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A genetically modified bacterium that outcompetes bacteria causing tooth decay

Lantern Bioworks says they have a cure for tooth decay. Their product is a genetically modified bacterium which infects your mouth, outcompetes all the tooth-decay-causing bacteria, and doesn’t cause tooth decay itself. If it works, it could make cavities a thing of the past (you should still brush for backup and cosmetic reasons).

I talked to Lantern founder Aaron Silverbook to get an idea of how this works, both in a biological and an economic sense. Aaron was very knowledgeable and forthcoming, although he uses the phrase “YOLO” somewhat more often than most biotech founders. This post isn’t a verbatim interview transcript, just a writeup of what I learned based on his answers.

[Conflict of interest notice: Lantern is mostly rationalists and includes some friends. My wife consulted for them early on. They offered my wife and me free samples (based on her work, not as compensation for writing this post); she accepted, and I’m still debating. Consider this an attempt to spotlight interesting work that people I like are doing, not a hard-hitting investigation.]

1: What is BCS3-L1?

BCS3-L1 (brand name “Lumina”) is a genetically-modified strain of the tooth decay bacterium streptococcus mutans.

S. mutans lives on your teeth and metabolizes any spare sugar that comes its way into the waste product lactic acid. If too much s. mutans gets together in one place, all the lactic acid dissolves the tooth’s enamel coating, causing cavities.

BCS3-LI has four main genetic modifications:

  1. It produces a weak antibiotic, mutacin-1140, which kills competing oral bacteria.

  2. It’s immune to mutacin-1140, so it doesn’t kill itself.

  3. It metabolizes sugar through a different chemical pathway that ends in alcohol instead of lactic acid.

  4. It lacks a peptide that its species usually uses to arrange gene transfers with other bacteria.

The antibiotic helps it win the Darwinian competition in your mouth to become King Of The Oral Bacteria. The alcohol metabolism means it won’t produce lactic acid (and so won’t cause tooth decay). The peptide knockout prevents it from transferring genes back and forth with other bacteria that might either inactivate it or leak its advantage.

1.1: Where did this come from? Who invented it?

Professor Jeffrey Hillman of the University of Florida. In 1985, he was surveying the microorganisms on his graduate students’ teeth (as you do). One grad student had an unusual strain of S. mutans with a natural version of mutations 1 and 2 (it produced mutacin-1140, and was resistant to it). Hillman realized the potential, and spent the next few decades adding mutations 3 and 4 and testing the results.

1.2: So how did it end up with a tiny startup in 2023?

Professor Hillman started a company “Oragenics” and applied for FDA approval. The FDA demanded a study of 100 subjects, all of whom had to be “age 18-30, with removable dentures, living alone and far from school zones”. Hillman wasn’t sure there even were 100 young people with dentures, but the FDA wouldn’t budge from requiring this impossible trial. Hillman gave up and switched to other projects (including an intranasal COVID vaccine!)

Aaron heard this story and figured that brash, move-fast-and-break-things Silicon Valley biotech might be able to find an alternative route to commercialization. The strain was off-patent, so he first tried to synthesize it himself from the clues in Hillman’s published papers. When that didn’t work, he made a deal with Oragenics for 10% of profits in exchange for samples and the full recipe.

2: How do you use it?

To apply, you brush your teeth with a special pumice-based product that removes your existing tooth bacteria, then swab it on with a q-tip.

One dose is sufficient; once you use it, it’s in your mouth approximately forever.

2.1: As users kiss their loved ones, who kiss others in turn, will this spread exponentially and take over the world?

There was originally some concern about this, but no.

Remember, the original bacterium was found in the wild, in a random grad student’s mouth forty years ago. There must be thousands of people walking around with various naturally-occurring BCS3-L1-like things. So probably this isn’t a risk for some kind of weird pandemic.

Existing mouth bacteria have fortified their position and have a strong home field advantage. This is why you need to brush your teeth with the special product to apply Lumina.

Lantern’s safety documents note that couples who kiss constantly do end up with similar oral microbiomes. So maybe enough kissing – especially kissing just after a dental cleaning when your existing bacteria are at their weakest – could spread the strain accidentally, very slowly. This rate of spread would be comparable to the rate of spread of every other mouth bacterium.

2.2: When a user kisses their newborn baby, will it spread to the baby?

Okay, this one is true.

Babies have no existing mouth bacteria, and get theirs from their parents’ kisses. Not necessarily their first kiss as a newborn (newborns have no teeth, and BCS3-L1 needs teeth to live), but their first kiss after teeth grow in. If you get this, you’re probably getting it for your whole future family line.

2.3: If you wanted to get rid of it, could you?

Some kind of extreme course of oral antibiotics that nukes everything growing in your mouth would probably eradicate BCS3-L1, but this hasn’t been tested and would have side effects.

3: Is it dangerous to have bacteria secreting an antibiotic in your mouth? Does this mean you’re on a weak antibiotic all the time?

There are already bacteria secreting antibiotics in your mouth. Microbes are in constant war with other microbes, and antibiotics are one of their favorite weapons – remember, penicillin comes from a fungus.

Because bacteria secrete just enough antibiotic to clear their local area, these are tiny quantities, much less than you’d get from taking a medical-grade antibiotic pill. Lantern says the levels of mutacin-1140 dilute to irrelevance “tens of microns” away from the secreting bacteria. In any case, it’s a weak antibiotic that doesn’t survive the digestive tract (Hillman originally hoped to market the antibiotic too, but found it didn’t get absorbed and broke down too quickly).

Neither the grad student with the original strain nor any of Hillman’s test subjects had any noticeable health issues.

See also Lantern’s Safety Review FAQ.

3.1: Is it bad to disrupt your normal mouth microbiome?

When talking about BCS3-L1 “taking over” the mouth, this just means it takes over the streptococcus mutans niche. There are still other bacteria and fungi in the mouth.

The mutacin antibiotic might still disrupt these other bacteria (probably not fungi). But strains like BCS3-L1 already exist in the wild (eg the original grad student), and lots of bacteria and fungi secrete antibiotics, so it doesn’t seem like having mutacin-secreting organisms in your mouth makes you some extreme oral microbiome outlier.

If you eat a normal Western diet, your mouth microbiome is already pretty far from the design specs, and it’s unclear if using Lumina makes things worse.

3.2: Will the other bacteria develop resistance to the antibiotic?

Mutation 4 prevents BCS3-L1 from “leaking” its own resistance. Although in theory other bacteria could develop resistance, mutacin-1140 is a hard antibiotic to develop resistance to, and the other bacteria would have to do it in the short period before BCS3-L1 kills them off and establishes its own home field advantage. In practice, Professor Hillman found that BCS3-L1 remained dominant over many years and nothing developed resistance to it.

Even if a mutacin-resistant strain does develop in one person’s mouth, it will have a hard time getting to anyone else’s mouth, so widespread immunity is unlikely.

4: Is it dangerous to have bacteria secreting alcohol in your mouth? Will you get drunk?

Most people already have some alcohol-secreting bacteria in their bodies.

(there’s a condition called auto-brewery syndrome where those bacteria get out of control and produce enough alcohol to make someone drunk. It’s vanishingly rare in real life, but more common in the legal system: “You gotta believe me, Officer, it was just auto-brewery syndrome!”)

The average person has enough of these bacteria in their gut to have a natural blood alcohol level – even after zero drinks – of about 0.1 mg/dl. Under pessimistic assumptions, BCS3-L1 will add another 0.2 mg/dl, bringing the total to 0.3. This is still a pretty normal number that some people have naturally (it would bring the average customer from the ~50th to the ~80th percentile of natural blood alcohol). It’s also far from the usual threshold for feeling tipsy (30 mg/dl) or too drunk to drive (80 mg/dl).

Under more realistic assumptions, the amount of alcohol produced by BCS3-L1 probably isn’t significant even by the very low standards of natural blood alcohol concentrations.

4.1: Are there some unusual scenarios where this amount of alcohol might matter?

I don’t think Lantern has studied Breathalyzers. Since the alcohol is directly in your mouth, it might have disproportionate effect on a Breathalyzer compared to alcohol in your blood. I think it’s probably still too low to matter, but this is a wild guess.

There is conjecture that “non-alcoholic steatohepatitis”, a liver disease in which non-alcoholics get the same kind of liver damage that alcoholics usually get, might be associated with endogenous blood alcohol in the high normal range. If I’m understanding this paper right, it’s probably because the gut produces levels of alcohol consistent with auto-brewery syndrome, the liver goes into overdrive and metabolizes it away (prevents auto-brewery syndrome from developing), but the liver is damaged in the process the same as if it had to go into overdrive to metabolize normal binge drinking. Since BCS3-L1 produces much less alcohol than auto-brewery, I think it wouldn’t cause non-alcoholic steatohepatitis, even though it might produce final blood alcohol levels similar to those associated with the condition.

I was originally worried that Lumina might activate Antabuse, an anti-alcoholism drug that prevents drinking by causing a very unpleasant (sometimes dangerous) reaction to ethanol. There are some past cases of Antabuse being activated by really trivial quantities, like the alcohol in a chicken marsala dish or a mouth wash. But no, I think BCS3-L1 is less than this too. Chicken marsala can contain several grams of alcohol per serving, but BCS3-L1 probably only produces a few milligrams per day. If you swallow 1/10 of your mouthwash, that’s about 200 mg of alcohol – again, BCS3-L1 is probably only a few milligrams a day. Antabuse usually activates around a BAC of 5 mg/dl; BCS3-L1 only gives you a BAC of about 0.3 mg/dl.

Again, this really is a tiny amount of alcohol.

There might be other edge cases like these. Lantern offers a $100 bounty to anyone who can come up with one they haven’t thought of yet (and sometimes extra if you’re willing to help them research them).

4.2: Has anyone tested this in real life?

As mentioned before, the mutacin-releasing strain (with mutations 1 and 2) exists in the wild and was extensively tested by Professor Hillman.

The full strain with all four mutations has undergone some testing by Dr. Hillman, but nobody had officially infected themselves with it until two months ago, when Aaron finally synthesized it and tried it on himself. He says he’s usually “a lightweight” as far as alcohol goes, and hasn’t felt any different over the past two months.

When first infected, BCS3-L1 makes up almost 100% of the microbiome (because you deliberately removed all your other bacteria, then infected yourself with it). Over time, other bacteria creep back in; over an even longer period (years?), BCS3-L1 reclaims lost territory and reaches a steady state. But the point is that Aaron probably has already passed his period of highest BCS3-L1 activity, and felt nothing.

Graph showing bacteria levels starting high, then going down, then going back up.

My wife infected herself about a month ago, and I haven’t noticed her having worse judgment or becoming more impulsive. But at baseline she was the sort of person who would infect herself with an untested genetically-modified bacteria strain, so there might be floor effects.

5: What’s the plan to sell Lumina?

The plan is:

  • Phase 1: (January 2024) Sell to biohackers in Prospera for $20,000.

  • Phase 2: (2025??) Sell to ordinary people in the US for a few hundred dollars.

Lantern spent $400,000 acquiring rights and synthesizing the organism. Their first priority is to get out of the hole. So to start, they’ll be selling Lumina in Prospera, a libertarian charter city in Honduras. Prospera allows the sale of any biotech product under an informed consent rule: as long as the company is open about risks and the patient signs a waiver saying they were informed, people can do what they want.

By good luck, Prospera will soon be hosting a two month super-conference of biotech and crypto entrepreneurs/enthusiasts. Aaron thinks they sound like the sorts of people who might want an experimental cavity-preventing bacterium and have $20,000 to spend, so he’s hoping to sell at least twenty doses. But also, anyone else who wants the product can go on a medical tourism trip to Prospera and get it in their experimental-treatment clinic.

To move beyond the demographic of people willing to fly to Prospera and pay $20,000, Lantern will need FDA permission. The FDA has already set unreachable standards for any drug approval study, so Aaron wants to try a different route.

The FDA has lower standards for probiotics than for drugs. And technically, a bacterium which you take in order to change your natural microbiome is a probiotic. The genetic modifications are no disqualification; a few genetically-modified probiotics have already been approved. Some are almost as creative as Lumina: Zbiotics is a genetically engineered Bacillus species which sits in your stomach and (supposedly; I have not investigated this claim) prevents hangovers by metabolizing alcohol byproducts for you.

Aaron thinks the FDA will most likely see things his way. If that works out, he has to do six months of animal studies (routine, there are companies that handle this) in order to qualify as GRAS (Generally Recognized As Safe) and sell his product as a probiotic supplement.

5.1: Is it kind of crazy that you can get this approved as a probiotic supplement?

If the FDA approves Lumina as safe, would that be the system as designed, or a loophole that works because nobody expected probiotics to be this disruptive? I’m not sure.

Do the six months of animal studies involve testing whether the animals get drunk or not? I can’t imagine there is any regulation that animal testers have to do this. But if not, how do they address the most plausible objection to the product? I trust Aaron and am glad he’s found a way to make this happen, but this is a surprising way for the system to work.

The FDA does have the option of reviewing their studies and asking additional questions, which might include questions about the drunkenness or other concerns.

5.2: Can’t people transfer the bacterium among themselves without paying Lantern?

Yes. The recipient would either have to wait until just after a high-powered teeth-cleaning session at the dentist’s, or research how to give themselves a dentist-quality teeth-cleaning. Then they would find someone who had already bought the bacterium, swab their teeth with a q-tip, and apply it to their own teeth.

(this would risk transferring other salivary pathogens; to avoid this, you could use the more involved process described here)

Aaron thinks of this as a mostly altruistic project, and although he wouldn’t mind getting rich, he doesn’t begrudge anyone who is desperate enough to read up on dentistry and swab their friends’ teeth. He thinks most people would rather just pay the one-time cost of a few hundred dollars.

5.3: Why is local Internet celebrity Aella on the org chart?

Aella ends up involved in everything interesting in the Bay Area, and I have long since stopped being surprised by this. Aaron describes her as “a media and marketing advisor.“

5.4: How can I get this / help with this?

If you’re rich and impatient, sign up here and they’ll contact you when the $20,000 version is ready in Honduras (current plan: January 18, 2024). This is obviously a lot of money for a product which will hopefully go down in price soon, and Lantern is thinking about how to sweeten the deal (they might throw in equity in their company).

Otherwise, scroll further down the page to sign up to hear when they have lower-priced options available (and I’ll try to announce it here too).

If you have some other way you can help (they’re looking for investors, wet lab experts, and dentists), go to https://www.lanternbioworks.com/ and connect with them. Remember that biotech investing is hard and anti-recommended for everyone except professionals.

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