EPISODE #1000: The Bacteria That Lets You Drink Alcohol Again – Zack Abbott, Ph.D.

You're listening to the Human Upgrade with Dave Asprey. You're listening to the Human Upgrade with Dave Asprey. This is the thousandth episode of the Human Upgrade and I wanted to do something special. So it's also the first podcast that I've ever recorded out of my new studios in Austin, Texas, where I am living for a while, which is fantastic and fun and it's helping me to support our Upgrade Labs franchise and lots of those going around. Guys, check out ownandupgradelabs.com if you ever wanted to bring biohacking to your town. And what else could I do that's special? How about we party?

What?

Well, we could have a party now, but I'm going to take you back to the second, maybe third blog post that I ever wrote back in late 2010 was, Hey, I hate to say this, but alcohol is bad for you. I know that we enjoy it as humans for lots of reasons, and you've heard me talk about alcohol replacements that hit similar, similar pathways in your brain, things like Trucava and all. But I do not believe in any way, shape or form that we are going to stop drinking as a species anytime soon. But what could you do when you want to enjoy a really good glass of wine, when you want to have some amazing tequila? I'm in Austin. Apparently, that's obligatory. So what do we do about that? And you've heard me talk about glutathione and vitamin C and NAC and all the precursors for glutathione and how it helps, but that's not what this show's about because, well, I already taught you that. And if you've been a listener, you probably already figured that one out and you figured out you can get away with it. But there's something new that is cutting edge biohacking. And that's what I wanted to talk about with you on the, on the thousandth episode, because this is the first of what I think is going to be very, very many companies with this innovative approach. It's a company I first spoke with about, what, four or five years ago about the potential for this, and it's just now ready for the market. And I'm so super stoked about it because it's a new, a new way of solving a problem that I think all of us have. And we're going to talk about probiotics and pre engineering them in a way that you haven't really heard of before. Our guest is Zach Abbott, who is the CEO and co founder of a company called ZBiotics. This is not like any probiotic or anything else I've ever talked about on the show before, because it's the first of its kind in the world. So this isn't like a hey, guys, I want you to go buy this kind of podcast. Although, frankly, I think this is a very worthy thing. This is a holy crap, we can do this now kind of podcast. It's super cool. Zach, welcome to the show.

Thanks so much for having me. And I love that introduction because that's exactly how I think about it as well, which is that I'm excited about the technology and the new category that we're building. Yeah, I'm excited about our product, and of course, it'd be great if everybody went out and bought it. But really what I'm excited about talking about is genetically engineered probiotics, and I think the future that we can build with them.

Well, there you go. You just said the words. A certain percentage of our audience is now up in arms. He said genetically engineering. That means glyphosate, Monsanto, and environmental devastation, doesn't it?

You know, my favorite topic is talking about genetic engineering. And. And certainly, look, the mission around the Bottix is to elevate the conversation around GMOs and genetic engineering. And I think that you're exactly right. I think that a technology has been conflated with bad business practices. So I certainly wouldn't advocate and say that all GMOs are good or all GMOs are bad. It's more like it's a tool. Right. You think of, like, let's say you're anti guns. You probably aren't anti metallurgy, the technology used to make the guns. Right. Because you recognize that metallurgy can also make a spoon, and that has a very different safety profile, a very different kind of use case. Right. And so genetic engineering is the same thing. It's a tool. It is a novel tool in our toolbox that as we've sort of advanced as a. In terms of science and biotechnology, it's something that we can do now pretty easily. And it's a matter of how it's applied. Is it applied responsibly, is applied for the benefit of the user? All those things are questions that we can do that or that we can ask when we're trying to use genetic engineering. And so I think that genetic engineering can be used to make a lot of things that are really amazing and advance humanity in ways that everybody can align on. Right. Like the purpose of Genetic engineering is to help us sort of combat some of the major existential crises facing humanity around. Climate change, emerging diseases, feeding a growing population of people. Genetic engineering is a tool. Biotechnology is a tool we can use, we can leverage for that. And I think that's something everybody get on board with now. Can also be used for things that people don't want. Absolutely. And so really trying to elevate that understanding of genetic engineering to a place where it's not, is it or isn't it good or bad? It's more like, is this use of it any good? And I think that there's a lot of really exciting use cases.

Do you know how we make citric acid these days?

Yeah, I mean, we use genetic engineering to make lots of things. I would say that my favorite example of genetic engineering used in a really positive way is human insulin. So go back to the 1960s and 70s. We were literally slaughtering tens of millions of cows and pigs and taking their livers and pancreases and loading them onto refrigerated train cars and then driving them to giant factories where we did a massive extraction of pig and cow insulin. And we gave that to people to keep them alive who had type 1 diabetes. And then this little plucky kind of new biotechnology company called Genentech took E. Coli and genetically engineered it so that it expressed human insulin. And then in the space of a fermenter, about the size of a refrigerator, we could completely eliminate the slaughter of tens of millions of animals that we raised and threw away, just took their livers and pancreas.

Didn't we also eat them? Or were they too stupid to do it? You're telling me that they didn't put them, we ate them.

Maybe, maybe not. It depends, you know, with the pharmaceutical industry, like, who knows if that was considered, you know, acceptable? So regardless, it was certainly a massively inefficient use of time and energy and animal life. And so the fact that we could then program a bacteria to make human insulin as opposed to cow or pig insulin, you know, we were massively able to scale up and now treat, you know, a growing population and growing demand that needs human insulin. And so nobody has a problem with GMOs if you're diabetic and you're going to die if you don't get insulin. Right. It's a very safe use case, and it's very valuable for humanity. And there are so many other things that we can do with genetic engineering. And. And as they say, it's not something that Uniformly will be used for good. And, you know, and I would argue that even in the scenario, right, with glyphosate, it's a. I think that the fundamental purpose of that initially, right, you could see was, was meant for sustainability, right? The idea that we could get more yield per acre, mow down less farm forests to make farms. And that's a good goal, right? Like the way it got applied maybe is definitely unsavory. And so I, I don't think that that's how it worked out. But the goal of engineering to make more sustainable crops is, is very possible. So there's really cool science being done right now with engineer microbes in fixing nitrogen from the, from the atmosphere into the root nodule of plants directly, as opposed to adding nitrogen fertilizer, which people talk a lot about, you know, pesticides as environmentally damaging. But nitrogen fertilizer arguably is one of the worst things we do agriculturally. All that nitrogen gets washed off the soil and goes into local waterways, causes algal blooms, one of the hugest sources of greenhouse gas. And so, but there's all that, you know, 70% of our atmosphere is nitrogen. There's all this nitrogen floating around there, right. And microbes are already capable of fixing that into something that a plant can use. So there's a, so that's a really great application of genetic engineering where we can actually be more sustainable in our agriculture, as an example. And so I think there's a lot of use cases for genetic engineering, if used responsibly and applied well, that could really elevate us as a humanity as we deal with existential crises.

I prefer natural solutions because there may be unintended consequences for anything. But there are some things we can do now and something that you just stepped up there with your big background and all this kind of stuff and said, what if we solved the alcohol problem and the alcohol problem. Just to be blunt, guys, if you drink even one drink per night, several nights a week, your brain won't look the same. I am on the board of Amen Clinics. Daniel Amen is a dear friend. He's got a quarter million brain scans and he shows people over and over what a little bit of alcohol does when you drink it. And the mechanism of action of alcohol is that it makes a lot of a chemical called aldehyde in the body. And all of the things I've taught you to do are to just blunt the aldehyde spike, the glutathione, the vitamin C and things like that. Aldehyde is something that Causes aging via the creation of advanced glycation end products. Talk to me about aldehyde for a little while and then tell me what you figured out with gut bacteria and aldehyde.

Absolutely. So aldehydes are sort of a class of chemicals that are highly reactive. They have a double bonded oxygen and they are able to react with a lot of things in your, a lot of things generally, but then, you know, specifically in your body. And so the molecule alcohol is sort of basically oxidized to acid aldehyde specifically, which is a, which is an aldehyde. And acetaldehyde is highly toxic. It's a, it's a small molecule like alcohol that is highly soluble. It kind of diffuses through your cell membranes. It can bind to DNA, creating DNA adducts and binds to protein, creating protein addicts. And these things are highly inflammatory and damaging, which causes cell death. And basically when you, when you're exposed to acetaldehyde, you kind of, you create all this sort of, you know, as you put it, Dave, you kind of gunk up the gears. You create a lot of cell death, you then. Which simulates a huge immune response and you sort of get this inflammatory response dealing with kind of this havoc that's being wreaked. It's kind of like the bull in the china shop. And it's a very small molecule, but it has this big outsize kind of impact. And so the best way to deal with that is to turn that aldehyde into another molecule that's not as reactive. So we basically remove that double bond and turn it into acetate, which is essentially acetic acid is vinegar. And so that's a short chain fatty acid. And I'm sure we've talked about that many times. Right. So things like butyrate, propionate, acetate, these are short chain fatty acids that are actually anti inflammatory. Good for your microbiome, good for your body. So we're taking this highly toxic molecule, acetaldehyde, and then we're converting it to acetate. And that's, that's the normal biological process that happens. Your liver expresses enzymes that break down the alcohol into acetaldehyde, but then immediately another enzyme that converts acetaldehyde to acetate. And so that's normally how the biology of your body works and how, how we detoxify alcohol. So that's, that, you know, that's generally speaking what your body's trying to do. And then I can kind of talk about where that goes wrong in the body.

Yeah, let's talk about what happens during that process? So I take a shot of tequila. So I'm not worried about at this point. I'm not worried about all the yeast and mold byproducts and histamines and other additives that can be present in wine or flavored alcohols and stuff like that. So I'm talking about a pure, mostly alcohol and water thing, like a vodka, tequila, whiskey, something like that. I take a shot of it. Okay. Goes into my stomach. How does it get to my liver?

Yeah. So basically, exactly. Look, you. Whatever you're drinking, if it has ethanol in it, I'm gonna tell the story. The ethanol, then there's all the other things that might be in there that you may have to deal with separately. But the ethanol basically, you know, goes exactly. Gets absorbed in your bloodstream at various stages during your digestive tract. Some of it actually gets absorbed in your mouth, some gets absorbed in your stomach, and then some gets absorbed in your intestines. And so that gets absorbed in your bloodstream. The ethanol circulates throughout your body, and it has the effects that it has, which is, generally speaking why people drink. And then it. Once it's in your bloodstream, then your liver has access to it. So everything kind of in your blood eventually gets filtered through your liver. And once it hits your liver, that alcohol is processed, as I said, in two stages. Basically, an alcohol dehydrogenase converts the alcohol into acetaldehyde, and then immediately that acetaldehyde is converted by another enzyme called acetaldehyde dehydrogenase, and it converts that acetaldehyde into acetate from acetate. Many other things happen metabolically to it, but from a toxicity standpoint, the ethanol has now been detoxified from your body. So the story is a little different, though. In your gut, most of the alcohol is absorbed into your bloodstream, and your liver is excellent at detoxifying it, unless you have a mutation in the acetyl dehydrogenase enzyme. But separate issue for most people, that's very straightforward. But what happens in the gut is that a small amount of the alcohol is. That reaches your gut before it's absorbed into the bloodstream, actually gets converted or gets metabolized in the gut directly, large part by your microbiome, by the microbes that are living in your gut and your microbes. You know, alcohol ethanol is toxic to human cells, but also to microbial cells. And so they express alcohol dehydrogenases pretty regularly. And so some small amount of alcohol that you drink is converted into acetaldehyde. By an alcohol dehydrogenase enzyme similar to one your liver uses. But subsequently, that acetaldehyde that forms in the gut is not converted to acetate because bacteria don't express acetaldehyde dehydrogenases as commonly. So what happens is, even though it's a very small site of alcohol metabolism, one that's honestly not discussed very often, the bacterial colonic pathway of alcohol metabolism, it actually ends up being the major source of acetalde in the body because the liver is so efficient at both steps, even though it metabolizes much more the alcohol. So we see colonic acetaldehyde concentrations at 300 to 500 micromolar, whereas blood acetaldehyde concentrations are closer to like 50 or 60 micromolar. So we're seeing like roughly 10x higher levels of acetaldehyde being formed in the colon rather than the bloodstream, even though it's the minor source of alcohol metabolism, which is really an interesting observation, kind of gets overlooked because we're talking about a relatively small amount of acetaldehyde, but sort of the dose makes the poison. A small amount of ac alli can wreak a lot of havoc throughout the body. So it forms in the colon, and much like the alcohol I described, it gets then absorbed in the bloodstream, wreaks havoc throughout your body. Bull in the china shop. And then it goes into your liver and your liver very effectively and quickly detoxifies it using an acetaldehyde dehydrogenase. So generally speaking, that's part of what you're dealing with when you drink.

People who have listened for a while know that there's kind of three things in the biotic world. There's prebiotics, which is stuff that feeds bacteria in the body. Right. And I tell you which ones to take. And all that kind of stuff. We've had lots of episodes about it. There's probiotic, which is certain species of bacteria that do things you want them to do. And then there's postbiotic, which is compounds made by bacteria in the gut. And you can take some of those. There's famous ones like spermidine that I talked about on the show and wrote about even before it was commercially available in my aging book. So there's those things. It's the food for the bacteria, the bacteria themselves, and let's call it the poop from the bacteria. Those are the three things we have to play with in the microbiome. And what you're saying is that alcohol itself, when we absorb it, isn't that Big of a deal, because our liver's got that covered. But when the alcohol functions as a prebiotic in the colon, that's when things get really shitty.

That's a very interesting way to think about it.

And bacteria in the colon make really bad levels of stuff that cause most of the damage from drinking.

Yeah, that's a really interesting way to phrase, to look at, to think of alcohol sort of as a prebiotic. I think that it may like a microbiologist might be upset by color because it's probably not necessarily feeding the microbes, which traditionally is kind of. But you're right, it's the same principle, right, that like it's an input to the microbiome and then the acetaldehyde is the output, which is what we traditionally think of as a postbiotic. And so it's true. That's exactly right. And so we're basically by. We take a live probiotic bacteria to try and change that output of the microbiome to change sort of the postbiotic output. It's a, it's a really good, good kind of analogy.

So that, that's what you did with Zbiotic. When you first pitched me on this idea, like five years ago, you were a tiny little company. The first VC I ever worked with, a guy named Rick Bollander. I haven't talked to him in literally like 25 years. He calls me, was like, dave, I found this company, it's going to change the world. And you were very early days. I think it was just you and another friend working on it. And I'm like, this is massive. Because no one's ever done a specific genetically engineered probiotic that's going to change the output of bacteria in the gut to take away the bad stuff. This is massively interesting. And what you finally sent me, I mean, it's taken a while. I tried something like years ago in a little unlabeled vial. I did a lot of unlabeled vials. But you've got the full on like pre alcohol probiotic drink that is. Yes, guys, it is genetically engineered, 100% with no shame to do stuff that your bacteria cannot possibly do. Right. So I'm gonna open it up here because I didn't open it ahead of time. Yes, I have a pocket knife in my pocket almost all the time unless I'm on an airplane because, well, that's how you're supposed to do it. And it's literally a little shot. You take this, it's got live bacteria, it doesn't have to be refrigerated Right.

And we can talk about.

So you can have this in your bag, you drink it and then you are protected from the acid aldehyde spike when you drink. How long before you drink do you have to consume zebiotic?

So pretty much immediately before you drink. So those are live bacteria in there. And I know in the sort of probiotics industry, there's sort of this belief that if they're really alive, then they have to be refrigerated. And that's actually not true. It's really just the commercially available probiotics we have now will grow in a liquid. And so you have to refrigerate them to stop them from growing. But we use a bacteria called Bacillus subtilis, which is a really common microbe. You likely eat it already every day of your life. It's ubiquitous in the environment. It's on fruits and vegetables. It's also been intentionally used in the fermentation of soybeans in Natto and Kombucha and things like that. And so this is a bacteria that is naturally evolved to exist in the environment. And it forms an endospore which is a highly resilient, basically hibernation state of the bacteria.

Spore forming.

Right, It's a spore forming bacteria, so means it can tolerate huge fluctuations in temperature. Like it can literally tolerate boiling water. It can for a brief period of time and freezing conditions, it can tolerate huge swings in ph. So it can pass your stomach acid unharmed in that in this sort of endospore in the shell. And then once it passes, and so it's in its dormant state, which means it shelf stable at room temperature, essentially forever. They've literally pulled Bacillus spores from ice flows that are 100,000 years old, and then they're able to culture them. They're still alive. And so, wow, once it passes through your stomach acid, it senses the congestive environment of the gut and it wakes up. And then we've engineered it to express the same enzyme, same type of enzyme that your liver uses to break down acetaldehyde. So the idea is really that we're delivering to you a live bacteria that has been specifically engineered to do one additional function. Right. We already know that Bacillus is basically the safest and most well studied bacteria on the planet. And then we engineered it to just perform a single extra function, which express an enzyme that already exists in your body. And we just moved it to where it was important, which is your gut.

Do you guys see how freaking cool this is? One of the earlier podcast episodes was about spore forming probiotics. I think I call them armor plated probiotics from outer space or something like that was the title of the episode because it was about this strain. And keep in mind guys, a strain can do many, many different things. Even E. Coli, there's good E. Coli, there's bad E. Coli, I mean there's thousands and sometimes tens of thousands of different strains. What you've done though is you've taken a well known spore former and you've given it a new superpower to handle alcohol in a way that bacteria haven't done before.

That's exactly.

And your bottle, it says proudly gmo, right? Like what a troll. Congrats on the marketing behind that, by the way. Just as a guy's willing to say yes, you can upgrade your own biology. People got really mad when I started talking about biohacking. And they'll probably get bad, they'll probably get mad at you for saying proudly gmo. But there's no glyphosate, there's no farm, there's nothing. You're doing it in a specific bioreactor. Now let me ask you this, okay? I'm going to take this the next time I drink. And guys, I don't drink very often. In particular because of this reason, I would love to enjoy sake a little bit more than I do and maybe even some wine, Although I think wine has issues with histamines and whatever. So I'm going to do that and then I'm going to poop.

That's true.

What's going to come out of me and what might the effects of that be?

I hope you do so. Great, great question. Fair point, Great question. And so this is exactly right. So the idea around genetic engineering. And so you mentioned earlier about terminat seeds, right? Like these seeds that, that, that you know, certain companies have developed that basically can't reproduce. Right. And so the purpose of that is to contain the genetically engineered organism. It's obviously been then leveraged for, for unsavory business practices. But originally that was sort of like a safety check, right, that like it couldn't replicate in the environment. And, and from that perspective, it's actually a good thing, right? So you don't want to build something that if it escapes into the environment, it's going to cause a problem. And so that is, is a principle that we started with at Zbiotics believing that like exactly like you say, we're giving you a live genetically engineered probiotic that you're going to eat and then you are going to pass out into the environment. It's definitively not contained. We strongly believe in the biotics that containment is not a solution because it is never going to be 100% right, like kind of like Jurassic park, like, life will always find a way. So at the end of the day, containment is not a successful strategy for moving genetic engineering forward. You have to build things that you are comfortable with going out into the environment. And so in this case, what we did was we didn't break any evolutionary boundaries. Right? So 70% of all life on the planet expresses an acetaldehyde dehydrogenase. Many of the microbes that are already in your gut make acetaldehyde dehydrogenases. So what we're doing here is we're not introducing a new function. We didn't take a gene from a bacteria in the Mariana Trench and introduce it into a microbe in your gut. Right, because that's sort of crossing ecosystems that. That wouldn't normally be crossed. What we did was we just ensured that you were getting enough of the enzyme at the right time. So there's. There are acetaldehyde dehydrogenases already in your gut, and they're just not necessarily turned on when you need them. They're turned on all the time and they're turned off. And the truth is that bacillus subtilis is, you know, interacts with all kinds of microbes in the soil that also have acetaldehyde, acetaldehyde dehydrogenases. So really, there's no reasonable expectation that Bacillus salts hasn't had this gene in its genome already. It's not introducing a new function into its ecosystem. So we're really combining.

That's a really. That's a really big explanation. And it's so important. There's something called plasmid level transfer. And this is a problem if you're going to take a jellyfish gene that makes a toxic venom or rattlesnake venom or something and put it in some kind of other thing that you're going to inject in people, and no one's ever done that before, for that would be untested. And that is a Jurassic park kind of scenario. Possibly. But what you're saying is there's plenty of this gene already available in other bacteria, so bacteria will swap superpowers with each other. But if zbiotic bacteria were to swap with other bacteria, those bacteria already have this playing card. They already have the superpower. It's just not turned on at the right place in the gut. So on top of that, the zebiotic probiotics are programmed so that they can't reproduce anyway, so there won't be any cell division. They won't reproduce. And even if they traded their special powers here, it wouldn't be a big deal.

Well, that I think it's.

So you have a double safety thing, which certainly passes muster for me, but I don't have a PhD in microbiology.

I just know how life works. I think I want to sort of adjust that a little bit. Like. So you're absolutely. The second part of that is absolutely true, right? That that transfer is not an issue here. And so we removed unknown unknowns, like you said. Like, if you put in a gene that has never seen that ecosystem before, you don't, you don't know if it's going to cause a problem. But the, the gene, as you described as a superpower, is not a superpower for the bacteria, doesn't provide the bacteria with any advantage because acetaldehyde is a very, it's a highly reactive and very unstable and therefore uncommon. It's not part of, like an ecosystem or an important nutrient. So, like, having the ability to break down acetaldehyde is not something that gives you a competitive advantage as a bacteria. It's only a superpower for humans. So the fact.

That's what I mean, superpower for humans. It doesn't make the bacteria stronger against other bacteria, you're saying.

Exactly.

And so there's no competitive advantage.

Exactly.

That's cool.

It happily will transfer the. And so you mentioned plasmids, which are sort of transferable elements of DNA. And so there's also a lot of design principles we do at zbiotics to ensure that we're not encouraging sort of like unsafe genetics. So, for instance, we don't use antibiotic resistance cassettes or other selection markers. We make markerless, scarless mutations. And they're only chromosomal, meaning they're on the gene, the, the chromosome of the bacteria, the main genome of the bacteria, and they're not transferable. Now, that doesn't mean that they can never be transferred, but the point is that if they are transferred, they're not giving any competitive advantage or exposing the bacteria to a gene that they don't already see every day anyway. So we broke no evolutionary boundaries, so we basically removed unknown unknowns. We're not introducing anything new to the ecosystem. And so there's, that means there's a lot of things that we could build that. We won't. By putting those guardrails on us ourselves, we, we ensure that we are doing things that we know are ecologically safe. And I think that's really important dimension that the bacteria don't replicate is not true. They, they do. That's we grow them up in a bioreactor, they will replicate. But it's a bacteria that Bacillus subtilis is an extremely common, ubiquitous bacteria and it's only expressing an enzyme that other bacteria that the ecosystem already has. So there's no issue with it basically being in the environment and replicating because it's not introducing anything new to that environment.

Got it. So the alcohol metabolizing gene in zbiotic, after you poop it out, enters the sewage system and all the gene is not new to the sewage system whatsoever.

Exactly.

And those bacteria are not even likely going to keep expressing it over time because after they reproduce there's no alcohol present. There'd be no need to.

Exactly right, exactly. That there's, there's no issue with acetaldehyde in the environment. So you know, this, this gene is not providing any, it isn't changing anything. Basically.

That's fantastically interesting. Which means that if people, when you go out to drink like you probably will over the holidays, if you do this, you're likely going to have a lot less hangover the next day. But maybe more importantly, heart disease, cancer, diabetes, all of which are risk factors for alcohol, will likely go down. I don't think you've had a chance to do any studies on that, but we know that acetaldehyde is a pathway for all of those things. So just being someone who can look at, you know, if you punch yourself in the face, there's no study it's going to hurt. But you can probably assume that if you don't punch yourself in the face, it's better. So I'm going to go via that kind of very advanced PhD level logic that says reducing this noxious chemical when you drink is going to reduce your risks of metabolic harm based diseases. So you're going to do some studies. What studies do you have on zbiotics?

Yeah, and I'm glad you brought that up. So we very care, you know, as a scientist is very careful to not imply or make any claims of that variety. Right. Yes. We know alphalide is a highly toxic molecule without a doubt, but we can't say for certain that breaking it down in the, in the, in the gut is going to create any sort of health advantages like that. Really what we focused on was how you feel the next day. And so I had a hypothesis that based on the fact that we know acetaldehyde wreaks havoc out the body, and we know that having lots of acetaldehyde creates the symptoms that you feel the next day. And very clear evidence of that, right? But nobody had sort of decoupled alcohol metabolism from acetaldehyde metabolism before, especially in the gut. And so the idea was that if the gut is the major source of acetaldehyde, and we know that acetaldehyde makes you feel like crap the next day, then if we can have some effect on gut derived acetaldehyde specifically, we could make an improvement there. And so that's really what we focused on. So our data is around, first and foremost, we showed that we built a car that runs right, like we made a bacteria that could express acetaldehyde dehydrogenase, and that acetaldehyde dehydrogenase enzyme could break down acetaldehyde at physiologically relevant rates. Meaning, like, we know how much acetaldehyde you're likely going to be exposed to. We know how efficient this enzyme is at breaking down that acetaldehyde. And then we show that it can do that in the gut environment. So if we show all those things, okay, we've built, we built a car that can run now the question becomes, does, do people want to drive that car? Right? Does it, does it provide them the benefit that they want? Do they feel better the next day? Can they perceive that benefit? And so we did a lot of internal testing to determine that, right? So if I'm going to bring the world's first ever genetically. And I want to emphasize that you said earlier kind of about how sort of like monumental technology advance, it is the world's first ever genetically engineered probiotic to go to market. So I mentioned earlier about Genentech making sort of bacteria that can make insulin, but at the end of the day, they bring the insulin to market, not the engineer microbe. And so we are actually the first company ever to bring a live microbe that has been engineered to market. And I think that that's an exciting advancement. And I think, you know, a lot of people are applying this technology to the drug industry and when people are sick, which is important, but the fact is that the technology has a lot of advantages and benefits, I think for healthy people as well, who want to be healthier, right? And that's our focus, right, is making healthy people healthier. I think that's kind of the whole Point of kind of the biohacker movement, that bringing this technology can really be a huge tool in our tool belt. It requires you to be responsible. It's not a get out of jail free card. Right. You have to make good choices, drink response with things like that. But ultimately, by using genetic engineering, we can bring this new function to your gut reliably. And so we wanted to show that that actually resulted in a benefit for people. And so at the end of the day, do you feel better the next day? That's a really important question. And so we did a lot of things internally to validate that we were biochemically creating that advantage. And then we did a lot of studies and questions and gathered a lot of data around whether or not a consumer, a healthy consumer, would perceive that benefit and would like that benefit. And we have a lot of data that's consistent with the hypothesis that we're creating that benefit. So for instance, we ask people like, there's all kinds of sort of like intermediate biochemistry we can, we can examine. And there are a lot of things we did. But at the end of the day, what matters is if we give somebody the product and then we ask them the next day, do you feel better than expected, the same as expected or worse than expected? Right. A very simple perception of efficacy. Right. So if we objectively create a benefit, let's say we say we make you feel 50% better, are you going to wake up the next day and say, well, I still feel something, so the product didn't work, or are you going to wake up and say, wow, I feel better than I thought I would. I think this product worked. That's an important question when you're giving it to people kind of in their, in a choice, in their healthy life. And so when we did that study, it was really interesting. Regardless of how many people we gave the product to, it was always about 94 or 95% of people who said that they felt better than expected and perceived a benefit of that. And then now they're on the market. We've sold hundreds of thousands of bottles of the product. We consistently see that that's the case. Customer satisfaction is right around 95%, which is really, really high, especially for a product kind of in the food or supplement space. So all that data is consistent with hypothesis that we're providing a real, that breaking down gut acetaldehyde actually provides a real benefit for people.

When you say a real benefit, feeling better. So am I going to go out and just have, you know, three, four drinks? Do I take one at the beginning of the first drink. Do I take one with every drink? How do I use it?

Yeah, yeah. So you take the product one. So that what's, this is what's great about this technology, right, is that we are delivering you a live enzyme factory that's going to be functional the entire time it's alive in your gut, which is, you know, for most people, this bacteria will pass your gut in about 18 to 24 hours. So one bottle of zbiotics that you before drinking will be actively producing enzyme the entire time it's passing through your gut. So all night long, regardless of whether you sort of like, you know, have one drink or more than one drink over the course of one hour or 10 hours, the bacteria are good for essentially a whole day and they're going to be producing that enzyme the entire time.

That is remarkable in terms of changing quality of human life. And this is a pro human use of genetic engineering with what looks like appropriate safeguards in place. And the idea that you're going to take a little vial of something probably before you go out, it doesn't mean that you should go out and drink an extra four bottles of wine, Right?

Exactly.

What are the negative effects of alcohol you would expect to still be there even though you've mitigated this big problem with zebiotic?

I love that question because it's exact. You know, look, this is science, not science fiction. This isn't a magical cure, all right? Like we are dealing with gut derived acetaldehyde. When you drink, you are dealing with sort of a symphony or really more like a cacophony of all kinds of interesting biology. Alcohol is a really interesting molecule, creates a lot of damage on its own, right? So you're kind of, it's kind of the story of two molecules, right? You've got ethanol and then you've got acetaldehyde. And so ethanol creates all kinds of problems on its own. That's the thing, right? When you think about liver health, your liver is doing the bulk of the metabolizing here. And so the dealing with the toxicity of the ethanol itself, that's largely your liver's job. And so this product is not helping with ethanol in any way. It doesn't break down alcohol at all. So you can't drink more. You still get just as drunk and you'll still have to deal with the toxicity of the ethanol itself, which, you know, in addition to, you know, putting strain on your liver and kidneys, it's, you know, one of the major things I think that people notice is that it creates poor sleep. Ethanol itself does that. It binds to receptors in your brain and creates sleep issues. So even if you lay in bed for eight hours, you're gonna wake up and you felt like. You feel like you only slept for maybe one or two because you really didn't get the deepest levels of sleep. And that's all ethanol. Acetaldehyde now kind of wreaks havoc at the body and creates some of that. That real deep misery that you feel the next day, you know, and so we're really dealing with that. But, like, you may wake up the next day depending on how much you drink and feel groggy because you didn't sleep well, you know, maybe have a slight headache or things like that. But the good news is that, like, that's sort of just like kind of the veneer of this. Of some of the symptoms that you might feel if you've been drinking. They're easily dealt with with, you know, some bulletproof coffee and. And a good breakfast, basically, like a little bit of caffeine or something like that. And so this is not a get out of jail free card. It's not go out and drink as much as you want. Right. I'm talking to this audience specifically, I think is a great audience, right? People who are trying to optimize. So you're already putting in place several things that are healthy and responsible, right? You're. You're probably, you know, not drinking on an empty stomach. You're pacing yourself, you're mixing in water between your drinks, and. And you're making sure that, most importantly, I think this is the least appreciated thing is that is sleep is if you stop, if you go to bed with your blood alcohol content at zero, you'll get good sleep. You'll be dealing with the effects of the acetaldehyde, which we're trying to help with, but you get good sleep. So the idea is stop drinking earlier in the night, I think, is like a huge thing as well. So if you do all of those things and then Z Bottoms helps you with the acetaldehyde, then you're gonna wake up and you're gonna be able to follow through on all the other healthy routines and habits you have in your life. And that's what's important. It's not about enabling the drinking. The drinking is the kind of thing that, as you said, Dave, just, you know, that people do, and that's. That's fine. That can be part of a healthy social and psychological behavior if done in moderation and done responsibly. Right. But it can then interfere with your healthy routines the next day, like, you know, making a morning workout or socializing with friends or whatever it might be that you do. And so that's what the is just trying to preserve for you, is the ability to continue with those healthy habits.

I think that it makes sense to do the stuff that has been in the world of biohacking since that very first infographic I put out there, like activated charcoal. It doesn't do that much if you're drinking pure vodka or Everclear, which is pretty much all, all ethanol. The more you distill it, the more pure, the higher the proof, the more it's just ethanol, which is responsible for making you feel a certain way, both the good and the bad parts of it. Activated charcoal works for the alcohols that have not been distilled, like beer and wine in particular. It makes a really big difference there. And alcohol may in all circumstances work well with charcoal because alcohol stresses other bacteria in the gut as well. And then they can make lipopolysaccharides, which are bacterial defense or bacterial stress toxins. And activated charcoal mops that up nicely. So I like the idea of having some charcoal present, especially with beer and wine, but I always take some when I drink. And there's no reason you couldn't take charcoal at the same time you take zbiotic or maybe spaced out by a couple minutes. The charcoal won't absorb the bacteria, as far as I understand.

No, not at all. There's no issue with taking anything with zebiotics because it's a bacteria you're already eating every day anyway. We just express this extra enzyme. So anything that's normally present in your diet, activated charcoal, especially in the quantities you'd be taking it as a supplement, would definitely have no effect whatsoever on B. Subtilis.

So I would say I'm adding zbiotic to my stack of things. If you're going to drink, you should take activated charcoal. You should take zbiotic. Not exactly at the same time as the activated charcoal. You might also want to take glutathione in a liposomal form, because glutathione helps the liver detoxify alcohol. And the liver is still doing work.

Right. Different pathways.

You might as well make it so it's easier to do the work.

Exactly. Yeah. And so I love that. And we think about it like that when we try to describe it that way. Right. This is a tool for your toolbox. It's not like now, you know, you get out of jail free, you get to do whatever you want. And you know, it's your one cure all. Layering on responsible habits, whatever they may be. It's, you know, if it's a supplement routine like you're describing, I think behavioral routines are really important. They're also making you more mindful. I think all those things are really important. So we definitely encourage you to kind of use the biotics alongside other things you already do. As somebody who invests in your health and your, in your responsible behavior, does.

Zebiotic change the feeling you get when you drink alcohol?

Yeah, so no, that's exactly right. And that's, you know, I think an important point as I made earlier is that like, this affects alcohol itself, ethanol itself, in no way. It does not affect your ability to metabolize ethanol. So you have to still know your limits. You have to drink responsibly. All those things are still important because it's not going to affect the way you, the way you get drunk or the way.

So you get just as buzzed, you get just as drunk when you are on zebiotic or when you're not on zbiotic, you just don't pay for it. With the aging and all the other bad things that happen when alcohol meets bacteria in your colon.

Exactly. I mean, we're dealing with the downstream metabolic product of ethanol. So after the ethanol has already been metabolized, like, that's, that's when zebiotics comes in. So. So really your metabolism of ethanol has not changed at all.

I'm remembering over the last couple years, there was this one weird company with probably slightly demonic ownership, and they swore up and down that if you introduced a genetically engineered compound into the shoulder muscle, it would magically stay in the shoulder muscle and not move elsewhere in the body, even though studies showed that it did. How do we know that zbiotic stays in the gut?

So that's actually a really important point. Is that like the, that we specifically. I think that this is a huge problem. And, you know, I wish we could go for another hour and talk about the microbiome, because I think that's actually what's really, really interesting. And one of the. So at Zbotics, one of the things I started with was like, was really around the principle of being as simple as possible. Right. Like, we start with a simple biochemical reaction, a single enzyme breaking down a single molecule that we know is present in the gut. Right. Like, you can do a lot of complex and interesting things with genetic engineering, but keeping it simple means less things to break and another aspect of that simplicity is around the idea of, like, you have this extremely complex microbial community in your gut, right? And probiotics as they currently exist today are predicated on the idea that somehow you're going to interact in some beneficial way with your microbial community, which, quite frankly, as a microbiologist, I can tell you is not a very strong hypothesis. So your microbiome today, Dave, and mine are very, very different. And yours today and yours in five months will be very different. So the idea that there's sort of this, like, silver bullet microbe that can come in and positively affect everybody's microbiome, the same is unlikely. So what ZBiotics is, is actually, you know, the fact that it's a probiotic is incidental. That's a chassis for a biological function. And so we really sidestep all of the complexity of the microbiome by ensuring that the bacteria actually are choosing a bacteria that actually doesn't seed the microbiome or really have to interact with the microbiome in any way. This bacteria is just known to pass through your gut in about 18 to 24 hours for most people. And there's good data to kind of support that. And so there's not really, you know, gut transit times are not going to vary that much. And so it's not going to see the gut, it's not going to interact in the microbiome, and it's just going to float down the river. And while it's flowing down the river, we've engineered it to make sure that it definitively, reliably will express our enzyme, acetaldehyde dehydrogenase. And so as it gets, as it floats down the river, and the acetaldehyde is in that river and it's going to passively diffuse through the bacterial membrane, which is another innovation we did to make sure that we got reliable, consistent results. And so it'll deal with acetaldehyde in the gut as it's passing through, and then you'll pass it out the other side. And so then if you're going to drink on Friday night and then again on Saturday night, you have to take another zebiotics, because we specifically chose a bacteria that doesn't seed the gut, which I think is actually a very important safety point, that trying to muscle your way into a very delicate ecosystem, which is your microbiome, is a bad idea. It can create problems that would be.

An invasive species if you engineered it that way.

Exactly. And so we did. We picked a bacteria that we know has loves to engage with the microbiome and just pass right through. It's something you eat already every day of your life. So really we, like I said, we tried to create something that was changed so little that, that we weren't introducing any unknowns. We relied on 3 billion years of natural evolution of the bacteria and in 150 million years of evolution of the bacteria with the gut, with human, human gut microbiome or humanoid gut microbiome. Right. So all these things we didn't change. We just piggybacked on something that was already happening with one single enzyme that performs one function. So it's really a delivery of a new biological function, which is why I'm so excited about the category of genetically engineered probiotics, because there are so many biological functions, any biological function on the planet. Right. Theoretically we can program into a bacteria and then that, then you can temporarily eat the bacteria and then temporarily gain that function. Now, we won't do every biological function because there's, there's risks with that statist. But even if you narrow that field down to like a small number, there's so much incredible benefit you can create by like introducing these biological functions in the gut where you know that there are issues.

I, I can see this future and it's better than the one we have right now. And yeah, we engineered some microbes. We've been doing it for a long time. We just never took them as probiotics because no one had the guts to do it. So thank you. I appreciate that you did.

I thank you so much. I, I exactly. I think you're pain. That's exactly the vision that we see for the. Well, right. Is that, and I'm going to say something kind of bold here and I think controversial in theory, but like, you know, if you let me explain myself, I think that you'll see that actually assuming you use good engineering practices, engineering a microbe to perform the function is actually safer than scouring safer and more efficient than scouring nature to find a strain that does it naturally. And here's why. I know it sounds like counterintuitive, but if you say so, you use spermidine as an example. So you scour nature, you try and find a bacteria that can make spermidine, but you don't know any of the other things that that bacteria does. Is that bacteria safe to eat? Does it produce surfactants? Or as you said, like lps, bacterial toxins, all kinds of things. So you're basically going to take that bacteria that we know nothing about, and then you're going to have to try and characterize its safety so that you can get that one function that you want. Right. And so there's countless examples in nature. People think of nature as safe. Nature is extremely dangerous. Right. Like all of our diseases and, and all the poisons come from plants. Like this is. That's, that's a very dangerous place to be.

Oh, yeah. So it's so safe. Just walk outside and eat something and see how you do whatever dirt or plant, it's going to just trash you. Right.

So nature in and of itself is, is, is dangerous. And we have to kind of filter that and make sure that we find things that are safe. So. And currently that's kind of where the technology was in the 1700s, which apparently people want to go back to raise a. You take something that's, that's natural and then you hope it's safe because it's natural. But what I would argue is that if we start with something that we have already extremely well characterized to know to be safe. So Bacillus subtilis being the safest bacteria on the planet, the second probably best studied organism in existence besides E. Coli, and we know that that bacteria is safe, and then we engineer it to do one specific function that we also know to be safe. Then now we have, we are leaning on decades of safety data already as opposed to starting from scratch with something we've isolated from the environment. So engineering becomes a way if, like I say, if done responsibly and. Right. There's big caveats to that. We talked about ways that engineering can be done irresponsibly, but if done responsibly, an engineer microbe can be better characterized, better, like less unknowns to your, to your human health, safer, more efficient, more effective, and, you know, essentially something that we can rely on better. And so I envision. And that's, that's, you know, the probably GMO thing isn't a gimmick. Right. That's because I believe strongly in the fact that genetically genetic engineering makes the product better and it's better for you. Right. Like, so we're not. If you walk into a store and you have a choice between GMO corn and non GMO corn, there's no benefit to you to take the GMO corn. Right. The GMO corn is for the farmer.

Right.

It's not for you, the user. Right. So we use genetic engineering to create a benefit for you, the user. And I think that's a really important difference. Right. And so the fact is that we're proud about the fact that we use genetic engineering because we created something that did not exist before. You cannot get this product somewhere else. It's not. This function didn't exist. We did that. And so genetic engineering is what made that possible. And so I'm very proud of that. And I think, I think that people should be excited about that. We're applying technology in a responsible way that creates real benefits. So I have the same vision as you that we walk into a grocery store 10 years from now and we look for the genetically engineered probiotics because they've demonstrated to be more effective, safer. And as long as I say we do these things responsibly. And so we're working on advocating for clear and transparent regulations around genetically engineered microbes so that we all can, can operate in sort of a safe sandbox. And I think that's another really important thing again, that I could talk for another hour about. But ultimately that's an exciting future that we're trying to create. For me, I think that regulation, it's not that inherently can't be trusted. It's that like, especially when it's reactive and political, then, then incentives are not aligned. And so I think that this is an important point and nexus for us as a, as a, as a kind of growing new category of genetically engineered microbes specifically is that if we can establish scientific and rational regulations now, then ahead of sort of a wild west scenario where stuff's all over the place and then there's sort of like a fear based, reactionary kind of, or to your point, or you know, I think there are many different kind of scenarios that result in bad regulation. So fear based, reactionary, reactionary, political or financially motivated, kind of like somebody wanting to exclude. And that's what happens a lot, right, Is that, you know, a lot of innovation get by little guys like ZBiotics, right, like by small new startup, innovative companies get squashed by the big players who have the money to go through the very bloated regulatory process. And to be very clear, regulation is important. I'm not saying that it isn't, but ideally it's done in a way that guarantees safety and prevents both. I say especially unintentional bad actors, people who are trying to do good but accidentally create something bad, but doesn't squash innovation. It allows that sandbox to be there for everybody, to build new great ideas.

It's funny because regulations don't stop bad actors. I mean, even if Congress says don't fund that kind of research, you could still fund it and get away with it and maybe even get like a little gold star for.

That's precisely.

So you know, it. Telling bad people to stop doing stuff doesn't matter. I want good people listening to understand what bad people might do so that we can see them doing it and we can literally stop them by taking hold of their throats. Because that's how you stop people like that. There is no other way. Then you can feed them their own creations until their eyes turn purple or whatever the heck happens. I don't even know. But what I. What I do want to know is that there is a level of industry regulation.

Yeah.

Where you guys identify. Don't do that. You know, gain of function for negative things in gut bacteria that might spread to humans would just be bad.

Exactly.

So let's do. Let's not do that. I think there's a very clear risk reward here. The risk appears to be very, very low. The reward appears to be very, very high. And you feel it the next day. And in my mind, that's a recipe for winter. Because if the reward is high and you don't ever feel it, we don't really do that as a species because we're lazy. And there's a reason we're lazy. It's to survive famines. That's all built into our hardware. So, anyway, I'm a fan of zebiotic. I am going to have some this evening. I'm going out for sushi and I'm ordering sake. I normally drink maybe once every month or two, and I like to make it older than I am. It's going to be very good sake tonight, I promise you that. And I'm going to take zebiotic right before I have it, and I'll probably feel pretty good tomorrow morning. And that's the whole point of it. Zach, thanks for being willing to take a really controversial but correct stand. You're not doing it from a place of making a ton of Money. You're a PhD microbiologist. You studied immune systems. You know what you're doing. You're actually doing something good. I'm so stoked and I'm so excited, and I'm honored to have an innovator in the field on for a thousandth episode.

Thank you so much. Honestly, it's been an honor to be on it. I love that takeaway. That is. That is the mission of the company is to elevate the conversation. Not good or bad. And I think that this is really the first of many for us. Right. Like, there's so much good we can do with this tech. And I think I'm really excited about that. And I'm also excited about the opportunity to kind of move this conversation forward. And so I love the idea about not being programmed. You have a very savvy audience, and I think that they're smart enough to know that. That everything is. There's always, you know, two sides to every story. And so I'm really excited to have been able to talk with you about it.

One more question before we go. I've got the three pack here of zbiotic and I've got the whatever the heck pack this is. Six bottles and a dozen bottles. How long does it last? Because there's a code you guys use. Code Dave. Who would imagine ZBiotics. Just the letter ZBiotics.com Dave. Use code Dave. They'll give you 15% off. But if I buy the big one and get my 15% off, how long will it store?

Yeah, I mean, so look, as I said, the bacteria are in an endospore. They'll last pretty much forever. And so we put an expiration or use by date of 18 months from bottling, mostly because the seal on the cap over time could degrade and whatever, but it's good for a very long time. So at least 18 months, I'd say.

Yeah, at least 18 months without refrigeration. If you toss them in the fridge, it's like it's going to be years and years. If you really want to.

Theoretically, we actually advise you don't put it in the fridge. Mostly because the bacteria, when they're going to get colder, can go into a deeper kind of hibernation state. And so, okay, room temperature. Room temp's the best, but, you know, the fridge won't kill it or anything. It's just, you know, your optimal storage conditions is room temperature. Yeah.

Takes longer to wake it up. Gotcha.

Yeah.

All right, guys, so order the 12 pack. Zbiotics.com Dave the reason you order 12 of these is the next time you have a drink, you're going to have a drink with a friend. You drink one, you give your friend one, you're probably gonna have a drink with several friends. You will go through the 12 pack very quickly. But it is an amazing gift. Just, hey, take this little thing. Just trust me, tomorrow morning, you'll feel better. Do not go on a bender. It's not good for you. But I promise you, Christmas Day, you're probably gonna have the eggnog. By the way, the fat's a good thing to have with it. That's fine. The sugar's probably not so good. Have some zebiotic. Get it for everyone in the house. Seriously, the next day, I'll feel better. New Year's Day doesn't have to be a zombie thing.

Yes.

And this, this is going to help. And while you got it, pick up some glutathione, pick up some activated charcoal. There's all kinds of good stuff out there. So you can have a celebration. You can do the primitive tribal alcohol thing we've always done. Maybe don't do it all the time. And when you do it, I'm serious. I'm not doing it without Zbiotic from here forward and without charcoal and without glutathione and all the stuff I've already taught you. This is a new recommend recommendation. Zbiotics.com Dave and use code. Dave, save your 15. Get the big pack. Be done with it. Zach, thanks for taking time right after Thanksgiving to film Upgrade Collective. Thank you for being here. I hope you enjoyed this. This is some cool. Like, this is. This is the future and it's happening. And part of my job is to bring you the stuff before you're probably going to hear about it anywhere else. And this has been on my radar for five years and wasn't ready yet, and now it is, so yay.

Thank you so much.

You're listening to the Human Upgrade with Dave Asprey.