so in order to genetically engineer the bacteria, we use a process that that the bacteria already use to edit their own DNA, that they've evolved to do over the last 3 billion years,

which, by the way, is three times as long as plants have been around and editing their DNA. So a plant crossbreeding is sort of a way that we have traditionally engineered the genetics of a plant, right, we say like, okay, like, this plant has a really juicy apple, and this plant has a really like crisp apple, and we want to combine them so that we get a really juicy, but also really crisp.

And so we just take them and then we, we crossbreed them, which just mashes all their DNA together. And then we have no idea what happens. And when at the end, we just start tasting the apples and until we find one that has the traits you wanted.

And so that means the DNA combined in a way we liked, it was a very imprecise way to leverage like the natural genetic editing that plants already do, right. Bacteria are way better and way more efficient at this, because they've been doing it a lot longer.

And so bacteria, so the process that we use is one that bacteria have evolved, it's called homologous recombination. And so basically, what it does is a bacteria are floating around in a pond, and there's constantly like DNA floating around in a tube from other cells that have died.

And so there's just DNA everywhere, right. And, and bacteria will naturally, as part of the DNA, and then they'll start comparing that that random piece of DNA to its own to their own genome. And in this process of homologous recombination, what happens is they find a site of homology, AKA an area where the two pieces of DNA are similar.

And so when they find this homologous area, then they will recombine. They'll cross this new piece of DNA and exchange it for their own DNA at that specific location in their genome. And the reason they do that is because they're always on the lookout for new traits that might be beneficial to them.

They'll just kind of swap this piece of DNA in and it's super precise down to exactly the string of code of DNA where the two pieces are similar. They do this process all the way, already on their own.

It's very natural process. And we've just in the last 30 years or so, 40 years or so, kind of begun to understand that this is how bacteria added their DNA in the same way that plant crossbreeding is a way that plants added their DNA.

And so now, like, for our... our first product, for instance, we just grew up the bacteria in a test tube, and then we gave it a piece of DNA that encoded for the acetylide, the hydrogenase enzyme, and then also had some homology to a very specific site on the bacterial genome where we wanted it to integrate.

And so then the bacteria then just takes up that DNA and then naturally crosses it over itself, and it did all that all on its own. It's basically just a guided natural gene editing process. And so what we've created then is a bacteria that took up a piece of DNA, and by the way, that DNA came from another soil microbe that our bacteria interacts with all the time.

And so odds are really good that, in fact, I would say on a numerical level, like about how many bacteria there are and how long evolutionary history has been, it's essentially impossible that this hasn't already happened countless millions of times that this bacteria has taken up this piece of DNA.

It just hasn't been very interesting to the bacteria, so it hasn't kept it. And so now, so we basically just recreated the situation, this mimicking things that have already happened in nature to create something that we know is beneficial for us.

And so the idea that like this would like escape or do something crazy, it's just not in line with how we understand how biology works, right? Like the bacteria can only do what's presented to them. And so in this case, what's presented to them is the ability to break down acetaldehyde, to express this gene.

And so it will express the gene, and if it's helpful, it will continue to express it, and if it won't, it'll eventually lose it. Or if it's neutral, it'll retain it. And that's what it does. So we have like a very clear understanding of what the bacteria can do.

And then the question like, well, will it transfer this to other bacteria? It's like, that's a really important question as well. And the answer is yes. Bacteria constantly are swapping DNA, and so you have to be concerned about like, okay, well, its ability to express this enzyme, if it's gonna transfer to somebody else, is that gonna be a problem?

And so being really thoughtful about what you're putting into the bacteria as well in the ecosystem that's gonna be involved in. So you're gonna eat this bacteria, and this bacteria is gonna get into your gut, and it's gonna be able to express this enzyme.

It's also theoretically gonna be able to, at some level, rate, transfer this trait to other bacteria. And so is that going to be risky? Is that something we need to be concerned about? And again, this is an enzyme that your body already makes.

In fact, many of the microbes in your gut already make this enzyme as well. They just don't make enough of it at the right time to help you because you didn't evolve to drink alcohol, right? Like alcohol, like humans have been around for 150,000 years.

We've only been drinking alcohol for the last like 6,000 years. So this is not a trait that is normally part of like expressed at high levels. And so all we've done is make sure that you get enough of the enzyme at the right time.

But if this bacteria were to transfer this trait, say to another bacteria in your gut, that's normal, this trait already exists in the gut. So that really wouldn't be an issue either. So I guess sort of that's a long way around of saying that like concerns about the safety of sort of engineering something, we have to think about the unique risks that we create with the technology, but I think we can reasonably do that.

Like as evidence here, right? We're taking a trait that already exists in the gut. We're transferring into a bacteria that likely has already had this trait before. We're not really introducing anything new.

We're only ensuring that you have the right microbe with the right ability at the right time. That's how we can mitigate risk and say that we're not creating something that's unknown. We're sticking to the things that are already known and already tested in the petri dish of nature.

I think that obviously that's a very conservative approach, but I think that that's the approach that the industry can currently take and be really confident that the products that we're making are safe.

And then as we learn more, we can be more and more aggressive in kind of how we how we build this technology up. But like we have to set guardrails of responsibility. And I think that there's ways we can do that, that demonstrate to the scientific community and the public at large that that that we can build something that is very reasonable and very safe.

This is so fascinating. That original that other soil microbe that has the the ability to create that enzyme. Why did you not use that one as the the periodic that we take? Yeah, because it's not one that you that you don't as commonly eat that bacteria.

Bacillus subtilis is this very like common soil microbe that we eat all the time. It has evolved the ability to kind of pass our stomach acid. This other microbe is not one you're ingesting commonly, and you probably do ingest it because it's in it's in the soil as well.

But like it's not evolved to pass your stomach acid unharmed. So it likely would just sort of die in your mouth or in your stomach. And so it's just not, you know, it's not set up for basically it's not it's not a known kind of probiotic.

Gotcha. So it had the the trait, but not it's not the best carrier for it. Right, exactly. And truthfully, 70% of all life on the planet, including your own body, your own cells, possesses an aldehyde dehydrogenase enzyme.

So there's like a really common enzyme. It's just a matter of getting expressed in the right place at the time. So many of the microbes in your gut also make this enzyme. And so that theoretically could have been another approach.

We could have taken an already existing microbe from the gut that makes this enzyme and then engineered it to make sure that it was that it was constitutively making the enzyme. making at the right time, that would have been a different approach than the one we took.

And really, like equally, I would say arguably, equally safe. But actually, I think that really the idea of taking a product like a bacteria like bacillus subtilis, one that you eat every day that doesn't join your gut is safer, right?

That like that engine, that engineered microbe will pass right through you, as opposed to one that could join the community in an altered state that could be more disruptive theoretically. How do you teach or tell the bacillus subtilis to keep the DNA?

Because you're saying that normally, it doesn't want to keep the things or might not keep the trait. Right, right, exactly. And so over time, it may not. But like over the course of time that we that we care about it, essentially, the number of so you know, we grow it up in a bioreactor and affirm it, you know, a big fermentation tank.

And so that there are several generations, you know, replication events that happen there and then and then you eat it and it will basically for the 24 hours that it's passing your gut, it may replicate one or two more times.

So we have a certain number of generations that we need it to be stable for. And after which point, if it ends up deciding that it doesn't like it and it wants to get rid of it, or it doesn't care about it, or find something else that's better, we don't really...

At that point, it doesn't really matter. That goes back to its normal state of interaction in the environment. And bacteria are constantly changing. I think that's another kind of misconception. I think that sort of an underpinning fear around genetic engineering is the idea that we're creating change.

And that wouldn't have happened already. That normally stasis is the norm. And that's not the case. That the environment and bacteria are incredibly dynamic and constantly changing. Any change we make fundamentally, that's normal for nature.

Nature's DNA is constantly shifting and changing. And so once it gets out in the environment, again, if it changes and shifts that we expect it to, that that's fine. But we really wanted to make sure that it's stable for the period of time in which we're manufacturing it and that you're eating it.

And so we can test that. And we can see how stable is this. And that is a good question to ask, because sometimes you see this a lot in biomanufacturing, that you'll engineer a microbe to do something.

And it doesn't really like doing it. And so it'll quickly kind of mutate or change that trait so that to essentially break it so that it no longer will do it. Basically figure out a way to turn it off.

Because it's been a lot of resources on this thing and it's not really giving me any benefits, so I'm going to turn it off. And so then the bacteria will find a way to do that. We found that in this case, because of where we selected to put it in the genome and because of the traits we decided to put into the bacteria, they are willing to kind of...

They don't really find it as a problem. So they're not motivated to kind of get rid of it. It doesn't really provide them any advantage either. It's sort of like a neutral. If anything, with this first product, we swapped it...

in, it normally has the ability to swim. And we sort of swapped in our ability to break down acetylide before that ability to swim. And so once it gets out into the... It doesn't need the ability to swim when it's in a bioreactor or in your stomach.

Once it gets out into the real world, out into the soil and the water systems and things like that, it'll want that ability to swim again. So it may very well... It is fundamentally attenuated, which I would argue from a genetic engineering safety perspective is a good thing.

That it's weaker than it would have been otherwise. So it'll just die off or it will reacquire to the ability to swim and go back to kind of the state it was in before we edited it. Oh, wow. So does that mean you basically need to always...

And I don't really know the process of... I don't know anything about the process of creating it, but does that mean you always have to kind of create this supplement as like a first generation rather than...

Can you just breed the continuing generation? No, as long as we keep it in... So we basically... We make the bacteria once and then you store it like you freeze down a vial of it in the freezer. And there are essentially like billions and billions of starters in that, in like one little vial, right?

Cause you know, bacteria are capable of mass replication. So you can add to a big fermenter, just a small amount of bacteria and then they'll grow up. And so in that, as long as in the process of growing it in the lab and in the bioreactors and everything, we don't, you know, we don't challenge it in any way where it would be motivated to get, to get rid of this, this function, it's happy to retain it.

And so we just need it. Yeah. So we need to, once we create the strain, we want to, we really want to create consistency. So we just freeze it down and then we draw from that same vial literally tens of thousands of times.

And it's really, these are all identical clones of each other. And those are all like identical starters to kind of start up the same fermentation process. Gotcha. And then you mentioned testing. So what testing have you conducted?

We've done all kinds of things to kind of test it. So obviously when we first built it, we needed to ensure that first and foremost that we felt like the product was safe. And a lot of that went into the design of the product.

As I described, we chose a microbiale every day. We chose an enzyme that is already exists in the ecosystem of the gut that your human body, the human body is used to being experienced with. We chose a donor that this bacteria already interacts with.

So all of those things, right? There was no reasonable expectation. This would be unsafe in any way. It's a safe bacteria expressing a safe enzyme that your body is already exposed to. It's already present in its ecosystem.

So all that, that's 90% of the way there, right? But then of course, once you build it, you want to just confirm or verify that all that holds true. And so we did extensive safety testing to demonstrate that the bacteria was not, didn't have any pathogenicity or allergenicity or virulence or ability to kill cells or anything like that.

There was no expectation that would, but we verified for sure that we didn't see any of those things. And so we were very confident that the product is safe. And indeed now we've been on the market for five or six years, the, all of that.

hundreds of thousands of people who have tried the product, there's been no issues. Six plus million bottles sold to date. It's all consistent with safety, which is really important, of course. But then we also wanted to determine, does it break down acetaldehyde?

And can it do that in the conditions of the gut? And then does that actually result in people feeling better the next day? Because that's the purpose, right? Even if it did break down acetaldehyde, it's not really going to have an effect on the way you feel.

We wanted to test those things as well. So we did a lot of testing of how much acetaldehyde it could break down, how quickly it breaks it down. Is that physiologically relevant, i.e., does it break down enough acetaldehyde to cover as much as you might be exposed to?

And does it do it quick enough to matter? And so we did a lot of testing on that and demonstrated that, yes, it was capable of breaking acetaldehyde. And we simulated the gut environment, the right acid and enzymes that were floating around in there, and bile salts and all the kind of things that would normally affect.

bacteria's ability to function. And so we saw that all that was good. But then ultimately, we wanted to know, was, okay, fine. It can break down acetaldehyde at a reasonable rate and in reasonable conditions, but does that actually result in people feeling better?

And so we did several tests to kind of see how people felt after taking the product and then drinking alcohol. And what we saw before we launched the product, because we really want to commit, we didn't want to launch something that wasn't going to work.

Because what's the point, right? We could sweep vitamins in a bottle the same as everybody else. We want to make something that wasn't going to work. Before we launched, we tested the product and to see if people felt like that it improved their experience the next day.

And we saw just a really strong response there that gave us a lot of confidence. So we saw that, you know, when we asked people the day after using the product, if they felt better than expected, the same as expected, or worse than expected, we saw that 95% of people said they felt better than expected the next day.

So we saw that this is huge. People definitely saw the benefits that we were supposed to see from the product, which is great, which is exactly what we wanted. And, you know, since we've been on the market, that number has actually held really firm that like, we've not I'd say with, you know, tens of thousands of customers, when we look at customer satisfaction rates and things like that, that that's very consistent that we see,

you know, above 90% of people who use the product are really are, you know, express like strong satisfaction, we have 100% money back guarantee and less than, you know, half a percent of people reach out and request a refund.

And we see, you know, very high star ratings, all the things that are consistent with the fact the practice working well, which gives a lot of confidence that that we've created something that actually is creating a real benefit for people.

Did you do any placebo controlled testing? So internally, we did do things to convince ourselves, right, that like, this wasn't just a placebo effect. That being said, we don't we can't we don't we were unable to design a, you know, and drawing on my background and clinical study design, there are rules and regulations around like kind of how like how to just how you can design a study that involves alcohol.

Oh, wow. Yeah, but there's a lot with that. There is and it's unfortunate and frustrating. There aren't like kind of results that we can sort of legally share about like sort of, we obviously did things internally to validate, as they say, our goal was not to create a placebo effect because anybody can do that, right?

And so why bother launching the world's first ever genetically engineered probiotic if it's no better than just kind of ran us. So we did things internally to really convince ourselves strongly that this house having a real effect.

Unfortunately, like, it is very difficult, you know, essentially, you need to do like drug level trials to kind of like, for anything that involves alcohol, especially. So we, you know, as a startup and not a drug company, we didn't have the resources or ability to kind of set that up.

So we satisfied ourselves that, you know, we were creating something that we really believed in that we saw, you know, really strong signal was creating a real benefit. But ultimately, you know, we recognize that, you know, this isn't a drug and we don't have placebo.

placebo controlled clinical trials that we can publish to the public. And so people are going to be trying this product without that, like a surety or guarantee, you know, so we have to make different kind of guarantees.

So that's why we offer 100% money back guarantee is that we want to make sure that people are able to try this risk free. And if they don't perceive a benefit, or even if they just don't feel like it's for them, right, like for whatever reason, we always refund them no questions asked.

So that's the best way that we can de risk it and say that like, look, numerically speaking, the vast majority of people use this product, really see a positive effect from it. We're very confident that you will too.

But of course, if you don't for any reason, then we really we definitely don't want to keep your money if we're not creating, creating real value for you. Have you met the company reputable? Oh, reputable health.

Yeah. Yes. Yeah. Because they like partner with companies and right. And so a lot of that is like sort of self reported outcomes, which again, gets tricky for us. I think I like I don't want to sidestep it.

I'm not trying to dodge the point that like, it's not I'm not saying that nothing could ever be done. I think we I think that there are things there are ways we can design it. The challenge becomes inconsistency when people so like you'd ideally like to specify like in a good control clinical trial, for instance, with alcohol, you'd specify exactly how much somebody drinks and how much time right and so that you have like reproducibility and control over their experiences,

right? Like, because you're talking about like, the readout right is perception of pain the next day, right? Somebody wakes up and they say like, Oh, I feel I don't feel good, I feel gross, or, you know, feel this or that, right?

Like, it's very much like, it's a it's a it's a subjective readout of their pain. And so that's a very variable response, right? You can imagine that person A and person B might perceive their pain very differently.

And so you have to have a lot of really strict controls over like, kind of how they behave, right? If you let them just sort of like, oh, just, you know, go out and drink or whatever, and have as much or as little as you want, you'll get so much variability that it'd be impossible to draw any conclusion.

So you people to drink a certain amount of alcohol. There's very tight regulation over that you kind of can't tell people to do that without like having them observed like in a hospital setting or whatever.

And then even then it has to be sort of like a relatively low amount. And then if you're having a low amount, then you know, it's unreliable whether or not you'll have symptoms or what symptoms you might have, right?

Like it's only kind of as you have more that like that signal to noise kind of like you get a better signal relative to noise. So it just becomes like really challenging. And so with some of these companies that are helping consumer like leverage or like consumer behavior to kind of get, you know, readouts and self reported outcomes, I think that can be really powerful for a lot of different products.

It just gets really tricky with alcohol because of kind of the basically the fact that alcohol is, you know, something that we know damages you. And so you kind of can't tell people how much to drink, but like getting a reproducible outcome kind of requires you to have some specificity.

Yeah, that totally makes sense. And that reminds me, I didn't ask probably one of the questions everybody is dying to know, which is, how does it affect somebody's perception of intoxication like being tipsy?

Because the product does not affect alcohol at all. It does not affect intoxication in any way. A product only works once your body's already broken down the alcohol and converted it into acid aldehyde.

It should have no effect on your level of intoxication. And that's an important thing to know in both directions. This product does not make alcohol any safer. It does not reduce the damage of the alcohol itself.

It doesn't make you any less intoxicated. It doesn't mean that you can now drink and drive. You still shouldn't text your ex when you've been drinking. All those things, all the same rules about alcohol safety still totally apply.

And this is really about helping you feel better the next day and land on your feet the next day. And really the primary benefit here is the ability to stick. I think, and we see this for a lot of our customers, is really to stick to your healthy habits and routines.

I think you have a few drinks with your friends and sometimes that's sort of like a zero sum decision. I either have the choice of going out and enjoying some alcohol in a social situation and then maybe not performing my best the next day or not making that morning workout or whatever else.

I sort of have to kind of either or those decisions. The idea is you can still stick to those healthy habits and routines when you decide to kind of have a drink with friends. I have a hack for tipsy texting I can share because I am so bad about it.

I just know I'm going to do it. So hopefully nobody who's listening to this is somebody I tipsy text. But now I pre-write my tipsy text while sober so then I know that I approve them. That is so smart.

Honestly, it's very analogous. I often say because the other thing that a lot of people see is that you sort of get like the drunk and munchies where you've been drinking and then you feel hungry. That biology is really interesting.

It's related to the alcohol itself. Ethanol kind of affects some of the hormones that regulate hunger and satiation. So even though there's a lot of calories and alcohol and you definitely are not, you shouldn't feel hungry because you've had plenty of calories.

It stimulates the starvation hormone and so it makes you feel like you're really hungry, which is why you crave especially really nutrient dense foods, like really fatty, greasy foods is because your body feels like you're starving.

And so I say, similar to your preloading with approved tacks, I often recommend to people to preload your fridge with approved healthy snacks. So there's still attractive and appealing, but you get home and you're like, oh yeah, this hummus wrap, it's ready to go.

It's easy, it looks delicious. And so then you're like, okay, there's some vegetables in there. It's not too bad for you. And hopefully it will satisfy those cravings. I love it. We got all the hacks here.

Oh my goodness. And I just realized, speaking of, so you have a second product that helps convert sugar to fiber. Yeah, exactly. So the second one, did you launch that? We just launched it in September and just really excited because it allows us to kind of tell this broad story, like the amazing things we can do with genetic engineering.

and genetically engineered probiotics. So the same bacteria, the psilocytolus, the same spot in the genome where it would be expressing this aldehyde dehydrogenase. Instead, we put in a different enzyme.

This enzyme basically converts sugar into fiber. The reason that I built this product was because of earlier when we were talking about probiotics and people were like, oh, I'd say like, oh, it's a probiotic.

It's genetically engineered to do, convert or help your body deal with acetaldehyde. And be like, oh, that's so cool. I love probiotics. Does it help with like your gut health? And I said, well, like, you know, probiotics generally, I don't think have like a super strong hypothesis for sort of consistently helping with your gut health, but that's what people wanted.

And so I thought like, huh, I wonder if we could use the same technology to make a probiotic that actually could reliably help with gut health. And so I thought like, okay, drawing on my expertise in microbiologists, like what are the things we know would actually help your gut like uniformly, agnostic to kind of the different microbial communities people have.

One of the things that we know, without a doubt, is that like diversity of the microbiome is, even though like everybody's microbiome is different, a more diverse microbiome is generally speaking, or more diverse I say gut microbiome is more, is we know is healthy.

And so you want to foster diversity. And the way to do that is by feeding it a diversity of foods and for bacteria, the food is fiber. So you want to get a lot of different, you basically want to make sure you eat enough fiber and you eat a lot of different kinds of fiber.

I thought like, well, one great way to improve gut health would be to just make sure that people are eating a diversity of fibers. And 95% of Americans, in fact, don't get enough fiber in their diet.

So this is like a very ubiquitous problem. We could take bacteria and then engineer them. So take a probiotic and engineer it to create fiber directly in your gut from the foods you're already eating.

Cause you can tell people to eat more fiber and we do that all the time. And some people want, some people won't, but like if we make, if we basically make a probiotic that helps you get more fiber from the foods you're already eating, that would have a huge impact on people's kind of like microbiomes in there.

microbial health. So that's exactly what we did. Essentially fiber is just a bunch of sugars stuck together into a long chain or in like a bush. Bacteria contain enzymes that can stack those sugars into fibers.

And so we basically just made sure this bacteria could actually, in this case, this is an enzyme that bacillus cellos already makes. It just doesn't make very much of it reliably in your gut normally.

So we just engineered it so that it was making a lot of this enzyme all the time when you eat it so that we can convert small amounts of sugar from the food you're already eating into a rare prebiotic fiber directly in the gut.

By making a rare fiber you don't already get very often, that fundamentally increases the diversity of fiber since you're not getting this from other foods that you're eating. How much sugar can it affect?

So would it have a measurable effect on blood glucose levels as well? No, it won't. And so we're talking five to ten grams of sugar a day. being converted into five to 10 grams of fiber. And so five to 10 grams of sugar is not a very meaningful amount of sugar, right?

But five to 10 grams of fiber is a very meaningful amount of fiber, right? Like on average, people should be getting about, about, you know, I'd say like 25 to 35 grams of fiber, depending on how many calories you eat every day, you know, 10 grams of fiber, that's, you know, that's on average, people get about half of the day, if I were to take so that means they're on average falling about, let's call it about 15 grams short.

And so our ability to create five to 10 grams of fiber is a meaningful covers a meaningful gap that people are kind of hitting or missing. Wow. So cool. Can I make a product request of what I would love?

I mean, I love both of those. Yeah, yeah, totally, please. I would love a probiotic engineer to create really high doses of the DAO enzyme to help with histamine. Mm hmm. Yeah, we hear we hear read a lot about kind of like histamine and right and sort of some of these interesting, you know, we have to, we have to think about do we think we can have a reasonable impact in the gut, in the time in the place in the gut,

right? And our bacteria is mostly going to be active later in the small intestines and in the large intestine. So I'd have to look into the science more to see if we have good access to that. But that's certainly something that I think could very well be feasible.

So yeah, that's a that's a great idea. There's definitely a market for it because you can order the DAO enzyme itself. It's really expensive, though, and I never found one that I really like. And then you can also order specifically like low histamine probiotics, because people, people struggle.

So I think there was like a probiotic that really helped you break down histamine, especially because when you're eating, it's often like histamine foods. Yeah, well, they can also get formed. And so like like many of the micros you got produce a lot of these types of molecules.

So it's certainly, it's certainly possible. It's really interesting. Yeah, and you know, one of the challenges in addition, so you mentioned that, you know, just taking the enzyme directly is an option, the fact that it's expensive is one thing.

But even if it wasn't, I mean, enzymes are proteins. And so like, if you eat an enzyme, it's you know, your body treats that really similar to eating like the protein and you know, muscle protein and like chicken or whatever it's gonna really quickly your body is like equipped with a ton of different mechanisms of just quickly breaking down that protein into its component amino acids to use as like,

you know, building blocks and energy. So if you eat an enzyme, it's unlikely to retain its function for long and some enzymes either naturally or through engineering can resist degradation for longer.

But in best case scenario, you're getting maybe an hour to a function. Whereas like, what we've done is we give you the protein factory, the enzyme factory. So we give you the bacteria, the bacteria can pass your stomach acid on harm to protect the enzyme from sort of degradation and then and then it makes that enzyme and as that enzyme potentially gets degraded, it'll just make more of it, right?

So you can have kind of continually resurfacing it. So there's multiple advantages to this process in addition to the fact that we can make something that would hopefully be more affordable, but also be more effective for a longer period of time.

Awesome. This has been one of the coolest, most fascinating conversations I've had. This is just so cool. I bet listeners are super eager to get these products right now. So listeners can go to zbiotics.com, and you can use the coupon code Melanie Avalon to get 10% off.

So thank you, Zach. Thank you so much for that. Oh, wait, is it called zbiotics? Why is it called zbiotics? Because your name is Zach. Yes, unfortunately, it is because of that. Really? Oh, yes, I love it.

I literally made it up like on the spot quickly at like a pitch competition because the other name I have for the company was taken. And I was like, it was just it was before I even started the company.

It was just like, Oh, it's a you know, I just need something as a placeholder and we'll change it if this ever becomes a thing. And then when it kind of became a thing, and we look to do naming exercises, it just like people liked the zbiotics and we owned the domain and it was like, Okay, so we're sticking with it.

But yeah, so the Z is for Zach. Unfortunately, I wish we had some better, you know, mission driven or scientific reason why that's the name. But my brand is Avalon X. And that's my name. And the X is just because it sounds cool.

So like we're in the same boat. Yeah, but you're you are your brand, right? Like you are what exists. So it makes sense that you know, you're, you're the most exciting product and part of your brand.

So I was I would have liked up something that was more, you know, science and micro focus, but it's it's cool. It is what it is. You could retroactively attribute some something to it. Totally. Yeah, I know.

I love that. That's amazing. Again, so listeners zbiotics.com the coupon code Melanie Avalon will get you 10% off. This was incredible. Was there anything else you wanted to share with with listeners about everything?

No, this was amazing, Melanie, I really can't thank you enough. This was like, I'm really glad we got to talk about GMOs. And we got to really dig into the site, you know, you have a very As you prepped me before the call, you're a very savvy kind of scientific audience.

So it was really fun for me as a scientist to kind of get into the nitty gritty and I really appreciate that a lot. So this was phenomenal and thank you so much. The last question, I actually ask every single guest on this show and it's because I realize more and more each day how important mindset is.

So what is something that you're grateful for? I'm grateful to have the resources and the knowledge to like invest in my health. I really think carefully about what I put into my body and I'm really grateful to know that because I think that life in our time on this planet is really precious and valuable.

And so being able to invest in that is probably one of the best things we can do and I'm just really grateful for the ability to do that. Well, I love that so much. And seriously, Zach, well, first of all, thank you for what you're doing.

This product is so incredible and I'm sure it will help so many people. I'm gonna start taking it every night before my wine and thank you, like really thank you for that conversation about the GMOs.

I realized I myself have had an incorrect perspective and this is completely paradigm shifting for me. So like, thank you for doing that and taking the initiative to really help educate the world and doing it so boldly.

I think that's really, really needed. So I just really appreciate everything that you're doing. Wow, I appreciate that a lot. Thank you, Melanie. So have a good rest of your day and I will have to talk to you later.

All right, sounds good.