> They offered my wife and I free samples (based on her work, not as compensation for writing this post); she accepted, and I’m still debating.
Amusing but still somewhat serious question: if their product, which they offered samples of, is a colony of bacteria that live in the mouth in perpetuity, and your wife takes it, then wouldn't any debating you do with yourself on the subject be rendered moot the next time you kiss your wife?
I think the worst possible consequences is the FDA blocking this avenue after this gets past them, and if we can only get ONE probiotic miracle past the enemies of all humanity, it would be a shame for that to be tooth decay precluding, say, Alzheimer's or something.
Why haven't you accepted their offer of a free trial yet? What are your reservations?
Also, you addressed the alcohol issue but is there any downside to the lack of lactic acid? Does lactic acid really not provide any benefits to your mouth?
So this brings up a question I've had before in the past...
Ethyl alcohol is metabolized to Acetaldehyde, which is carcinogenic. But there's not consensus on whether there's a safe level of acetaldehyde. I mean, there are beneficial levels of radiation, so it seems reasonable that there might be a beneficial level of acetaldehyde. But this hasn't been proven. The long term effects of low dose alcohol may be beneficial. (Reduced cardiac events. Better hormonal profile.) They may be neutral. Or they may be negative. ( increased deaths from tuberculosis was one item that was supposedly associated with drink-a-day levels of alcohol consumption due to immune suppression, IIRC) I'm curious if anyone has a take on the topic.
I don't like the idea of selling drugs to people when they haven't undergone extensive safety testing. We have no real evidence of the long-term safety of this drug besides the say-so of the inventor, and we have zero information about the manufacturing controls of Lantern. I wouldn't ingest a genetically modified bacteria from a factory that has not been inspected [edited for pedants in the comments].
On a side note, I really doubt that this will become commercially available after Lantern has thumbed their nose at the FDA by selling it in Prospera. There's no chance they'll find that amusing.
1. What's your prediction (%) on whether this - or a similar product - will be proven to be highly effective and in common use by 2029? (BTW, curious about the implications to the dentists)
2. Why shouldn't individuals interested in the product consider Aella's involvement as a red flag? Not sharing a personal opinion here, but a rationalist colleague has just reminded me about her guide on squeezing the most money from (vulnerable?) men watching webcams, and her engagement in the failed dating service that cost many people a lot of money.
As an adult with a water-pic and decent self control, this is of limited utility, but as a young adult with neither of those who hated flossing, it might have saved me a mouth full of cavities
Anywho, i imagine there’s a % of the population due to genetics or micro biome that have a really high propensity to caries and might be very interested in the product. I can see the Instagram ad now: DENTISTS HATE THIS ONE WEIRD TRUCK
Will be interesting to see how this compares to BLIS M18 which has been readily available online for years now and of which I originally learned of as a bacteria strain that was advertised to do exactly the same thing - populate the mouth with something that dominates the decay-inducong bacteria.
We should start a crowdfunding campaign to pay for one person to go to Próspera and become infected. Then they could transfer it to everyone who contributed to the campaign. Would anyone be open to this?
Oh man, I remember reading about this bacteria that produces alcohol (probably in either Popular Science magazine, or maybe reddit) well over a decade ago. I immediately thought about it when I saw the subtitle, and was pleasantly surprised to realize it was one and the same (1.1).
It's cool to get some closure (1.2) about the neat thing I read about so long ago and have wondered on and off whatever became of it... and slightly less cool to have yet another thing in the pile towards convincing me the FDA is awful.
...This was the straw that motivated Tuesday's article, isn't it?
_S. mutans_ is possibly associated with cardiovascular disease[1]. Does alcohol instead of lactic acid impact that role? That's the unknown that's stopping me from jumping on this now.
"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."
You might be able to round up that many hockey players or something; even moreso in the 80s. Then pay them to live alone during the offseason or something?
I notice I'm confused though -- does the FDA want to check whether the product prevents cavities *in dentures*?
Wait, people just know about real hangover cures and have not been saying anything? Does this zbiotics thing really work? This could give me many hours of my life back.
Has anyone tried it? I'd order it myself but they only offer shipping inside the US.
I’d be down to chip in $500 for someone to fly to Honduras, get these bacteria, then transfer them to me back in the US. If you’d be down too, please reply to this comment. I’m sure we could find a trustworthy rationality community member to actually fly to Honduras if there’s enough interest.
If I were trying to earn back the $400k, I would probably try to sell it to 200 people for $2,000 each, instead of to 20 people for $20,000? Though admittedly I have no expertise in setting prices for anything.
(Epistemic status: Know nothing about dentistry and this is entirely based off of things I vaguely half-remember people who may have been dentists mentioning in casual conversation long ago..)
I believe the point of brushing your teeth has little to do with "scrubbing" them clean, like you'd scrub dirty dishes or wash a car or whatever; rather, you're actually trying to distribute fluoride throughly into every nook and cranny, to create an unfavourable environment for bacteria. (That's why we're told not to rinse with water after washing; it removes most of the fluoride we've just gone to the trouble of laying down..)
The bacteria aren't just a threat to your teeth; they also cause gum disease. If gum disease is caused by lactic acid (doubt it, but of course what do I know..) then we're all right - but if some other bacterium in some other niche is causing gum disease by some other mechanism (and assuming BCS3-L1 can't outcompete *all* other bacteria, as the chart in section 4.2 seems to suggest) it would still be necessary to brush regularly with fluoride for the sake of one's gums even if one's teeth weren't at-risk of decay.
If this is wrong I'd be awfully glad to be corrected, of course!
>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 is a bad idea since it might spread saliva-borne pathogens (for example cytomegalovirus, HSV, Neisseria meningitidis, etc). As a better idea, swab their teeth, plate the swab onto agar dishes, and isolate bacterial colonies. (To make this more effective you could add mutacin-1140 so only resistant bacteria will grow, although this is not strictly necessary). Then pick the colonies and test them to see if they are the correct bacteria. Finally, put the correct bacteria in people's mouths.
Anyway, someone with basic microbiology skills could easily pirate this product.
Great post -- put me into such a buying frenzy that I immediately pulled trigger on a ZBiotics pack. Hopefully it will be here in time for the holiday festivities.
Perhaps some of portion of the rat/EA charity funds could be turned to creating a think tank / pressure group that lobbies & brings strategic litigation for medical freedom.
What is the chart about? Proportion of the modified S. mutans among all S. mutans? (Wasn't it supposed to stay near 100%?) Proportion of all S. mutans among all mouth bacteria?
----
> To move beyond the demographic of people willing to fly to Prospera and pay $20,000, Lantern will need FDA permission.
As you may be aware, Prospera and the USA are not the only two jurisdictions in the World.
This is fascinating. I’m wondering however, will the idea of “cavity prevention” lead to counterproductive behaviors? Imagine a world where people take this probiotic.
Those who brush and floss normally (or even half-decently) don’t get cavities.
However, some people with poor hygiene really let themselves loose once they apply the paste to their teeth. A-few-times-a-week (wink wink) flossing becomes never. Will the loss of hygiene end up counteracting the cavity prevention in any meaningful way?
Is there any data on Aaron's current oral health? Does he still brush and floss? Has he been to the dentist for a checkup? What about data from the original study - did the participants' oral health objectively improve?
I'm pretty bad about flossing and would pay for this right now. $20k is a bit much but I'd definitely be willing to shell out $1k if it was shown to materially improve oral health outcomes.
As somebody entirely unaffiliated with the company, it is my expert opinion that this is basically fine and something I'll probably get for myself once it gets approved for sale in the states. Looking through the literature, Hillman did the appropriate animal studies and this is ready for human testing, where I expect it to have precisely zero side effects (the metabolic rate of biomass in the mouth is basically zero except considered locally.)
I am an expert on this exact field. I did my PhD on synthetic biology of gram-positive bacteria and currently work at a startup developing engineered live biotheraputics. We are going down the FDA drug approval path for a couple different things, but it's true that the supplement approach is so, so much easier. But then insurance won't pay for it. *waves in the direction of the healthcare system*. The supplement path is probably right for this.
As a side note I'd like to say that this kind of genetic engineering of a non-model bacterial strain is not trivial, even with modern CRISPR/Cas9 tools. So bravo to Aaron for succeeding on that front. If he's willing to provide the whole-genome sequence of the modified strain with annotations of the edited regions it would help remove any last specks of doubt on my end.
I'd love for some kind of long-term tracking of people who take this, though in this context it would have to be self-reported and that would make it hard to get anything useful. Still, if the effect size is as large as claimed then it should still be pretty obvious.
Bacteria evolve to be antibiotic resistant all the time. So would not this bacteria loose it's advantage pretty quickly?
I think a better way would be to make it able to digest several substances that are hard to digest for other bacteria and add those substances to toothpaste randomly.
This way it will have advantage that is hard to get for other bacteria and it is easy to get rid of.
I can't really comment on the medical or chemical aspects. I am concerned about the business plan. If the product really works it should be pretty easy for them to raise money on much better terms than they're asking. And why do they need $400k? Are they in debt to someone? And giving away equity is arguably the last thing they should be doing unless they've already got a fair bit of revenue and have already raised. The go to market plan is a bit lacking as well.
Is this by chance a team of scientists with little to no business experience?
Immunology seems to be a perpetual blind spot for people developing new therapies of any kind and this doesn't seem like an exception. Both lactate and ethanol have immunosuppressive effects but are mechanistically distinct and it would be stupid not to look at changes in oral immune cell composition and function after this treatment. If there were any negative effect from this treatment I would guess it would be increased rates of autoimmunity in oral tissues.
Seems like there might be a rule-consequentialist argument that people shouldn't release mostly-untested bioengineered microorganisms into the wild, even when they believe based on preliminary short-term testing that they'll be safe.
Very cool; thanks for writing this. I'm pretty tempted, but I think I can wait a year or two for a $19,000+ discount.
The other interesting thing in this "prepackaged biohacking" space I'm aware of is the follistatin gene therapy at https://minicircle.io/our-therapies/. (Also currently being tested in Prospera.) Again, I am tempted to get it now, but suspect waiting a year or two for more efficacy data, lower costs, and easier distribution is the smarter move.
Are there other interesting things in this space worth keeping an eye on?
(My personal dream would be a gene therapy to give me that gene that lets you sleep less per night...)
Very cool idea. However, I've met Aaron and I wouldn't trust him with anything of significance. The 'YOLO's are not cosmetic, he seems averse to ever second-guessing anything.
I wonder what the effect is on plaque? If plaque is reduced, that would have a positive effect on gum disease. Or if plaque is increased, that would be a trade-off.
Hi, I'm an endodontist. Are there any other dentists reading or commenting here? I see lots of people discussing this who probably have never diagnosed a cavity and almost certainly have no idea how rare well-designed long-term clinical trials are in dentistry.
0% chance this takes off. Happy to discuss further if anyone is interested.
This whole concept, killing off potential harmful local bacteria and replacing it wholesale with something harmless that will fill the same niche, reminds me of an idea I had recently.
I had a minor surgery a couple weeks ago, and a big part of the pre-op prep was wiping down my skin with various antiseptics to kill as much of my normal skin bacteria as practical in order to prevent the surgery from causing bacteria to wind up where they shouldn't be and making a nuisance of themselves.
As I understand it, the main problematic local skin bacteria is S. aureus, which is definitely not a necessary part of normal skin bacteria because only 20-30% of the population has significantly population of it. It seems like when you're doing a whole-body antiseptic treatment anyway, that's a great opportunity to see a benign mix of microbiota to keep any S aureus from moving back in. Especially if you're in a hospital, as hospitals are notorious for having nasty strains of antibiotic-resistant S aureus lurking about in the environment despite the cleaning staff's best efforts.
> Babies have no existing mouth bacteria, and get theirs from their parents’ kisses.
This is contrary to my expectations; for one thing, parent/child mouth-to-mouth kissing is far from a universal thing.
The theory I was aware of was that babies get their oral microbiome from their mother's vaginal fluid as a side effect of birth. This is why babies delivered by C-section may be deliberately swabbed with the mother's vaginal fluid.
Since this is completely legal under the law of Arkansas, the state charged the girl with solicitation of a minor. (You can't just not punish people simply because they aren't breaking the law, and the age threshold below which solicitation of sex is illegal is higher than the age threshold below which having sex is illegal.)
Those charges got tossed out of court on the theory that the first amendment protects solicitation of lawful conduct.
So the state filed different charges, accusing the girl of indecent exposure because the boy could see her genitals while engaging in sexual behavior with her.
This got the girl convicted of a felony (sentence: 24 months of probation, plus you're registered as a sex offender for the rest of your life) because, while speech soliciting a completely legal act can't be prohibited, there is no problem with prohibiting necessary side effects of completely legal behavior.
The court specifically notes that the first amendment does not protect the girl's nudity here because, instead of conveying a message, the nudity serves a functional purpose.
The court ends its judgment by noting that this result is absurd, but that's not a problem because the source of the absurdity is the legislature and not the executive.
Leveraging normal flora to outcompete pathogens could treat bacterial diseases caused by toxins, rather than those invading human cells. This method might not be effective for pathogens like listeria or chlamydia, but could work against some gram-negative bacteria. It could also be beneficial for diseases like gonorrhea, where inflammation is a key issue. I hope this takes off
"The antibiotics mess up your mouth microbiome" seems like the only risk I can think of. Maybe it kills a bunch of other bacteria weak to mutacin-1140, upsetting the balance of your microbiome and somehow causing you to get more cavities as some other species expands to fill the newly-available space. Or maybe the streptococcus mutans has some secondary metabolite that also damages teeth and the mutant strain fills up all the available space and still gives you cavities. The grad student here only sets a ceiling on how bad this can be: clearly it doesn't make all your teeth fall out or we'd have noticed, but how would we know if the net effect is just mildly worse than normal?
If there's some baseline percentage of the population who already have S. mutans that expresses mutacin-1140, does that mean they wouldn't be able to get this treatment? Or would it just be more difficult on the uptake? Like maybe you'd need a few treatments to get it established, since it can't use it's antimicrobial to help it out compete the native flora.
I found it a little confusing how you kept going back to the alcohol thing. Once you established that it was 2 orders of magnitude less alcohol per day than accidentally swallowing a small bit of mouthwash I thought that should have settled the matter entirely and no further thought should be given to it.
One concern I didn't see brought up by anyone: would having bacteria excreting alcohol in your mouth all the time increase your risk of oral cancer? Using alcohol-based mouthwashes may do so (disputed) - those have quite a high concentration of alcohol, but they're also only in your mouth briefly, so I have no idea how "negligible quantities, but all the time" would compare. This seems particularly concerning because it's a problem which wouldn't show up for many years, and the increased risk would only be detectable in aggregate.
Scott was wondering recently on "paid", about better not write up 'high-temp'-topics (neo-reactionary is dead). My take was: My dearest MD S.A.S. just write essays about whatever YOU feel like writing about. - Glad to see once again: That is the way! - Oh, and I WANT those bacteria in my mouth!
On the topic of bacterial exchange and microbiome more generally:
When I first visited China, eating the food there would give me diarrhea. (It didn't really matter which food. Nothing was wrong with the food.)
This was so common that the effect was well known under the name "traveler's diarrhea". Given enough time, it stops happening. By the time my family came to visit me, they all experienced traveler's diarrhea eating food that gave me no problems.
It is straightforward to explain traveler's diarrhea by appealing to the idea that your guts are adapted to the food you're accustomed to eating, and there's something different about the food in whatever far-off region you've suddenly teleported to by airplane. But there are some interesting questions this might suggest:
- Does adapting to one locale impair your ability to eat food from your original locale? (This didn't happen to me; I maintained a normal ability to eat American food.)
- Will adaptation wear off over time? (This also didn't happen to me; a span of several years outside China was not sufficient to give me traveler's diarrhea after returning. Interestingly, during this span I did take a course of strong antibiotics which were intended to nuke my stomach and also nuked my gut.)
- How does adaptation occur? The obvious candidate mechanisms appear to be "the food contains bacteria that will colonize your gut, eventually enabling you to eat the food without problems" or "the food will enable the differential success of bacteria already in your gut that, once they've grown to sufficient levels, will let you eat the food without problems". The fact that adaptation doesn't appear to wear off tends to support the first of those ideas over the second one.
If either of those ideas is correct, then it would seem pretty likely that the food you eat also has a very strong influence on your oral microbiome, and might source it after events like birth or a course of strong antibiotics.
> 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.
Huh, I wonder if that is why I've never had a cavity
It shouldn't cause any difficulties with breathalysers; they're designed to function by drawing deep lung air and for the ones I'm familiar with (the Lion Intoxilyser, the Camic Datamaster and the Intoximeter), the operating cycle will intentionally fail if you try and blow air from your mouth into it.
I don't know even enough to be dangerous on the subject, and it was a long time ago, but I read some renegade dentist claimed that tooth decay was an exacerbating cause of heart disease.
As I said, the proponent was a renegade, but apparently there was some evidentiary support for his theory.
There is more to bacterial competition/cooperation than the secretion (or inhibition!) of antibiotics. For example, small RNAs. Your oral microbiome is continuously pumping out regulatory RNAs that cross species boundaries. And theres phage. We know next to nothing about the natural history of these viruses in the oral microbiome. A phage might re-engineer your bacteria in just a few microbial generations to do something not aligned with human health.
Dentists have developed very small microbial incubators that are attached to teeth and continuously and unbiasedly collect microbes from the oral space. I think the 100 “denture” study is the right idea but 1,000 would be better and 10,000 would convince even the dinosaurs at the FDA.
Gatekeepers be like: But cavities are a sign of slovenliness, substance abuse, bad parenting and low class! Why would you take away a natural consequence of moral turpitude?? You can’t change the social fabric!! What would to stop people from putting Mountain Dew into baby bottles?
> It lacks a peptide that its species usually uses to arrange gene transfers with other bacteria.
I do not fully understand why evolution would favor bacteria which go out of their way to give copies of their +3 Plasmid Ring of Mutacin Resistance to other bacteria. I mean, it is obviously in the interests of the genes on the plasmid, but also not in the interests of the bacterial genome, which will not get copied.
After all, if that other bacteria was closely related to the first one, it likely would already have their own +3PRoMR. The bacteria most likely to profit from the resistance are the same ones the donor goes out of their way to kill using antibiotics.
Wikipedia suggests that the the genes for creating conjugative pili are encoded on the plasmids which get transferred, which seems reasonable. Still, I would expect an arms race between the main DNA of the bacterium and the plasmid, with the main DNA finding better ways to avoid becoming a donor and the plasmid evolving better ways to circumvent them.
Wikipedia (on which what little I have in terms of bacterial sex education is based) depicts bacterial conjugation as having a clear donor and a clear recipient. If instead the transfer of plasmids was more symmetrical, I could see it as being advantageous to the bacterium in certain situations. In "thrive" mode, bacteria might prefer to just create copies of themselves, but if you are in "survive" mode, barely clinging to life, then it might be beneficial to hump some equally destitute stranger bacterium and hope that they give you some plasmid which makes your life easier.
I've sometimes wondered in the past why it isn't possible to coat every tooth with a kind of artificial enamel or "varnish" which would be completely impervious to acids produced by mouth bacteria or ingested.
My conclusion was that it would put most dentists out of business, so no dental specialist in their right mind would want to pursue that avenue!
But this bacteria sounds a great idea, again unless you're a dentist! The only question I have is whether it will cause faster and deeper plaque buildup, because presumably the acid secreted by "normal" oral bacteria tends to dissolve the plaque as well as the tooth enamel!
Would this alleviate the aftertaste created by eating sugary foods? Not everyone knows about or detects this but some of us dislike it greatly and mitigate it by chewing gum (what I do), having a sugar-free mint, brushing our teeth or eating something salty (my wife's chosen method).
There's more than one kind of sensodyne. There's the normal kind, which includes stannous (tin) fluoride that "zaps" your nerves via your dentine tubes and deadens them, and sensodyne "repair and protect" which contains "Novamin" a microscopic ceramic that lodges itself in those dentine holes and physically blocks them. It was available in the US for a short period and then banned by the FDA, so being an EU resident I sleeked it out and found it worked exactly as advertised.
I have since moved to "colgate sensitive instant relief enamel repair" because I got a strange warm-teeth feeling from the prior one, and it works almost as well. Strangely, both have the MD (medical device) logo printed on the tube.
"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)."
Honduras. Of course. This may be legit, but it does nothing to halt the impression of "so we're going to a South American country because of their very weak and corrupt governments that will let us do anything so long as we bung a bribe to the right ministers".
Apart from that, this makes me think of the Ray Bradbury story, "Skeleton":
I suppose I'm just too old-fashioned (and not American) to think "but why not just brush your teeth?" instead of getting this, especially when you'll still have to brush your teeth anyway afterwards. But hurrah, Science Marches On, and all that jazz.
"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."
Yeah, well I'm with the FDA on this one. If the organism turns out to have Unwanted Side Effects, it's a lot easier to take out your dentures and nuke 'em from orbit than it is to remove your full set of teeth. Same with the living alone and far from school zones requirement, so the organism can't get out into the wild but is confined to the test subjects.
Maybe this is crazy levels of red tape, but remember: Biology Is Complicated and things happen in vivo that never showed up in vitro. It's all very well to say "But the grad student!", but that was naturally occurring, not a hopped-up strain artificially produced and deliberately introduced. Suppose this moves from the mouth to other internal microbiomes, like the intestinal gut flora? There's a lot of maybes about this one. But good luck to your wife!
Very cool idea. However, I've met Aaron and I wouldn't trust him with anything of significance. The 'YOLO's are not cosmetic, he seems averse to ever second-guessing anything.
I used different pasts for enamel rebuilding and so far the best was Biorepair.
I have severe problems with my gums, they are retracted because of my complicated bite issues and too many years of wearing braces. So you can literally see 2-3 mm on each tooth the space that should be under the gums. And it used to hurt a lot, very sensitive.
Biorepair fixed it for me for good, I used the red one and the version for the night. After a few weeks, and after I finished the day tube, the problem was fixed and it hasn't come back which is shocking. I used the night version from time to time because I have a habit to use baking soda on my teeth (I know) to get them smooth, so biorepair as prevention. It was recommended to me by a gum specialist (periodontologist) as it has some certificates for stuff that actually builds the enamel back (I'm not a scientist).
Anyway works perrrfect I'm so happy. Recommend to try for the "mystery pain". Or find something similar.
Why didn’t they make it bioluminescent? They’re called Lantern Bioworks🏮 & their stuff doesn’t glow?
Also the chart shows that it’s not very successful at colonising the mouth, is 10-50% good enough? Seems like they should engineer this to colonise the oral cavity more successfully.
A mechanism that doubles as a kill switch would be handy
I remember reading about this bacteria in Popular Science magazine...about 15 years ago. I always wondered what happened to it. The article was like "This is the future of dental care!" and then it disappeared. Thanks FDA!
Note that Manifold in practice has a hard time distinguishing "2%" from "0%", especially on markets that don't have a lot of trader attention and which won't resolve for years.
I was literally at the dentist the day this was published struggling to recall the details of this story from the vague recollection I had of a dental innovation related to bacteria. A very timely post!
Have you guys tried Manuka Honey before sleep. I just started and will see what happens. I just eat half spoon full of the Wedderspoon Raw Premium Manuka Honey, KFactor 16, try to put all around my teeth and don't brush afterwards. The idea is that the antibiotics from the Manuka honey will kill all the bad bacteria in the mouth.
> Babies have no existing mouth bacteria, and get theirs from their parents’ kisses.
Is it literally that simple?
A while back it occured to me to be curious about how we get the mouth bacteria responsible for cavities, and about how, as a civilisation, we take them so much for granted. Are we born with them, or if not, how and when does transmission occur, can it be stopped even in principle, why is the problem hard, and why is the question nowhere on the radar.
I tried to ask my dentist about it. He and I chat about politics and culture, so why not this? I tried to be very clear I'm not asking for the standard "how to not get cavities" advice. He literally couldn't understand me. Kept talking about things like eat less sugar. I came out briefly half-convinced there's a dentist conspiracy around this.
Google was the same. No matter how I formed the question, I could hardly find a treatment purely of the problem of transmission. It's always "brush your teeth". Maybe I'm bad at googling.
So yeah, I still have that question. Could the transmission of the mouth bacteria to the next generations be stopped if we simply chose to?
Could it be that parents have a real, practical choice whether to inflict this lifelong problem on their children, and therefore maybe a moral duty not to? Could this in fact the reason why the problem is so unthinkable, because nobody is going to stick their neck out to tell basically all of adult humanity that they have an annoying moral duty they didn't know before?
I'm sure the real answer is somewhere between "literally impossible" and "impractically difficult", but still. I'd like to see the problem discussed in a way that doesn't make me feel like I'm crazy for even being able to think of it.
"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."
There are probably lots of other things besides that producing lactic acid in your mouth. They should have some charts of postprandial oral pH to show that it is actually doing anything relevant significant to tooth decay.
Did anyone else receive an email, purportedly from Astral Codex Ten, in response to a comment here, wanting TO INTRODUCE YOU TO AN AMAZING FINANCIAL OPPORTUNITY THAT WILL CHANGE YOUR FINANCIAL LIFE, etc.
The strange thing is, there is no such comment in the thread, and the user does not exist.
Very strange indeed.
I did screen captures if anyone wants to investigate.
If the Prospera conference actually results in this getting funded, then I'll admit that I was wrong to be so skeptical of Prospera. I still think there were a lot of daft ideas in the original plans, but it has proven much more successful than I expected.
"This initial study was expected to be conducted in eleven couples and an additional four unattached males at Hill Top Research in West Palm Beach, Florida and would look at the safety of Replacement Therapy and the potential for horizontal transmission of the Replacement Therapy organism to the non-treated member of each couple. All of the participants in the trial, according to the FDA approved protocol, were required to be without teeth, with full sets of dentures, and under the age of 55." 11 couples, 4 males, under 55. no denture
"On December 2, 2005, due to the enrollment of only one subject in our initial clinical study, we re-submitted a new protocol to the FDA that was less restrictive. In January 2006, we held discussions with the FDA about our problems with patient enrollment and how we could modify our protocol. The critical changes to the study are that it will be conducted in 10 patients who have teeth and the patients will be quarantined to a hospital-type setting for up to 12 days with a 2 month follow-up phase." 10 people, have denture, hospitalization
"We initiated our first Phase 1 clinical trial in April 2005, but we found it difficult to find subjects who fit the FDA’s highly cautious inclusion and exclusion criteria, particularly with respect to the subjects’ lack of dentition. We concluded this trial early after enrolling only two of the 15 planned subjects. The FDA then recommended that we revise the protocol for the evaluation of ten healthy male subjects, ranging from 18 to 30 years old and with normal dentition, in an institutionalized setting. After we submitted additional information, the FDA issued another clinical hold letter in June 2007 for the proposed trial with the attenuated strain, citing the need for a plan with respect to serious adverse effects; a plan for the eradication of the attenuated strain in trial subjects’ offspring; and a required pregnancy test for female partners of subjects. We submitted additional protocols in response to the FDA’s concerns. In August 2007, the FDA issued another clinical hold letter with required revisions to the protocol for offspring of subjects. We submitted a response to the clinical hold letter in September 2007, and the FDA removed the clinical hold for our Phase 1 trial in the attenuated strain in October 2007." So it's probably 10 males ages 18-30, have denture, hospitalization.
"While we commenced a Phase 1b clinical trial for SMaRT Replacement Therapy during the first quarter of 2011, the very restrictive study enrollment criteria required by the FDA made the enrollment of candidates meeting the restrictive criteria difficult. Due to the enrollment difficulty we encountered with our initial our Phase 1a clinical trial and now with our phase 1b clinical trial, we determined to discontinue pursuit of our Phase 1b clinical trial and instead focus our efforts on possible partnering opportunities that may exist for our SMaRT Replacement Therapy." Yeah, in 2014 they shelved the project
TL;DR, it seems like they had 2 Phase 1 trials for attenuated strain. Phase 1a was completed, Phase 1b was discontinued. Phase 1 trial for non-attenuated strain was clinical hold and never lifted. I haven't found info on 100 subjects or from school zones(hospitalization requirement maybe?)
OMG, I wish they had been able to commercialize this as soon as it was discovered/developed! I have spent far more than $20000 on dental treatment over the decades, and would have been DELIGHTED to pay the $20000 and not had to deal with ... you know, dental treatments!
I also have Alcohol Flushing Syndrome, one of its many variants, so would have been an ideal guinea pig.
I used to get cavities frequently but in the last 5+ years I haven't gotten any. The main difference between then and now is that I've upped my intake of vitamin A (from animal sources, like cod liver oil or liver, not just beta carotene) and try to get adequate K2, magnesium, calcium, and go out in the sun to make vitamin D (and supplement when I can't). My guess is that a lot of people consume suboptimal levels of these vitamins and minerals, which are needed for dental health. I also eat somewhat less sugar than I used to, though don't avoid it entirely. My dental hygiene has remained the same (flossing 1x/day, brushing 2x per day).
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> They offered my wife and I free samples (based on her work, not as compensation for writing this post); she accepted, and I’m still debating.
Amusing but still somewhat serious question: if their product, which they offered samples of, is a colony of bacteria that live in the mouth in perpetuity, and your wife takes it, then wouldn't any debating you do with yourself on the subject be rendered moot the next time you kiss your wife?
Clearly this has been thought through carefully by some very bright people.
Even so, putting genetically modified bacteria into your body is high on my list of things likely to have unintended consequences.
I think the worst possible consequences is the FDA blocking this avenue after this gets past them, and if we can only get ONE probiotic miracle past the enemies of all humanity, it would be a shame for that to be tooth decay precluding, say, Alzheimer's or something.
Why haven't you accepted their offer of a free trial yet? What are your reservations?
Also, you addressed the alcohol issue but is there any downside to the lack of lactic acid? Does lactic acid really not provide any benefits to your mouth?
So this brings up a question I've had before in the past...
Ethyl alcohol is metabolized to Acetaldehyde, which is carcinogenic. But there's not consensus on whether there's a safe level of acetaldehyde. I mean, there are beneficial levels of radiation, so it seems reasonable that there might be a beneficial level of acetaldehyde. But this hasn't been proven. The long term effects of low dose alcohol may be beneficial. (Reduced cardiac events. Better hormonal profile.) They may be neutral. Or they may be negative. ( increased deaths from tuberculosis was one item that was supposedly associated with drink-a-day levels of alcohol consumption due to immune suppression, IIRC) I'm curious if anyone has a take on the topic.
I don't like the idea of selling drugs to people when they haven't undergone extensive safety testing. We have no real evidence of the long-term safety of this drug besides the say-so of the inventor, and we have zero information about the manufacturing controls of Lantern. I wouldn't ingest a genetically modified bacteria from a factory that has not been inspected [edited for pedants in the comments].
On a side note, I really doubt that this will become commercially available after Lantern has thumbed their nose at the FDA by selling it in Prospera. There's no chance they'll find that amusing.
Just two questions:
1. What's your prediction (%) on whether this - or a similar product - will be proven to be highly effective and in common use by 2029? (BTW, curious about the implications to the dentists)
2. Why shouldn't individuals interested in the product consider Aella's involvement as a red flag? Not sharing a personal opinion here, but a rationalist colleague has just reminded me about her guide on squeezing the most money from (vulnerable?) men watching webcams, and her engagement in the failed dating service that cost many people a lot of money.
As an adult with a water-pic and decent self control, this is of limited utility, but as a young adult with neither of those who hated flossing, it might have saved me a mouth full of cavities
Anywho, i imagine there’s a % of the population due to genetics or micro biome that have a really high propensity to caries and might be very interested in the product. I can see the Instagram ad now: DENTISTS HATE THIS ONE WEIRD TRUCK
Will be interesting to see how this compares to BLIS M18 which has been readily available online for years now and of which I originally learned of as a bacteria strain that was advertised to do exactly the same thing - populate the mouth with something that dominates the decay-inducong bacteria.
Does anyone know how this compares to the already available Probiora? My weak understanding is that it is very similar but with two differences:
1) Probiora produces hydrogen peroxide instead of alcohol (is that better or worse?)
2) Probiora doesn’t permanently outcompete existing bacterial, so you have to chew the pills everyday. So in theory you could stop if you wanted.
Cost is about $20/month
https://probiorahealth.com/patented-formula/
We should start a crowdfunding campaign to pay for one person to go to Próspera and become infected. Then they could transfer it to everyone who contributed to the campaign. Would anyone be open to this?
Oh man, I remember reading about this bacteria that produces alcohol (probably in either Popular Science magazine, or maybe reddit) well over a decade ago. I immediately thought about it when I saw the subtitle, and was pleasantly surprised to realize it was one and the same (1.1).
It's cool to get some closure (1.2) about the neat thing I read about so long ago and have wondered on and off whatever became of it... and slightly less cool to have yet another thing in the pile towards convincing me the FDA is awful.
...This was the straw that motivated Tuesday's article, isn't it?
_S. mutans_ is possibly associated with cardiovascular disease[1]. Does alcohol instead of lactic acid impact that role? That's the unknown that's stopping me from jumping on this now.
1 - https://www.sciencedirect.com/science/article/pii/S1882761608000045
Two related manifold markets:
Will Aella get any new cavities by 2026: (22%) https://manifold.markets/Aella/will-i-get-any-new-cavities-after-a?r=Tmlrb3M
Will 10k+ people receive this treatment by 2030: (42%) https://manifold.markets/jcb/if-lantern-bioworks-successfully-re?r=Tmlrb3M
"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."
You might be able to round up that many hockey players or something; even moreso in the 80s. Then pay them to live alone during the offseason or something?
I notice I'm confused though -- does the FDA want to check whether the product prevents cavities *in dentures*?
People kiss their children on the mouth?
Scott, gah, it's "They offered my wife and me", not "They offered my wife and I". Try it both ways without "my wife and".
I loved "(as you do)". I love your marvellous understated wit.
Prediction market on if it will be approved: https://manifold.markets/BruhMoment1d78/will-lantern-bioworks-treatment-be
Wait, people just know about real hangover cures and have not been saying anything? Does this zbiotics thing really work? This could give me many hours of my life back.
Has anyone tried it? I'd order it myself but they only offer shipping inside the US.
I’d be down to chip in $500 for someone to fly to Honduras, get these bacteria, then transfer them to me back in the US. If you’d be down too, please reply to this comment. I’m sure we could find a trustworthy rationality community member to actually fly to Honduras if there’s enough interest.
If I were trying to earn back the $400k, I would probably try to sell it to 200 people for $2,000 each, instead of to 20 people for $20,000? Though admittedly I have no expertise in setting prices for anything.
(Epistemic status: Know nothing about dentistry and this is entirely based off of things I vaguely half-remember people who may have been dentists mentioning in casual conversation long ago..)
I believe the point of brushing your teeth has little to do with "scrubbing" them clean, like you'd scrub dirty dishes or wash a car or whatever; rather, you're actually trying to distribute fluoride throughly into every nook and cranny, to create an unfavourable environment for bacteria. (That's why we're told not to rinse with water after washing; it removes most of the fluoride we've just gone to the trouble of laying down..)
The bacteria aren't just a threat to your teeth; they also cause gum disease. If gum disease is caused by lactic acid (doubt it, but of course what do I know..) then we're all right - but if some other bacterium in some other niche is causing gum disease by some other mechanism (and assuming BCS3-L1 can't outcompete *all* other bacteria, as the chart in section 4.2 seems to suggest) it would still be necessary to brush regularly with fluoride for the sake of one's gums even if one's teeth weren't at-risk of decay.
If this is wrong I'd be awfully glad to be corrected, of course!
>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 is a bad idea since it might spread saliva-borne pathogens (for example cytomegalovirus, HSV, Neisseria meningitidis, etc). As a better idea, swab their teeth, plate the swab onto agar dishes, and isolate bacterial colonies. (To make this more effective you could add mutacin-1140 so only resistant bacteria will grow, although this is not strictly necessary). Then pick the colonies and test them to see if they are the correct bacteria. Finally, put the correct bacteria in people's mouths.
Anyway, someone with basic microbiology skills could easily pirate this product.
(Also, I previously wrote about the topic on my blog, but Scott's post has more info than mine. https://denovo.substack.com/p/stomach-ulcers-and-dental-cavities )
Great post -- put me into such a buying frenzy that I immediately pulled trigger on a ZBiotics pack. Hopefully it will be here in time for the holiday festivities.
Perhaps some of portion of the rat/EA charity funds could be turned to creating a think tank / pressure group that lobbies & brings strategic litigation for medical freedom.
What is the chart about? Proportion of the modified S. mutans among all S. mutans? (Wasn't it supposed to stay near 100%?) Proportion of all S. mutans among all mouth bacteria?
----
> To move beyond the demographic of people willing to fly to Prospera and pay $20,000, Lantern will need FDA permission.
As you may be aware, Prospera and the USA are not the only two jurisdictions in the World.
This is fascinating. I’m wondering however, will the idea of “cavity prevention” lead to counterproductive behaviors? Imagine a world where people take this probiotic.
Those who brush and floss normally (or even half-decently) don’t get cavities.
However, some people with poor hygiene really let themselves loose once they apply the paste to their teeth. A-few-times-a-week (wink wink) flossing becomes never. Will the loss of hygiene end up counteracting the cavity prevention in any meaningful way?
Is there any data on Aaron's current oral health? Does he still brush and floss? Has he been to the dentist for a checkup? What about data from the original study - did the participants' oral health objectively improve?
I'm pretty bad about flossing and would pay for this right now. $20k is a bit much but I'd definitely be willing to shell out $1k if it was shown to materially improve oral health outcomes.
As somebody entirely unaffiliated with the company, it is my expert opinion that this is basically fine and something I'll probably get for myself once it gets approved for sale in the states. Looking through the literature, Hillman did the appropriate animal studies and this is ready for human testing, where I expect it to have precisely zero side effects (the metabolic rate of biomass in the mouth is basically zero except considered locally.)
I am an expert on this exact field. I did my PhD on synthetic biology of gram-positive bacteria and currently work at a startup developing engineered live biotheraputics. We are going down the FDA drug approval path for a couple different things, but it's true that the supplement approach is so, so much easier. But then insurance won't pay for it. *waves in the direction of the healthcare system*. The supplement path is probably right for this.
As a side note I'd like to say that this kind of genetic engineering of a non-model bacterial strain is not trivial, even with modern CRISPR/Cas9 tools. So bravo to Aaron for succeeding on that front. If he's willing to provide the whole-genome sequence of the modified strain with annotations of the edited regions it would help remove any last specks of doubt on my end.
I'd love for some kind of long-term tracking of people who take this, though in this context it would have to be self-reported and that would make it hard to get anything useful. Still, if the effect size is as large as claimed then it should still be pretty obvious.
Bacteria evolve to be antibiotic resistant all the time. So would not this bacteria loose it's advantage pretty quickly?
I think a better way would be to make it able to digest several substances that are hard to digest for other bacteria and add those substances to toothpaste randomly.
This way it will have advantage that is hard to get for other bacteria and it is easy to get rid of.
I can't really comment on the medical or chemical aspects. I am concerned about the business plan. If the product really works it should be pretty easy for them to raise money on much better terms than they're asking. And why do they need $400k? Are they in debt to someone? And giving away equity is arguably the last thing they should be doing unless they've already got a fair bit of revenue and have already raised. The go to market plan is a bit lacking as well.
Is this by chance a team of scientists with little to no business experience?
Immunology seems to be a perpetual blind spot for people developing new therapies of any kind and this doesn't seem like an exception. Both lactate and ethanol have immunosuppressive effects but are mechanistically distinct and it would be stupid not to look at changes in oral immune cell composition and function after this treatment. If there were any negative effect from this treatment I would guess it would be increased rates of autoimmunity in oral tissues.
Seems like there might be a rule-consequentialist argument that people shouldn't release mostly-untested bioengineered microorganisms into the wild, even when they believe based on preliminary short-term testing that they'll be safe.
Very cool; thanks for writing this. I'm pretty tempted, but I think I can wait a year or two for a $19,000+ discount.
The other interesting thing in this "prepackaged biohacking" space I'm aware of is the follistatin gene therapy at https://minicircle.io/our-therapies/. (Also currently being tested in Prospera.) Again, I am tempted to get it now, but suspect waiting a year or two for more efficacy data, lower costs, and easier distribution is the smarter move.
Are there other interesting things in this space worth keeping an eye on?
(My personal dream would be a gene therapy to give me that gene that lets you sleep less per night...)
Very cool idea. However, I've met Aaron and I wouldn't trust him with anything of significance. The 'YOLO's are not cosmetic, he seems averse to ever second-guessing anything.
I wonder what the effect is on plaque? If plaque is reduced, that would have a positive effect on gum disease. Or if plaque is increased, that would be a trade-off.
are you going to have to reapply it every time you get a dentist grade cleaning ?
Hi, I'm an endodontist. Are there any other dentists reading or commenting here? I see lots of people discussing this who probably have never diagnosed a cavity and almost certainly have no idea how rare well-designed long-term clinical trials are in dentistry.
0% chance this takes off. Happy to discuss further if anyone is interested.
Any impact on gut biotic? Can it reproduce in the gut?
Is this a joke? Sounds to good to be true.
Anyway, people will still have to brush their teeth to deal with halitosis, cosmetic yellowing, and the discomfort of having gunk on your teeth.
Count on denture makers and large companies like Colgate-Palmolive to lobby against approval.
This whole concept, killing off potential harmful local bacteria and replacing it wholesale with something harmless that will fill the same niche, reminds me of an idea I had recently.
I had a minor surgery a couple weeks ago, and a big part of the pre-op prep was wiping down my skin with various antiseptics to kill as much of my normal skin bacteria as practical in order to prevent the surgery from causing bacteria to wind up where they shouldn't be and making a nuisance of themselves.
As I understand it, the main problematic local skin bacteria is S. aureus, which is definitely not a necessary part of normal skin bacteria because only 20-30% of the population has significantly population of it. It seems like when you're doing a whole-body antiseptic treatment anyway, that's a great opportunity to see a benign mix of microbiota to keep any S aureus from moving back in. Especially if you're in a hospital, as hospitals are notorious for having nasty strains of antibiotic-resistant S aureus lurking about in the environment despite the cleaning staff's best efforts.
> Okay, this one is true.
> Babies have no existing mouth bacteria, and get theirs from their parents’ kisses.
This is contrary to my expectations; for one thing, parent/child mouth-to-mouth kissing is far from a universal thing.
The theory I was aware of was that babies get their oral microbiome from their mother's vaginal fluid as a side effect of birth. This is why babies delivered by C-section may be deliberately swabbed with the mother's vaginal fluid.
Great PR opportunity.
“It metabolizes sugar through a different chemical pathway that ends in alcohol instead of lactic acid.”
> 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.
That is generally not a concern of anyone participating in the system. Compare this travesty of a legal case ( https://reason.com/volokh/2023/12/06/youre-18-and-having-sex-with-14-year-old-no-problem-in-arkansas-but-better-not-show-your-genitals/ ), in which two Arkansas parents were outraged that their 14-year-old son had had sex with his 18-year-old girlfriend.
Since this is completely legal under the law of Arkansas, the state charged the girl with solicitation of a minor. (You can't just not punish people simply because they aren't breaking the law, and the age threshold below which solicitation of sex is illegal is higher than the age threshold below which having sex is illegal.)
Those charges got tossed out of court on the theory that the first amendment protects solicitation of lawful conduct.
So the state filed different charges, accusing the girl of indecent exposure because the boy could see her genitals while engaging in sexual behavior with her.
This got the girl convicted of a felony (sentence: 24 months of probation, plus you're registered as a sex offender for the rest of your life) because, while speech soliciting a completely legal act can't be prohibited, there is no problem with prohibiting necessary side effects of completely legal behavior.
The court specifically notes that the first amendment does not protect the girl's nudity here because, instead of conveying a message, the nudity serves a functional purpose.
The court ends its judgment by noting that this result is absurd, but that's not a problem because the source of the absurdity is the legislature and not the executive.
Leveraging normal flora to outcompete pathogens could treat bacterial diseases caused by toxins, rather than those invading human cells. This method might not be effective for pathogens like listeria or chlamydia, but could work against some gram-negative bacteria. It could also be beneficial for diseases like gonorrhea, where inflammation is a key issue. I hope this takes off
"The antibiotics mess up your mouth microbiome" seems like the only risk I can think of. Maybe it kills a bunch of other bacteria weak to mutacin-1140, upsetting the balance of your microbiome and somehow causing you to get more cavities as some other species expands to fill the newly-available space. Or maybe the streptococcus mutans has some secondary metabolite that also damages teeth and the mutant strain fills up all the available space and still gives you cavities. The grad student here only sets a ceiling on how bad this can be: clearly it doesn't make all your teeth fall out or we'd have noticed, but how would we know if the net effect is just mildly worse than normal?
If there's some baseline percentage of the population who already have S. mutans that expresses mutacin-1140, does that mean they wouldn't be able to get this treatment? Or would it just be more difficult on the uptake? Like maybe you'd need a few treatments to get it established, since it can't use it's antimicrobial to help it out compete the native flora.
I found it a little confusing how you kept going back to the alcohol thing. Once you established that it was 2 orders of magnitude less alcohol per day than accidentally swallowing a small bit of mouthwash I thought that should have settled the matter entirely and no further thought should be given to it.
One concern I didn't see brought up by anyone: would having bacteria excreting alcohol in your mouth all the time increase your risk of oral cancer? Using alcohol-based mouthwashes may do so (disputed) - those have quite a high concentration of alcohol, but they're also only in your mouth briefly, so I have no idea how "negligible quantities, but all the time" would compare. This seems particularly concerning because it's a problem which wouldn't show up for many years, and the increased risk would only be detectable in aggregate.
Scott was wondering recently on "paid", about better not write up 'high-temp'-topics (neo-reactionary is dead). My take was: My dearest MD S.A.S. just write essays about whatever YOU feel like writing about. - Glad to see once again: That is the way! - Oh, and I WANT those bacteria in my mouth!
Why did the FDA demand the study be done on such young people? (18-30?)
On the topic of bacterial exchange and microbiome more generally:
When I first visited China, eating the food there would give me diarrhea. (It didn't really matter which food. Nothing was wrong with the food.)
This was so common that the effect was well known under the name "traveler's diarrhea". Given enough time, it stops happening. By the time my family came to visit me, they all experienced traveler's diarrhea eating food that gave me no problems.
It is straightforward to explain traveler's diarrhea by appealing to the idea that your guts are adapted to the food you're accustomed to eating, and there's something different about the food in whatever far-off region you've suddenly teleported to by airplane. But there are some interesting questions this might suggest:
- Does adapting to one locale impair your ability to eat food from your original locale? (This didn't happen to me; I maintained a normal ability to eat American food.)
- Will adaptation wear off over time? (This also didn't happen to me; a span of several years outside China was not sufficient to give me traveler's diarrhea after returning. Interestingly, during this span I did take a course of strong antibiotics which were intended to nuke my stomach and also nuked my gut.)
- How does adaptation occur? The obvious candidate mechanisms appear to be "the food contains bacteria that will colonize your gut, eventually enabling you to eat the food without problems" or "the food will enable the differential success of bacteria already in your gut that, once they've grown to sufficient levels, will let you eat the food without problems". The fact that adaptation doesn't appear to wear off tends to support the first of those ideas over the second one.
If either of those ideas is correct, then it would seem pretty likely that the food you eat also has a very strong influence on your oral microbiome, and might source it after events like birth or a course of strong antibiotics.
> 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.
Huh, I wonder if that is why I've never had a cavity
I do love a bit of mad science.
It shouldn't cause any difficulties with breathalysers; they're designed to function by drawing deep lung air and for the ones I'm familiar with (the Lion Intoxilyser, the Camic Datamaster and the Intoximeter), the operating cycle will intentionally fail if you try and blow air from your mouth into it.
I don't know even enough to be dangerous on the subject, and it was a long time ago, but I read some renegade dentist claimed that tooth decay was an exacerbating cause of heart disease.
As I said, the proponent was a renegade, but apparently there was some evidentiary support for his theory.
I suppose we may find out.
There is more to bacterial competition/cooperation than the secretion (or inhibition!) of antibiotics. For example, small RNAs. Your oral microbiome is continuously pumping out regulatory RNAs that cross species boundaries. And theres phage. We know next to nothing about the natural history of these viruses in the oral microbiome. A phage might re-engineer your bacteria in just a few microbial generations to do something not aligned with human health.
Dentists have developed very small microbial incubators that are attached to teeth and continuously and unbiasedly collect microbes from the oral space. I think the 100 “denture” study is the right idea but 1,000 would be better and 10,000 would convince even the dinosaurs at the FDA.
Safety aside, I wonder how will we know if it works?
It seems like there's this assumption along the lines of "we know exactly where cavities come from so we don't have to be empiricists".
I'm not convinced. To show that it works, you'd have to follow subjects and controls for decades. Are they doing that?
Gatekeepers be like: But cavities are a sign of slovenliness, substance abuse, bad parenting and low class! Why would you take away a natural consequence of moral turpitude?? You can’t change the social fabric!! What would to stop people from putting Mountain Dew into baby bottles?
> It lacks a peptide that its species usually uses to arrange gene transfers with other bacteria.
I do not fully understand why evolution would favor bacteria which go out of their way to give copies of their +3 Plasmid Ring of Mutacin Resistance to other bacteria. I mean, it is obviously in the interests of the genes on the plasmid, but also not in the interests of the bacterial genome, which will not get copied.
After all, if that other bacteria was closely related to the first one, it likely would already have their own +3PRoMR. The bacteria most likely to profit from the resistance are the same ones the donor goes out of their way to kill using antibiotics.
Wikipedia suggests that the the genes for creating conjugative pili are encoded on the plasmids which get transferred, which seems reasonable. Still, I would expect an arms race between the main DNA of the bacterium and the plasmid, with the main DNA finding better ways to avoid becoming a donor and the plasmid evolving better ways to circumvent them.
Wikipedia (on which what little I have in terms of bacterial sex education is based) depicts bacterial conjugation as having a clear donor and a clear recipient. If instead the transfer of plasmids was more symmetrical, I could see it as being advantageous to the bacterium in certain situations. In "thrive" mode, bacteria might prefer to just create copies of themselves, but if you are in "survive" mode, barely clinging to life, then it might be beneficial to hump some equally destitute stranger bacterium and hope that they give you some plasmid which makes your life easier.
I've sometimes wondered in the past why it isn't possible to coat every tooth with a kind of artificial enamel or "varnish" which would be completely impervious to acids produced by mouth bacteria or ingested.
My conclusion was that it would put most dentists out of business, so no dental specialist in their right mind would want to pursue that avenue!
But this bacteria sounds a great idea, again unless you're a dentist! The only question I have is whether it will cause faster and deeper plaque buildup, because presumably the acid secreted by "normal" oral bacteria tends to dissolve the plaque as well as the tooth enamel!
Would this alleviate the aftertaste created by eating sugary foods? Not everyone knows about or detects this but some of us dislike it greatly and mitigate it by chewing gum (what I do), having a sugar-free mint, brushing our teeth or eating something salty (my wife's chosen method).
can it be build to spread like the flu with some more bionengineering? no more toothdecay !!
There's more than one kind of sensodyne. There's the normal kind, which includes stannous (tin) fluoride that "zaps" your nerves via your dentine tubes and deadens them, and sensodyne "repair and protect" which contains "Novamin" a microscopic ceramic that lodges itself in those dentine holes and physically blocks them. It was available in the US for a short period and then banned by the FDA, so being an EU resident I sleeked it out and found it worked exactly as advertised.
I have since moved to "colgate sensitive instant relief enamel repair" because I got a strange warm-teeth feeling from the prior one, and it works almost as well. Strangely, both have the MD (medical device) logo printed on the tube.
"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)."
Honduras. Of course. This may be legit, but it does nothing to halt the impression of "so we're going to a South American country because of their very weak and corrupt governments that will let us do anything so long as we bung a bribe to the right ministers".
Apart from that, this makes me think of the Ray Bradbury story, "Skeleton":
https://talesofmytery.blogspot.com/2013/06/ray-bradbury-skeleton.html
I suppose I'm just too old-fashioned (and not American) to think "but why not just brush your teeth?" instead of getting this, especially when you'll still have to brush your teeth anyway afterwards. But hurrah, Science Marches On, and all that jazz.
"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."
Yeah, well I'm with the FDA on this one. If the organism turns out to have Unwanted Side Effects, it's a lot easier to take out your dentures and nuke 'em from orbit than it is to remove your full set of teeth. Same with the living alone and far from school zones requirement, so the organism can't get out into the wild but is confined to the test subjects.
Maybe this is crazy levels of red tape, but remember: Biology Is Complicated and things happen in vivo that never showed up in vitro. It's all very well to say "But the grad student!", but that was naturally occurring, not a hopped-up strain artificially produced and deliberately introduced. Suppose this moves from the mouth to other internal microbiomes, like the intestinal gut flora? There's a lot of maybes about this one. But good luck to your wife!
Very cool idea. However, I've met Aaron and I wouldn't trust him with anything of significance. The 'YOLO's are not cosmetic, he seems averse to ever second-guessing anything.
I used different pasts for enamel rebuilding and so far the best was Biorepair.
I have severe problems with my gums, they are retracted because of my complicated bite issues and too many years of wearing braces. So you can literally see 2-3 mm on each tooth the space that should be under the gums. And it used to hurt a lot, very sensitive.
Biorepair fixed it for me for good, I used the red one and the version for the night. After a few weeks, and after I finished the day tube, the problem was fixed and it hasn't come back which is shocking. I used the night version from time to time because I have a habit to use baking soda on my teeth (I know) to get them smooth, so biorepair as prevention. It was recommended to me by a gum specialist (periodontologist) as it has some certificates for stuff that actually builds the enamel back (I'm not a scientist).
Anyway works perrrfect I'm so happy. Recommend to try for the "mystery pain". Or find something similar.
Why didn’t they make it bioluminescent? They’re called Lantern Bioworks🏮 & their stuff doesn’t glow?
Also the chart shows that it’s not very successful at colonising the mouth, is 10-50% good enough? Seems like they should engineer this to colonise the oral cavity more successfully.
A mechanism that doubles as a kill switch would be handy
I remember reading about this bacteria in Popular Science magazine...about 15 years ago. I always wondered what happened to it. The article was like "This is the future of dental care!" and then it disappeared. Thanks FDA!
Readers may be interested in (and in trading on) this market about whether this treatment will eventually be found to have serious downsides: https://manifold.markets/WilliamEhlhardt/will-lantern-bioworkss-cavitycuring?r=V2lsbGlhbUVobGhhcmR0
Note that Manifold in practice has a hard time distinguishing "2%" from "0%", especially on markets that don't have a lot of trader attention and which won't resolve for years.
I was literally at the dentist the day this was published struggling to recall the details of this story from the vague recollection I had of a dental innovation related to bacteria. A very timely post!
Have you guys tried Manuka Honey before sleep. I just started and will see what happens. I just eat half spoon full of the Wedderspoon Raw Premium Manuka Honey, KFactor 16, try to put all around my teeth and don't brush afterwards. The idea is that the antibiotics from the Manuka honey will kill all the bad bacteria in the mouth.
> Babies have no existing mouth bacteria, and get theirs from their parents’ kisses.
Is it literally that simple?
A while back it occured to me to be curious about how we get the mouth bacteria responsible for cavities, and about how, as a civilisation, we take them so much for granted. Are we born with them, or if not, how and when does transmission occur, can it be stopped even in principle, why is the problem hard, and why is the question nowhere on the radar.
I tried to ask my dentist about it. He and I chat about politics and culture, so why not this? I tried to be very clear I'm not asking for the standard "how to not get cavities" advice. He literally couldn't understand me. Kept talking about things like eat less sugar. I came out briefly half-convinced there's a dentist conspiracy around this.
Google was the same. No matter how I formed the question, I could hardly find a treatment purely of the problem of transmission. It's always "brush your teeth". Maybe I'm bad at googling.
So yeah, I still have that question. Could the transmission of the mouth bacteria to the next generations be stopped if we simply chose to?
Could it be that parents have a real, practical choice whether to inflict this lifelong problem on their children, and therefore maybe a moral duty not to? Could this in fact the reason why the problem is so unthinkable, because nobody is going to stick their neck out to tell basically all of adult humanity that they have an annoying moral duty they didn't know before?
I'm sure the real answer is somewhere between "literally impossible" and "impractically difficult", but still. I'd like to see the problem discussed in a way that doesn't make me feel like I'm crazy for even being able to think of it.
"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."
There are probably lots of other things besides that producing lactic acid in your mouth. They should have some charts of postprandial oral pH to show that it is actually doing anything relevant significant to tooth decay.
Did anyone else receive an email, purportedly from Astral Codex Ten, in response to a comment here, wanting TO INTRODUCE YOU TO AN AMAZING FINANCIAL OPPORTUNITY THAT WILL CHANGE YOUR FINANCIAL LIFE, etc.
The strange thing is, there is no such comment in the thread, and the user does not exist.
Very strange indeed.
I did screen captures if anyone wants to investigate.
If the Prospera conference actually results in this getting funded, then I'll admit that I was wrong to be so skeptical of Prospera. I still think there were a lot of daft ideas in the original plans, but it has proven much more successful than I expected.
So, about FDA thing
I found https://ir.oragenics.com/all-sec-filings/content/0001193125-07-062141/d10ksb.htm
"This initial study was expected to be conducted in eleven couples and an additional four unattached males at Hill Top Research in West Palm Beach, Florida and would look at the safety of Replacement Therapy and the potential for horizontal transmission of the Replacement Therapy organism to the non-treated member of each couple. All of the participants in the trial, according to the FDA approved protocol, were required to be without teeth, with full sets of dentures, and under the age of 55." 11 couples, 4 males, under 55. no denture
"On December 2, 2005, due to the enrollment of only one subject in our initial clinical study, we re-submitted a new protocol to the FDA that was less restrictive. In January 2006, we held discussions with the FDA about our problems with patient enrollment and how we could modify our protocol. The critical changes to the study are that it will be conducted in 10 patients who have teeth and the patients will be quarantined to a hospital-type setting for up to 12 days with a 2 month follow-up phase." 10 people, have denture, hospitalization
https://ir.oragenics.com/annual-reports/content/0001193125-15-070177/d833684d10k.htm
"We initiated our first Phase 1 clinical trial in April 2005, but we found it difficult to find subjects who fit the FDA’s highly cautious inclusion and exclusion criteria, particularly with respect to the subjects’ lack of dentition. We concluded this trial early after enrolling only two of the 15 planned subjects. The FDA then recommended that we revise the protocol for the evaluation of ten healthy male subjects, ranging from 18 to 30 years old and with normal dentition, in an institutionalized setting. After we submitted additional information, the FDA issued another clinical hold letter in June 2007 for the proposed trial with the attenuated strain, citing the need for a plan with respect to serious adverse effects; a plan for the eradication of the attenuated strain in trial subjects’ offspring; and a required pregnancy test for female partners of subjects. We submitted additional protocols in response to the FDA’s concerns. In August 2007, the FDA issued another clinical hold letter with required revisions to the protocol for offspring of subjects. We submitted a response to the clinical hold letter in September 2007, and the FDA removed the clinical hold for our Phase 1 trial in the attenuated strain in October 2007." So it's probably 10 males ages 18-30, have denture, hospitalization.
"While we commenced a Phase 1b clinical trial for SMaRT Replacement Therapy during the first quarter of 2011, the very restrictive study enrollment criteria required by the FDA made the enrollment of candidates meeting the restrictive criteria difficult. Due to the enrollment difficulty we encountered with our initial our Phase 1a clinical trial and now with our phase 1b clinical trial, we determined to discontinue pursuit of our Phase 1b clinical trial and instead focus our efforts on possible partnering opportunities that may exist for our SMaRT Replacement Therapy." Yeah, in 2014 they shelved the project
TL;DR, it seems like they had 2 Phase 1 trials for attenuated strain. Phase 1a was completed, Phase 1b was discontinued. Phase 1 trial for non-attenuated strain was clinical hold and never lifted. I haven't found info on 100 subjects or from school zones(hospitalization requirement maybe?)
Does the fact that this bacteria produces alcohol mean that its use would be prohibited by Muslims, Mormons, and abstentionist Christian sects?
OMG, I wish they had been able to commercialize this as soon as it was discovered/developed! I have spent far more than $20000 on dental treatment over the decades, and would have been DELIGHTED to pay the $20000 and not had to deal with ... you know, dental treatments!
I also have Alcohol Flushing Syndrome, one of its many variants, so would have been an ideal guinea pig.
> If you eat a normal Western diet, your mouth microbiome is already pretty far from the design specs…
Any further reading or citations on this, or the “design specs” referred to?
Never have I ever had a cavity, but I’d be curious if this bacteria can compete with periodontitis
For some reason my i7-8550 CPU starts really dying when it tries to load this blog post
> you should still brush for backup and cosmetic reasons
Also gingivitis and plaque formation. I worry that downplaying it this much will actually cause some optimizers here to hurt themselves.
I used to get cavities frequently but in the last 5+ years I haven't gotten any. The main difference between then and now is that I've upped my intake of vitamin A (from animal sources, like cod liver oil or liver, not just beta carotene) and try to get adequate K2, magnesium, calcium, and go out in the sun to make vitamin D (and supplement when I can't). My guess is that a lot of people consume suboptimal levels of these vitamins and minerals, which are needed for dental health. I also eat somewhat less sugar than I used to, though don't avoid it entirely. My dental hygiene has remained the same (flossing 1x/day, brushing 2x per day).
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