Written by Christopher Kelly
Feb. 12, 2015
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Christopher: Hello and welcome to the Nourish Balance Thrive Podcast. My name is Christopher Kelly. Today I am joined by David Salamon, the CEO of General Biotics. Hi, David.
David: Hi, Christopher.
Christopher: Yeah. We're laughing because I botched his name in the original introduction but we'll go with this one because I know that if I do it again it won't be…
David is a computer scientist, a man after my own heart. I've got a degree in computer science. But that's not what he's focused on right now. He's the CEO of a new probiotic company and the name of the probiotic is called Equilibrium. I'm excited to have him on the show today because this is a different sort of product. I've never seen anything like this before.
David, why don't you start by telling us a bit about the probiotic? What problem did you see and what opportunity do you think exists?
David: Sure. Yeah. Okay. Just to give you a little more background here. It's computer science but most of it has been statistics and machinery.
Christopher: Right.
David: Which is to say that sort of BioChromatics and that sort of stuff has been a passion of mine. I've been volunteering as adjunct faculty at San Diego State University which has a really phenomenal microbiome program. We've got Forest Rohwer down there who's one of the big names.
From this BioChromatic stuff there's been a lot of really interesting discoveries which I'm sure a lot of people have heard about here about human digestion and how it links to health and how it's sort of much more important and much more complex than we previously viewed it as. That's how I got into this, with hanging around these people, hearing these crazy stories about these magnificent correlations with, oh, that this cluster of microbes… Yes. So that's really what got me into it, these crazy studies.
The premise for the probiotic is that basically our gut, the actual microbial makeup of our stomach is not particularly stable. You get a lot of microbes from your parents but the actual makeup of them, the way that they are structured and the way that they all work together is supposed to -- a natural environment for an evolved human is supposed to come from the diet bringing this constant influx of microbes.
The microbes are essentially the things that are really digesting the food you eat so if these will not be ones that are happy digesting food that you give them but some of them will be happy becoming domesticated. I mean, a tribe of people, well, you'll get ones applied by your comrades which are ones that are symbiotic, right?
Christopher: Right.
David: Basically everyone's coded in a bunch of symbiotic microbes. In the modern society we've taken great steps to remove these microbes and that's because stuff like E. coli and salmonella grow and as we began producing food in sort of very impressive and awesome quantities, well, you get the pathogen problem. The solution to the pathogen problem has been to just sterilize everything, right?
Christopher: Right.
David: The 0.1% or whatever of microbes that are just truly horrific, the solution is to kill them all. At least the data that Beltran was showing me before we founded the company and then the data we've got after founding and sort of giving our solution to a bunch of people, yeah, basically had them convinced that the central error is that sort of humans evolve to receive a lot of dietary microbes and we've removed them.
Christopher: Okay. The product is actually an offshoot of the NIH's Human Microbiome Project which I thought was really interesting. I actually did the samples. We sent those in. I've been doing – I think it's in collaboration with the University of Colorado who have been doing a training course which I think might have ended now but, yeah, go check that out. I put some links in in the show notes. See if you can find that. Can you tell me a bit about that project and how it helped you formulate a probiotic?
David: Yeah. I think you might be talking about -- is it the American Gut Project?
Christopher: Oh, yeah.
David: Yeah.
Christopher: Oh, am I getting the two things confused?
David: No. No, no, no. Beltran did his post-doctoral work at the Human Microbiome Project. That's one of the big ones. The American Gut Project and uBiome are two big ones trying to get basically a humongous census.
Christopher: Right.
David: The Human Microbiome Project did I think 213 sort of closed sequences which is you basically take a sample and you sequence every single microbe.
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Christopher: Right.
David: And that's it. So here's the full DNA. Stuff like the American Gut Project, stuff like uBiome, which a lot of people are using, those guys do 16S sequencing so there's this small region of DNA that happens to mutate a lot. You could sort of use that to do typing.
Christopher: Okay.
David: So different approaches. Yeah. Basically, if you're looking to figure out what kind of microbes we should be eating, if you're going to do that in a satisfying way, you could do it two ways. You could it the way that Elie – hah! I've never pronounced his name – Metchnikoff? The gentleman that sort of was responsible for coming up with the premise of probiotics did it which was he looked around and he was like, "Oh, okay. These guys seem to be eating a lot of microbes and they seem healthy." That's a pretty good idea that maybe those are the good microbes to eat.
The other way is just to actually look. Okay. Well, here's the metabolic function for a very healthy human. Here's exactly what it should look like. Metabolic function here means turns glucose into – it's like here's an actual metabolic [0:06:23] [Indiscernible] right here. In your stomach, if you put glucose in, here's what's going to happen. Here's what the microbes are going to do to it. Actually, probably a better example that I know is true is the construction of folic acid.
That's basically how it became an offshoot is we have the data. Here's what an unhealthy gentleman in Colorado looks like. Here's what a sort of very exceptionally healthy person in New York looks like. Here's what a medium healthy person in Arizona looks like. We have that data. We have access to that data because of this $150 million science projects that's aptly funded.
Christopher: How did you know, how did they know which is the cause and which is the effect then? We have established that this is the flora belonging to a healthy person and then the opposite is true too. How do you know which is the cause and which is the effect?
David: Yeah. There's some extent to which someone's general health can cause microbes. There's also extent to which the microbes themselves – I don't know if you've been reading this but it's been freaky -- basically can cause you to be sort of excited about eating different foods and that can change your microbial makeup. So hunger, maybe it did through microbes. Both of those are true.
Basically, in modern environment, the sources of additional microbes are first of all limited. Second of all, you've got like on a single micro level you could say, okay, here's what it's producing so you can look at a microbe, you can look at the DNA and you could say, okay, well, here's what it codes for.
Christopher: Right.
David: So it's fairly easy in some cases to go like, well, that's a parasite; that thing's not.
Christopher: Okay.
David: Right. We've got a list of pathogens. We've got a list of like, oh, well, maybe that stuff's useful. And then we've got the list of stuff where – so a really famous example is the ones that we think basically cause peanut allergies.
Christopher: Okay. I was not completely aware of this.
David: Oh, yeah. There's a couple of microbes. In fact, I think there's one chronic one they use for their studies which can cure peanut allergies in mice.
Christopher: Okay.
David: Send you a link to – yeah. For some of them it's just sort of easy in the sense that like that thing on its own, if you're doing sort of like a Fisher style experiment, yeah, you can just say, okay, yeah, that one's extremely good. For some of them, you can't. For some of them, you're just sort of like you're looking at it and you're like: this one's much less diverse than that one. So like just on a pure diversity scale, there's a disconnect.
Why would you want diversity? Diversity is extremely important because they basically regulate each other. If you're worried about having like a bacterial overgrowth or if you're looking at –
I should pause here because I just talked about a bunch of diseases. I'm going to explain how this stuff connects, the Equilibrium stuff, but I'm not trying to say you're going to get cured from peanut allergies if you take it. We don't have those microbes in there because that's more of a long-term goal. We want to establish safety before we put that stuff into it but I should have premised this entire discussion with that. That's maybe a beginner.
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Christopher: Okay.
David: Great.
Christopher: Yeah, so –
David: Yeah.
Christopher: So what's changed is this technology has come along and enabled us to identify these different microbes that live in our gut, and we have established that some of them do us some good and then some of us do us some harm. Basically, you figured out the difference between the entire community of microbes between that of a healthy person and an unhealthy person. How does Equilibrium, how does the probiotic come in to close that gap? Is that even possible? It must be or else the product wouldn't exist, right?
David: Yeah, yeah. Just to sort of do a recap of what I attempted to explain, yeah, some are just known to be horrible; some are just known to be awesome but, in general, palliative health outcomes seem to be correlated with highly diverse microbiomes. That's because you can't get destabilization from pathogen. If it's much harder to –
Potato famine happens just in Ireland. That happens because all the potatoes are the same kind so a single blight can come along and it can wipe them out.
Christopher: Right.
David: You instead have fields that none of them contain the same potatoes, you can't get a plague that knocks them out, right? So just from like an evolutionary pesticide perspective, you want diverse potatoes and you want diverse microbes inside your gut. So a very healthy human's got perhaps I think it's 1,400 strains depending on how you're defining what a strain is in like a Hadza tribes member and it's maybe about a thousand strains for someone in the U.S. So there's a gap there.
As people go down, I know we were looking at ulcerative colitis in children. Basically, if you catch ulcerative colitis and you've got about a hundred strains in your gut, you're not going to be curable with current methods. If you've got around 500 strains in your gut, you are curable with current methods. So again, yeah, not trying to talk of cures but I think basically all the good science here happens to deal with disease so if I'm talking about studies, if we're trying to keep it evidence-based – yeah.
So, yes, how was it that we can construct what a healthy gut microbiome is from the data? That's the question. We became convinced that there was sort of nutritional deficit going on that basically if we're looking at the Hadza and we're looking at humans or we're looking at sort of indigenous people in Puerto Rico which we have got phenomenal data on because basically someone has been devoting their entire career to sequencing indigenous people in South Africa and their ancestors because you can use coprolites which is fossilized feces to figure out, oh, okay, well, that's what the microbiome looks like over there. There're also some nice Australian indigenous people.
What you could do is you could try to figure out like what kind of bacteria and viruses and microbes, yeasts? What are these people getting in their diet that modern humans no longer get? That's not enough of a question because undoubtedly they're getting some horrible stuff in their diet but more specifically what kind of microbes were they getting in their diet that first of all we actually think are likely beneficial? We basically take that as, okay, well, it has a metabolic pathway that's likely to be beneficial, which is broadly it appears in healthier samples, healthier people from these data sets we've got. And, two, can we also look at modern people that eat them and that's a safety concern. Basically, can we find some rural individuals who are in fact consuming this microbe?
Christopher: Okay.
David: That's a basic approach is trying to find stuff that we're supposed to eat using data to find what we're supposed to eat. If it looks sort of safe for consumption, then it seems like a good thing to improve.
Christopher: Okay. So you think it's important then these people are actually consuming microbes rather than just eating foods that are providing, creating the environment for the microbes to grow? Which is more important? Or are they both important?
David: Yeah. Equilibrium is a nutritional supplement so if we're going to make a nutritional supplement like, yeah, I mean, people do FMT, people do sort of bacteria therapy stuff for diseases all the time and I think that is tremendously important. If you get C. difficile infection or you get H. pylori, you get stuff – oh, H. pylori. Anyway…
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If you get a disease, I think, yeah, shifting the fundamentals probably through sort of strong invasive therapy, I think that's tremendously important. I think if you're just talking like nutrition stuff, I think it is quite important to maintain the balance there. Of course, if you're taking antibiotics or something because you caught a disease, I mean, obviously, that's more important than keeping your gut flora healthy depending on what it was. If you just had a light fever or you had the flu or something, probably not worth taking antibiotics although your doctor probably thinks that too.
But, yeah, I think if we're just talking about keeping a normal healthy person with good gut flora, I think basically no one's talking about how do we get our nutritional flora. The existing probiotics are basically yogurt, extracts and/or bread extracts. It's one to two strains. It's very questionable whether or not our ancestors consumed them. For instance, if you go to the Hadza, they don't have ovens so…
Christopher: Okay.
David: Anyway, it's not like advanced bread making. Yeast can actually – it's questionable. If you are looking at like evolutionary nutrition type stuff, milk's a pretty recent invention but I think both of those are sort of questionable choices for microbial supplementation.
Christopher: Okay. So these questionable choices are the microbes that are in the sort of common, storable probiotics that you might see in the refrigerator section of your local supermarket. So how are the microbes in Equilibrium differently? How did you select them?
David: Sure. Yeah. We started with sort of what are the large deltas that you could see if you look at, say, a Hadza or, say, a Puerto Rican sample and then we used those to figure out, okay, well, is there a dietary infection or the dietary microbes? Basically, the criteria selection is sort of err on the side of caution with respect to anything that looks like a pathogen.
There're some interesting studies. Again, I should premise this with -- well, Beltran's the one to ask for most of these studies but there's some interesting studies on C. difficile actually sort of helping people with asthma in the sense that if you look at a two-year-old and they've got colonization by C. difficile, they are less likely to have asthma as an adult. But that one is also sort of known as a pathogen so that one, you don't go with that one.
Christopher: Okay.
David: Even if there's a correlation, there's a risk there. But if we're just talking a general microbe, if we're just talking like, oh, okay, we've managed to locate some people in the rural environment who are consuming it and it seems like sort of pretty present in modern society and definitely present in sort of an ancestral microbiome, we say green light. Yup.
Christopher: But you must have had so many different organisms to choose from. How did you narrow it down? There's 115 different species in Equilibrium, right?
David: Yeah. Yeah, yeah, yeah. The 1,000 number and the 1,400 number are like what really are – if you go to OTUs which is a pretty used metric in microbiology, you can justify that there's sort of 10,000 strains let's say. So, yeah, I think it's a hard question which ones to go in. Future versions, we're hoping to take the strain kind of up to, say, 500 or 350. Beltran's going to kill me for talking numbers here –
Christopher: Beltran I should say is the Chief Science Officer at General Biotics.
David: Yup.
Christopher: Yeah, I know.
David: Sorry.
Christopher: Yeah. You're doing a great job.
David: Okay. Yeah. Good. Yeah, so the main thing that you want to look at if you've got a limited number of strains – and I really want to impress upon you that 115 strains, there's not a lot to work with if we're talking sort of keeping a gut microbiome healthy. The main thing you use is metabolic function. So if you already have a strain that basically does X, well, we need a strain that does Y instead. You don't want to include 15 different strains at all to X.
Christopher: Right.
David: Yeah. Basically, it's sort of you're not going to be able to get a complete metabolic function for a human microbiome in 115 strains but you could try to get the span and you can go, okay, well, which ones sort of vanish? That's a lot of what you do when you're doing a delta between an unhealthy person and a healthy person is sort of looking at where the disconnect, where the lack of coverage is in terms of the ability to digest.
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But you could also be looking at like, okay, this microbe's producing something perfectly unhealthy. That basically is the definition of a pathogen.
Christopher: Okay.
David: Yeah.
Christopher: Okay. So just to summarize, we've got this NIH project that's identified these microbes, these small organisms that live in our gut and we've figured out which are the good guys, which are the bad guys and we've figured out the differences between a healthy person and an unhealthy person. Now you're in a really great position to where you can look at these different microbes and say, okay, I want this one, this one, and this one in my probiotic.
But how does that become like a practical concern? I'm sure there must be – some of these microbes maybe they are anaerobes and so you can't grow them in an environment with oxygen. How did that cross over? Were you limited on what you could choose based on how practical it was to put into a product?
David: Yeah. Bigger practical concerns are like the plate count anomaly which is to say that there's a lot of microbes that we sort of can't culture, can't grow. Like anaerobic, we have methods, right. It's anaerobic chamber. A lot of microbes, you can sort of look it up. Okay, well, here's –
It all seems like sort of old witchcraft recipe. One drop of [0:21:44] [Indiscernible] infusion, one drop – anyway, so one drop of this, one drop of that. But, yeah, definitely, we would appreciate if society knew how to grow more microbes. That's definitely true. And the answer is if you can't grow it, you can't use it. It's unfortunate but, yeah, there's no sort of way around not being able to grow something.
Christopher: Okay. I wanted to talk to you about, you know, I know you can't tell me which microbes are in this probiotic which has been causing some controversy. What's the state of that? Why is that? Is that likely to change in the future?
David: Okay. Basically, if we're going to get sort of funding to do – well, it's actually prescription probiotic development which is that's what Beltran's quite passionate about. That's one of the things I'm quite passionate about is like the ulcerative colitis thing I was quoting earlier. We want to go after that. We think if you've got clear data on – I can send you the paper over. The paper is talking about these strain counts as determining health outcomes for treatment, for the current treatment methods.
If we're going to manage to get funding to do that, it can sort of be something but you can just clone but to go through an FDA trial you basically need to own the stuff at the end if you're going to get funding for that. So just from the perspective of figuring out how to sort of protect the IP, doing a full disclosure is how you don't have patentability.
Christopher: Okay. Interesting. How is that likely to change in the future then? Are you ever going to get to the point where you can say what's in it?
David: Yeah. Yeah, yeah, yeah. Well, yeah. I think we definitely will be able to get to the point where we can disclose it. The question is figuring out which paperwork needs to be filed, which bureaucracy first such that ownership – yeah.
Christopher: Okay. Tell me about the manufacturing process. I'm quite interested in that. The whole thing is designed here in California but where is it manufactured?
David: Sure. Yup. We've got a lab down in San Diego which is sort of close to the SDSU BioChromatics lab I was describing to you before. It's being done in small batches. I don't know if you've ever seen sort of freeze-dried microbes but a gram, that's ten years supply or something. That's an incredible number. That's way more than ten – yeah. A gram is – basically, a dose is like the tip of a pin.
Christopher: Right.
David: So actually it's sort of produced in the way that you'd produce microbes in a microbiology lab. We sat down. Okay, here's this sample. And then we proceeded to grow all 115 strains ourselves in a microbiology lab down at San Diego.
Christopher: Wow. So this is a really, really small facility then. It's not like you just phone somebody up in China and said, "Hey, I need this." That's not possible.
David: We wouldn't have phoned someone up in China because basically if you start investigating how to manufacture probiotic, one of the conclusions you're going to come to is be very sure about the lab conditions for that probiotic. That's how companies get sued. That's how companies die. You want to be really sure that there's no contamination there.
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Christopher: Okay.
David: And the microbe that you're buying is actually the microbe that you're getting. It's sort of if you've ever tried to source bulk ingredients, the same issue comes up. Oh, okay. Great. Thank you for the white powder, sir.
Christopher: I get it. Tell me about the viability of the probiotic. I sometimes wonder about that. So, okay, so we've gone through the manufacturing process and the powder is in the pill, what are the chances of that organism still being viable by the time I get it and am ready to take it?
David: Another interesting question is if it is viable and if there becomes moisture in the pill, it can reproduce in the pill and it can sort of evolve in the pill. I think those are both concerns.
Basically, if you freeze dry a microbe, that thing lasts. Microbes, you really can engage in cryonics. Microbes, it's one of the few organisms. Yeah. We are conservative with our expiration dates so we list them as three to four months depending on how gloriously we think we did the packaging at that time. We freeze dry the microbes before placing them into the capsules. Yeah, it works I guess. I wish I understood sort of more about why it works but, I mean, it sort of demonstratively works. It sort of – yeah.
Christopher: Okay. Have you looked at all how many of these microbes are actually making it into the gut? Do you have any information about that or is it not known?
David: Yeah. Definitely, they're [0:27:00] [Indiscernible] whether or not on a given day you're going to get sort of that microbe is going to take for that sort of stuff. That's gambling, but in aggregate, if you're taking it over the course of let's say a week or a month, yeah, they're making it. Yeah.
Christopher: Okay. That's good to know. Tell me about the clinical trials. There is a clinical trial underway, right?
David: Sorry. A clinical trial is – that's code for treating of disease.
Christopher: Okay.
David: There's a placebo-controlled double-blind experiment underway.
Christopher: Ah. Okay. Tell me about the experiment.
David: Sure. Yeah, yeah, yeah. We've got two populations of people. One are receiving essentially every single thing that's in Equilibrium except for the microbes so that's at the late release capsule and some ground organic [0:27:49] [Indiscernible]. The other group is receiving the same thing but with our microbes added. They're answering a variety of daily questions which cover things like mood, cover things like energy level – basically stuff like you might if you were giving someone, hey, does my new diet work? Does eating five servings of fruit and vegetables per day help you? It's those kinds of questions.
We also have questions like what does your stool look like? Did you have a bowel movement today? But they're sort of basic questions. They're sort of questions you might want to know if you wanted to know if you should take the product basically. It's almost a marketing study. You could call it a study designed for the purposes of demonstrating that the product works.
Christopher: Okay. How has that been going? Is that still ongoing at the moment?
David: Yes. Yeah, yeah, yeah. That's slightly nightmarish in terms of sort of getting it to the finish line. But, yes, that's ongoing. I don't know if you caught this but we announced that we're going to be open sourcing the tools that we're using for the experiment.
Christopher: Oh, cool. No, I did not.
David: Oh. Cool. We actually think that – okay, so first of all, this version, it's just one version. I think anyone that produces something sees a variety of different things they want to do for the next version so this study is going to stand for maybe six months or something before we're going to have to replace it, we release V2. I think that's actually going to be a broad concern. I think there's going to be a lot more sort of biotech startups that come out and they're wanting to prove stuff. I think there's also a lot of existing companies so you see a productivity tool and the productivity tool says: "Install this app and you're going to be 10% more productive." It will be nice if those people also had some demonstration.
I think the reason why we're not seeing this more often is because basically the cost of a study is tremendously high. So if you have to treat it very seriously and it's a six-figure study, small sort of is never going to do it. In our case, we know how to do a study. I think that's the thing that's walking the productivity tools is that we know how to do a study.
So it's called Prove It For Real. It's still sort of very early but we're doing sort of calls for participation. We've got a couple of PhDs from Berkeley onboard. We've got a couple of PhDs from Yale that may or may not be onboard. PhDs and grad students I should say. We've got some folks from the Quantified Self. They're excited about it. We're basically just making easy-to-use ways of automatically running experiments.
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That's the method that we have been using for this experiment. Like any first user of our own product, it's been nightmarish but hopefully soon it will be less nightmarish and you can just sort of use it if you're looking to test some stuff.
Christopher: Okay. So what have the results been like? How have the answers to the questions that you've been asking people that are taking the probiotic change from those that haven't?
David: Sure. Yes. The results will come out soon. Beltran would literally kill me but obviously it's not far afield of the pilot study that we did. Basically, I mean, my girlfriend and I were some of the first people that took the product. I don't have post-meal stomach pain. I never have. She did. I mean, she takes it every day because it sort of helps remove the stomach pain. In my case, I feel sort of more energetic. Those are the kind of things that we're going to demonstrate but, yeah, announcing results ahead of the study results is bad but we do have the pilot study results on the website. Those are of course real results.
Christopher: Excellent. The place to find you then, generalbiotics.com. You can order the product online which is kind of [0:32:00] [Indiscernible]. Right. So I'm never going to be seeing this in the supermarket, is that correct?
David: You may see it. It's just a question of, yeah, what sort of production ramp up looks like and if we can work out better ways of storing it. We kind of like the idea of going directly to consumers, honestly, or going directly through nutritionists.
Christopher: Right.
David: Those forms seem better. It kind of feels like if the person's not receiving sort of good advice about eating in an evolutionary manner and that sort of stuff, they should. I guess, yeah, it feels like there's complete lack of information on diet so finding good nutritionists and selling through them seems extremely reasonable.
Christopher: Exactly. Yes. So that's where we fall in I suppose so it's not we're using your probiotic as part of a protocol that consists of a lot of diet and lifestyle coaching and so, yeah, no one thing is just enough on its own. But all the individual pieces can be important.
David: Yeah.
Christopher: So that's great. So it sounds like the story is still evolving very rapidly and maybe we'd have to get back on and talk some more about what's been going on and where you're at right now.
David: Yeah. That sounds fantastic. Yeah, I mean, it is. It's small. We've got awesome people involved. I think you hit this point where a company will stabilize so in my past software gigs, we're in the process of building the business, right? We built the product but the business needs to be constructed quite badly. Yeah.
Christopher: Okay. Excellent. Well, thank you so much for your time today, David. I really appreciate it.
David: Thank you, Christopher. It's great.
Christopher: Yes.
David: Yup.
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