Symbiosis as a Business Model

I’ve been pitching Constellation to investors, lately—trying to raise the funds I’ll need to hire someone, get the Astrobacillus through the proof-of-concept work and out to market, and run a clinical trial.

In these conversations, I’ve been clear on what I see as one of the most exciting things about what I’m building: the potential to have long-term impacts on people’s health with a short-course intervention. If we can get engraftment—where an introduced species really takes root in your gut and joins your microbiome indefinitely—it’s a whole new ballgame.

See, if introducing a cholesterol-reducer works as well in humans as it does in animal studies, it almost doesn’t feel right to call the product a “probiotic”. It’d still meet the technical definition of the term, but it feels like a fundamentally different category of thing than the freeze-dried yogurt-starters-in-a-pill that you take once a day (and which, by and large, do nothing). If we’re successful, the end result has less in common with Culturelle than it does with LASIK, or orthodontia: semi-permanent upgrades for your body. I’m chewing on what to call this category (I think “Trait” captures it nicely), and if you have suggestions feel free to leave them in the comments, but that’s not really the point of this post.

See, I’ll never forget the first time I got this one piece of feedback from an investor. I’m on a video call with this potential angel; an English guy, very blue-blood vibes. I explain the vision to him, and at a certain point in the conversation he sort of steeples his fingers and says in his posh accent:

Well, it’s not a very good business model, is it? If they only have to buy it once.

And I’m glad that, the first time someone said something like that to me, it was phrased in such a way—and said in such an accent—that it was downright comical, how obviously evil the thought behind it was. Because I’ve gotten it a number of times since then, usually phrased more euphemistically—I discussed it with the team and there were some concerns about the strategy of one-time rather than continuous dosing, that kind of thing—but the underlying sentiment has been the same.

“What if we made it worse, so that people had to buy more?”

Because it turns out the wingnuts out there ranting about They’re suppressing the cure for cancer, so that they can keep us hooked on toxic treatments!—they’re tapping into something, although it’s never that overtly sinister, right? It’s not executives meeting in a smoky back-room, putting out hits on researchers getting too close to the truth. The banal reality is that, in any domain, “cures” programs have a harder time getting funded. But the net effect on our society is the same, and it’s a manifestation of the same mentality, which is what I’d call pathogen mentality.

A pathogen takes as much as it can from its host—extracting maximum value at every turn. It does not live in stable equilibrium with the creatures around it, instead reproducing (you might say “scaling”) as rapidly as possible, producing toxins that get it coughed out, or shit out into the water supply so it can do the same thing to its next victim.

It’s a fantastically fit strategy. For a time.

But eventually, when your core strategy is to take without restraint, to take as much as you can, you’re liable to sicken and kill the larger organism that makes your existence possible. And that lands you the same place it lands the host: six feet under.

And this is why, of the thousands of species you find in the human microbiome, a vanishingly small fraction are overt pathogens. Because the most wildly virulent success, in that framework, ends in the host’s death—followed shortly by your own. A more restrained pathogen (take Giardia, for example) can do well enough for a while, by attenuating: just take enough to sicken the host, without killing them. But this creates a selection pressure: eventually a Giardia-proof human will show up, outcompete his sickly, susceptible cousins, and put the parasite out of a job.

And so my response to everyone who’s suggested engineering in a “suicide circuit”, or some kind of auxotrophy, such that you’d have to take a daily supplement in order to keep the cholesterol-reducer alive, has generally been a jovial: Fuck off, you cartoon villain.

Because that’s pathogen mentality. It’s trying to win at life, because you’ve failed to recognize that a “win” means game over, just as much as a loss. The goal of life, the only success to be had, is to keep the game going—and to that end there is only one strategy that works in the long run.

Symbiosis.

The only creatures that succeed in this long, long game of life are those that thrive by helping everything around them thrive. Taking what they need, yes, but giving back. Not more, but different. This is not a charity ethos; it’s rooted in the simple fact that one man’s trash is another man’s treasure.

Take fiber. What can we do with fiber on our own? Nothing! That’s part of why plants lock away all their carbohydrates in these indigestible polysaccharides—because, in the wild, something like sugarcane would be eaten to extinction in five minutes flat. But your gut bacteria look at cellulose and xylan, all the inert roughage in broccoli or oats, and go Oh, I’ll eat that! And the waste they produce, in the process: acetate, butyrate, the short-chain fatty acids—these are the grease that keeps the gears of your molecular machinery running smoothly. Bug shit! You can’t live without it!

Everyone’s heard the story, right? The fairy tale about the woman who meets a little imp that can spin straw into gold?

Well I, too, am a little imp, and I have found a way to spin the cheapest part of the pig, a little bit of soup, and literal shit into that most priceless of commodities: human life. Quality and quantity of it. Time on this Earth.

We have a chance to give that to people. To sell it to them, at a very handsome premium! If that doesn’t already feel dirty enough—if you’re not interested unless you can extract rent on it? I don’t think I need your money.

And I think there’s still room in the world for this kind of thing, if we can resist the temptation of “shrink-flation”, of greed. After all, think about what happens when, the first time somebody orders a product from you, you deliver a minor miracle to their doorstep; something that adds ten years to their expected lifespan, because it drops their cholesterol by 65 points. That is how you create a lifelong evangelist, that is what we call organic reach. Now think about the value in creating a lifelong evangelist who is going to live an unusually long time. That is symbiosis.

And, y’know, inshallah we put ourselves out of a job because there’s no more diseases left to cure, but people are not going to stop taking antibiotics anytime in the foreseeable future: the average American takes them once a year, which we know means something like a 10% chance of losing your coprostanol-producing bacteria. And yes, that’s recurring revenue—but you know what’s going to happen, the second time a person has to come and pay us $5,000 to re-acquire this trait?

They’re gonna be a little more careful with it. And the next time they go to the doctor with an ear infection, and the doctor says “I’m writing you a scrip for erythromycin,” they’ll say “Wait a minute doc, don’t they make, like, antibiotic ear drops? Can we do the drops instead?”

And they do! And a lot of the time, you can. And so we won’t get a third $5,000 from that guy, but y’know what? Mazel tov.

Because, as I’ve written about before, taking any oral antibiotic increases your chances of ending up with MS, and depression, and Parkinson’s, and infertility—and now this guy’s risk of those conditions has not gone up, the way it would have if he had taken the drug. And so among our customers, just by creating this cognizance—there is more to you than the human—there will be less depression, and fewer suicides. The kind of fringe benefits that it’s hard to quantify, so which we call luck.

So now our lifelong evangelist is not just unusually long-lived, but unusually lucky. He’s happy, his skin is good, his kids are healthy. He ages gracefully, and doesn’t suffer the cognitive decline that sours the hearts and closes off the minds of some of his peers. And when he recommends this eye-wateringly expensive product to his neighbors, maybe the sour-faced ones will say to themselves Feh! Of course Mr. Lucky has $5,000 to blow on magic ice cream. But some of them will listen. Will recognize that, to really get lucky, you have to bet on yourself—to invest in yourself.

That is what we’re offering people: the ability to invest in themselves, in this screamingly literal way, and to actually own what they buy. Maybe not forever—but for as long as they can keep it alive. Maybe that’s a lifetime, maybe it’s several lifetimes—because bacteria don’t age the way we do. The strains we’re selling, they’re already heirlooms; they’ve been passed down for a thousand generations, and if you take care of them, eat right, avoid antibiotics—your kids will inherit them too, and their kids after them.

Life is the fruit of the orchard I am planting here, and money will grow on these trees regardless. And yes, little worms will come to nibble at those leaves: inefficiencies that could be optimized out. But let them be, and I think you’ll be delighted to find: they spin the most marvelous silk.

🖖🏼💩