> 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?
My teenage daughter is allergic to fluoride (horrible mouth rash) and subsequently gets a lot of cavities. We have tried all of the holistic hippie approaches to dentistry , including some nonspecific probiotics and no dice. We don’t have 20k (but have spent at least that on her teeth so far) so will bookmark and keep an eye out. She’s been convinced that the people who never get cavities just have a different mouth biome than her. Hopefully, she’s right and soon these bacteria will be safely living in her mouth.
> She’s been convinced that the people who never get cavities just have a different mouth biome than her.
A friend of mine says that he was recently told something similar to this, by his dentist. I don't remember the exact details, but basically there are two basic "mouth types." There's the type that gets cavities easily, and the type that doesn't, but that second type is far more likely to get gum disease instead.
Huh. As someone who has never had a cavity (despite plenty of sugar and less-than-stellar dental hygiene), and who has had constant low-level gingivitis for as long as I can remember, this is very interesting to hear.
Long before there was any threat of me getting a cavity, I started experiencing pain in some of my teeth (the bicuspids) while chewing things that might be termed "soft candy", such as gummy bears and chocolate chips. I complained about this to my dentist several times, he investigated the teeth that hurt, and he informed me that as far as he could determine there was absolutely nothing wrong with them.
I still have no idea what this phenomenon is about (it's still happening).
I have the same thing. My dentist said it's the enamel wearing away on my teeth where there's a misalignment where the teeth are rubbing. Apparently it's a non-issue beyond the pain, and sensodyne toothpaste is a good enough solution. I've been using for the past few weeks and have been enjoying chewing with the left side of my mouth. Maybe you've got something similar.
Agree. I have terrible dental hygiene (I floss every now and then, and rarely brush) but I haven't gotten a cavity since in twenty years. But my gums bleed easily and every dentist I've ever met has told me I need to do something about my gums before they get worse.
Been wondering about this for a long time. I've never gotten a cavity despite literal zero dental hygiene and eating whatever I want for decades, which kept surprising my dentists..."you must brush and floss a lot!" Like, they refused to believe it was possible not to and not get cavities. But they did always warn about gingivitis, which has admittedly been less successful. At least my teeth will be hearty and hale when they fall out!
Anyway, it's an exciting product and I hope it's successful. Pretty sure I have one of those S. mutans variants myself, but could never figure out how to get into studies for this kind of thing. If only I'd gone to grad school, I guess?
There is a strong genetic effect on whether you get cavities. Most dentists are aware of this. I am in a similar position to you, though I did get a cavity at the age of 36.
My dentist's comment was just "you have your mother's teeth".
It's possible that the genetic effect is intermediated by a difference in oral microbiome, but that's certainly not the only possibility, and even if it is the case, it does not follow that transferring the oral microbiome will successfully transfer the cavity resistance.
I thought this mechanism was well understood and has to do with the ph of your saliva. Us no-cavitiers get gum disease because less acid and more plaque.
That's the rub though: I'm the *only* one in my family who doesn't get cavities. For everyone else it's been a lifelong struggle, not just with cavities but with the more serious dental stuff as well. There are some dietary differences - I've got the typical autist oversensitivity to certain gustatories, so lots of common foods are Right Out - but it's not like I never consume any simple carbs or acid. (Childhood dentist *hated* that I eat raw lemons.) So, if indeed more genetic than environmental, it's a weird nat20 roll.
I mean, if you go to a dentist you're likely to have either cavities or gum disease. The potentially much larger category "healthy" just doesn't see a dentist.
My dentist told me the same thing in a more folksy way. I dismissed it as i thought he was just trying to condition me for usual reprimands about flossing more (I was the sort with good teeth bad gums). Maybe i should update. (Any bacteria strains that prevent gum disease?)
We haven’t tested extensively but she drinks filtered water almost all the time and our house has a filter. We have heard of people who can’t shower or swim in water that has fluoride and that sounds miserable. She gets mouth sores a couple of times a year that I and her doctor had written off as viral, but I’m wondering now if they coincide with fluoride exposure somewhere.
Does your house have a filtration system that removes fluoride? They're a pretty involved setup I believe. My house has 2 cartridge filters but those won't touch fluoride
She shouldn't rely on water which has had all minerals filtered out though, as would be the case if she drank distilled water for example. That is because in the body it will dissolve out vital minerals, to equalize concentrations, and lead to malnutrition.
For the same reason, people stranded in remote locations should not drink "pure" water, such as rain water or melted snow, for long without adding a pinch of clay to it.
Not sure if you've looked into it, but check her preferred toothpaste and see if it contains Sodium Lauryl Sulfate; it is notorious for causing mouth sores, and could be contributing to the problem. Once I switched to a toothpaste free of SLS, common mouth sore frequency notably decreased.
Have you all tried xylitol? It seems to work for me. I don't have a fluoride allergy and I'm not a dentist, so take with a bunch of grains of salt, assuming you haven't tried xylitol already.
ETA: I realize my question might be condescending, especially if you've already tried it. But I had horrible teeth and xylitol seemed to help and wanted to let you know about it on the off chance you hadn't heard of it. That said, I have no idea if it's safe, and I've found precious little info on it, though I haven't looked as hard as I should.
I use xylitol mints, a couple after I eat something, or about 10 grams per day.
ETA: I'll add that it can get kind of expensive, about $100 for a two- to three-month supply. I'm also a bit nervous that maybe it's not really all that good more me. I should also say that when I started taking xylitol, I also changed my dental hygiene regimen pretty significantly, so it's always possible that if my teeth are doing better, it's because of that regimen and not (or not only) because of the xylitol.
There’s a brand called Apagard Premio that you can get on Amazon for a reasonable price. People seem to think it’s better than flouride for tooth health, especially for teeth sensitivity. I’ve been using it for around a year and it’s been good enough — I didn’t get cavities before, but I still don’t.
Thanks everyone! She has tried xylitol and hydroxylatite. Still getting 4-8 cavities per year. The goal is to get to cavity zero but it seems like every time she gets teeth filled, there are more in the next round of x-rays. And yes, we’ve had multiple dentists and have a hygienist in the family- not just getting scammed with fake treatment. Based on some other comments she’s going to try some of the other oral probiotics and she has already emailed this company offering to volunteer if they end up doing research at Texas A&M (a possibility listed in investor docs).
Have you looked into nano-hydroxyapatite? It's a toothpaste additive that's been in use in Japan since the 1990's that remineralizes tooth enamel. Anecdotally, I've been using it for about six months, and on last checkup, my dentist noted that my teeth were in the best state he's ever seen them.
I was disappointed for moment to see Scott would write "They offered my wife and I free samples", but it's just misquoted. The original sentence is grammatically correct: "They offered my wife and me free samples". At least now it is.
This is a good intuition to have, EXCEPT that there being large amounts of bacteria in your mouth doing nasty things to your teeth, the "natural" status quo, sounds like a problem to solve.
I'm actually not as sure as you about the "thought through carefully" part as you: this seems like the kind of cool idea that biohackers (or people who like the idea of being biohackers but have a much lower risk tolerance) would enthusiastically embrace without overthinking it because it FEELS reasonably safe (and probably IS): it doesn't promise too much, it's not messing about with complex bits like the eyes or the brain or whatever, and it's relatively easily reversible if you really wanted to.
The easiest way to disrupt this “status quo” is by brushing twice a day and flossing once a day. If the Lantern product seems safe, regular dental hygiene risk is functionally zero. However, I agree that if this process is safe it’s a no-brainer.
Then replace "aging" with "obesity", and you end up in the same place. We know eating healthy and exercising prevents obesity, and yet we end up with a very overweight population.
Aging isn't a disease much like alcohol isn't a drug: it totally is, but we're too used to it to notice, most of it the time.
It's functionally indistinguishable from a disease, certainly — I don't care if the thing making me become weaker, slower, dumber, uglier, and deader is a genetic disorder, a pathogen, or Nature's Natural Way of Wisdom™: I want that shit to stop regardless.
If you really do want it to stop, you will need to be aware that it isn't a disease. When two processes occur for radically different reasons, the approaches to stopping them are going to be different.
Note that for as long as the historical record permits us to see, people have railed against aging and wished that it could be stopped, prevented, and reversed. Nobody has ever described it as anything other than awful. We are used to it, and we know that it's not a disease, but there are no illusions about whether it is good or bad. It just isn't a disease. There can be more than one kind of bad thing in the world.
If I were responsible for that second panel, it would manage to include as large of a human diplomatic delegation as could be crammed into the frame, and all of them would be giving the aliens the stoniest glare that it's possible for a human to draw.
Brushing twice a day and flossing once isn't optimal for oral hygiene - it's just the optimal balance between oral hygiene and "not so onerous that people just won't bother" (see also eg. "five portions of fresh fruit & veg per day" &c.)
I've been told that if we were really optimising for hygiene, instead we'd brush after every meal, plus in the morning and evening even if we hadn't eaten then, plus rinse our mouths out thoroughly immediately after snacking or drinking something with sugars, acids, or tannins (so pretty much anything..)
Honestly wouldn't know! I was told that by a navy dentist who mayyyy have been tailoring his advice for navigational watchkeepers who essentially live biphasically rather than having a 'morning' and 'evening'. Could maybe also be one of those things (eg. rescue breaths in CPR, removing somebody's helmet after a motorcycle crash, etc.) where the best available advice sees to flip 180° every decade or so, perhaps?
This is why dentists recommend soft-bristle brushes, and why modern toothbrushes are much crappier at making your teeth feel clean than they used to be.
My cat's veterinarian recommends brushing their teeth with a kleenex. I can't imagine soft tissue paper would pose any risk to your enamel but apparently it's better than nothing. Wipe your teeth with a clean napkin after eating and you'll probably come out ahead.
I get cavities really easily and to prevent them I have to brush after every meal or snack plus brush and floss before bed.
If I use whitening toothpaste then like you say it causes its own issues, but as long as I use non-whitening toothpaste and don't scrub too hard it's fine.
Technically the natural status quo is that you have a large number of bacteria in your mouth not really doing much. Ancient skulls still have fine teeth today.
Premodern skulls don't; what changed was the introduction of dietary sugar.
> Not surprisingly, tooth decay was actually much less prevalent in the Middle Ages than it became in later centuries, when mass imports of sugar from the tropics made it a staple rather than a rarity. Surveys of archaeological data from the medieval period show that an average of only 20 percent of teeth show any sign of decay, as opposed to up to 90 percent in some early 20th-century populations.
Assuming that prehistoric people had perfect teeth, which we know they didn't, do you really think that going from 0% experiencing tooth decay to 20% is worse than going from 20% to 90%?
(The stated figures are not like measurements. But the difference is so large that it doesn't really matter.)
A lot of dental problems in former times were caused not so much by the agricultural product eaten but the sandstones they used to grind it. It was the microscopic grit particles worn off these while grinding wheat and similar which eroded the enamel.
As for brushing teeth, they would wee into a pot the previous evening and leave it overnight to settle. Then in the morning they could dip the end of a slightly frayed willow twig into it and scrub their teeth with that. Worked a treat! :-)
Could this not be because those people died young, before their teeth decayed, and they stopped eating when they died, essentially starving the bacteria that cause this kind of decay? Could population-level tooth decay essentially just be tracking life expectancy?
(I've no special knowledge here; just wild hypothesising!)
I can tell you that during the Han dynasty (roughly 200 BC - 200 AD), the cultural assumption existed that by 70 years old you would have lost your teeth.
It is not clear to me how different the situation today is. I have seen someone tell the story of an older female relative (so, the relatively recent history of the United States) who received, as a wedding gift, the prophylactic extraction of all of her teeth, so that as she aged she wouldn't have to worry about them.†
Similarly, the last time I saw a dentist, I had to fill out a questionnaire that included the question "do you want to keep your original teeth?".
But it is clear that the premodern period was much worse than today.
† This was based on a mistaken assumption; the health of your jawbones is maintained by the roots of your teeth, which dentures don't have. In general, I think prophylactic dentistry is unwise.
The pre-modern norm for life expectancy is horrendous mortality rates in early childhood and a higher attrition rate in adulthood, but a substantial portion of people who survive to adolescent make it to or beyond what's now considered middle age.
As for teeth vs diet, the pattern I'm familiar with is that hunter-gatherer societies tend to have excellent teeth, early agricultural societies (especially ones that use wheat, rye, or barley as their main staple crops) tend to get really nasty wear because grit from the grindstones gets into their flour, and societies with access to refined sugar tend to get a ton of cavities.
Hunter gatherer societies that eat a lot of fruit, or especially a lot of honey (like the Hadza) do tend to get cavities. It's not purely a disease of civilization.
The GMO variety has the advantage of secreting an antibiotic (which it's resistant to), so to introduce it you just need some cleaned surfaces on your teeth where it can get started. Then its advantage let's it eventually take over.
To reverse it, you have to completely wipe out the GMO variety before putting the normal ones back (apparently this requires "harsh antibiotics"). You might not be able to get back to the same ecological balance you started with (maybe Migratory's spit freezing idea could help with that, I don't know).
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.
When I read, ' 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,” ' I wondered if risk vs reward entered their thinking, if that position was just a bureaucratic reflex, or if they were under the thumb of "big dentistry." (just kidding, sorta).
BTW, I'm over 50 and have never had a cavity. I usually brush 1-2 times a day, use a dental pick to remove the calculus behind my lower incisors, and floss when I'm really bored. Quit seeing dentists years ago. I'm grateful and if there's a way for everybody to have this good fortune, I'd love to see it.
Gut microbiomes can change when people get older, so I would think that might happen with the oral microbiome.
About the time I turned 80, I started to get cavities again (I had them as a child/teenager) and my dentist said that people's mouths change with age. I wonder if it the biome?
When I read, ' 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,” ' I got real skeptical. Show me the receipts. This sounds like someone framing a ruling they didn't like in the most infuriating way possible to try to get sympathy.
Seems like the receipts would be in the possession of the original inventor, Professor Hillman, and that he would probably be eager to share them to someone motivated enough to ask, so it's not a particularly dickish thing to wonder about.
Of perhaps greater interest is the *entire* FDA evaluation that resulted in them declining to give Hillman an easier path to approval. Someone who is curious about the efficacy and safety of this novel product - a pretty reasonable, middle-of-the-road kind of position - would probably be greatly interested in the evaluation of an organization that is architected to be somewhat adversarial here. Nobody else has a motivation to uncover problems, even if Lantern seems pretty open and accepting of input.
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?
Reading this back later those questions sound weirdly confrontation. Definitely didn't mean it that way. I'd heard about this before and am pretty excited about it. Not "$20,000 plus flight to Honduras" excited but definitely a couple hundred bucks excited.
Your answer to question 1 makes a ton of sense. If I had thousands of people to bounce ideas off of I would definitely take advantage. I do think there isn't really a reason a priori to expect the lactic acid levels in our mouths to be optimal. Our diets are much higher in sugar than in the evolutionary environment, which is why cavities and dentists are a thing at all.
Good point, also isn't alcohol a rather potent topical antiseptic? Probably it's fine or positive even, but possibly it might disrupt the biome or clear a niche for microbes that otherwise couldn't get a foothold to cause other problems like gum disease.
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.
"there are beneficial levels of radiation" My impression is that this has been claimed, but still under dispute.
(and the level from this treatment would be considerably below drink-a-day levels - so I'd expect any effect (except in people who are hypersensitive to ethanol for some reason) to be lost in the noise)
<mild snark>Is the tiny amount of ethanol enough the Moslem and Mormons would have an issue?</mild snark>
The optimum dose of alcohol is significantly less than drink-a-day levels. I'm not sure it's been proved that a drink a day reduces lifespan relative to zero drinks. A large Meta study saying that a drink a day decreases lifespan include things like increased deaths from tuberculosis and increased drunk driving deaths. The increased drunk driving deaths make me suspicious about how well they actually tracked dosages. The increased deaths from tuberculosis make me question how well the results would generalize to first world countries where the incidence of fatal transmissible disease is lower.
I'm suspicious of any study that relies on self-reported alcohol consumption, since we're pretty sure self-reported alcohol consumption is hideously inaccurate at the population level. Specifically, the level of total consumption implied by self-reports is about half the level implied by retail alcoholic beverage sales. Some of the gap is probably due to waste, alcohol used in cooking, and stuff that sits on shelves for years before being consumed. Buy a lot of it has to be underreporting.
There doesn't seem to be a good indication of where the underreporting is concentrated, though, and it makes a big difference whether it's mostly people who say they seldom or never drink actually having several drinks a month, people who say they average one drink a day actually averaging two, or raging alcoholics who say they're averaging five drinks a day when they're actually averaging ten. Or even raging alcoholics who claim to be moderate drinkers or teetotalers.
With spirits there's also wild ambiguity in measures. For example, the standard measure of a sixth of a gill is barely a drop and could easily be quadrupled or more by a generous pouring of spirits without using a measuring cup.
Unfortunately that's nearly all of them. But this in turn makes me wonder about the actual level of alcohol consumption by that cohort that shows up with the lowest all cause mortality, in those studies that give you graphs of acm-by-alcohol-consumption. It's well known that the lowest acm is not at zero, but I've seen variations that show the low at anywhere from 0.8 to 2.5 drinks per day, depending on what kind of corrections they tried to apply and what population they were looking at.
But if underreporting is uniform then the real level would presumably be higher.
"The increased drunk driving deaths make me suspicious about how well they actually tracked dosages." Yup, that would make me suspicious too.
Do you have a url for the study?
One other thing that seems odd: In the usa there are about 4x10^4 driving deaths per year (and presumably fewer drunk driving deaths) out of a population of 3x10^8, so one driving death per 0.75x10^4 person-years. To see even a 2X difference at even a 1 sigma level, the study would need to see roughly 1 death in one arm and 2 in the other, around 2.2x10^4 person-years. To see a 2X difference at a 3 sigma level they would need around 2x10^5 person-years. Did they have this large-lengthy a study?
I'm inclined to believe them, and the observation studies showing otherwise have probably not fully controlled for confounders, which is a known issue with observation studies. Don't think it extrapolates to the bacteria though, just because, as Scott points out, it's 10-100 times lower alcohol levels than what you get from even one drink.
Correction - it's CVD, not CBD. The study looked at the effects of alcohol on cardio-vascular disease, and has nothing to do with cannabidiol, it's just a typo on my part.
I'd vaguely remembered that there had been some sort of connection found between CVD and dental health, and was hoping that the primary effect of this treatment on dental health and then a follow-on benefit to CVD would be larger than an effect of a 0.01 - 0.1 drink-per-day effective ethanol intake from the engineered oral bacteria. But a preliminary google turned up https://www.health.harvard.edu/diseases-and-conditions/gum-disease-and-the-connection-to-heart-disease and their (at least tentative) conclusion was:
"When smoking status was considered, the connection between tooth loss and cardiovascular disease largely disappeared"
Oh well.
( I think I spent too long in the electronics industry. My default expansion of CVD was "chemical vapor deposition"... :-) )
Oh really? I haven't heard that it was mostly explained by smoking and other confounders, but of course it makes much sense. The explanation I've heard was through oral inflammation -> systemic inflammation -> atherosclerosis, although in that case BCS3-L1 would still not be very helpful, since (according to people elsewhere in the comments) gum disease is driven by different bacteria.
[Also I feel compelled to nit-pick that, going by the numbers from the post, the alcohol intake is rather on the order of 0.001 - 0.0001 drink-per-day]
Many Thanks! The inflammation pathway was one that the authors of that web page explicitly considered, but their tentative conclusion was that the smoking confounder fit better. Thanks for the correction on the drinks-per-day equivalent!
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.
I think people around here think of the FDA as a bunch of vindictive storybook villains, because a bunch of bloggers are always emphasizing bad/dumb FDA decisions and their harmful effects. I can't specifically contradict that view since I don't know anyone at the FDA (I used to know one, but he was on the food side). But I know plenty of government bureaucrats and they are overwhelmingly somewhere on the spectrum from well-meaning to apathetic. Many have a strong habit of doing things by the book without too much regard for the effect of delays or unnecessary requirements on their "customers" (the public). They do not, in general, try to take revenge on anyone, feel personally offended when someone uses a "loophole" in the rules, or take into account what anyone has done in other countries.
I've met one years ago, whom I asked about 23andme before it was fda-approved at all. And they were so vitriolic about the company's nerve tho market something without their approval! I was taken aback. It was just the one person, with one company, but it colored my view towards the more negative.
You wouldn't buy a bowl of chili from a cook-off, brownie from a bake-sale fundraiser, or any of the foods from a farmer's market? That's fine I suppose, although it seems like a fairly extreme position as far as caution goes. I do hope that you wouldn't try to compel others into the same narrow range of choice, as your first sentence seems to imply.
Exactly. This is also why I require people to prove that the bacteria inhabiting their relevant biomes are judged safe by the FDA. If I have to ingest food or fluids for which the vendor can make no such assurances, I play it safe and either cook it for 30 minutes in a pressure cooker first or subject it to 50kGray of ionizing radiation. </sarcasm>
>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.
So in addition to being inefficient, slow and lacking in common sense, they're also self-important and touchy?
I'm sure that there are self-important and touchy people working for the FDA. If you've got bad luck, one of them may be deciding. More likely, though, the requirement is based on an anti-GMO feeling, or more precisely, not wanting to be the target of an anti-GMO based attack.
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.
For (2), presumably the kind of libertarian biohackers this post is targeted at aren't interested in shaming consenting adults for what they choose to spend money on, and the rest is just marketing.
I think that even libertarian biohackers may want to exercise extra caution when considering this type of promising (may it work!) but highly speculative and potentially risky novel treatment option. Also, without taking a strong personal stance on (2), isn’t the criticism of consensual consumer choices a generally valid activity, frequently practiced even by libertarian types who e.g. recognize the presence of various forms of „market failures”? We do it all the time for meat, diamonds, smoking, fortune telling, and countless other things.
Meat, conflict diamonds and smoking all have obvious negative externalities.
I think a case can be made that fortune telling should be protected as a religious activity, and I don't think libertarians generally want to ban it.
My assumption is that Aella is involved in marketing Lantern because she is well connected in the ratsphere and mostly well-regarded. Your counter-hypothesis would be that Lantern hired her because they want to squeeze as much money as possible out of a target population, and thought "well, Aella is really good at marketing on OnlyFans (or whatever), obviously her skills can be transferred to market our medical treatment." I do not find that plausible.
A real red flag would be if Elizabeth Holmes was involved with the company (which she is not).
I don't think anyone mentioned banning anything. As a consumer, I would view it as a red flag if a business chose to associate with someone involved with fortune telling or other fraudulent or semifraudulent activities.
> presumably the kind of libertarian biohackers this post is targeted at aren't interested in shaming consenting adults for what they choose to spend money on
I disagree with this. Being a libertarian is about not wanting to use government violence to enforce certain behaviors. Shaming people is very different than using government violence (almost all laws are ultimately enforced with violence if you resist long enough) Personally I believe that the majority of men who spend large amounts of money on the services of cam girls are exhibiting dissonant emotions and a lack of self respect and that social shame would be an acceptable response towards such men. However as a libertarian I would strongly object to a law against cam sites.
Re 1), (how) would you update from 30% if I added „effective, safe, at least moderately accessible (no major regulatory huddles), and less expensive than the conventional treatment of cavities”?
I agree with dogiv - the gold is essentially inert but it is usually put in place as a mercury-alloy amalgam. I also agree with you that none of these materials is a significant worry.
( Albeit for just about _anything_ there is going to be an open question about the effects over a span of multiple decades. Even the best double-blinded RCT can only run so long... )
Plenty of successful entrepreneurs had many failures before finding success, so I don't see why Aella's failed dating service matters. I also suspect that many successful entrepreneurs are personally repugnant people (see: Steve Jobs) so I don't think that provides much predictive power.
I agree she mostly sucks. But she's also internet-famous despite mostly sucking so that seems to qualify her as _some_ sort of expert on online marketing. As long as she sticks to that limited advisory role then I don't see what problems her involvement could reasonably cause.
For me, it just helps it to pattern-match to something like FTX. There were no super-obvious red flags around FTX, just a general stench of weird internet people carelessly doing something that they should have done in the boring, normal, conventional, legally-compliant way.
>There were no super-obvious red flags around FTX.
Well, the whole crypto industry was a giant red flag for as long as it existed, underscored by the constant onslaught of scams and hacks. FTX didn't look worse than other things, but that's about as faint a praise as you could muster. That the whole "rationalist"/EA sphere downplayed the obvious risks always felt weird to me, but it was entirely understandable that the glut of crypto money in their ecosystem colored judgements.
1. No clue. Suspect that any dentist who supports eg. regular brushing, fluorinated toothpaste, etc. would also support this (if it works)
2. Because it doesn't really have anything to do with the product itself. Given that marketing is such a universally ethically objectionable field (for pretty solid Moloch-related reasons..) learning that a marketing officer for a particular product was an ethically objectionable person shouldn't really shift your beliefs regarding the product itself much. To put it another way: if you're going to exclusively buy products whose marketing officers are paragons of virtue and would never manipulate or mislead anybody, you're going to end up leading a remarkably ascetic life...
80 or 90% of businesses don't take, so being involved in an unsuccessful business is extremely strong evidence that Aella is a totally average Joe like you or me
My interpretation of her attitude towards sex work things is that she tends to think if people pay for something it really did have high value for them
> her guide on squeezing the most money from (vulnerable?) men watching webcams
What's wrong with this? It's sex work, people do it to make money, and unless there's some sort of fraud or coercion involved, there's nothing wrong with making money from webcams. Is the "vulnerable?" intended to imply that the men who pay sex workers don't know what they're doing or can't be trusted to make their own decisions?
I think it's generally considered to be a complicated and controversial issue, so I wouldn't want to take a strong position or steer away from the core topic too much. It might be also about different expectations when it comes to marketing and communications used e.g. in arts/entertainment vs. medicine.
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
Slight off-topic, but what kind of water-pic do you use? It’s great, but the duct tends to get moldy or affected by scale deposits, and you usually cannot clean it from the inside, so curious if it’s hygienic enough after a longer use.
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.
This seems relevant, wonder if Scott or anyone can comment on it. I did a quick google on BLIS M18 and found at least one paper featuring a small randomized trial that suggested significant results from using BLIS M18 lozenges (also apparently there's something similar, BLIS K12?)
As far as I can tell, S. salivarius M18, while it possibly inhibits S. mutans and other more pathogenic mouth bacteria (https://www.nature.com/articles/s41598-020-70024-y), still produces its own lactic acid, so I don’t really understand how it works. Maybe it produces less lactic acid? Maybe the mechanisms for it benefiting oral health are different from just decreasing lactic acid?
I think they took the same sidestep by labeling it as a probiotic rather than a drug:
> In the United States, we market ProBiora3® as a food ingredient under self-affirmed Generally Recognized as Safe, or GRAS, status. GRAS is available for food ingredients that are generally recognized as being safe for human use and do not claim to treat, prevent, or cure a disease.
> Results: The primary and secondary outcome measures were significantly (p < 0.05) improved at the 12- and the 24-week evaluation in both groups. However, no significant inter-group differences could be detected at any time point, except from the % of sites with plaque that were significantly lower in the probiotic group than in the control group at the 24-week evaluation. In addition, at the 12-week time point, the salivary Prevotella intermedia counts were significantly lower in the probiotic group.
They really only investigated primary and secondary markers of gum disease rather than tooth decay, and the treatment didn't seem to show much promise in terms of preventing gum disease. However, given that the treatment significantly reduced plaque formation and successfully displaced Prevotella intermedia populations, I think the results show promise with regard to preventing the formation of cavities. I wouldn't be surprised if the treatment strains also displaced pathological populations of bacteria more directly responsible for tooth decay like Streptococcus mutans.
Interesting. They claim that it does compete favorably with other mouth organisms. I wonder if you could get long-term effects by using it after a tooth cleaning?
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?
You'd need ~100 people for this to be worthwhile, and that's not counting the hassle (and expense EDIT: okay, I just read more, and that should be negligible) of figuring out how to do the transfer correctly. I'm not going to pay $20,000, but I would actually pay a few hundred bucks for this; I think that's cheap enough that your proposed circumvention is unnecessary.
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.
IIUC, the paper says that effects on CVD are driven not by what it secretes, but by different strains having different surface proteins, some of which protect it from phagocytosis and allow survive longer in the bloodstream. So the question is, which strain of this bacterium they used as the basis, if it's the normal strain, you actually want it to replace all others since it would reduce CVD effects. But also, those effects are tiny either way.
"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*?
The first trial would be for safety, not efficacy. I'd guess the point of the dentures would be so that if anything looked even slightly wrong health-wise, they could all be confiscated and put into an autoclave and incinerated to a fare-thee-well. Hard to do that with regular teeth.
I'm *hoping* that people kiss their children on the forehead/cheek/whatever, the children touch their faces and later put their fingers into their mouths; the alternative is just too utterly bloody weird to contemplate.
It's gone out of fashion in the West but yes, it used to be normal, at least in my neck of the woods a few generations back (rural France, last instance I heard of would have been pre-WWII).
I suspect that lots of parents get their kids to eat stuff by putting it in their own mouth and having a nibble in front of the kid, and then directly putting the food in the kid's mouth.
This really bugs me actually. My family used to always kiss each other on the (closed) mouth. I was kissed as a child. I kissed my children. I was NOT molested. I was NOT a molester. I had a lovely childhood. Just bc television has shamenormed all the inherited culture/language out of huge swaths of previously richly unique geographic areas of the US in a single generation doesn’t mean it’s right. There’s NOTHING wrong with showing familial affection by chaste kissing on the mouth and it pisses me off so hard that you’ve made whole fams feel weird about it! Cut that s*** out!
I know perfectly well that it’s wrong too, but I hear it so often that it doesn’t jangle in my ear the way it used to. One of these days I’ll probably start saying it without noticing the transition. We’re language sponges, you know? But I will never never start saying “sounds good” instead of
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.
Regarding Zbiotics: lots of people used them at my lab retreat in 2022. They still ended up with hangovers, but given the amount of drinking that happened I'm not sure how much the probiotics realistically could have done. I wish we had organized a randomized trial.
I mean, if the zbiotics only work if you don't drink too much, they...don't work. I suppose they could still be useful if they reduce hangover severity, but so many factors go into that it's hard to judge outside an actual controlled trial
Edit: my priors are low considering that all other hangover cures seem to not work, with the exception of uh not drinking.
I haven't checked recently but years ago I read a marginally convincing study that showed a 50% reduction in hangover symptoms from taking large amounts of vitamin b6 before and during the drinking.
Well, I've always been low on hangovers, so don't take this too seriously, but my preferred hangover avoidance is to drink a bit over a pint of water before going to sleep.
With the caveat that N =1, it seemed to be ~80% effective. No headaches, nausea or sensitivity to noise. I was tired and rather lethargic all day, but could just as easily due to general lack of sleep.
From reading reviews online, I think it'll be hard to come to any conclusions without a proper trial. Mild hangovers are subtle, so subject to the placebo effect. But if you drink enough for a heavy hangover, it's likely that it'll overwhelm any effect the zbiotics has. So it'll be very hard to get a clear signal.
Plus, it doesn't help with the other main cause of hangovers, dehydration. So you have to eliminate that as a factor in both your control and test cases.
Zbiotics peaked my interest after reading this, but after reviewing their site and their links, I think there are reasons to be skeptical. Zbiotics claims to reduce hangovers by ingesting their probiotic, which contains a recombinant gene and resides in the gut and breaks down one of the toxic byproducts of alcohol metabolism, acetaldehyde, into a less toxic acetate (okay so far). In normal circumstances though, alcohol metabolism and therefore production of acetaldehyde, occurs largely in the liver, after gut absoprtion of the alcohol has already occurred. They have good seeming data showing that their bacteria does indeed break down acetaldehyde, but I am skeptical it would do much of anything in humans, and I don't see any links to any kind of human studies, aside from personal reviews - placebo?
I use zbiotics and like it. I can't rule out a strong placebo effect, but it works well enough for me that I buy it in bulk.
Notes:
• it just addresses one factor in hangovers; you still need to stay hydrated
• you're still going to feel like shit if you drink enough to black out
• I don't notice an effect if I'm only having one drink
• some friends who have tried it like it, others don't notice any effect
If you're curious, find a referral code. Order a 12-pack subscription. Immediately push the next shipment out as far as it will let you, and set a calendar reminder to cancel it. Last I looked, this brought the price to something like $66 for 12.
A friend of mine started a business to produce hangover prevention gummies: https://alwaystoast.com/
- It's prevention, not cure. You take 'em ideally before you start drinking, though during or even a little after can still be fine, just as long as it's before you go to sleep that night.
- The principal active ingredient (n-acetylcysteine, or NAC) has long been known to have this effect, and pills with it are available over the counter. However, distributing pills in bars has the annoying side effect of getting you thrown out for distributing drugs, hence his focus on the gummies form-factor.
- He was deep into the very-tiny scientific research community that was focused on the problem, I think they had occasional meetings called the Hangover Research Group or something, but in any case there were studies and journals and such things. I skimmed a few.
- As a result of that research, he included ~3 other active ingredients besides NAC, I think I remember two of them being prickly pear extract and milk thistle.
- I remember him telling me there are a bunch of other hangover-prevention products on the market but they generally do absolutely nothing and have not taken advantage of the research on it at all. Enough of them are much better at marketing than he is that it's become a cottage industry of snake-oil, though.
- The principal downside of the gummies is that his initial versions smelled really bad and tasted worse, though they indeed had the consistency of normal gummy bears and I didn't find it hard to get them down (my wife and her friends absolutely refused after the first try though). Subsequent versions have much improved that characteristic, but by my wife's evaluation, not by nearly enough.
- Efficacy: I swear by them, and have some in my pantry for all occasions where I expect to be drinking. I'm not super prone to hangovers, but certainly have gotten them when sufficiently earned, and I've never had anything more than a mild dehydration headache after taking these gummies.
Anyway, if that's an area of interest for you, give it a try. I'm not compensated / incentivized for this in any way, I just know Sean and advised him a little bit and think the product's pretty good.
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.
- If you've got to fly to Prospera anyway, that's a several day trip, so you're already limiting it to people who are willing to make large sacrifices, so you might as well collect some of that.
- One-time windfall of a conference of rich entrepreneurs in Prospera, might as well get as much as you can from that.
(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!
Yeah, was leaving out the food detritus part for simplicity (thinking of eg. the necessity to brush one's teeth in the morning even if one isn't having breakfast) but I didn't understand the enamel hardening thing at all and was totally mixed-up about what fluoride did - thanks for the correction!
When they market toothpaste as (eg.) "fights plaque", is that literally just marketing bulshytt, then, or are there other chemicals in the toothpaste that do this?
I believe that’s mostly due to the cleaning away of food debris. The toothpaste helps with that; I’m not sure if the fluoride makes much of a difference.
It's (slightly) worse than that. Too much fluoride makes your teeth brittle. This, however, mainly matters while they are growing. Toothpaste is just a surface treatment, and a thin hard+brittle external surface isn't bad.
Caution: I'm not any sort of dentist or medical professional, but:
As for "fights plaque", well, yesssss. Perhaps some actively fight it, but mainly the process of applying it fights the plaque. None of them get rid of plaque that's hardened in place. Before it hardens, plaque is a bacterial film. It's *relatively* impermeable to externally applied chemicals. But it's not very resistant to mechanical stresses. So toothbrush disrupts the film. Then the toothpaste can get at the tooth below the film, and prevent the film from reattaching.
The preceding paragraph was based on info that's around a decade old, but it's probably still true.
Since they also advise you not to use a fluoride mouthwash directly after brushing your teeth because it washes away the fluoride (https://www.nhs.uk/live-well/healthy-teeth-and-gums/how-to-keep-your-teeth-clean) I would guess that maybe the fluoride concentration achievable with a mouthwash is either lower or else less well-distributed than with a paste applied with a brush?
Different brands have different concentrations, but theyre generally lower than toothpaste (normal toothpaste has about ~1450 ppm, I think Listerine is at 300ppm). I would also guess that the residue of toothpaste "sticks better" to the teeth than a mouthwash.
Brushing is absolutely designed to disrupt and remove the biofilm on the teeth.
But that is as much to remove the precursors of calculus (the hard matter your dentist removes when they are cleaning your teeth) as it is to prevent cavities.
Both are bad for your tooth/gum health.
Fluoride enhances tooth enamel, it does nothing to bacteria.
>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, regarding Zbiotics: lots of people used them at my lab retreat in 2022. They still ended up with hangovers, but given the amount of drinking that happened I'm not sure how much the probiotics realistically could have done. I wish we had organized a randomized trial.
Even easier: since they ship you a sample of the bacteria to apply in the first place, growing more of it from that initial sample would presumably be pretty trivial, and saves to hassle of identifying/isolating it from a mouth sample.
That's just the first treatment (and just for the Prospera trial). Prospera patients can get additional culture to [re]apply later, and the site suggests the commercial product will also be an at-home treatment.
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.
I should clarify that I know nothing about Zbiotics and am not endorsing them (even to whatever weak degree I could be considered to be endorsing Lantern), I just know they're an example of something that the FDA allows.
* The sad story of Snus, which have saved so many lives in Sweden yet are loaded down with such huge regulatory burdens stateside that it's almost more economical to just smoke.
* And recall the saga of DMAA, which a likely-erroneous study concluded was present in geraniums or something, meaning it could be sold as a supplement -- I expect soon some genius of commerce will transfect amphetamine/cocaine-producing tissue into a badger or something for a new supplement. Would scream off the shelves at GNC.
> I expect soon some genius of commerce will transfect amphetamine/cocaine-producing tissue into a badger or something for a new supplement.
Why would that be necessary for cocaine? It's already refined from a plant. It's controlled by being specifically listed as a controlled substance, not because it doesn't qualify as a supplement.
This suggests that, although methamphetamine is not refined from a natural product, it also wouldn't benefit from becoming a natural product.
The other, more popular dope that one can get usable quantities of from a single (potted!) plant -- is still technically banned in USA, but in practice has for some time been available from convenience shops where I live (Wash. DC region.) Suppose that suddenly one didn't need an entire conspicuous (and in the right geography) plantation's worth of coca to get 1kg of cocaine?
Perhaps you should read Sigmund Freud on cocaine. It was legal at the time. First he enthusiastically recommended it, then he strongly changed his mind. There are reasons it was banned.
Personally, I feel that opium poppies and coca leaves should not be banned to adults, but any extracts from them should be forbidden from sale. That would eliminate most of the bad effects of the current legislation. (Well, except for regulated medicinal purposes.)
That said, once bio-hacking really gets going, we're definitely going to need a different set of regulations. This bacteria is only the start of where things can go....and they sure aren't all desirable.
FWIW I did read Freud, and have no particular desire to take cocaine. But in re: biohacking, I cheer any and all technologies which could potentially make a dent in the totalitarian police state's practical ability to enforce bans. In a hypothetical world where one could "print" drugs, FDA and similar busybodies will be relegated to the position of the RIAA. "You wouldn't download a car!" "I would if I could, go stuff it".
But the motivation is specifically stated: "soon some genius of commerce will transfect amphetamine/cocaine-producing tissue into a badger or something 𝗳𝗼𝗿 𝗮 𝗻𝗲𝘄 𝘀𝘂𝗽𝗽𝗹𝗲𝗺𝗲𝗻𝘁."
Marijuana has been available from convenience shops because its legal status changed. Cocaine remains unavailable because its legal status hasn't changed, and the proposal would have no effect on its legal status.
Do you think that the legal changes re: marijuana had nothing whatsoever to do with the fact that one can grow N doses in a potted plant? Or that there are not enough prisons in USA to house even one user in ten?
Incidentally IANAL but AFAIK it is still banned, on paper. The "warriors on drugs" simply capitulated on enforcement.
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.
The mechanism is different. PH changes from lactic acid metabolism is the main route by which the bacteria damage tooth enamel, while it sounds like the soft tissue of the gums is damaged by mostly endotoxin secretion.
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.
Thanks, good to hear from someone who properly understands this. Do you see any risks from the specific knock-on impacts of the genetic mutations on mouth microbiome, in particular regarding:
- Other types of bacteria that are already resistant to this antibacterial; and
- Types of bacteria which can transfer genetic information despite the peptide modification?
Recognise diet, region, etc already change the mouth microbiome, but those have the benefit of being relatively exhaustively tested, if not in a structured way.
When this was discussed on Twitter a couple months ago, many people brought up issues with other strains of S. mutans causing ulcerative colitis, eg https://pubmed.ncbi.nlm.nih.gov/22451861/ (a random paper I found)
Yes and no. You can make any strain do bad things by giving it to sick enough animals. The study you linked is a DSS model, where they administer a chemical that tears into the intestinal lining and causes the mice to shit blood. It's commonly used as a model for inflammation and IBD, but after some personal experience with it I'm not convinced it's a very useful model for studying chronic inflammation (which is what they're using it for here).
That being said, there is clinical evidence that certain strains of S. mutans are pathogenic, and are associated with colitis. One issue here is that often your commensal bacteria are opportunistic - if there's an injury then they'll switch to a pathogenic state to take advantage, and undergo rapid selection for increased pathogenicity in the wounded tissue. So it's not clear that the S. mutans is causative. Some other studies injected (large) amounts of S. mutans into the bloodstream and saw bad things, but maybe that's because bacteria in your bloodstream is generally bad.
Additionally, this is strain-dependent. Even that study used a different strain of S. mutans as a negative control, which did not worsen the DSS-induced inflammation. There appear to be a few strain types that are more pathogenic, primarily isolated from patients with colitis or bacteremia (bacteria in the blood). A whole genome sequence of BCS3-L1 or even just a strain typing analysis would tell us if that's something to be worried about here. I doubt it, because the 'good' strains are usually isolated from the mouth (like this originally was by Hillman back in the 80's), and the 'bad' ones from other places where you usually don't want bacteria.
For reference, a whole genome sequence of this strain would cost $105 including sample prep through a sequencing provider.
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?
I get the impression that they're not really trying to turn this into a business, they're running it more altruistically. But still, the most effective way of getting this into as name mouths as possible would generally mean using solid business practices.
Yeah. Unless you want to just give away the patent (which honestly I think is suboptimal but I understand) then having solid organizational and business experience is key to having maximum impact. I'm not saying they necessarily need to be ruthless capitalists. They can set things up as a non-profit if they want. But they do need their financial and operational affairs in order.
I had the same impression as you; I think they need either someone within the company itself, or a venture capital/private equity type to invest and be on their board to push this.
To be frank, USD400k is a trivially small amount of money for a good idea; I'm not at a point of my life where I'm taking big risks with investments, but even someone like me (top 1 percent, not top 0.1 percent) could fund it solo. Do they just not have the right connections?
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.
Isn't the counterargument that huge populations of people already put lactate, alcohol or both in their mouths daily and in orders o magnitude higher quantities? So if it has some crazily negative effects we'd probably noticed.
Not really a coherent counterargument given that alcohol has a crazily negative effect that we have long since noticed called cancer. This has been easy to notice because we can somewhat easily control/ monitor ethanol intake and make correlations. Given the ubiquity of lactate-producing bacteria, we don't really have any control groups to compare to to determine any of the long term effects of the treatment.
1) Negative effects of alcohol are well-known, of course, but the major pathways for those are not through oral immune system, it's CVD and liver/systemic toxicity. Oral cancers are among those effects too, but no at the top of the list.
2) At the lower end of the alcohol consumption spectrum, these effects are low enough that epidemiological studies routinely get confused and find no to positive effects. [I'm not saying there is no negative effects at the lower end, mind you. I'm saying they are really small].
3) The bacterium is going to produce at worst 2-3 orders of magnitude less alcohol per day than what is usually used as lowest alcohol consumption bucket in these studies.
4) So on one hand, at every dose where we can see the effects clearly, alcohol's biggest risk factors are systemic (CVD, liver disease, non-oral cancers). On the other hand, there is no evidence [that I know of] that natural levels of alcohol affect these endpoints. And on the gripping hand, the excess alcohol from BCS3-L1 is not going to bring you outside of the natural levels. So you have to postulate a very specific biology where at all measurable levels the systemic negative effects of alcohol are more significant than oral, but at extremely low levels they switch, *and* as you decrease the dose oral effects remain significant long after systemic effects disappear. This is not impossible, but it seems highly unlikely and I wouldn't be terribly concerned about it without some specific evidence.
The point about alcohol having toxic effects beyond oral cancer seems irrelevant. Those being worse or more common than oral cancer really has no bearing on whether or not ethanol causes oral cancer. Regarding the very specific biology you're describing, it doesn't seem particularly far-fetched to guess that the ethanol being produced in the mouth would primarily have effects in the mouth where it is locally concentrated. A pretty small amount of ethanol held on your gums or sublingually will still cause irritation etc. despite having negligible systemic effects.
It is relevant if you actually read carefully, esp the point 4. Let me explain again: if even the stronger effects disappear at level X, it is reasonable to expect that the weaker effect will also disappear at dosage X, and even more so at dosage X/100 or less. Yes it is possible in principle that it's not the case, but you need evidence for that. I don't think the fact that it's produced in the mouth counts for much, since it's how all external alcohol comes into the body. And yes you swallow it, but you also swallow saliva. The "small" amounts of ethanol that will cause irritation are still orders of magnitude larger than what is produced by these bacteria in a day.
Seems like you might be confused on lactose vs lactate. They could get their lactate from the milk with the help of lactose fermentation by lactate-producing bacteria.
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.
Unless you believe, as I do, that there should be a lot more genetic engineering, decentralized and democratized. There are a lot of cool things people can do with that tech, most of which wouldn't happen if there were some injunction against bioengineered microorganisms getting released into the wild.
Rules like "be more safe" aren't useful without clear thresholds for what constitutes safe enough. Otherwise they just create an unopposed incentive that drives all innovation to zero.
So unless you can provide a clear and reasonable definition of "safe enough" then I think this is a bad rule to follow.
Not when you factor in s-risk or future lives, but for just x-risk of those alive today, which is what most people are concerned about, I think they're pretty similar.
Nope, still not even close, if you take AI risk even 1/10th as seriously as MIRI does. For an engineered [by humans] plague, to wipe out humanity is an extreme edge case, it is possible in theory but you have to be trying *incredibly* hard. For AGI [under MIRI's assumptions] wiping out the humanity is the default, and you have to be trying *much harder still* to avoid this.
The spectrum of "bioengineered microorganisms" is very large.
On the scary side, you have the products of gain-of-function research. My position on that is that it seems like a terrible idea for multiple reasons, for example the possibility of unintentional leaks or making the job of some bioterrorists easier.
By contrast, this seems to be some twelve orders of magnitude safer. The bacterium they started with occurs naturally in healthy humans. Producing an antibiotic and being antibiotic-resistant are both common outcomes of eons of chemical warfare among microorganisms. Favoring a pathway of breaking down sugar into alcohol has also been done before. And the lack of some peptide does not seem very nightmare-inducing either.
> His point was simple: The model may or may not be dangerous, we don’t know for sure. I’ve heard incredibly convincing arguments that go both ways. But that does not matter.
> Because this isn’t just about GPT2. What matters is that at some point in the future, someone will create something truly dangerous and there need to be commonly accepted safety norms before that happens.
Honestly, I have not thought too much about it. While I am a doomer, I do not think I agree with MIRI very much here.
In my opinion, the dangerous part (as with gain of function research) is creating the models in the first place, not distributing them or not. If ASI is created by someone, it think it will be by a big lab training a new model, not some kid downloading an open source LLM and moving the IQ slider from 100 to 1000.
Of course, you could argue that small LLMs are precursors to larger LLMs, which might eventually become ASI, and that we should restrict them like someone might want to restrict designs for nuclear reactors because they might serve as precursor steps to creating nukes.
I mostly do not think that keeping information on state of the art LLMs contained will work out very well. After all, the employees of big-name AI companies are not conveniently located in some facility in rural Siberia where you can just put a fence around them and shoot them if they try to leave. Anyone with enough resources to have a shot at building ASI can probably find someone qualified willing to work for them.
Just like with genetic engineering, AI is a field which at the moment seems to run on the paradigm of open scientific exchange. I think the biggest difference is that in genetic engineering, the dangerous corners are much further away from the useful corners. If you manage to create a variant of COVID which is twice as infectious and ten times as lethal, that will let you do some publications. If you create a strain of wheat which is 20% more resistant to dryness, that will possibly make you rich. By contrast, ASI is both desirable (if aligned) and dangerous (otherwise).
Much like AI, progress and the future shouldn't be arbitrarily held back because of baseless doomsaying speculation. Maybe we should all be living in shit subsistence farming with no technology whatsoever, can't be too careful!!
I understand how it's possible to reasonably think AI has a <10% chance of destroying the world, but I don't think there's any good faith way to read the basic arguments and think the chance is <0.0000001%. (~1 life, which seems like the natural threshold for "baseless speculation" over "relevant concern".)
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...)
Thanks for sharing the link on the follistatin therapy, I wasn't aware this existed, or that Prospera allowed a broader genemod testing / deployment regime.
You mentioned cost, but I couldn't find anything about it, just that you'd need to get a new injection every 1-1.5 years, and they want a $250 deposit to talk to you. Do you know the present total cost of the therapy?
This is an area I'm pretty interested in too, but don't see much activity - Atkin posted his lactose tolerance cure plasmid to creative commons, but you need to DIY, there's not really anywhere you can go and get any sort of gene treatment from professionals (except Mini Circle, apparently).
I was referring mostly to the costs of flying to and from Prospera. (I think this might be cheaper for people living in the US, due to geographic proximity? I live in Tokyo.) I believe they also want monthly Dexa scans from you for a period afterward as part of the study, but I'm unsure who they're expecting to pay for that.
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.
well you might not be so confident in the new technology to reduce cavities that you're willing to stop the traditional cleaning intervention. And unclear from the article whether the gmo microbiome intervention will address all mouth related issues, might you not still get gum disease if you don't do normal 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.
Well if it actually works then doesn't that obviate the need for a long-term trial? As long as it's on the market then it'll spread through word-of-mouth and positive anecdotal evidence.
If anecdotal evidence is positive then use will spread. If it's not then it'll stay at the level of homeopathic cures. As long as there's no large downside health risk then ordinary market forces seem perfectly adequate for judging its effectiveness. There are plenty of useless products out there. The FDA doesn't need to study everything. Caveat emptor.
The claim is strong enough that it's pretty easy to falsify just by surveying recipients a year or three down the road. Their website claims near-complete elimination of cavities, based on Hillman's rat studies and Oragenics's human volunteers, so any non-trivial level of cavities showing up in survey data would be refute at least the strong claim they're making now.
Some back of the envelope math from statistics about cavities by age suggests to me that the base rate is something an average of about 18-20 new cavities per 100 adults (age 20-64) per year, which is high enough that if simple survey of a few thousand recipients were to show a near-zero rate of new cavities after a few years, that would be pretty strong evidence that there's significant benefits, despite obvious flaws around blinding, response bias, selection effects, and lack of a formal control group.
See below my response to myst-05. There are many, many cariogenic pathogens in the oral flora - strep mutans is just the biggest one. This is not a debatable point; it's accepted science. The fact that nowhere on the website is that noted is a huge red flag in my opinion. What do the 5-10 year outcomes look like in a group of patients who think they are "immune" to caries but actually are not, and who potentially change their diets and habits under the impression that they are? Might they have an even greater incidence of new decay than a control group who never took the vaccine? These are hard questions. Unfortunately, no one cares enough about dentistry to pay the tens of millions of dollars needed to properly answer them. I think there is a fair amount of hubris on Lantern Bioworks' end to make these types of claims. Tread carefully...
I'm not one bit convinced that it works, but the back-and-forth is convincing me that there's definitely a possibility here for a new product on the market that claims to do the divil an' all for your teeth. Especially if the "please continue to brush and floss" advice is emphasised enough, that'll keep the cavities at bay while 'fancy new treatment' gets the credit.
After all, if people are willing to sit under UV lights to whiten their teeth, they'll surely pony up for something less risky (even if it's not beneficial or only in part).
Sort something out for clinical trials and I think this could reward investors for yet another product that straddles the cosmetics/supplements/medical treatments line for healthcare. Get in on the ground floor now!
I concur that well designed oral care long term clinical trials are extremely rare. But… I don’t think that precludes this taking off. Look at how many people here are interested.
That's part of what surprises me. There's plenty of intelligent people here who are interested, but I don't see how anyone can possibly know if it actually works, ever. I'm honestly a bit surprised Scott wrote all this up.
Well if they get approval in 2025, by 2027 they could call up all their old patients and ask "So, gotten any cavities lately?" If zero of a thousand people have, seems like it works.
There are many pathogens involved in gingivitis and periodontitis. I'm not sure if a mutated form of strep mutans would have any affect on gum disease. Maybe it would make things better, maybe it would be the same, maybe it would make things worse. It's a lot of fun to speculate on these types of things. Unfortunately, we don't find the answers by inoculating germ-free rats and seeing what happens. Humans are not germ free! The mouth is very complicated... and populated... place.
Are you claiming that it’s impossible to design a good experiment for oral health and thus we could never know whether or not it works? Or that such experiments are too expensive to run? Or that a properly designed experiment has a 0% chance of proving this works because that’s not how cavities work?
All of the above. No one cares enough about dentistry to invest the millions (or tens of millions) of dollars to construct and run a propely-designed trial to evaluate this question. And yes, cavity formation is not linear with pathogenic strep mutans presence. There are many, many cariogenic pathogens in the oral flora - strep mutans is just the biggest one. This is not a debatable point; it's accepted science. The fact that nowhere on the website is that noted is a huge red flag in my opinion. What do the 5-10 year outcomes look like in a group of patients who think they are "immune" to caries but actually are not, and who potentially change their diets and habits under the impression that they are? Might they have an even greater incidence of new decay than a control group who never took the vaccine?
It also has no mention of the clinical challenges of evaluating and treating dental caries in the "real world." How do you classify previous restorations where the bonding breaks down and starts leaking? Technically, those are "cavities..." This is part of the larger issue of overdiagnosis and overtreatment in dentistry. I could speak for hours on the topic.
It sounds to me like they really haven't consulted with any clinical dentist on this. I just read through their whole website and their "literature," and it's even worse than I thought. One animal study on germ-free rats. No humans studies that I can find. That's embarrassing!
Seriously, if anyone is considering paying $20k for this BS, just contact me at doctor at BergenEndoCare dot com. I'd be happy to accept half that of that and actually give you good advice ;-). Please, please, do not pay any significant amount of money for this.
Scott - if you are reading this - this post is not in the greater community's best interest, IMO. I'd be happy to discuss this with you in detail, if you'd like.
Not intended as a gotchas, but if what you're saying is true
1. Why brush teeth?
2. Why floss?
3. Why have a 6 month period between cleaning cycles?
4. What does a dental cleaning do?
5. What does wisdom teeth removal do?
All seem like reasonable questions to ask assuming you're in this epistemic frame. Are there answers that can be given that also pass the bar you've set out previously? (I actually would expect "Yes, here's the paper" for most of these btw)
I'd like commentary on this too. It seems like most of whats recommended in dentistry doesn't have a strong evidence base. Theres Cochrane reports for a lot of interventions and its not very encouraging. Add to that, the embarrassing level of clinical variability.
If someone would like to share how they would define "preventing cavities" - in a realistic way that can be applied to a theoretical study of this question - I'd be happy to provide my estimate. How you define and study preventing cavities is, in and of itself, a very complicated question. And, to study this exact product, quite a costly one.
I will add that after 5+ years of reading SSC/ACX, I'm ecstatic that something was finally posted that I have some domain expertise in. It was worth the wait :-)
Why are you so sure it can't work as a business? Even granting that you're right that it's impossible to study, many probiotics have worked without knock-down evidence that they do what they say.
I'll let Aaron know about these comments and see if he wants to reach out.
EDIT: Actually, I see there was already a multi-way email conversation between you, me and Aaron last year - feel free to reach out to him if you want, otherwise I'll link him here.
I think you have it backwards. This has a much higher chance of taking off as a business than it does of taking off as a useful clinical treatment at scale. Homeopathy and crystal therapy are large and thriving industries, despite provably doing nothing.
As you mention, a study that could distinguish between lumina helping, hurting, and doing nothing, to any useful degree of certainty, is well beyond the capacity of Lantern Bioworks. If they get approval to sell this in the US, we won't know for decades what effects it has, and they'll already have made a substantial profit.
That's exactly the point. Homeopathy is a thriving industry, but not to rationalists. Do you think holistic folks will want to partake of this treatment? Heck no. At this current stage (no FDA approval, zero human studies), there is a very small subset of the population that this appeals to - perhaps a sliver of the rationalist community who are cavity-prone and have $20k to burn. There's a whole lot of work that needs to be done in order to make this endeavor more appealing to the wider population so it can be profitable in the long-term. Frankly, from what I have seen on the Lantern website, that will almost certainly not happen. But hey - YOLO!
"Do you think holistic folks will want to partake of this treatment?"
Word it differently for different markets.
For the rationalist lot, go heavy on the SCIENCE! Bio-engineered! Excretes antibiotic! Lactic acid metabolism pathways! Lots of pictures (as they have on their website) of bacterial chains etc. with that cool blue lighting.
For the hand-knitted yoghurt lot, emphasise the NATURALLY OCCURRING bit. Present in people's mouths already! Fights malign bacteria! No chemical processes or treatments required, just deep-clean your teeth then paint this on and Mother Nature does the rest! Pastel greens for this ad, smiling models of wholesome, corn-fed health with their shiny white teeth, leaves of various herbs and plants all over the shop.
I have family members deep into the biodynamic/anthroposophical stuff and there's ways of selling that make you a multi-million business while keeping the organic image (Dr. Hauschka and Weleda come to mind).
I think holistic health folks are an especially gullible lot, and it is probably well within the capacity of Lantern Bioworks to get enough of that market to be profitable, conditional on them getting FDA approval and keeping their costs low.
Yeah, if they get this marketed as a probiotic or supplement, they can promise it will water your crops and muck out the cow byre, without needing to prove efficacy (if they get the ad guys to word it carefully enough, and for a business to make money, they will be working on that). So long as it doesn't actually make your teeth fall out or turn your intestines into pretzels, they can claim "laboratory studies demonstrate this works" until the cows come home.
I would gladly pay a few hundred for it. Your objections don't seem very coherent to me. So it doesn't eliminate all cariogenic pathogens, so what? Converting half the cariogenic population in your mouth to be non-cariogenic won't be helpful? Doesn't pass the smell test to me.
What level of evidence do you currently have to believe that it can actually do what it claims? Have you read the literature they have on their website? I'm not seeing anything convincing.
Take a second look at the chart in section 4.2 of the post. Lumina doesn't just fail to replace all cariogenic pathogens. It fails to replace strep mutans specifically. In a year, their best performing subject had just under 50% of their strep mutans as the Lumina strain.
The entire premise of the project is that Lumina outcompetes cariogenic oral bacteria, and they haven't even shown that.
I am not a dentist. I'm in training to be a Dental Hygienist. But even the little I already know about cariogenesis is enough to make it skeptical of the whole project.
The process of developing dental caries is an enormously complex one, just counting the known and well-studied factors (diet and oral hygiene habits). While I don't doubt the less well-studied factors (oral microbiome, but also saliva composition and vague hereditary factors) matter, selecting one factor and saying 'fixing this will cure dental caries for life' is wildly overoptimistic.
Even if they had the funding to study Lumina at scale, I doubt you could get any study worth conducting past and IRB these days. There are too many known factors in cariogenesis that are virtually impossible to control for, to say nothing of the difficult of diagnosing caries.
I think it's worth investigating, but the people in this thread who are hoping for a miracle cure for the caries prone will likely get nothing but disappointment.
If there as a prediction market for Lumina working well that had reliable resolution criteria, I would be going heavy on the negative right now.
I wondered that too. If it could survive stomach acid and take up residence and flourish in the intestines, churning out alcohol all the way along, instead of only tiny amounts in the mouth, then the host might end up permanently pissed as a pudding, to put it crudely! :-)
This is precisely the problem that the FDA wants a study; will this thing remain confined to the mouth or spread elsewhere? How do you prevent bacteria in the mouth from being swallowed along with saliva and food and travelling to the digestive system? Will they be destroyed there or can they colonise the stomach/intestines, and if they do, what will be the effects?
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.
The bacteria on teeth has to come from somewhere else, since teeth are a prerequisite, but I agree that mouth-to-mouth kissing your baby can't be universal.
Another possible route is sharing food, drink, or utensils. Our daughter loved taking sips of our drinks or mooching bites of food from our plates as a toddler.
This is taboo for Hindus for obvious adaptational reasons, though I would tend to agree that people are likely to make exceptions for babies and toddlers.
Really? That's the exact opposite of my experience: sharing food is far more taboo (though that's too strong a word; "rude" perhaps, and at any rate, less common) in America than in India. A preliminary Google search suggests my experience is typical.
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.
Why the hell is an 18 year old (legal adult) woman having sex with a 14 year old youth? Maybe he's very tall and 'mature' for his age, and can pass for 18, but hell's bells.
When she's 24, will she still be banging 14 year olds? I'm not surprised the boy's parents were spitting feathers, I'd be furious too.
Well, you could call her a legal adult, or you could call her a high school student. By the time she's 24, she probably won't be going to school with any 14 year olds.
That's the problem, isn't it? When it comes to things like "contraception, abortion, puberty blockers" and so forth, then 18 is plenty old and mature and legally adult.
When it comes to other things, then it's "only a high school student". I submit if she's fucking 14 year olds, she's the adult (supposedly) here. I know this is back in the time when dinosaurs roamed the earth, but when I was at school there was a clear distinction between 17-18 year olds and 14 year olds. It's amazing how young and small the new batch of 12 year olds look when you're 17 yourself, and I do wonder about how old does this boy look, because damn it, this is period of life when small differences in age make a huge difference (see what a year can do pre- and then mid-puberty).
And sure, when she's 24, she won't be going to school with any 14 year olds - unless she decides to become a teacher - but that doesn't mean her sexual preferences will have changed and she will now have moved on to "must be minimum of 18".
Mme. Macron is the oft-quoted case here, she and her now-husband encountered one another when he was 15 year old student and she was 39 year old married with three kids teacher, but the parents managed to separate them and they didn't meet up again until he was 18, then married him at 30.
> Mme. Macron is the oft-quoted case here, she and her now-husband encountered one another when he was 15 year old student and she was 39 year old married with three kids teacher, but the parents managed to separate them and they didn't meet up again until he was 18, then married him at 30.
Is the problem that the girl might not marry the boy, or that she might?
The problem is that an 18 year old should not be having sex with a 14 year old, boy girl or other. I'm on the parents' side here, and were it me, I'd be after the little bitch with a shovel to beat some sense into her.
Now, if she sticks around and waits until he's 18 and she's 22, marriage or no resulting, that's not ideal but at least it's better than the alternative, which is that she likes them younger than her and once he 'ages out' of the range she finds appealing, she'll be after another 14 year old, and so on as she gets older but the age she finds sexually appealing doesn't change.
I don't know if she's an ephebophile or if this is just a case of romance too early, but I think that there does need to be caution around dismissing this as "the law is so dumb, look at what they did" when this might be the only way the parents could get a legal decision to stop her hanging around and continuing to have sex with their son. Go away, stay away without trying to contact him, wait and come back when he's 18 and then we'll see.
Most states in the U.S. have "Romeo and Juliet statutes," which make an exception to age of consent laws in cases where the age difference is less than a set amount of years (usually 3-5 years, but it varies). That must have been the case here, since the age of consent in Arkansas is 16, not 14. A 24 year old hooking up with 14 year olds would be unambiguously illegal.
I can't blame the boy's parents for being outraged, but I can't agree with how the judicial system handled this either. If the law was bad, then the law should be changed. Using obscure legal loopholes to prosecute people is a tactic that I oppose on principle, especially since it usually tends to set bad precedents that can all too easily be abused and exploited in future cases.
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.
Good question, I don't know! I'm not sure whether many people have mutacin-1140 specifically, or just some other unusual bacterium that does something with some antibiotic - and I don't know whether this strain would outcompete other unusual bacterial strains.
A lot probably depends on the metabolic efficiency of the lactic acid pathway versus the alcohol. If one strain is more "sickly", it might always diminish in the presence of the stronger strain. (Although metabolic pathway might not be the only meaningful difference between strains.)
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!
Presumably because that's the demographic who are the main market for this? I'm assuming that 18 is the lower bound since that's the age you are legally not a minor.
Older than that, you either have good teeth already or dentures already (the older, the more likely). People most likely to want to prevent cavities by taking a short cut like this, and being able to pay for it, are in the 18-30 age range. EDIT: And should be in generally good health, so if something does go wrong, it can't be blamed on "but they were already high-risk because of this, that and the other factors!"
Though I do think there would need to be follow-up studies done over years, because "I did this two months ago and I feel fine!" isn't long enough to be meaningful. What happens five years down the line from having a mouth full of these mutant bacteria? Ten years? Could it be that they secrete tiny amounts of something else that builds up in your system over time and turns out to be not so good for you?
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.
It seems to me that development of immunity to the foreign bacterial community would also explain your observations while being more consistent with the results of your treatment with 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
Sorry, I misphrased that. Many people are walking around with natural mutacin-secreting bacteria, but as far as I know nobody naturally has the version that switches to alcohol metabolism and doesn't cause tooth decay.
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.
That is established fact now. Surgeons these days are reluctant to perform heart surgery on patients with gum disease, because some bacteria from the gums can enter the bloodstream and cause inflamation of heart valves.
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!
There's something like this called silver diamine fluoride. Aaron was looking into it too. It has high risk of discoloring the teeth, so it's only used on very disabled people who can't possibly be convinced to brush and floss.
As far as I know silver diamine fluoride only affects, and discolors, cavities. It supposedly stops the cavity from expanding, permanently. Therefore it should be perfectly fine to use on cavities between teeth or on rear inside surfaces that are not generally visible. However dentists for whatever reason are loathe to use it.
Studies show silver diamine fluoride stops decay in 60 to 70 percent of cases with one application. A second application six months later boosts the treatment’s long-term effectiveness to more than 90 percent.
In addition to killing cavity-causing bacteria, the treatment hardens tooth structure, desensitizes the tooth and even stops new cavities from forming. Applying the liquid on the exposed root surfaces of older adults once a year is “a simple, inexpensive, and effective way” to prevent cavities, a 2018 study concluded
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!
honestly i dont see the fda as the bad guy in this situation; a near-permanent and even infectable genetic change like this should need extremely high standards required. Cavities are something that at least be treated and aren't urgent enough to suspend judgement for a trial.
But on the other hand, testing it on a bunch of rich people and then if nothing horrible happens to them moving on to poor people sounds like an ethical improvement over the usual way of doing it the other way around, no?
"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."
If you read the rest of the post, you'll see this is Prospera, a charter city. It's not a bribe, believing in this stuff is part of their reason for existing.
Prospera are having their troubles with the new government, though, precisely because they wouldn't stay bought, with a new party in charge.
So I'm sticking with "you pick a country where you feel the advantage is a weak government that won't get in your way, and you end up with a weak government that won't get in your way until they get turfed out by a new lot who want to take over the golden goose".
A more robust government might not have been willing to hand over so much authority to Prospera, but by the same token, once an agreement was signed, that would stick. They wanted malleability, they got it, and I wonder how much they like it now?
Well it's not a matter of "just brush your teeth" now is it? As you noted, there are still good reasons to brush one's teeth after getting this treatment, so never having to brush again can't be the motive behind developing this treatment. And more importantly, one can brush and floss religiously and *still get cavities*. Sometimes the old-fashioned ways are best, but other times they're inadequate to the purpose and at most form a necessary but not sufficient part of a strategy.
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
one of the things that tipped me more to the luddite scale was going to a petsmart and finding out you could buy genetic engineered glow in the dark fish called Glofish. So you never know...
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!
But isn’t it the ‘4 out of 5’ cartel of dentists that paid off the FDA commissioners to include the ridiculous rules ( imagine meme of politicians doubling over in laughter “we’ll require them to be 20 year-old loners with full dentures “ ) in order to save their collective careers.
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?
See 2.1
My teenage daughter is allergic to fluoride (horrible mouth rash) and subsequently gets a lot of cavities. We have tried all of the holistic hippie approaches to dentistry , including some nonspecific probiotics and no dice. We don’t have 20k (but have spent at least that on her teeth so far) so will bookmark and keep an eye out. She’s been convinced that the people who never get cavities just have a different mouth biome than her. Hopefully, she’s right and soon these bacteria will be safely living in her mouth.
> She’s been convinced that the people who never get cavities just have a different mouth biome than her.
A friend of mine says that he was recently told something similar to this, by his dentist. I don't remember the exact details, but basically there are two basic "mouth types." There's the type that gets cavities easily, and the type that doesn't, but that second type is far more likely to get gum disease instead.
Huh. As someone who has never had a cavity (despite plenty of sugar and less-than-stellar dental hygiene), and who has had constant low-level gingivitis for as long as I can remember, this is very interesting to hear.
Sounds like me too.
Huh. My brother is the same way. I however get cavities easily even when I brush and floss every day; a water pick seems to be necessary.
I am similar but did ultimately get a cavity.
Long before there was any threat of me getting a cavity, I started experiencing pain in some of my teeth (the bicuspids) while chewing things that might be termed "soft candy", such as gummy bears and chocolate chips. I complained about this to my dentist several times, he investigated the teeth that hurt, and he informed me that as far as he could determine there was absolutely nothing wrong with them.
I still have no idea what this phenomenon is about (it's still happening).
I have the same thing. My dentist said it's the enamel wearing away on my teeth where there's a misalignment where the teeth are rubbing. Apparently it's a non-issue beyond the pain, and sensodyne toothpaste is a good enough solution. I've been using for the past few weeks and have been enjoying chewing with the left side of my mouth. Maybe you've got something similar.
Agree. I have terrible dental hygiene (I floss every now and then, and rarely brush) but I haven't gotten a cavity since in twenty years. But my gums bleed easily and every dentist I've ever met has told me I need to do something about my gums before they get worse.
Been wondering about this for a long time. I've never gotten a cavity despite literal zero dental hygiene and eating whatever I want for decades, which kept surprising my dentists..."you must brush and floss a lot!" Like, they refused to believe it was possible not to and not get cavities. But they did always warn about gingivitis, which has admittedly been less successful. At least my teeth will be hearty and hale when they fall out!
Anyway, it's an exciting product and I hope it's successful. Pretty sure I have one of those S. mutans variants myself, but could never figure out how to get into studies for this kind of thing. If only I'd gone to grad school, I guess?
There is a strong genetic effect on whether you get cavities. Most dentists are aware of this. I am in a similar position to you, though I did get a cavity at the age of 36.
My dentist's comment was just "you have your mother's teeth".
It's possible that the genetic effect is intermediated by a difference in oral microbiome, but that's certainly not the only possibility, and even if it is the case, it does not follow that transferring the oral microbiome will successfully transfer the cavity resistance.
I thought this mechanism was well understood and has to do with the ph of your saliva. Us no-cavitiers get gum disease because less acid and more plaque.
That's the rub though: I'm the *only* one in my family who doesn't get cavities. For everyone else it's been a lifelong struggle, not just with cavities but with the more serious dental stuff as well. There are some dietary differences - I've got the typical autist oversensitivity to certain gustatories, so lots of common foods are Right Out - but it's not like I never consume any simple carbs or acid. (Childhood dentist *hated* that I eat raw lemons.) So, if indeed more genetic than environmental, it's a weird nat20 roll.
I mean, if you go to a dentist you're likely to have either cavities or gum disease. The potentially much larger category "healthy" just doesn't see a dentist.
My dentist told me the same thing in a more folksy way. I dismissed it as i thought he was just trying to condition me for usual reprimands about flossing more (I was the sort with good teeth bad gums). Maybe i should update. (Any bacteria strains that prevent gum disease?)
shit. I am virtually immune to cavities, and have gum disease
Allergy to fluoride sounds hard. Is she unable to drink any water that hasn't been through a special filter?
We haven’t tested extensively but she drinks filtered water almost all the time and our house has a filter. We have heard of people who can’t shower or swim in water that has fluoride and that sounds miserable. She gets mouth sores a couple of times a year that I and her doctor had written off as viral, but I’m wondering now if they coincide with fluoride exposure somewhere.
Does your house have a filtration system that removes fluoride? They're a pretty involved setup I believe. My house has 2 cartridge filters but those won't touch fluoride
I'm told that letting fluoridated water sit out on the counter in an unsealed container for a day allows the fluoride to evaporate.
I do that for plants, but would not want to experiment on someone allergic to it.
I thought that was chlorine. A quick google suggests that fluoride doesn't evaporate out of water.
She shouldn't rely on water which has had all minerals filtered out though, as would be the case if she drank distilled water for example. That is because in the body it will dissolve out vital minerals, to equalize concentrations, and lead to malnutrition.
For the same reason, people stranded in remote locations should not drink "pure" water, such as rain water or melted snow, for long without adding a pinch of clay to it.
Not sure if you've looked into it, but check her preferred toothpaste and see if it contains Sodium Lauryl Sulfate; it is notorious for causing mouth sores, and could be contributing to the problem. Once I switched to a toothpaste free of SLS, common mouth sore frequency notably decreased.
Thanks! That was our first guess when she was a toddler, but nope! It’s definitely fluoride.
Have you all tried xylitol? It seems to work for me. I don't have a fluoride allergy and I'm not a dentist, so take with a bunch of grains of salt, assuming you haven't tried xylitol already.
ETA: I realize my question might be condescending, especially if you've already tried it. But I had horrible teeth and xylitol seemed to help and wanted to let you know about it on the off chance you hadn't heard of it. That said, I have no idea if it's safe, and I've found precious little info on it, though I haven't looked as hard as I should.
How do you use xylitol?
I use xylitol mints, a couple after I eat something, or about 10 grams per day.
ETA: I'll add that it can get kind of expensive, about $100 for a two- to three-month supply. I'm also a bit nervous that maybe it's not really all that good more me. I should also say that when I started taking xylitol, I also changed my dental hygiene regimen pretty significantly, so it's always possible that if my teeth are doing better, it's because of that regimen and not (or not only) because of the xylitol.
This makes me laugh. Finland has endless supply of xylitol gum
Have you tried toothpaste with hydroxyapatite? Has a similar remineralization effect as Fluoride, according to early studies
There’s a brand called Apagard Premio that you can get on Amazon for a reasonable price. People seem to think it’s better than flouride for tooth health, especially for teeth sensitivity. I’ve been using it for around a year and it’s been good enough — I didn’t get cavities before, but I still don’t.
She might benefit from using these: https://betterbiom.com/products/nobs-toothpaste-tablets?variant=44347081982262. They were created by a dentist and use calcium hydroxyapatite as an alternative to fluoride.
Thanks everyone! She has tried xylitol and hydroxylatite. Still getting 4-8 cavities per year. The goal is to get to cavity zero but it seems like every time she gets teeth filled, there are more in the next round of x-rays. And yes, we’ve had multiple dentists and have a hygienist in the family- not just getting scammed with fake treatment. Based on some other comments she’s going to try some of the other oral probiotics and she has already emailed this company offering to volunteer if they end up doing research at Texas A&M (a possibility listed in investor docs).
Sounds like she is short of minerals of some kind - See my post above.
Have you looked into nano-hydroxyapatite? It's a toothpaste additive that's been in use in Japan since the 1990's that remineralizes tooth enamel. Anecdotally, I've been using it for about six months, and on last checkup, my dentist noted that my teeth were in the best state he's ever seen them.
In India, Villager’s use stick of neem tree(Azadirachta indica) to brush teeth. Read more about it here. Maybe it will help
Heh. Guess that's what I get for asking the obvious question before reading the whole article.
I was disappointed for moment to see Scott would write "They offered my wife and I free samples", but it's just misquoted. The original sentence is grammatically correct: "They offered my wife and me free samples". At least now it is.
It was not misquoted when I quoted it; that was a direct copy-paste. Scott must have edited it at some later point. Good catch, though.
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.
This is a good intuition to have, EXCEPT that there being large amounts of bacteria in your mouth doing nasty things to your teeth, the "natural" status quo, sounds like a problem to solve.
I'm actually not as sure as you about the "thought through carefully" part as you: this seems like the kind of cool idea that biohackers (or people who like the idea of being biohackers but have a much lower risk tolerance) would enthusiastically embrace without overthinking it because it FEELS reasonably safe (and probably IS): it doesn't promise too much, it's not messing about with complex bits like the eyes or the brain or whatever, and it's relatively easily reversible if you really wanted to.
The easiest way to disrupt this “status quo” is by brushing twice a day and flossing once a day. If the Lantern product seems safe, regular dental hygiene risk is functionally zero. However, I agree that if this process is safe it’s a no-brainer.
This seems to be the equivalent of advising "eat healthy and exercise" to someone trying to cure aging.
Except aging is not a disease, nor is brushing and flossing an attempt to “cure” anything. It’s preventative care, same as this treatment would be.
Then replace "aging" with "obesity", and you end up in the same place. We know eating healthy and exercising prevents obesity, and yet we end up with a very overweight population.
Aging isn't a disease much like alcohol isn't a drug: it totally is, but we're too used to it to notice, most of it the time.
It's functionally indistinguishable from a disease, certainly — I don't care if the thing making me become weaker, slower, dumber, uglier, and deader is a genetic disorder, a pathogen, or Nature's Natural Way of Wisdom™: I want that shit to stop regardless.
If you really do want it to stop, you will need to be aware that it isn't a disease. When two processes occur for radically different reasons, the approaches to stopping them are going to be different.
Note that for as long as the historical record permits us to see, people have railed against aging and wished that it could be stopped, prevented, and reversed. Nobody has ever described it as anything other than awful. We are used to it, and we know that it's not a disease, but there are no illusions about whether it is good or bad. It just isn't a disease. There can be more than one kind of bad thing in the world.
Tangential: https://www.smbc-comics.com/comic/2010-01-06
If I were responsible for that second panel, it would manage to include as large of a human diplomatic delegation as could be crammed into the frame, and all of them would be giving the aliens the stoniest glare that it's possible for a human to draw.
Brushing twice a day and flossing once isn't optimal for oral hygiene - it's just the optimal balance between oral hygiene and "not so onerous that people just won't bother" (see also eg. "five portions of fresh fruit & veg per day" &c.)
I've been told that if we were really optimising for hygiene, instead we'd brush after every meal, plus in the morning and evening even if we hadn't eaten then, plus rinse our mouths out thoroughly immediately after snacking or drinking something with sugars, acids, or tannins (so pretty much anything..)
I was under the impression that more than twice per day starts to get counterproductive due to enamel wear.
Honestly wouldn't know! I was told that by a navy dentist who mayyyy have been tailoring his advice for navigational watchkeepers who essentially live biphasically rather than having a 'morning' and 'evening'. Could maybe also be one of those things (eg. rescue breaths in CPR, removing somebody's helmet after a motorcycle crash, etc.) where the best available advice sees to flip 180° every decade or so, perhaps?
(Disclaimer: not a dentist.)
This is why dentists recommend soft-bristle brushes, and why modern toothbrushes are much crappier at making your teeth feel clean than they used to be.
My cat's veterinarian recommends brushing their teeth with a kleenex. I can't imagine soft tissue paper would pose any risk to your enamel but apparently it's better than nothing. Wipe your teeth with a clean napkin after eating and you'll probably come out ahead.
My own anecdote on this:
I get cavities really easily and to prevent them I have to brush after every meal or snack plus brush and floss before bed.
If I use whitening toothpaste then like you say it causes its own issues, but as long as I use non-whitening toothpaste and don't scrub too hard it's fine.
Probably want some efficacy evidence too
Technically the natural status quo is that you have a large number of bacteria in your mouth not really doing much. Ancient skulls still have fine teeth today.
Premodern skulls don't; what changed was the introduction of dietary sugar.
Yeah, yeah, the Agricultural Revolution and its consequences have been a disaster for the human race.
The agricultural revolution predates dietary sugar by tens of thousands of years.
The prehistorical dental record shows that agriculture was the worst catastrophe in the history of teeth. Sugar is not the mechanism.
But that's completely false. The pre-agricultural dental record shows some cavities.
Compare this from Slate ( https://slate.com/human-interest/2015/04/dental-hygiene-did-people-in-the-middle-ages-have-bad-teeth.html ):
> Not surprisingly, tooth decay was actually much less prevalent in the Middle Ages than it became in later centuries, when mass imports of sugar from the tropics made it a staple rather than a rarity. Surveys of archaeological data from the medieval period show that an average of only 20 percent of teeth show any sign of decay, as opposed to up to 90 percent in some early 20th-century populations.
Assuming that prehistoric people had perfect teeth, which we know they didn't, do you really think that going from 0% experiencing tooth decay to 20% is worse than going from 20% to 90%?
(The stated figures are not like measurements. But the difference is so large that it doesn't really matter.)
A lot of dental problems in former times were caused not so much by the agricultural product eaten but the sandstones they used to grind it. It was the microscopic grit particles worn off these while grinding wheat and similar which eroded the enamel.
As for brushing teeth, they would wee into a pot the previous evening and leave it overnight to settle. Then in the morning they could dip the end of a slightly frayed willow twig into it and scrub their teeth with that. Worked a treat! :-)
^^ I say this constantly
Could this not be because those people died young, before their teeth decayed, and they stopped eating when they died, essentially starving the bacteria that cause this kind of decay? Could population-level tooth decay essentially just be tracking life expectancy?
(I've no special knowledge here; just wild hypothesising!)
I can tell you that during the Han dynasty (roughly 200 BC - 200 AD), the cultural assumption existed that by 70 years old you would have lost your teeth.
It is not clear to me how different the situation today is. I have seen someone tell the story of an older female relative (so, the relatively recent history of the United States) who received, as a wedding gift, the prophylactic extraction of all of her teeth, so that as she aged she wouldn't have to worry about them.†
Similarly, the last time I saw a dentist, I had to fill out a questionnaire that included the question "do you want to keep your original teeth?".
But it is clear that the premodern period was much worse than today.
† This was based on a mistaken assumption; the health of your jawbones is maintained by the roots of your teeth, which dentures don't have. In general, I think prophylactic dentistry is unwise.
The pre-modern norm for life expectancy is horrendous mortality rates in early childhood and a higher attrition rate in adulthood, but a substantial portion of people who survive to adolescent make it to or beyond what's now considered middle age.
As for teeth vs diet, the pattern I'm familiar with is that hunter-gatherer societies tend to have excellent teeth, early agricultural societies (especially ones that use wheat, rye, or barley as their main staple crops) tend to get really nasty wear because grit from the grindstones gets into their flour, and societies with access to refined sugar tend to get a ton of cavities.
Hunter gatherer societies that eat a lot of fruit, or especially a lot of honey (like the Hadza) do tend to get cavities. It's not purely a disease of civilization.
> it's relatively easily reversible if you really wanted to.
Um, from reading section 2.3, it sounds quite difficult to reverse.
Couldn't you just do the exact same process, but introduce normal bacteria instead of the GMO variety?
The GMO variety has the advantage of secreting an antibiotic (which it's resistant to), so to introduce it you just need some cleaned surfaces on your teeth where it can get started. Then its advantage let's it eventually take over.
To reverse it, you have to completely wipe out the GMO variety before putting the normal ones back (apparently this requires "harsh antibiotics"). You might not be able to get back to the same ecological balance you started with (maybe Migratory's spit freezing idea could help with that, I don't know).
I plan to do this once it's cheap enough, but I will also freeze vials of my spit first in case I find a need to go back to my old biome.
Yeah I was torn between wanting to reply with the "leaving humanity behind" meme or the "me am play god!" meme.
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.
Yeah.
When I read, ' 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,” ' I wondered if risk vs reward entered their thinking, if that position was just a bureaucratic reflex, or if they were under the thumb of "big dentistry." (just kidding, sorta).
BTW, I'm over 50 and have never had a cavity. I usually brush 1-2 times a day, use a dental pick to remove the calculus behind my lower incisors, and floss when I'm really bored. Quit seeing dentists years ago. I'm grateful and if there's a way for everybody to have this good fortune, I'd love to see it.
Gut microbiomes can change when people get older, so I would think that might happen with the oral microbiome.
I think the regulations were different back then.
About the time I turned 80, I started to get cavities again (I had them as a child/teenager) and my dentist said that people's mouths change with age. I wonder if it the biome?
When I read, ' 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,” ' I got real skeptical. Show me the receipts. This sounds like someone framing a ruling they didn't like in the most infuriating way possible to try to get sympathy.
Are you skeptical enough to demand receipts from Lantern Bioworks founder Aaron Silverbook?
Or just skeptical enough to demand them here in the comments from people who don't have access to them?
Let me know what you find out.
Seems like the receipts would be in the possession of the original inventor, Professor Hillman, and that he would probably be eager to share them to someone motivated enough to ask, so it's not a particularly dickish thing to wonder about.
Of perhaps greater interest is the *entire* FDA evaluation that resulted in them declining to give Hillman an easier path to approval. Someone who is curious about the efficacy and safety of this novel product - a pretty reasonable, middle-of-the-road kind of position - would probably be greatly interested in the evaluation of an organization that is architected to be somewhat adversarial here. Nobody else has a motivation to uncover problems, even if Lantern seems pretty open and accepting of input.
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?
I would be astonished if it did, but this is an interesting idea.
I was waiting to write this post and see if any commenters noticed a danger I'd missed!
We probably have way more lactic acid in our mouths than the design specs given the rate at which people get cavities.
> We probably have way more lactic acid in our mouths than the design specs given the rate at which people get cavities.
That is clearly true, but going below spec can still be a problem.
Reading this back later those questions sound weirdly confrontation. Definitely didn't mean it that way. I'd heard about this before and am pretty excited about it. Not "$20,000 plus flight to Honduras" excited but definitely a couple hundred bucks excited.
Your answer to question 1 makes a ton of sense. If I had thousands of people to bounce ideas off of I would definitely take advantage. I do think there isn't really a reason a priori to expect the lactic acid levels in our mouths to be optimal. Our diets are much higher in sugar than in the evolutionary environment, which is why cavities and dentists are a thing at all.
If people who get cavities less get gum disease more, it’s possible that it’s lactic acid that suppresses gum disease
Good point, also isn't alcohol a rather potent topical antiseptic? Probably it's fine or positive even, but possibly it might disrupt the biome or clear a niche for microbes that otherwise couldn't get a foothold to cause other problems like gum disease.
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.
"there are beneficial levels of radiation" My impression is that this has been claimed, but still under dispute.
(and the level from this treatment would be considerably below drink-a-day levels - so I'd expect any effect (except in people who are hypersensitive to ethanol for some reason) to be lost in the noise)
<mild snark>Is the tiny amount of ethanol enough the Moslem and Mormons would have an issue?</mild snark>
The optimum dose of alcohol is significantly less than drink-a-day levels. I'm not sure it's been proved that a drink a day reduces lifespan relative to zero drinks. A large Meta study saying that a drink a day decreases lifespan include things like increased deaths from tuberculosis and increased drunk driving deaths. The increased drunk driving deaths make me suspicious about how well they actually tracked dosages. The increased deaths from tuberculosis make me question how well the results would generalize to first world countries where the incidence of fatal transmissible disease is lower.
I'm suspicious of any study that relies on self-reported alcohol consumption, since we're pretty sure self-reported alcohol consumption is hideously inaccurate at the population level. Specifically, the level of total consumption implied by self-reports is about half the level implied by retail alcoholic beverage sales. Some of the gap is probably due to waste, alcohol used in cooking, and stuff that sits on shelves for years before being consumed. Buy a lot of it has to be underreporting.
There doesn't seem to be a good indication of where the underreporting is concentrated, though, and it makes a big difference whether it's mostly people who say they seldom or never drink actually having several drinks a month, people who say they average one drink a day actually averaging two, or raging alcoholics who say they're averaging five drinks a day when they're actually averaging ten. Or even raging alcoholics who claim to be moderate drinkers or teetotalers.
With spirits there's also wild ambiguity in measures. For example, the standard measure of a sixth of a gill is barely a drop and could easily be quadrupled or more by a generous pouring of spirits without using a measuring cup.
Unfortunately that's nearly all of them. But this in turn makes me wonder about the actual level of alcohol consumption by that cohort that shows up with the lowest all cause mortality, in those studies that give you graphs of acm-by-alcohol-consumption. It's well known that the lowest acm is not at zero, but I've seen variations that show the low at anywhere from 0.8 to 2.5 drinks per day, depending on what kind of corrections they tried to apply and what population they were looking at.
But if underreporting is uniform then the real level would presumably be higher.
"The increased drunk driving deaths make me suspicious about how well they actually tracked dosages." Yup, that would make me suspicious too.
Do you have a url for the study?
One other thing that seems odd: In the usa there are about 4x10^4 driving deaths per year (and presumably fewer drunk driving deaths) out of a population of 3x10^8, so one driving death per 0.75x10^4 person-years. To see even a 2X difference at even a 1 sigma level, the study would need to see roughly 1 death in one arm and 2 in the other, around 2.2x10^4 person-years. To see a 2X difference at a 3 sigma level they would need around 2x10^5 person-years. Did they have this large-lengthy a study?
edit: just typos
There was a Mendelian randomization study in UK Biobank looking at that, and their conclusion was that any amount is worse than 0, at least for CBD https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2790520
I'm inclined to believe them, and the observation studies showing otherwise have probably not fully controlled for confounders, which is a known issue with observation studies. Don't think it extrapolates to the bacteria though, just because, as Scott points out, it's 10-100 times lower alcohol levels than what you get from even one drink.
Correction - it's CVD, not CBD. The study looked at the effects of alcohol on cardio-vascular disease, and has nothing to do with cannabidiol, it's just a typo on my part.
I'd vaguely remembered that there had been some sort of connection found between CVD and dental health, and was hoping that the primary effect of this treatment on dental health and then a follow-on benefit to CVD would be larger than an effect of a 0.01 - 0.1 drink-per-day effective ethanol intake from the engineered oral bacteria. But a preliminary google turned up https://www.health.harvard.edu/diseases-and-conditions/gum-disease-and-the-connection-to-heart-disease and their (at least tentative) conclusion was:
"When smoking status was considered, the connection between tooth loss and cardiovascular disease largely disappeared"
Oh well.
( I think I spent too long in the electronics industry. My default expansion of CVD was "chemical vapor deposition"... :-) )
Oh really? I haven't heard that it was mostly explained by smoking and other confounders, but of course it makes much sense. The explanation I've heard was through oral inflammation -> systemic inflammation -> atherosclerosis, although in that case BCS3-L1 would still not be very helpful, since (according to people elsewhere in the comments) gum disease is driven by different bacteria.
[Also I feel compelled to nit-pick that, going by the numbers from the post, the alcohol intake is rather on the order of 0.001 - 0.0001 drink-per-day]
Many Thanks! The inflammation pathway was one that the authors of that web page explicitly considered, but their tentative conclusion was that the smoking confounder fit better. Thanks for the correction on the drinks-per-day equivalent!
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.
Why would the FDA be upset about people selling a treatment outside of the FDA's jurisdiction? Is that a thing the FDA has gotten upset about before?
Not to my knowledge.
I think people around here think of the FDA as a bunch of vindictive storybook villains, because a bunch of bloggers are always emphasizing bad/dumb FDA decisions and their harmful effects. I can't specifically contradict that view since I don't know anyone at the FDA (I used to know one, but he was on the food side). But I know plenty of government bureaucrats and they are overwhelmingly somewhere on the spectrum from well-meaning to apathetic. Many have a strong habit of doing things by the book without too much regard for the effect of delays or unnecessary requirements on their "customers" (the public). They do not, in general, try to take revenge on anyone, feel personally offended when someone uses a "loophole" in the rules, or take into account what anyone has done in other countries.
I've met one years ago, whom I asked about 23andme before it was fda-approved at all. And they were so vitriolic about the company's nerve tho market something without their approval! I was taken aback. It was just the one person, with one company, but it colored my view towards the more negative.
> I wouldn't ingest food that was made in a facility that hasn't been inspected by health inspectors
... You don't eat food prepared in your friends' kitchens?
You wouldn't buy a bowl of chili from a cook-off, brownie from a bake-sale fundraiser, or any of the foods from a farmer's market? That's fine I suppose, although it seems like a fairly extreme position as far as caution goes. I do hope that you wouldn't try to compel others into the same narrow range of choice, as your first sentence seems to imply.
Exactly. This is also why I require people to prove that the bacteria inhabiting their relevant biomes are judged safe by the FDA. If I have to ingest food or fluids for which the vendor can make no such assurances, I play it safe and either cook it for 30 minutes in a pressure cooker first or subject it to 50kGray of ionizing radiation. </sarcasm>
>I wouldn't ingest a genetically modified bacteria from a factory that has not been inspected [edited for pedants in the comments].
The singular is "bacterium".
But the singular can refer to the species. Consider "The lion is found all over Africa." doesn't imply that one particular lion is delocalized.
Yes, but that is not pertinent; Trevor used the plural ("bacteria") with a singular article ("a").
Based on the article and this sounding pretty cool I at least will be buying and taking it when more widely available. Not for 20 grand though
>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.
So in addition to being inefficient, slow and lacking in common sense, they're also self-important and touchy?
I'm sure that there are self-important and touchy people working for the FDA. If you've got bad luck, one of them may be deciding. More likely, though, the requirement is based on an anti-GMO feeling, or more precisely, not wanting to be the target of an anti-GMO based attack.
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.
For (2), presumably the kind of libertarian biohackers this post is targeted at aren't interested in shaming consenting adults for what they choose to spend money on, and the rest is just marketing.
I think that even libertarian biohackers may want to exercise extra caution when considering this type of promising (may it work!) but highly speculative and potentially risky novel treatment option. Also, without taking a strong personal stance on (2), isn’t the criticism of consensual consumer choices a generally valid activity, frequently practiced even by libertarian types who e.g. recognize the presence of various forms of „market failures”? We do it all the time for meat, diamonds, smoking, fortune telling, and countless other things.
Meat, conflict diamonds and smoking all have obvious negative externalities.
I think a case can be made that fortune telling should be protected as a religious activity, and I don't think libertarians generally want to ban it.
My assumption is that Aella is involved in marketing Lantern because she is well connected in the ratsphere and mostly well-regarded. Your counter-hypothesis would be that Lantern hired her because they want to squeeze as much money as possible out of a target population, and thought "well, Aella is really good at marketing on OnlyFans (or whatever), obviously her skills can be transferred to market our medical treatment." I do not find that plausible.
A real red flag would be if Elizabeth Holmes was involved with the company (which she is not).
I don't think anyone mentioned banning anything. As a consumer, I would view it as a red flag if a business chose to associate with someone involved with fortune telling or other fraudulent or semifraudulent activities.
> presumably the kind of libertarian biohackers this post is targeted at aren't interested in shaming consenting adults for what they choose to spend money on
I disagree with this. Being a libertarian is about not wanting to use government violence to enforce certain behaviors. Shaming people is very different than using government violence (almost all laws are ultimately enforced with violence if you resist long enough) Personally I believe that the majority of men who spend large amounts of money on the services of cam girls are exhibiting dissonant emotions and a lack of self respect and that social shame would be an acceptable response towards such men. However as a libertarian I would strongly object to a law against cam sites.
1) 20% it actually gets rid of cavities, 30% it’s widespread by 2029 conditional on it working. So around 6%.
2) I don’t care either way is my answer.
Re 1), (how) would you update from 30% if I added „effective, safe, at least moderately accessible (no major regulatory huddles), and less expensive than the conventional treatment of cavities”?
"less expensive than the conventional treatment"
Arguably less invasive as well. Drilling and filling is routine, but still counts as invasive and adding a foreign material.
If you're worried about adding foreign material, gold fillings should solve that problem. Gold's not going to do anything.
Modern fillings are a white ceramic. I assume they are about as inert as the gold would be, but I don't know that.
A lot of fillings are still done with mercury-alloy amalgam. It's not particularly dangerous but I can see why it would freak people out.
I agree with dogiv - the gold is essentially inert but it is usually put in place as a mercury-alloy amalgam. I also agree with you that none of these materials is a significant worry.
( Albeit for just about _anything_ there is going to be an open question about the effects over a span of multiple decades. Even the best double-blinded RCT can only run so long... )
Plenty of successful entrepreneurs had many failures before finding success, so I don't see why Aella's failed dating service matters. I also suspect that many successful entrepreneurs are personally repugnant people (see: Steve Jobs) so I don't think that provides much predictive power.
I agree she mostly sucks. But she's also internet-famous despite mostly sucking so that seems to qualify her as _some_ sort of expert on online marketing. As long as she sticks to that limited advisory role then I don't see what problems her involvement could reasonably cause.
For me, it just helps it to pattern-match to something like FTX. There were no super-obvious red flags around FTX, just a general stench of weird internet people carelessly doing something that they should have done in the boring, normal, conventional, legally-compliant way.
>There were no super-obvious red flags around FTX.
Well, the whole crypto industry was a giant red flag for as long as it existed, underscored by the constant onslaught of scams and hacks. FTX didn't look worse than other things, but that's about as faint a praise as you could muster. That the whole "rationalist"/EA sphere downplayed the obvious risks always felt weird to me, but it was entirely understandable that the glut of crypto money in their ecosystem colored judgements.
1. No clue. Suspect that any dentist who supports eg. regular brushing, fluorinated toothpaste, etc. would also support this (if it works)
2. Because it doesn't really have anything to do with the product itself. Given that marketing is such a universally ethically objectionable field (for pretty solid Moloch-related reasons..) learning that a marketing officer for a particular product was an ethically objectionable person shouldn't really shift your beliefs regarding the product itself much. To put it another way: if you're going to exclusively buy products whose marketing officers are paragons of virtue and would never manipulate or mislead anybody, you're going to end up leading a remarkably ascetic life...
80 or 90% of businesses don't take, so being involved in an unsuccessful business is extremely strong evidence that Aella is a totally average Joe like you or me
My interpretation of her attitude towards sex work things is that she tends to think if people pay for something it really did have high value for them
> her guide on squeezing the most money from (vulnerable?) men watching webcams
What's wrong with this? It's sex work, people do it to make money, and unless there's some sort of fraud or coercion involved, there's nothing wrong with making money from webcams. Is the "vulnerable?" intended to imply that the men who pay sex workers don't know what they're doing or can't be trusted to make their own decisions?
I think it's generally considered to be a complicated and controversial issue, so I wouldn't want to take a strong position or steer away from the core topic too much. It might be also about different expectations when it comes to marketing and communications used e.g. in arts/entertainment vs. medicine.
I'd only be concerned if the tactics she trained people in left their customers feeling worse, or made them exhibit addictive behaviors.
> her guide on squeezing the most money from (vulnerable?) men watching webcams
Is this the video guide that she put online so that anyone, including vulnerable men, can see it and learn?
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
Slight off-topic, but what kind of water-pic do you use? It’s great, but the duct tends to get moldy or affected by scale deposits, and you usually cannot clean it from the inside, so curious if it’s hygienic enough after a longer use.
I swear by the kind that directly attach to your sink or shower for under $50 on Amazon
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.
This seems relevant, wonder if Scott or anyone can comment on it. I did a quick google on BLIS M18 and found at least one paper featuring a small randomized trial that suggested significant results from using BLIS M18 lozenges (also apparently there's something similar, BLIS K12?)
Wow, this is very interesting.
was this the paper you found? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9012604/
As far as I can tell, S. salivarius M18, while it possibly inhibits S. mutans and other more pathogenic mouth bacteria (https://www.nature.com/articles/s41598-020-70024-y), still produces its own lactic acid, so I don’t really understand how it works. Maybe it produces less lactic acid? Maybe the mechanisms for it benefiting oral health are different from just decreasing lactic acid?
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/
Interesting. I guess he was able to get that one through the FDA?
I think they took the same sidestep by labeling it as a probiotic rather than a drug:
> In the United States, we market ProBiora3® as a food ingredient under self-affirmed Generally Recognized as Safe, or GRAS, status. GRAS is available for food ingredients that are generally recognized as being safe for human use and do not claim to treat, prevent, or cure a disease.
https://probiorahealth.com/regulatory-status/
Are there any independent studies demonstrating effectiveness?
Only one I've found so far: https://pubmed.ncbi.nlm.nih.gov/26427036/
> Results: The primary and secondary outcome measures were significantly (p < 0.05) improved at the 12- and the 24-week evaluation in both groups. However, no significant inter-group differences could be detected at any time point, except from the % of sites with plaque that were significantly lower in the probiotic group than in the control group at the 24-week evaluation. In addition, at the 12-week time point, the salivary Prevotella intermedia counts were significantly lower in the probiotic group.
They really only investigated primary and secondary markers of gum disease rather than tooth decay, and the treatment didn't seem to show much promise in terms of preventing gum disease. However, given that the treatment significantly reduced plaque formation and successfully displaced Prevotella intermedia populations, I think the results show promise with regard to preventing the formation of cavities. I wouldn't be surprised if the treatment strains also displaced pathological populations of bacteria more directly responsible for tooth decay like Streptococcus mutans.
Also, n = 48.
Interesting. They claim that it does compete favorably with other mouth organisms. I wonder if you could get long-term effects by using it after a tooth cleaning?
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?
You'd need ~100 people for this to be worthwhile, and that's not counting the hassle (and expense EDIT: okay, I just read more, and that should be negligible) of figuring out how to do the transfer correctly. I'm not going to pay $20,000, but I would actually pay a few hundred bucks for this; I think that's cheap enough that your proposed circumvention is unnecessary.
Assuming the transfer can be shown to be effective then yeah, I'd be willing to pay a few hundred bucks for 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
But you already have mutans in your mouth right now! This is just switching out one kind of mutans for another.
IIUC, the paper says that effects on CVD are driven not by what it secretes, but by different strains having different surface proteins, some of which protect it from phagocytosis and allow survive longer in the bloodstream. So the question is, which strain of this bacterium they used as the basis, if it's the normal strain, you actually want it to replace all others since it would reduce CVD effects. But also, those effects are tiny either way.
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
One new one:
Cheap Lumina by 2025 in America: https://manifold.markets/ZachSteinPerlman/cheap-lumina-by-2025
"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*?
The first trial would be for safety, not efficacy. I'd guess the point of the dentures would be so that if anything looked even slightly wrong health-wise, they could all be confiscated and put into an autoclave and incinerated to a fare-thee-well. Hard to do that with regular teeth.
People kiss their children on the mouth?
I'm *hoping* that people kiss their children on the forehead/cheek/whatever, the children touch their faces and later put their fingers into their mouths; the alternative is just too utterly bloody weird to contemplate.
It's gone out of fashion in the West but yes, it used to be normal, at least in my neck of the woods a few generations back (rural France, last instance I heard of would have been pre-WWII).
It might still be normal in some cultures.
“Do you have a kiss for daddy?”
(From Ferris Bueller's Day Off)
David Beckham kisses his kids on the mouth (why on earth do I know this? I had a kid with a huge fan of Victoria Beckham).
Kissed kid here! But not by my parents, so disqualified from your precise question.
Follow-up question: In cultures where people don't kiss their children on the mouth, how do oral bacteria spread?
Sharing food, I guess? I don't think breast milk has oral bacteria in it...
I suspect that lots of parents get their kids to eat stuff by putting it in their own mouth and having a nibble in front of the kid, and then directly putting the food in the kid's mouth.
This really bugs me actually. My family used to always kiss each other on the (closed) mouth. I was kissed as a child. I kissed my children. I was NOT molested. I was NOT a molester. I had a lovely childhood. Just bc television has shamenormed all the inherited culture/language out of huge swaths of previously richly unique geographic areas of the US in a single generation doesn’t mean it’s right. There’s NOTHING wrong with showing familial affection by chaste kissing on the mouth and it pisses me off so hard that you’ve made whole fams feel weird about it! Cut that s*** out!
I had no idea anyone was suppose to feel ashamed of that. Kissing your kids on the mouth is perfectly normal.
Thank you!
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.
Sorry, fixed, thanks.
The spread of this hyper-nominative case is both annoying and amusing.
I know perfectly well that it’s wrong too, but I hear it so often that it doesn’t jangle in my ear the way it used to. One of these days I’ll probably start saying it without noticing the transition. We’re language sponges, you know? But I will never never start saying “sounds good” instead of
“OK.”
I agree, it's very common, and doesn't grate like it once did - I usually have to think it through.
One instance that has stuck was the theme song from The Land Before Time, which ended with "... for you and I".
As a parent of then-preschoolers, I heard this one quite a few times.
I agree, but I just found out even Shakespeare did it: https://en.wikipedia.org/wiki/Between_you_and_I
And here I thought it was all Hollywood's fault.
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.
Regarding Zbiotics: lots of people used them at my lab retreat in 2022. They still ended up with hangovers, but given the amount of drinking that happened I'm not sure how much the probiotics realistically could have done. I wish we had organized a randomized trial.
Sounds like a fun lab retreat. I'll give them a shot
I mean, if the zbiotics only work if you don't drink too much, they...don't work. I suppose they could still be useful if they reduce hangover severity, but so many factors go into that it's hard to judge outside an actual controlled trial
Edit: my priors are low considering that all other hangover cures seem to not work, with the exception of uh not drinking.
I haven't checked recently but years ago I read a marginally convincing study that showed a 50% reduction in hangover symptoms from taking large amounts of vitamin b6 before and during the drinking.
Well, I've always been low on hangovers, so don't take this too seriously, but my preferred hangover avoidance is to drink a bit over a pint of water before going to sleep.
I just ordered some for NYE and will report back.
Please do!
With the caveat that N =1, it seemed to be ~80% effective. No headaches, nausea or sensitivity to noise. I was tired and rather lethargic all day, but could just as easily due to general lack of sleep.
From reading reviews online, I think it'll be hard to come to any conclusions without a proper trial. Mild hangovers are subtle, so subject to the placebo effect. But if you drink enough for a heavy hangover, it's likely that it'll overwhelm any effect the zbiotics has. So it'll be very hard to get a clear signal.
Plus, it doesn't help with the other main cause of hangovers, dehydration. So you have to eliminate that as a factor in both your control and test cases.
Zbiotics peaked my interest after reading this, but after reviewing their site and their links, I think there are reasons to be skeptical. Zbiotics claims to reduce hangovers by ingesting their probiotic, which contains a recombinant gene and resides in the gut and breaks down one of the toxic byproducts of alcohol metabolism, acetaldehyde, into a less toxic acetate (okay so far). In normal circumstances though, alcohol metabolism and therefore production of acetaldehyde, occurs largely in the liver, after gut absoprtion of the alcohol has already occurred. They have good seeming data showing that their bacteria does indeed break down acetaldehyde, but I am skeptical it would do much of anything in humans, and I don't see any links to any kind of human studies, aside from personal reviews - placebo?
*piqued
thank you
Wait till you find out about ro15-4513. Fast ethanol antidote, banned by busybodies on "ethical grounds". ( See e.g. https://archive.is/jW1pv )
I use zbiotics and like it. I can't rule out a strong placebo effect, but it works well enough for me that I buy it in bulk.
Notes:
• it just addresses one factor in hangovers; you still need to stay hydrated
• you're still going to feel like shit if you drink enough to black out
• I don't notice an effect if I'm only having one drink
• some friends who have tried it like it, others don't notice any effect
If you're curious, find a referral code. Order a 12-pack subscription. Immediately push the next shipment out as far as it will let you, and set a calendar reminder to cancel it. Last I looked, this brought the price to something like $66 for 12.
A friend of mine started a business to produce hangover prevention gummies: https://alwaystoast.com/
- It's prevention, not cure. You take 'em ideally before you start drinking, though during or even a little after can still be fine, just as long as it's before you go to sleep that night.
- The principal active ingredient (n-acetylcysteine, or NAC) has long been known to have this effect, and pills with it are available over the counter. However, distributing pills in bars has the annoying side effect of getting you thrown out for distributing drugs, hence his focus on the gummies form-factor.
- He was deep into the very-tiny scientific research community that was focused on the problem, I think they had occasional meetings called the Hangover Research Group or something, but in any case there were studies and journals and such things. I skimmed a few.
- As a result of that research, he included ~3 other active ingredients besides NAC, I think I remember two of them being prickly pear extract and milk thistle.
- I remember him telling me there are a bunch of other hangover-prevention products on the market but they generally do absolutely nothing and have not taken advantage of the research on it at all. Enough of them are much better at marketing than he is that it's become a cottage industry of snake-oil, though.
- The principal downside of the gummies is that his initial versions smelled really bad and tasted worse, though they indeed had the consistency of normal gummy bears and I didn't find it hard to get them down (my wife and her friends absolutely refused after the first try though). Subsequent versions have much improved that characteristic, but by my wife's evaluation, not by nearly enough.
- Efficacy: I swear by them, and have some in my pantry for all occasions where I expect to be drinking. I'm not super prone to hangovers, but certainly have gotten them when sufficiently earned, and I've never had anything more than a mild dehydration headache after taking these gummies.
Anyway, if that's an area of interest for you, give it a try. I'm not compensated / incentivized for this in any way, I just know Sean and advised him a little bit and think the product's pretty good.
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.
I'm down.
Why not just collect it from Scott's wife, culture it, etc?
The only problem with doing it in the US is the FDA won't let you do it for money.
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.
I think there are two counterbalancing factors:
- If you've got to fly to Prospera anyway, that's a several day trip, so you're already limiting it to people who are willing to make large sacrifices, so you might as well collect some of that.
- One-time windfall of a conference of rich entrepreneurs in Prospera, might as well get as much as you can from that.
Selling it to 20 people for $20k each and then to 180 people for $2k each seems even better, tho.
(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!
Fluoride doesn’t work on bacteria; it hardens tooth enamel. Brushing also remove the food detritus that the bacteria feed on.
Yeah, was leaving out the food detritus part for simplicity (thinking of eg. the necessity to brush one's teeth in the morning even if one isn't having breakfast) but I didn't understand the enamel hardening thing at all and was totally mixed-up about what fluoride did - thanks for the correction!
When they market toothpaste as (eg.) "fights plaque", is that literally just marketing bulshytt, then, or are there other chemicals in the toothpaste that do this?
I believe that’s mostly due to the cleaning away of food debris. The toothpaste helps with that; I’m not sure if the fluoride makes much of a difference.
It's (slightly) worse than that. Too much fluoride makes your teeth brittle. This, however, mainly matters while they are growing. Toothpaste is just a surface treatment, and a thin hard+brittle external surface isn't bad.
Caution: I'm not any sort of dentist or medical professional, but:
As for "fights plaque", well, yesssss. Perhaps some actively fight it, but mainly the process of applying it fights the plaque. None of them get rid of plaque that's hardened in place. Before it hardens, plaque is a bacterial film. It's *relatively* impermeable to externally applied chemicals. But it's not very resistant to mechanical stresses. So toothbrush disrupts the film. Then the toothpaste can get at the tooth below the film, and prevent the film from reattaching.
The preceding paragraph was based on info that's around a decade old, but it's probably still true.
Brushing removes plaque, otherwise all you needed would be a mouthwash with fluoride
Since they also advise you not to use a fluoride mouthwash directly after brushing your teeth because it washes away the fluoride (https://www.nhs.uk/live-well/healthy-teeth-and-gums/how-to-keep-your-teeth-clean) I would guess that maybe the fluoride concentration achievable with a mouthwash is either lower or else less well-distributed than with a paste applied with a brush?
Different brands have different concentrations, but theyre generally lower than toothpaste (normal toothpaste has about ~1450 ppm, I think Listerine is at 300ppm). I would also guess that the residue of toothpaste "sticks better" to the teeth than a mouthwash.
Brushing is absolutely designed to disrupt and remove the biofilm on the teeth.
But that is as much to remove the precursors of calculus (the hard matter your dentist removes when they are cleaning your teeth) as it is to prevent cavities.
Both are bad for your tooth/gum health.
Fluoride enhances tooth enamel, it does nothing to bacteria.
Understood; thanks for the correction!
>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 )
Also, regarding Zbiotics: lots of people used them at my lab retreat in 2022. They still ended up with hangovers, but given the amount of drinking that happened I'm not sure how much the probiotics realistically could have done. I wish we had organized a randomized trial.
Thanks, I've mentioned this in the post.
Even easier: since they ship you a sample of the bacteria to apply in the first place, growing more of it from that initial sample would presumably be pretty trivial, and saves to hassle of identifying/isolating it from a mouth sample.
Do they ship it? I thought they just put it in your mouth in Prospera.
That's just the first treatment (and just for the Prospera trial). Prospera patients can get additional culture to [re]apply later, and the site suggests the commercial product will also be an at-home treatment.
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.
I should clarify that I know nothing about Zbiotics and am not endorsing them (even to whatever weak degree I could be considered to be endorsing Lantern), I just know they're an example of something that the FDA allows.
Noted! I did not think (/ think to imply) otherwise.
FDA regs are really dumb! Three examples:
* Lots of regs preventing doctors from telling truthful, even life-saving, info to patients. E.g., https://rtp.fedsoc.org/wp-content/uploads/RTP-FDA-Health-Working-Group-Paper-Off-Label-Communications.pdf
* The sad story of Snus, which have saved so many lives in Sweden yet are loaded down with such huge regulatory burdens stateside that it's almost more economical to just smoke.
* And recall the saga of DMAA, which a likely-erroneous study concluded was present in geraniums or something, meaning it could be sold as a supplement -- I expect soon some genius of commerce will transfect amphetamine/cocaine-producing tissue into a badger or something for a new supplement. Would scream off the shelves at GNC.
> I expect soon some genius of commerce will transfect amphetamine/cocaine-producing tissue into a badger or something for a new supplement.
Why would that be necessary for cocaine? It's already refined from a plant. It's controlled by being specifically listed as a controlled substance, not because it doesn't qualify as a supplement.
This suggests that, although methamphetamine is not refined from a natural product, it also wouldn't benefit from becoming a natural product.
The other, more popular dope that one can get usable quantities of from a single (potted!) plant -- is still technically banned in USA, but in practice has for some time been available from convenience shops where I live (Wash. DC region.) Suppose that suddenly one didn't need an entire conspicuous (and in the right geography) plantation's worth of coca to get 1kg of cocaine?
Perhaps you should read Sigmund Freud on cocaine. It was legal at the time. First he enthusiastically recommended it, then he strongly changed his mind. There are reasons it was banned.
Personally, I feel that opium poppies and coca leaves should not be banned to adults, but any extracts from them should be forbidden from sale. That would eliminate most of the bad effects of the current legislation. (Well, except for regulated medicinal purposes.)
That said, once bio-hacking really gets going, we're definitely going to need a different set of regulations. This bacteria is only the start of where things can go....and they sure aren't all desirable.
FWIW I did read Freud, and have no particular desire to take cocaine. But in re: biohacking, I cheer any and all technologies which could potentially make a dent in the totalitarian police state's practical ability to enforce bans. In a hypothetical world where one could "print" drugs, FDA and similar busybodies will be relegated to the position of the RIAA. "You wouldn't download a car!" "I would if I could, go stuff it".
But the motivation is specifically stated: "soon some genius of commerce will transfect amphetamine/cocaine-producing tissue into a badger or something 𝗳𝗼𝗿 𝗮 𝗻𝗲𝘄 𝘀𝘂𝗽𝗽𝗹𝗲𝗺𝗲𝗻𝘁."
Marijuana has been available from convenience shops because its legal status changed. Cocaine remains unavailable because its legal status hasn't changed, and the proposal would have no effect on its legal status.
Do you think that the legal changes re: marijuana had nothing whatsoever to do with the fact that one can grow N doses in a potted plant? Or that there are not enough prisons in USA to house even one user in ten?
Incidentally IANAL but AFAIK it is still banned, on paper. The "warriors on drugs" simply capitulated on enforcement.
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.
Same reaction. Does this mean that patients 2 and 3's mouths are 70% regular S. mutans? If so, is this meaningful cavity protection?
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?
https://en.wikipedia.org/wiki/Risk_compensation
Usually the net benefit is still positive.
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 far as I understand, these bacteria won't prevent gum disease, so you'd still have to floss.
Why not? The bacteria that cause gum disease are the same bacteria that cause cavities.
The mechanism is different. PH changes from lactic acid metabolism is the main route by which the bacteria damage tooth enamel, while it sounds like the soft tissue of the gums is damaged by mostly endotoxin secretion.
I thought it was the same. Bacteria-secreted acid destroys bone which is the real problem with gum disease. Soft tissue grows back, bone doesn't.
It's different bacteria: https://www.ncbi.nlm.nih.gov/books/NBK8259/
> Streptococcus mutans is the main cause of dental decay.
> Periodontal infections are usually mixed, most often involving anaerobes such as Treponema denticola and Porphyromonas gingivalis.
Huh, TIL. Thanks.
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.
Thanks, good to hear from someone who properly understands this. Do you see any risks from the specific knock-on impacts of the genetic mutations on mouth microbiome, in particular regarding:
- Other types of bacteria that are already resistant to this antibacterial; and
- Types of bacteria which can transfer genetic information despite the peptide modification?
Recognise diet, region, etc already change the mouth microbiome, but those have the benefit of being relatively exhaustively tested, if not in a structured way.
Thanks for the info, that’s good to hear.
When this was discussed on Twitter a couple months ago, many people brought up issues with other strains of S. mutans causing ulcerative colitis, eg https://pubmed.ncbi.nlm.nih.gov/22451861/ (a random paper I found)
Is this a relevant concern?
Yes and no. You can make any strain do bad things by giving it to sick enough animals. The study you linked is a DSS model, where they administer a chemical that tears into the intestinal lining and causes the mice to shit blood. It's commonly used as a model for inflammation and IBD, but after some personal experience with it I'm not convinced it's a very useful model for studying chronic inflammation (which is what they're using it for here).
That being said, there is clinical evidence that certain strains of S. mutans are pathogenic, and are associated with colitis. One issue here is that often your commensal bacteria are opportunistic - if there's an injury then they'll switch to a pathogenic state to take advantage, and undergo rapid selection for increased pathogenicity in the wounded tissue. So it's not clear that the S. mutans is causative. Some other studies injected (large) amounts of S. mutans into the bloodstream and saw bad things, but maybe that's because bacteria in your bloodstream is generally bad.
Additionally, this is strain-dependent. Even that study used a different strain of S. mutans as a negative control, which did not worsen the DSS-induced inflammation. There appear to be a few strain types that are more pathogenic, primarily isolated from patients with colitis or bacteremia (bacteria in the blood). A whole genome sequence of BCS3-L1 or even just a strain typing analysis would tell us if that's something to be worried about here. I doubt it, because the 'good' strains are usually isolated from the mouth (like this originally was by Hillman back in the 80's), and the 'bad' ones from other places where you usually don't want bacteria.
For reference, a whole genome sequence of this strain would cost $105 including sample prep through a sequencing provider.
Thanks, this is very useful info!
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 think that kind of evolved immunity usually involves transfer across people, which it sounds like wouldn’t be happening here.
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?
I get the impression that they're not really trying to turn this into a business, they're running it more altruistically. But still, the most effective way of getting this into as name mouths as possible would generally mean using solid business practices.
Yeah. Unless you want to just give away the patent (which honestly I think is suboptimal but I understand) then having solid organizational and business experience is key to having maximum impact. I'm not saying they necessarily need to be ruthless capitalists. They can set things up as a non-profit if they want. But they do need their financial and operational affairs in order.
I had the same impression as you; I think they need either someone within the company itself, or a venture capital/private equity type to invest and be on their board to push this.
To be frank, USD400k is a trivially small amount of money for a good idea; I'm not at a point of my life where I'm taking big risks with investments, but even someone like me (top 1 percent, not top 0.1 percent) could fund it solo. Do they just not have the right connections?
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.
Isn't the counterargument that huge populations of people already put lactate, alcohol or both in their mouths daily and in orders o magnitude higher quantities? So if it has some crazily negative effects we'd probably noticed.
Not really a coherent counterargument given that alcohol has a crazily negative effect that we have long since noticed called cancer. This has been easy to notice because we can somewhat easily control/ monitor ethanol intake and make correlations. Given the ubiquity of lactate-producing bacteria, we don't really have any control groups to compare to to determine any of the long term effects of the treatment.
Ok, let me expand a bit:
1) Negative effects of alcohol are well-known, of course, but the major pathways for those are not through oral immune system, it's CVD and liver/systemic toxicity. Oral cancers are among those effects too, but no at the top of the list.
2) At the lower end of the alcohol consumption spectrum, these effects are low enough that epidemiological studies routinely get confused and find no to positive effects. [I'm not saying there is no negative effects at the lower end, mind you. I'm saying they are really small].
3) The bacterium is going to produce at worst 2-3 orders of magnitude less alcohol per day than what is usually used as lowest alcohol consumption bucket in these studies.
4) So on one hand, at every dose where we can see the effects clearly, alcohol's biggest risk factors are systemic (CVD, liver disease, non-oral cancers). On the other hand, there is no evidence [that I know of] that natural levels of alcohol affect these endpoints. And on the gripping hand, the excess alcohol from BCS3-L1 is not going to bring you outside of the natural levels. So you have to postulate a very specific biology where at all measurable levels the systemic negative effects of alcohol are more significant than oral, but at extremely low levels they switch, *and* as you decrease the dose oral effects remain significant long after systemic effects disappear. This is not impossible, but it seems highly unlikely and I wouldn't be terribly concerned about it without some specific evidence.
The point about alcohol having toxic effects beyond oral cancer seems irrelevant. Those being worse or more common than oral cancer really has no bearing on whether or not ethanol causes oral cancer. Regarding the very specific biology you're describing, it doesn't seem particularly far-fetched to guess that the ethanol being produced in the mouth would primarily have effects in the mouth where it is locally concentrated. A pretty small amount of ethanol held on your gums or sublingually will still cause irritation etc. despite having negligible systemic effects.
It is relevant if you actually read carefully, esp the point 4. Let me explain again: if even the stronger effects disappear at level X, it is reasonable to expect that the weaker effect will also disappear at dosage X, and even more so at dosage X/100 or less. Yes it is possible in principle that it's not the case, but you need evidence for that. I don't think the fact that it's produced in the mouth counts for much, since it's how all external alcohol comes into the body. And yes you swallow it, but you also swallow saliva. The "small" amounts of ethanol that will cause irritation are still orders of magnitude larger than what is produced by these bacteria in a day.
Re lactate, I dunno but what's the worst outcome, users will have to drink extra 0.1ml of milk per day to compensate?
Seems like you might be confused on lactose vs lactate. They could get their lactate from the milk with the help of lactose fermentation by lactate-producing bacteria.
Well make it yogurt then. Jeez.
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.
Unless you believe, as I do, that there should be a lot more genetic engineering, decentralized and democratized. There are a lot of cool things people can do with that tech, most of which wouldn't happen if there were some injunction against bioengineered microorganisms getting released into the wild.
Rules like "be more safe" aren't useful without clear thresholds for what constitutes safe enough. Otherwise they just create an unopposed incentive that drives all innovation to zero.
So unless you can provide a clear and reasonable definition of "safe enough" then I think this is a bad rule to follow.
Do you also disagree with MIRI's argument to Connor Leahy about AI safety norms?
https://medium.com/@NPCollapse/the-hacker-learns-to-trust-62f3c1490f51
That's not AI safety though. Tail risks are nowhere near as huge.
Not when you factor in s-risk or future lives, but for just x-risk of those alive today, which is what most people are concerned about, I think they're pretty similar.
Nope, still not even close, if you take AI risk even 1/10th as seriously as MIRI does. For an engineered [by humans] plague, to wipe out humanity is an extreme edge case, it is possible in theory but you have to be trying *incredibly* hard. For AGI [under MIRI's assumptions] wiping out the humanity is the default, and you have to be trying *much harder still* to avoid this.
Yes. I think the arguments around AI safety are terrible.
The spectrum of "bioengineered microorganisms" is very large.
On the scary side, you have the products of gain-of-function research. My position on that is that it seems like a terrible idea for multiple reasons, for example the possibility of unintentional leaks or making the job of some bioterrorists easier.
By contrast, this seems to be some twelve orders of magnitude safer. The bacterium they started with occurs naturally in healthy humans. Producing an antibiotic and being antibiotic-resistant are both common outcomes of eons of chemical warfare among microorganisms. Favoring a pathway of breaking down sugar into alcohol has also been done before. And the lack of some peptide does not seem very nightmare-inducing either.
https://dresdencodak.com/2009/09/22/caveman-science-fiction/
Do you also disagree with MIRI's argument to Connor Leahy about AI safety norms? If not, what's the difference?
https://medium.com/@NPCollapse/the-hacker-learns-to-trust-62f3c1490f51
That would be the following:
> His point was simple: The model may or may not be dangerous, we don’t know for sure. I’ve heard incredibly convincing arguments that go both ways. But that does not matter.
> Because this isn’t just about GPT2. What matters is that at some point in the future, someone will create something truly dangerous and there need to be commonly accepted safety norms before that happens.
Honestly, I have not thought too much about it. While I am a doomer, I do not think I agree with MIRI very much here.
In my opinion, the dangerous part (as with gain of function research) is creating the models in the first place, not distributing them or not. If ASI is created by someone, it think it will be by a big lab training a new model, not some kid downloading an open source LLM and moving the IQ slider from 100 to 1000.
Of course, you could argue that small LLMs are precursors to larger LLMs, which might eventually become ASI, and that we should restrict them like someone might want to restrict designs for nuclear reactors because they might serve as precursor steps to creating nukes.
I mostly do not think that keeping information on state of the art LLMs contained will work out very well. After all, the employees of big-name AI companies are not conveniently located in some facility in rural Siberia where you can just put a fence around them and shoot them if they try to leave. Anyone with enough resources to have a shot at building ASI can probably find someone qualified willing to work for them.
Just like with genetic engineering, AI is a field which at the moment seems to run on the paradigm of open scientific exchange. I think the biggest difference is that in genetic engineering, the dangerous corners are much further away from the useful corners. If you manage to create a variant of COVID which is twice as infectious and ten times as lethal, that will let you do some publications. If you create a strain of wheat which is 20% more resistant to dryness, that will possibly make you rich. By contrast, ASI is both desirable (if aligned) and dangerous (otherwise).
Much like AI, progress and the future shouldn't be arbitrarily held back because of baseless doomsaying speculation. Maybe we should all be living in shit subsistence farming with no technology whatsoever, can't be too careful!!
I understand how it's possible to reasonably think AI has a <10% chance of destroying the world, but I don't think there's any good faith way to read the basic arguments and think the chance is <0.0000001%. (~1 life, which seems like the natural threshold for "baseless speculation" over "relevant concern".)
1 life is not a realistic threshold if you want any medicine [for common disease] developed ever.
Do you think that people should proceed with developing new technologies without even considering the risks?
No, that's not what I think or what I said, that's a strawman.
So what is the threshold at which they should consider the risks?
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...)
Thanks for sharing the link on the follistatin therapy, I wasn't aware this existed, or that Prospera allowed a broader genemod testing / deployment regime.
You mentioned cost, but I couldn't find anything about it, just that you'd need to get a new injection every 1-1.5 years, and they want a $250 deposit to talk to you. Do you know the present total cost of the therapy?
This is an area I'm pretty interested in too, but don't see much activity - Atkin posted his lactose tolerance cure plasmid to creative commons, but you need to DIY, there's not really anywhere you can go and get any sort of gene treatment from professionals (except Mini Circle, apparently).
I have the same questions.
I was referring mostly to the costs of flying to and from Prospera. (I think this might be cheaper for people living in the US, due to geographic proximity? I live in Tokyo.) I believe they also want monthly Dexa scans from you for a period afterward as part of the study, but I'm unsure who they're expecting to pay for that.
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.
If you going go though all the effort to replace all the letters with homoglyphs why not use a better one for F?
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 ?
Probably enough mutans longer to self-reproduce, but I’m not sure.
If it works why would you have to get a cleaning?
Impacted wisdom teeth extraction, perhaps.
well you might not be so confident in the new technology to reduce cavities that you're willing to stop the traditional cleaning intervention. And unclear from the article whether the gmo microbiome intervention will address all mouth related issues, might you not still get gum disease if you don't do normal 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.
Well if it actually works then doesn't that obviate the need for a long-term trial? As long as it's on the market then it'll spread through word-of-mouth and positive anecdotal evidence.
How does one ascertain if it works?
Why is that important?
If anecdotal evidence is positive then use will spread. If it's not then it'll stay at the level of homeopathic cures. As long as there's no large downside health risk then ordinary market forces seem perfectly adequate for judging its effectiveness. There are plenty of useless products out there. The FDA doesn't need to study everything. Caveat emptor.
The claim is strong enough that it's pretty easy to falsify just by surveying recipients a year or three down the road. Their website claims near-complete elimination of cavities, based on Hillman's rat studies and Oragenics's human volunteers, so any non-trivial level of cavities showing up in survey data would be refute at least the strong claim they're making now.
Some back of the envelope math from statistics about cavities by age suggests to me that the base rate is something an average of about 18-20 new cavities per 100 adults (age 20-64) per year, which is high enough that if simple survey of a few thousand recipients were to show a near-zero rate of new cavities after a few years, that would be pretty strong evidence that there's significant benefits, despite obvious flaws around blinding, response bias, selection effects, and lack of a formal control group.
See below my response to myst-05. There are many, many cariogenic pathogens in the oral flora - strep mutans is just the biggest one. This is not a debatable point; it's accepted science. The fact that nowhere on the website is that noted is a huge red flag in my opinion. What do the 5-10 year outcomes look like in a group of patients who think they are "immune" to caries but actually are not, and who potentially change their diets and habits under the impression that they are? Might they have an even greater incidence of new decay than a control group who never took the vaccine? These are hard questions. Unfortunately, no one cares enough about dentistry to pay the tens of millions of dollars needed to properly answer them. I think there is a fair amount of hubris on Lantern Bioworks' end to make these types of claims. Tread carefully...
I'm not one bit convinced that it works, but the back-and-forth is convincing me that there's definitely a possibility here for a new product on the market that claims to do the divil an' all for your teeth. Especially if the "please continue to brush and floss" advice is emphasised enough, that'll keep the cavities at bay while 'fancy new treatment' gets the credit.
After all, if people are willing to sit under UV lights to whiten their teeth, they'll surely pony up for something less risky (even if it's not beneficial or only in part).
https://metrosmiles.com/blog/uv-lighting-does-it-work-for-teeth-whitening/
Sort something out for clinical trials and I think this could reward investors for yet another product that straddles the cosmetics/supplements/medical treatments line for healthcare. Get in on the ground floor now!
Also through mouth-to-mouth badabing!
I concur that well designed oral care long term clinical trials are extremely rare. But… I don’t think that precludes this taking off. Look at how many people here are interested.
That's part of what surprises me. There's plenty of intelligent people here who are interested, but I don't see how anyone can possibly know if it actually works, ever. I'm honestly a bit surprised Scott wrote all this up.
From the description, it sounds like there's w small reversible downside and a large potential upside. It sounds like a good risk to take.
Well if they get approval in 2025, by 2027 they could call up all their old patients and ask "So, gotten any cavities lately?" If zero of a thousand people have, seems like it works.
No. It's not that simple. See my response below to myst_05.
What would you expect the effect of this to be on gum health, in broad brush strokes?
There are many pathogens involved in gingivitis and periodontitis. I'm not sure if a mutated form of strep mutans would have any affect on gum disease. Maybe it would make things better, maybe it would be the same, maybe it would make things worse. It's a lot of fun to speculate on these types of things. Unfortunately, we don't find the answers by inoculating germ-free rats and seeing what happens. Humans are not germ free! The mouth is very complicated... and populated... place.
Are you claiming that it’s impossible to design a good experiment for oral health and thus we could never know whether or not it works? Or that such experiments are too expensive to run? Or that a properly designed experiment has a 0% chance of proving this works because that’s not how cavities work?
All of the above. No one cares enough about dentistry to invest the millions (or tens of millions) of dollars to construct and run a propely-designed trial to evaluate this question. And yes, cavity formation is not linear with pathogenic strep mutans presence. There are many, many cariogenic pathogens in the oral flora - strep mutans is just the biggest one. This is not a debatable point; it's accepted science. The fact that nowhere on the website is that noted is a huge red flag in my opinion. What do the 5-10 year outcomes look like in a group of patients who think they are "immune" to caries but actually are not, and who potentially change their diets and habits under the impression that they are? Might they have an even greater incidence of new decay than a control group who never took the vaccine?
It also has no mention of the clinical challenges of evaluating and treating dental caries in the "real world." How do you classify previous restorations where the bonding breaks down and starts leaking? Technically, those are "cavities..." This is part of the larger issue of overdiagnosis and overtreatment in dentistry. I could speak for hours on the topic.
It sounds to me like they really haven't consulted with any clinical dentist on this. I just read through their whole website and their "literature," and it's even worse than I thought. One animal study on germ-free rats. No humans studies that I can find. That's embarrassing!
Seriously, if anyone is considering paying $20k for this BS, just contact me at doctor at BergenEndoCare dot com. I'd be happy to accept half that of that and actually give you good advice ;-). Please, please, do not pay any significant amount of money for this.
Scott - if you are reading this - this post is not in the greater community's best interest, IMO. I'd be happy to discuss this with you in detail, if you'd like.
Not intended as a gotchas, but if what you're saying is true
1. Why brush teeth?
2. Why floss?
3. Why have a 6 month period between cleaning cycles?
4. What does a dental cleaning do?
5. What does wisdom teeth removal do?
All seem like reasonable questions to ask assuming you're in this epistemic frame. Are there answers that can be given that also pass the bar you've set out previously? (I actually would expect "Yes, here's the paper" for most of these btw)
I'd like commentary on this too. It seems like most of whats recommended in dentistry doesn't have a strong evidence base. Theres Cochrane reports for a lot of interventions and its not very encouraging. Add to that, the embarrassing level of clinical variability.
>"This is not a debatable point; it's accepted science."
This sort of statement about anything reduces a speaker's credibility.
By "0% chance this takes off", do you mean 0% chance it works at preventing cavities, 0% chance it works as a business, or something else?
0% chance it works as a business (long-term).
If someone would like to share how they would define "preventing cavities" - in a realistic way that can be applied to a theoretical study of this question - I'd be happy to provide my estimate. How you define and study preventing cavities is, in and of itself, a very complicated question. And, to study this exact product, quite a costly one.
I will add that after 5+ years of reading SSC/ACX, I'm ecstatic that something was finally posted that I have some domain expertise in. It was worth the wait :-)
Why are you so sure it can't work as a business? Even granting that you're right that it's impossible to study, many probiotics have worked without knock-down evidence that they do what they say.
I'll let Aaron know about these comments and see if he wants to reach out.
EDIT: Actually, I see there was already a multi-way email conversation between you, me and Aaron last year - feel free to reach out to him if you want, otherwise I'll link him here.
I think you have it backwards. This has a much higher chance of taking off as a business than it does of taking off as a useful clinical treatment at scale. Homeopathy and crystal therapy are large and thriving industries, despite provably doing nothing.
As you mention, a study that could distinguish between lumina helping, hurting, and doing nothing, to any useful degree of certainty, is well beyond the capacity of Lantern Bioworks. If they get approval to sell this in the US, we won't know for decades what effects it has, and they'll already have made a substantial profit.
That's exactly the point. Homeopathy is a thriving industry, but not to rationalists. Do you think holistic folks will want to partake of this treatment? Heck no. At this current stage (no FDA approval, zero human studies), there is a very small subset of the population that this appeals to - perhaps a sliver of the rationalist community who are cavity-prone and have $20k to burn. There's a whole lot of work that needs to be done in order to make this endeavor more appealing to the wider population so it can be profitable in the long-term. Frankly, from what I have seen on the Lantern website, that will almost certainly not happen. But hey - YOLO!
"Do you think holistic folks will want to partake of this treatment?"
Word it differently for different markets.
For the rationalist lot, go heavy on the SCIENCE! Bio-engineered! Excretes antibiotic! Lactic acid metabolism pathways! Lots of pictures (as they have on their website) of bacterial chains etc. with that cool blue lighting.
For the hand-knitted yoghurt lot, emphasise the NATURALLY OCCURRING bit. Present in people's mouths already! Fights malign bacteria! No chemical processes or treatments required, just deep-clean your teeth then paint this on and Mother Nature does the rest! Pastel greens for this ad, smiling models of wholesome, corn-fed health with their shiny white teeth, leaves of various herbs and plants all over the shop.
I have family members deep into the biodynamic/anthroposophical stuff and there's ways of selling that make you a multi-million business while keeping the organic image (Dr. Hauschka and Weleda come to mind).
https://www.drhauschka.com/our-herb-garden/powers-of-nature/
https://www.weleda.com/weleda
I think holistic health folks are an especially gullible lot, and it is probably well within the capacity of Lantern Bioworks to get enough of that market to be profitable, conditional on them getting FDA approval and keeping their costs low.
Yeah, if they get this marketed as a probiotic or supplement, they can promise it will water your crops and muck out the cow byre, without needing to prove efficacy (if they get the ad guys to word it carefully enough, and for a business to make money, they will be working on that). So long as it doesn't actually make your teeth fall out or turn your intestines into pretzels, they can claim "laboratory studies demonstrate this works" until the cows come home.
I would gladly pay a few hundred for it. Your objections don't seem very coherent to me. So it doesn't eliminate all cariogenic pathogens, so what? Converting half the cariogenic population in your mouth to be non-cariogenic won't be helpful? Doesn't pass the smell test to me.
What level of evidence do you currently have to believe that it can actually do what it claims? Have you read the literature they have on their website? I'm not seeing anything convincing.
Take a second look at the chart in section 4.2 of the post. Lumina doesn't just fail to replace all cariogenic pathogens. It fails to replace strep mutans specifically. In a year, their best performing subject had just under 50% of their strep mutans as the Lumina strain.
The entire premise of the project is that Lumina outcompetes cariogenic oral bacteria, and they haven't even shown that.
To me, that doesn't pass the smell test.
I am not a dentist. I'm in training to be a Dental Hygienist. But even the little I already know about cariogenesis is enough to make it skeptical of the whole project.
The process of developing dental caries is an enormously complex one, just counting the known and well-studied factors (diet and oral hygiene habits). While I don't doubt the less well-studied factors (oral microbiome, but also saliva composition and vague hereditary factors) matter, selecting one factor and saying 'fixing this will cure dental caries for life' is wildly overoptimistic.
Even if they had the funding to study Lumina at scale, I doubt you could get any study worth conducting past and IRB these days. There are too many known factors in cariogenesis that are virtually impossible to control for, to say nothing of the difficult of diagnosing caries.
I think it's worth investigating, but the people in this thread who are hoping for a miracle cure for the caries prone will likely get nothing but disappointment.
If there as a prediction market for Lumina working well that had reliable resolution criteria, I would be going heavy on the negative right now.
Have a handful of markets which might interest you:
https://manifold.markets/WilliamEhlhardt/will-lantern-bioworkss-cavitycuring?r=Sm9oblNtaXRoYjliZQ
https://manifold.markets/Aella/will-i-get-any-new-cavities-after-a?r=Sm9oblNtaXRoYjliZQ
I’m currently wordsmithing a market about whether this stuff will work, but defining “work” is a bit complicated.
Any impact on gut biotic? Can it reproduce in the gut?
Gut biota
I wondered that too. If it could survive stomach acid and take up residence and flourish in the intestines, churning out alcohol all the way along, instead of only tiny amounts in the mouth, then the host might end up permanently pissed as a pudding, to put it crudely! :-)
This is precisely the problem that the FDA wants a study; will this thing remain confined to the mouth or spread elsewhere? How do you prevent bacteria in the mouth from being swallowed along with saliva and food and travelling to the digestive system? Will they be destroyed there or can they colonise the stomach/intestines, and if they do, what will be the effects?
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.
The bacteria on teeth has to come from somewhere else, since teeth are a prerequisite, but I agree that mouth-to-mouth kissing your baby can't be universal.
Another possible route is sharing food, drink, or utensils. Our daughter loved taking sips of our drinks or mooching bites of food from our plates as a toddler.
This is taboo for Hindus for obvious adaptational reasons, though I would tend to agree that people are likely to make exceptions for babies and toddlers.
Really? That's the exact opposite of my experience: sharing food is far more taboo (though that's too strong a word; "rude" perhaps, and at any rate, less common) in America than in India. A preliminary Google search suggests my experience is typical.
What are the "obvious" reasons?
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.
Here the judiciary failed its duty. It is supposed to be a check against bad legislation and bad execution.
Why the hell is an 18 year old (legal adult) woman having sex with a 14 year old youth? Maybe he's very tall and 'mature' for his age, and can pass for 18, but hell's bells.
When she's 24, will she still be banging 14 year olds? I'm not surprised the boy's parents were spitting feathers, I'd be furious too.
Well, you could call her a legal adult, or you could call her a high school student. By the time she's 24, she probably won't be going to school with any 14 year olds.
That's the problem, isn't it? When it comes to things like "contraception, abortion, puberty blockers" and so forth, then 18 is plenty old and mature and legally adult.
When it comes to other things, then it's "only a high school student". I submit if she's fucking 14 year olds, she's the adult (supposedly) here. I know this is back in the time when dinosaurs roamed the earth, but when I was at school there was a clear distinction between 17-18 year olds and 14 year olds. It's amazing how young and small the new batch of 12 year olds look when you're 17 yourself, and I do wonder about how old does this boy look, because damn it, this is period of life when small differences in age make a huge difference (see what a year can do pre- and then mid-puberty).
And sure, when she's 24, she won't be going to school with any 14 year olds - unless she decides to become a teacher - but that doesn't mean her sexual preferences will have changed and she will now have moved on to "must be minimum of 18".
Mme. Macron is the oft-quoted case here, she and her now-husband encountered one another when he was 15 year old student and she was 39 year old married with three kids teacher, but the parents managed to separate them and they didn't meet up again until he was 18, then married him at 30.
So maybe our lassie here will remain faithful to her beau until he's legally old enough to drive a tractor (https://www.osha.gov/etools/youth-agriculture/tractors#:~:text=HO%2FA%20%231%20The%20FLSA,parts%20to%20such%20a%20tractor.) and then once he's old enough to get married, it will be True Love Bliss.
Or maybe she's MAP and will keep trying to sleep with 14 year old boys.
> Mme. Macron is the oft-quoted case here, she and her now-husband encountered one another when he was 15 year old student and she was 39 year old married with three kids teacher, but the parents managed to separate them and they didn't meet up again until he was 18, then married him at 30.
Is the problem that the girl might not marry the boy, or that she might?
The problem is that an 18 year old should not be having sex with a 14 year old, boy girl or other. I'm on the parents' side here, and were it me, I'd be after the little bitch with a shovel to beat some sense into her.
Now, if she sticks around and waits until he's 18 and she's 22, marriage or no resulting, that's not ideal but at least it's better than the alternative, which is that she likes them younger than her and once he 'ages out' of the range she finds appealing, she'll be after another 14 year old, and so on as she gets older but the age she finds sexually appealing doesn't change.
I don't know if she's an ephebophile or if this is just a case of romance too early, but I think that there does need to be caution around dismissing this as "the law is so dumb, look at what they did" when this might be the only way the parents could get a legal decision to stop her hanging around and continuing to have sex with their son. Go away, stay away without trying to contact him, wait and come back when he's 18 and then we'll see.
> The problem is that an 18 year old should not be having sex with a 14 year old
As best I can tell, this is a problem because she might dump him in the future. How does splitting them up in the present improve on that?
Most states in the U.S. have "Romeo and Juliet statutes," which make an exception to age of consent laws in cases where the age difference is less than a set amount of years (usually 3-5 years, but it varies). That must have been the case here, since the age of consent in Arkansas is 16, not 14. A 24 year old hooking up with 14 year olds would be unambiguously illegal.
I can't blame the boy's parents for being outraged, but I can't agree with how the judicial system handled this either. If the law was bad, then the law should be changed. Using obscure legal loopholes to prosecute people is a tactic that I oppose on principle, especially since it usually tends to set bad precedents that can all too easily be abused and exploited in future cases.
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.
Good question, I don't know! I'm not sure whether many people have mutacin-1140 specifically, or just some other unusual bacterium that does something with some antibiotic - and I don't know whether this strain would outcompete other unusual bacterial strains.
A lot probably depends on the metabolic efficiency of the lactic acid pathway versus the alcohol. If one strain is more "sickly", it might always diminish in the presence of the stronger strain. (Although metabolic pathway might not be the only meaningful difference between strains.)
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.
Americans get hung up on the stupidest things. Best to be proactive and quash potential moral panic from every possible angle.
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?)
Presumably because that's the demographic who are the main market for this? I'm assuming that 18 is the lower bound since that's the age you are legally not a minor.
Older than that, you either have good teeth already or dentures already (the older, the more likely). People most likely to want to prevent cavities by taking a short cut like this, and being able to pay for it, are in the 18-30 age range. EDIT: And should be in generally good health, so if something does go wrong, it can't be blamed on "but they were already high-risk because of this, that and the other factors!"
Though I do think there would need to be follow-up studies done over years, because "I did this two months ago and I feel fine!" isn't long enough to be meaningful. What happens five years down the line from having a mouth full of these mutant bacteria? Ten years? Could it be that they secrete tiny amounts of something else that builds up in your system over time and turns out to be not so good for you?
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.
It seems to me that development of immunity to the foreign bacterial community would also explain your observations while being more consistent with the results of your treatment with antibiotics.
Makes sense!
> 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
Sorry, I misphrased that. Many people are walking around with natural mutacin-secreting bacteria, but as far as I know nobody naturally has the version that switches to alcohol metabolism and doesn't cause tooth decay.
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.
That is established fact now. Surgeons these days are reluctant to perform heart surgery on patients with gum disease, because some bacteria from the gums can enter the bloodstream and cause inflamation of heart valves.
As I said, I don't even know enough to be dangerous.
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?
I think it sounds like the FDA wanted it tried out on some meth mouths, which could be viewed as altruistic depending on your perspective.
> 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!
no the acids make plaques under which the acid dissolves enemal, normally acid in the mouth would dissolve as we have a lot of water in our mouths.
There's something like this called silver diamine fluoride. Aaron was looking into it too. It has high risk of discoloring the teeth, so it's only used on very disabled people who can't possibly be convinced to brush and floss.
As far as I know silver diamine fluoride only affects, and discolors, cavities. It supposedly stops the cavity from expanding, permanently. Therefore it should be perfectly fine to use on cavities between teeth or on rear inside surfaces that are not generally visible. However dentists for whatever reason are loathe to use it.
was wondering.
silver diamine fluoride. from MarginalRevolution
Studies show silver diamine fluoride stops decay in 60 to 70 percent of cases with one application. A second application six months later boosts the treatment’s long-term effectiveness to more than 90 percent.
In addition to killing cavity-causing bacteria, the treatment hardens tooth structure, desensitizes the tooth and even stops new cavities from forming. Applying the liquid on the exposed root surfaces of older adults once a year is “a simple, inexpensive, and effective way” to prevent cavities, a 2018 study concluded
https://marginalrevolution.com/marginalrevolution/2020/09/the-great-forgetting-how-to-stop-tooth-decay.html
also WP
https://www.washingtonpost.com/health/tooth-decay-fixed-without-drilling-silver-diamine/2020/09/11/d9a87e4c-d104-11ea-8d32-1ebf4e9d8e0d_story.html
WP piece sounds like it's mostly used in actual cavities, rather than prevention. but the MR seems to indicate otherwise?
I tried sourcing it. difficult.
maybe the crowd here have an explanation to this?
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!
i agree with you.
honestly i dont see the fda as the bad guy in this situation; a near-permanent and even infectable genetic change like this should need extremely high standards required. Cavities are something that at least be treated and aren't urgent enough to suspend judgement for a trial.
People can't throw away their judgment so easily.
But on the other hand, testing it on a bunch of rich people and then if nothing horrible happens to them moving on to poor people sounds like an ethical improvement over the usual way of doing it the other way around, no?
Rich people eaten by their own teeth has that Hammer Horror anthology film sense of pleasingness, I must agree.
https://www.youtube.com/watch?v=tc27GuFudfA
"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."
If you read the rest of the post, you'll see this is Prospera, a charter city. It's not a bribe, believing in this stuff is part of their reason for existing.
Prospera are having their troubles with the new government, though, precisely because they wouldn't stay bought, with a new party in charge.
So I'm sticking with "you pick a country where you feel the advantage is a weak government that won't get in your way, and you end up with a weak government that won't get in your way until they get turfed out by a new lot who want to take over the golden goose".
A more robust government might not have been willing to hand over so much authority to Prospera, but by the same token, once an agreement was signed, that would stick. They wanted malleability, they got it, and I wonder how much they like it now?
Well it's not a matter of "just brush your teeth" now is it? As you noted, there are still good reasons to brush one's teeth after getting this treatment, so never having to brush again can't be the motive behind developing this treatment. And more importantly, one can brush and floss religiously and *still get cavities*. Sometimes the old-fashioned ways are best, but other times they're inadequate to the purpose and at most form a necessary but not sufficient part of a strategy.
Fun story though; thanks for the link.
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
one of the things that tipped me more to the luddite scale was going to a petsmart and finding out you could buy genetic engineered glow in the dark fish called Glofish. So you never know...
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!
But isn’t it the ‘4 out of 5’ cartel of dentists that paid off the FDA commissioners to include the ridiculous rules ( imagine meme of politicians doubling over in laughter “we’ll require them to be 20 year-old loners with full dentures “ ) in order to save their collective careers.
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.
Coating your teeth in sugar sounds like quite a gamble, but at least it would be easier to get past IRB than the GMO bacteria strategy.
> 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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