A week ago, I posted a thread about trying Lumina, the probiotic dental caries treatment from Lantern Bioworks. It got way, way more visibility than I expected (good), but given the popularity of the thread, I felt it would be responsible to address a number of concerns, objections, and skepticisms it uncovered.

Instead of doing this in the marketing-friendly bite-sized tweet storm format, I will do this in a more long-form format, which is more conducive to nuance and detail:

1. Disclosure: I am an investor in Lantern Bioworks!

(I am sorry it didn't occur to me to bring this up right at the beginning but the thread started out as a "look at this crazy thing I am doing" and then ended up later sounding promotional, if you can call it that)

Anyhow, yes I am an investor!

However, it doesn’t work exactly the way you think. The cached-thought reflex most people have is “investor = wants to get rich, shills for company; don’t believe what he says!”

First, my investment is something like 0.05% of the company [details elided here about SAFEs, caps, etc]. Similarly, the equity I hold in Lantern is also a tiny portion of my net worth.

Second, I invested in LB because I knew about this dental caries cure 10-15 years ago. If you’ve been paying attention, the basic research had been done in the 80s and 90s, and in the early 2000s, the inventor was attempting to get it approved by the FDA as a medically-approved treatment, and it was under patent.

At the time I found out about it (mid-2000s), that was the status quo: a cure (technically: preventative vaccine) for caries existed, but it was under patent. So all we [normal people] could do was wait, and hope it came to market.

It never came to market. For various reasons (more on this later), it wasn’t able to even start to get FDA approval, and the company is basically defunct.

My overriding priority, therefore, is to help get this out to humanity. If you’ve read Cremieux’s piece [] on the history of dental caries, it is global problem that has plagued us since the dawn of history, and if we could eliminate (or even greatly reduce it), it would result in a profound improvement in the human condition.

Hence, when I found that a company was working on it, I was intrigued. It turns out that yes, many other people were willing to experiment with this, but the company needed a bit of capital to ramp up production. The amount of money needed was an amount that I felt I - in addition to more investors within my network that I thought I could bring to the table - could provide.

In fact, I invested ONLY because the company decided to pursue what I consider the LESS profitable route of distribution:

When I first learned about Lantern (Sep 2023), they were mulling over their go-to-market plans. At the time, they had concluded that:

- Just making and distributing the cure would not be particularly profitable, as it was a one-time treatment and if successful, that’d be the end of things. And, being as it was out of patent, other companies could clone/pirate the same treatment and just copy them.

- The more profitable thing would be to slightly tweak the bacteria in a trivial way so that it would be patentable, get a patent, then sell it to Pfizer, have Pfizer drag it through the FDA approval process. It was anticipated that this process could take 2-10 years to before it would get the bacteria into peoples’ mouths. At the time, Lantern seemed to slightly prefer this plan.

I did not like this plan. My feeling about this cure is that it is game-chantingly important for mankind, and not something to be subject to our monstrously dysfunctional public-private FDA-Big-Pharma late-stage-capitalist regulatory-capture system. So I didn’t invest.

(There was another third plan, which was to pursue approval in other, faster countries, with the caveat that the FDA holds a grudge against you if do that, so it was sort of a worst-of-both-worlds plan)

Months later in ~Feb 2024, Cremieux posted about having gotten the treatment himself at Prospera, and answered a message from me with an offer to introduce me to Lantern’s founder, Aaron.

By then, Lantern had apparently decided not to deal with creating a tweaked strain, patenting, and dealing with Pfizer, and were intending to just make and distribute it as a cosmetic (probiotic supplement), which doesn’t require FDA approval, and presumably make a healthy return selling a one-time treatment to all of mankind, which is still 8 billion people.

The idea is that they were selling it for $20,000 per treatment at Prospera to rich guys like Cremieux, then it came down to $5k, and now they’re taking pre-orders for $250 each, putting it in the budget of well-off biohackers and other early adopters. They’ll drive the price down at each stage, and eventually the last billion doses will probably be sub-$1 production cost distributed by NGOs in developing countries.

But in order to make the jump from bespoke lab bench treatments at $5k each to producing 1000 units/month at $250 each, they needed to scale up a small production facility, and that’s why I invested - to help them make this next step.

I should mention that even if this investment does well, I won’t actually personally make money from this. I invested through a charitable donor-advised fund that I contributed to, and any returns on the investment will just go back into the charitable fund, to be deployed into other similar investments. I can’t actually claim any of the returns.

My role as an investor (and indirectly, apparently as a marketer) is to accelerate the production and deployment of this as a cure to as many people who want it as possible. I am not doing this for the money. I am doing it because I’m hoping to remove hurdles (financial or otherwise) for something that I think will be beneficial to mankind - after 20+ years of development hell - to finally see the light of day.

Next: FDA approval - no?cremieux.xyz/p/46ebd66b-8a6…

2. It's not approved by the FDA?

The short answer here is that FDA approval is extremely difficult to get for reasons unrelated to the efficacy and safety of the proposed intervention, and not because the intervention is necessarily unsafe or ineffective.

While there are many unapproved therapies that ARE unsafe or ineffective, this does not mean that when something is not FDA approved that it is necessarily unsafe or ineffective.

This is an important distinction to make in our day and age, when the FDA is in that awkward slow-collapse state of being not completely useless while largely failing to live up to its intended function. (Friends at the FDA: it’s not your fault - you’re trapped in a huge dysfunctional system you cannot really control)

Some history:

The company originally founded by Dr. Hillman (the researcher who discovered the cure) was called Oragenics. Back in 2003, after the treatment had passed animal trials, Pfizer actually tried to purchase SMaRT (as the treatment was called back then) from Oragenics for $64 million but Oragenics refused, choosing instead to try and carry it through the FDA themselves.

But the FDA required them to find a cohort of 300 healthy 18-30 year olds who lived alone, not near a school zone, and had fully removable teeth. Let me repeat that: they wanted Oragenics to find 300 young people with dentures.

That is basically IMPOSSIBLE, so Oragenics failed even before they started. The company floundered about for a bit, the patent expired, and then a couple years ago Lantern Bioworks bought all the IP.

Lantern itself seriously considered tweaking the formula slightly to qualify for patent protection and to sell it to Pfizer, and rely on Pfizer’s corporate muscle to drag it through the FDA testing and approval process, and hope that 2-10 years from now it might hit the market.

I WOULD NOT HAVE INVESTED IF THEY WERE DOING THAT.

In fact, as I chatted with other prospective investors, more than one of them asked whether the product was going through the FDA approval process and responded POSITIVELY when I answered that they were not. Apparently the FDA process these days is so onerous and cumbersome and sufficiently removed from the questions of safety and efficacy that they are considered something that makes a company uninvestable to many.

(This is not to say that the FDA approval and testing process has no value - it certainly yields some useful data on safety and efficacy - it is just that it also imposes disproportionate time and energy cost whose risk often does not match upside outcomes. The questionable results (on both sides) of potential treatments during the pandemic are a clear symptom of this)

Finally, the fact that a company capable of enduring the FDA process would never do it unless they owned a monopoly patent on the treatment was unacceptable to me. Because the bacteria is in the public domain, no drug company wants to try to carry it through the FDA - doing so would just mean that anyone could then sell the drug that they just spent half a billion dollars to get approved.

Remember, this is not some new fly-by-night GMO tech. The research was done, tested, and peer-reviewed over 20 years ago. In looking back at the supporting research that fed into it, I found that Dr. Hillman had published foundational papers as far back as 1978, before I was even born, characterizing effector strains that had the potential to create a therapy for dental caries.

Published in 1978:

So here’s where we stand:

- Pfizer (who are no fools) already offered to purchase this for $64 million in 2003 based on the positive results of animal trials. Adjusting for inflation, this is maybe ~$110m now
- No drug company CAN drag this through an FDA approval process, and the reasons for that have little to do with efficacy and safety.
- The only “maybe” way to do so is to patent a tweaked formula, but that still means of a delay of up to a decade and the same potential market danger of a generic competitor simply selling the original formula, with the FDA-approved formula now under the monopoly ownership of a Big Pharma company.

This treatment, if it works, is worth about $45B a year in saved dental work in America alone, plus the lives of hundreds of people who die annually from tooth infections and dental anesthesia mishaps. It’s a civilizational embarrassment that this drug is held back by red tape.

What I think is the best way forward:

Because it’s relatively certain that the treatment is safe (and I’ll address a couple safety questions that came up later in this post too - but probably the best argument is that Pfizer offered $64m for it), the best thing to do seems to be:

1. Move forward with manufacturing and distributing this as a probiotic supplement
2. Once a critical mass of biohackers and early adopters take this treatment, other third-party research can get involved

Rather than being done under the auspices of a drug company (which would even have an economic motive to see certain results), independent labs can do research on cohorts of people who apply the treatment vs not, and we’ll get much better, larger datasets of results. Labs do this all the time - answering a question like “are people who eat muffins happier in the morning” doesn’t require muffins to be a patented new intervention - you can just do the research because you are curious: and many people will be.

If you’re not an early-adopting biohacker, you should favor this approach. You should want this product out there, and your risk-taking friends to be trying it (or if you are really afraid, then your risk-taking enemies), so that a critical mass of test subjects can be recruited for some nice large-population-set data. Then subsequent potential users with a different risk profile can make their decision after more data is available.

Next... genetically stable what?ncbi.nlm.nih.gov/pmc/articles/P…

3. It’s genetically stable? Also, any possible kill-switch in case things go wrong?

In one of my posts in the prior thread (), I mentioned “4. It’s genetically stable.”

That was rightly treated with some skepticism, given that I didn’t provide any details.

I had elided the details because it was just complex enough that it would have made that part of the thread overly verbose and technical. I will provide those details now here:

First, S.mutans has a proclivity for horizontal gene transfer (exchange DNA) with other bacteria. This means it tends to mutate “faster” than average. This actually produces many other sub-strains (one of them is harmful - more on this later), and what we would ideally like to do is for OUR beneficial strain to do the the helpful thing it does (plus no harmful things) and NOT mutate.

Well, it turns out you can do this by introducing a small deletion in one of the genes (called “comE”), which causes the strain to lose this DNA-exchange ability. Subsequently, the bacteria with this change no longer mutates as quickly.

The paper outlining that change is here:


Incidentally, this paper also describes another tweak, where they installed a “kill-switch” for the bacteria: you can wipe it out by taking oral chlorhexidine (a specific anti-microbial mouthwash).

Both the kill-switch and genetic-stability tweaks were added for human trials, specifically to enable rapid elimination of the strain in case of adverse side effects, and to yield genetic stability (to make sure the kill-switch stayed intact, among other things).

Next: does it colonize the gut?

https://twitter.com/yishan/status/1777926639495905750

academic.oup.com/jambio/article…

I’m about to do the Lumina treatment, a cure for dental cavities developed by Lantern Bioworks.

I figured I’d do an unboxing and let you come with me on this journey. Here’s the box:

It’s a one-time at-home treatment, which replaces the bacteria in your mouth with a slightly different bacteria - one that doesn’t secrete the acid that attacks tooth enamel and causes cavities.

Ingredients:

Hmm, it’s half sugar. I guess that’s to give the bacteria something to snack on once it’s reconstituted?

What if the world’s forests had a system to detect wildfires almost instantly as soon as they started, even before the fire was visible?

Such a system is possible, and it’s low-cost and highly-scalable. Here’s more…

Carsten Brinkschulte is CEO of Dryad. They make simple IOT devices to detect smoke from wildfires while the fires are small, passing the info along inexpensive mesh networks to a monitoring station, so that firefighters can respond within minutes.

terraformation.com/blog/how-the-i…

Solutions to address climate change need to be implementable at scale, and this often means using components that are small, simple, and cheap.

Dryad’s solution is all of these, and it performs far faster than other, more complex solutions.

Google’s Gemini issue is not really about woke/DEI, and everyone who is obsessing over it has failed to notice the much, MUCH bigger problem that it represents.

(1/n)

First, to recap: Google injected special instructions into Gemini so that when it was asked to draw pictures, it would draw people with “diverse” (non-white) racial backgrounds.

This resulted in lots of weird results where people would ask it to draw pictures of people who were historically white (e.g. Vikings, 1940s Germans) and it would output black people or Asians.

I am probably one of a small number of people who have had the chance to work directly with both @AdamDAngelo and @Sama and get to know them.

Here’s what you need to know about these two guys:

First, I worked with Adam as an engineer and then director of engineering while he was CTO at Facebook, and then later I did consulting work for Quora.

I worked with Sam when he helped me raised Reddit’s Series B round and served together with me on Reddit’s board. His firm (him and his brother Max) is also the lead investor in my company @TF_Global.

Our society today is basically just about yelling incoherently about things without regard for facts instead of doing anything real…

… which is exactly what you’d expect from a gerontocracy, right?

What if the problem is not political polarization or lack of education or wokeness or fascism or any of those things but merely that our society is a reflection of the fact that our senior leaders are really old people?

Really old people don’t DO things, they just complain.

Trump is 77, Biden is 80, Mitch McConell is 81, and Pelosi is 83.

In your own family, does anyone you know who is that age lead the way with bold and concrete vision and clear solutions? Or do they just… sit around and talk?