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A genetically modified bacterium that outcompetes bacteria causing tooth decay (astralcodexten.com)
382 points by vwoolf 12 months ago | hide | past | favorite | 150 comments



This story has been around for far too long and evidence is unbelievably weak, and the claims border on fraudulent.

1. The claim that this strain outcompetes the same S mutans from occupying the same niche cannot be true unless this strain is also capable of creating and tolerating environments with low pH. By definition if it creates acid to the same degree it will also cause cavities.

2. Single applications are insufficient to cause any persistent colonization. Even multiple daily applications of oral probiotics don’t lead to colonization. Oral probiotics function primarily through bacteriocins, not through colonization (except in very rare cases). This is because the existing microbiome is incredibly difficult to outcompete. The community in your mouth has evolved for as long as you have lived, and in some ways was shaped for generations before as it’s technically inherited from your ancestors.

3. S mutans is not the only species that causes cavities. S sobrinus, S wiggsiae, B dentium, about a dozen other acidogenic species also cause cavities.

Source: I’m a cofounder at Bristle Health, the oral microbiome company.


From the article, the claim is that this strain of S mutans variant produces mutacin-1140 which allows it to outcompete other strains of S mutans and other Gram-positive bacteria.

I have no particular opinion about whether this claim is plausible or true, but you don't address this at all in your comment even though it's directly relevant.

For example, if this strain's production of mutacin-1140 allows it to kill other bacteria locally then it could maintain a niche despite higher pH. One way to view this is bacteriocin production substituting for lactic acid production as a weapon against competing bacteria.

Also, the percentage of the novel S mutans strain colonization is being measured in the first chart and shows initial 90%+ followed by a later drop and stabilization. It would be helpful to more directly address the evidence as presented.

EDIT: Also, this S mutans strain doesn't need to outcompete the entire existing oral microbiome. Even if mutacin-1140 is less effective than lactic acid at creating a niche, it suffices to just maintain a toehold in the microbiome while outcompeting existing acid-producing S mutans strains.


> if this strain's production of mutacin-1140 allows it to kill other bacteria ...

Wonder if it could in a different direction, giving rise to other oral bacteria also unaffected by mutacin-1140?


The mutation that allows it to produce this (and to survive it) is a naturally occurring one. This strain, with that mutation, was found in the wild, which was what gave rise to the idea to use it in this way in the first place. One of the modifications they _did_ do was to break this bacteria's lateral gene transfer machinery so that it can't spread these genes to other strains.

However it is likely that, since this one strain managed to evolve this trait, that others have as well.


The article includes evidence that shows persistent colonization for a year after a single application. And it appears to be a steady prevalence for the last 6 months of that.

Now, to be fair, what I would have _liked_ to see is actually percent prevalense of the various cavity causing bacteria for that year, since that's the thing we really care about (in case this bacteria _isn't_ succesfully killing those strains).

But it certainly appears that they have succesfully engineered a strain that can persist in your mouth after a single application (although they admittedly claim that this application needs to follow a special cleaning procedure to remove most of the existing bacteria)

Your comment seems to really not address any of the specific information provided in the article and seems to be a generic response to the idea.

I love hearing from experts who disagree with an article, it's important to hear those views. But this would have been a much more valuable comment if it could have responded more specifically to the claims and information in the article rather than the general idea.


Your first point seems wrong.

> cannot be true unless this strain is also capable of creating and tolerating environments with low pH

Whether it can tolerate low pH environments is not particularly related to whether it creates low pH environments. If it's agnostic to pH levels around that range, then it can inhabit that niche whether or not there is acid being secreted.


I should clarify: there’s some more details to why S mutans actually requires low pH. The correct term wouldn’t be “tolerate low pH” but rather “requires low pH” for its stable colonization.

S mutans creates incipient lesions by making acid, incipient lesions are micro environments where the low pH that causes enamel decay is determined by the biofilm on its surface. S mutans cannot thrive in environments with neutral or high pH. the existing community (including other Streptococcus species) create local alkaline environment via multiple metabolic pathways, including the most well studied and prevalent arginine deiminase system. A “normal” healthy community antagonizes S mutans by maintaining a normal pH in saliva and the tooth surface, preventing stable colonization by S mutans.

Without acid production, S mutans cannot stably colonize. and is readily outcompeted by the existing community. Any novel strains of S mutans to “compete for the same niche” will suffer the same weakness unless they create acid. but if this “probiotic” also creates acid, then by definition it also causes cavities.

edit: adding citation https://www.futuremedicine.com/doi/10.2217/fmb-2018-0043


The article gives this as the explanation of how it is supposed to work:

  BCS3-LI has four main genetic modifications:

  It produces a weak antibiotic, mutacin-1140, which kills competing oral bacteria.
  It’s immune to mutacin-1140, so it doesn’t kill itself.
  It metabolizes sugar through a different chemical pathway that ends in alcohol instead of lactic acid.
  It lacks a peptide that its species usually uses to arrange gene transfers with other bacteria.

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


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

That alone isn’t enough for long term colonization as it’s not the only bacteria resistant to mutacin-1140.


There's also a graph claiming to show colonization results. I don't know how good it is, but it's supposedly actual experimental data.


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

It'd be quite funny to live in a future where cavities don't exist, but breathalysers are useless. (without rinsing your mouth out first, I guess) Hopefully it doesn't dry out gums and cause gum disease.


The article extensively talks about the amount produced. While it has not been tested against breathalyzers, it is producing so little alcohol that it seems unlikely to be a problem. The claim in the article is that, across 24 hours, you might consume a few miligrams of alcohol, as compared to "if you swallowed 1/10th of your mouthwash, that would be ~200 milligrams of alcohol". So across the entire day, you are producing a couple orders of magnitude less alcohol than is in 1/10th of a mouthwash treatment (or 1/5th I guess if you use it twice a day).


So to be specific what you're skeptical of here is that S. mutans can outcompete other bacteria without its ability to generate acid If this engineered version can stay in the mouth it should be able to live in the exact same lesions the non mutated version can right? It should still have all the adaptations to live in a low pH environment. I guess this is an extraordinary claim so it's right to be more cautious than the internet usually is, but that also seems to be an easy thing to test for. You can swab someone's mouth who's taken this and see if they still have the mutated bacteria or if it's been out competed


Also keep in mind that this strain was discovered about 50 years ago in a human host (the "grad student" reference). The tech is in mutating it further to prevent adaptation, but the beneficial mutation (secretion of mutacin-1140) appears to be the product of natural evolution.


The beneficial mutation is not secretion of mutacin-1140, but absence of lactic acid production. Transplanting only the original mutacin-1140-producing strain wouldn't help anyone, since it still produces lactic acid that would destroy your teeth all the same.

david_l_lin upthread is stressing that lactic acid is ordinary Streptococcus mutans' primary defense against other bacteria and it wouldn't be able to survive without it.

The significance of mutacin-1140 is that it provides an alternative means of defense against other bacteria (or maybe offense would be a better word) which potentially makes lactic acid redundant.


Any thoughts on these folks? (They are your direct competitor.)

https://probiorahealth.com/product/probiora/

A decade or so ago, their founder started with genetically modified bacteria that supposedly outcompete wildtype strains. The regulators responded in the only sane way possible, and it didn't go to human trials, from what I can tell.

List of publications from their founder:

https://pubmed.ncbi.nlm.nih.gov/?term=Hillman+JD&cauthor_id=...

Later, they just cultured a large number of wild strains, looking for ones with the desired properties, and now sell a mixture of three of them.

(Edit: I just realized the company in the article is selling the old work from Hillman's lab, but he is not a member of the team. I'm guessing you don't have a high opinion of this follow on work either then?)


Your first link redirects to Google.

     curl -v https://probiorahealth.com/product/probiora/

    > GET /product/probiora/ HTTP/1.1
    > Host: probiorahealth.com
    > User-Agent: curl/8.1.2
    > Accept: */*
    > 
    < HTTP/1.1 302 Moved Temporarily
    < Server: nginx/1.14.0 (Ubuntu)
    < Date: ...
    < Content-Type: text/html
    < Content-Length: 170
    < Connection: keep-alive
    < Location: https://www.google.com
    < Strict-Transport-Security: max-age=63072000; includeSubDomains; preload
    < X-Frame-Options: SAMEORIGIN
    < X-Content-Type-Options: nosniff
    < X-XSS-Protection: 1; mode=block
    < Referrer-Policy: strict-origin
    < Permissions-Policy: geolocation=(),midi=(),sync-xhr=(),microphone=(),camera=(),magnetometer=(),gyroscope=(),fullscreen=(self),payment=()


Absolutely anecdotal - for a couple months Ive been taking a probioria tab every night before bed, and my mouth seems to be less gross pasty sticky in the morning.

I’m curious to see whether my dental hygienist notices any improvement next visit.


A part of the story that has always made the claim more plausible to me is the claim that apes tend not to get cavities at the same rate we do. Since they have teeth that are as susceptible to acid as ours the story goes their diet tends to lead to other populations of bacteria in their mouthes out competing the cavity causing ones. Then people will go on to say that this ecosystem of mouth bacteria have co-evolved. The reason we have so much trouble is that we've changed our diets drastically relatively recently aka a few hundred thousand years. It sounds like you would argue that some part of that story is wrong. Maybe the bit where eventually a less damaging microbiome would evolve?


The idea that primates get cavities less frequently than modern humans is a bit outdated and not terribly supported by recent studies. The main difference is in the location of the cavities, not frequency – apes tend to get cavities in their front teeth, humans tend to get cavities in the molars.


Oh interesting. I didn't realize. Are there theories on what causes that difference? Is it diet?


I read up on this a bit. It seems that it is diet. Captive primates eat a more grain rich diet while the wild ones get most of their sugar from fruit


I'll take your remark into account but you are a competitor and also biased. Doesn't mean what you say isn't true, but it's definitely misaligned incentives. Thank you for your input.


Yes, I remember reading about something like this a very long time ago. You’d wake up with a fresh breath (alcohol) instead of spoiled milk (lactic acid). And less cavities. Just like revolutionary batteries, I’ll believe it when we reach the millions of users.


> Oral probiotics function primarily through bacteriocins

What does this mean exactly?


FTA, the process is: blast mouth with oral antibiotics then swab the stuff on.

It'll be interesting to see if it works.


I know nothing about oral bacteria, but I like the cut of your jib.

I'm with this science guy!


> The FDA demanded a study of 100 subjects, all of whom had to be “age 18-30, with removable dentures, living alone and far from school zones”. Hillman wasn’t sure there even were 100 young people with dentures, but the FDA wouldn’t budge from requiring this impossible trial. Hillman gave up and switched to other projects

Interesting that the FDA can request such things. Would be a good way to block disruptive products that larger companies wouldn’t like.


The FDA is often bad: https://jakeseliger.com/2023/07/22/i-am-dying-of-squamous-ce....

It is good at "protecting" people from things that might help them. Like many others, I'm being protected from treatments that might harm me, so the cancer I've got can kill me instead.


Any luck with that federal Right To Try angle?


Hello Jake, I just wanted to tell you that I admire your fighting spirit. Best of luck to you and your wife.


It's wild we aren't digging into bacteria phages and instead roll down the antibiotics road while it's ok to use them for sandwich meats. Yes they are living and adapt but so does bacteria.


Somehow I keep loosing confidence in the FDA. That basically sounds like a special interest group giving unreasonable requirements to prevent it succeeding.

What’s the chance that some of the FDA personnel were linked to companies in dental or dental care products? Perhaps some national association of dentists?


It's actually a lot better than it used to be. You wouldn't see a situation where beta blockers were available in Europe a decade ahead of the US nowadays.


[flagged]


I trust the sceince just fine, i dont trust corporate interests and how heavily and deeply coporate rot has penetrated into our institutions.

I activly expect dishonesty on the part of corporate interest, and corporate interest is increasingly if not already entierly, government interest.


Same here. I also think it’s “we the people’s” fault to a large degree as well. These institutions require citizens to elect leaders who will put them in check. We don’t do that. The system largely works so people don’t really care that much, myself included.


Considering all the literal poison and bacteria infested shit in our food I'm not even convinced it mostly works. The FDA simply isn't doing their job.


Do you have any examples of how the FDA is starting to put corporate interest ahead of public interest?


I’d say corporate and good-old-boy senior researcher clubs: https://www.nbcnews.com/news/amp/rcna63662


It's very difficult for any major institution to not have problems similar to this, as there will always be individuals in positions of power who take it upon themselves to make decisions that can be construed as corrupt. However, the fact this issue was revealed to the public, reported widely and also found to be a highly dubious shows the institute is working fine. They appear to have systems and processes in place to help stop these kinds of dubious decisions, and because of the blowback from this rather poor decision, I'm certain the people at the FDA working the next round of approvals will make sure they hold up to scrutiny, which will be stronger than ever.


Of course major institutions will always face these sorta problems.

However your comment seems to assume the FDA self-corrected. They faced a lot of external criticism and eventually partially capitulated. Even then they just restricted its listed audience.

> They appear to have systems and processes in place to help stop these kinds of dubious decisions

Except that it was external pressure that forced changes, not internal processes. The congressional report found that the FDA violated their own processes. Thankfully we still have a fairly transparent government and the incident was made public.

Though congress seems to have just given them a slap in the wrist. No officials were fired AFAICT, why wouldn't other FDA officials do the same in the future? Based on the parent article it might still be happening.


FDA Warning Letters: your pharmaceutical manufacturing plant was found to have adulteration and QA issues (again). Your medication actually has other medications or precursor/intermediate chemicals in it (again). FDA's response: a wag of the finger (again). So you "fix" the issue the next time the FDA Boy Scout comes around. All set.

Rinse and repeat.


And yet, modern science involves humans, human interests, and human failings. Science practice is as flawed as the people that do it.


Yes, but the pay is shit, the social recognition is non existent, etc. So its not going to attract as many of the dark triad types like law or upper managment would.


Hmmm that’s an important factor. It’s one reason I still “trust in scientific process”. While it’s corruptible, imperfect, etc enough scientists still believe in the ideals of science. Otherwise why do it at all?

Still at a top institution like the FDA will attract the grafters and dark triad types in the field. Some of the most conceited self-centered types I’ve ever met are top researchers / academics and I’ve met a handful of VC CEOs. Look at the disdain for the “average joe” that leaks out of the emails between Dr Fauci and Dr Collins when they wanted to squash scientific debate on Covid (1).

1: https://www.wsj.com/articles/fauci-collins-emails-great-barr...


I'd ask for proof of that assertion but...


Yes, but Not the People.


I worked for a place that recruited people to test stuff like toothpaste, mouthwash, and other personal care products way back in mid 00s. We worked with a lot of big-name companies, and one of them was trying to get approval for a very similar product. The criteria were very similar to what's described here, where the person had to be perfectly healthy and also wear dentures. I think it took us about a year to recruit like 3 people before they just gave up and dropped the whole thing.


In 2020 the FDA wanted people developing tests for Covid-19 to get some SARS to make sure their test didn't accidentally show a false positive when SARS was present. But of course there was no way the CDC was going to hand out SARS to random research labs.

I'm pretty sure this is just someone at the FDA trying to be diligent in their own way. Mostly this is downstream of powerful companies being able to sue the FDA for allowing things if the FDA doesn't follow procedure, which the FDA wants to avoid.


> They offered my wife and me free samples (based on her work, not as compensation for writing this post); she accepted, and I’m still debating.

Given that it's an oral colonist it seems likely that the author has tried the free sample as well, even if they were to live in a no-kissing houshold.

The title is a lovely garden path sentence: "A genetically modified bacterium that outcompetes bacteria causing tooth decay" -- a straightforward parse leads you to the plausible assumption that the genetically modified bacterium causes tooth decay. The insertion of a "the" before "bacteria" would remove the ambiguity.


> Given that it's an oral colonist it seems likely that the author has tried the free sample as well, even if they were to live in a no-kissing houshold.

The author addresses this under the header "2.1: As users kiss their loved ones, who kiss others in turn, will this spread exponentially and take over the world?"


funny how one "the" flips the meaning of the sentence

I thought I was being paranoid until I started reading the article

I choose to believe this is a freudian slip, which means they're trying to cause tooth decay while pretending to do the opposite.

If I were dentistry as a business, I wouldn't like this permanent (final) solution to tooth decay because of my unreasonably suspicions that the odontological treatment I received as a child was unconsciously intended to make me continue to need 'dental care' instead of fixing anything. Last time I was at a (very expensive private) dental clinic the treatment they pushed on to me was killing my tooth so I would buy one. I'm pretty sure some hugely powerful branch of dentistry is betting on people in my demographic (who get their teeth killed off) buying a full set of teeth from them in the future.

But I would only accept Thompson teeth, the only teeth capable of chewing other teeth


Rise up sheeple, and rinse out your mouth with bleach twice daily to remove any gentech germs! Big Teeth and their engineered bacteria are keeping us down!


Teeth are an abomination and your body works hard to reject them, purifying your mouth and your soul so you can die appropriately shriven of your sin. Big Dentistry is trying to keep you from heaven!


Reject luxury bones.


back to invertebrates, turning into worms


Anecdote time: My great grandmother lived to be 102 and never had a cavity. Kept all her teeth to the end.

One time, an orderly who thought she was just being senile tried to reach into her mouth to take out her teeth (thinking she had dentures). My great grandmother bit that person; hope they learned not all old people are senile!

I’m 40% of the way there. No cavities and rave reviews from my dentist. I brush—-best case —-once a day.

I’d not be surprised if it’s a genetic lottery of tooth enamel, tooth size (small) and mouth biome.


I'm very similar. I have excellent oral health... brush 2x/day, don't floss. Two interesting datapoints:

1. I changed jobs a few times, and for various reasons I neglected to see a dentist for 10 years. When I finally went back, had perfect oral health and no cavities. My hygienist still remembers me because this event was so far outside her experience + expectations.

2. My wife had "normal" tooth decay problems throughout her life, until we started dating, at which point she's had no further cavities. ;)

To answer the normal questions: I don't do anything particularly special with my diet except a general avoidance of sweetened drinks - no soda pop, no sweeteners in my coffee.

If anyone wants to swab my mouth and pay me a small licensing royalty for commercialization please get in touch. Heh.


You should start a company providing kissing therapies


One suggestion/theory I'd like to posit about this. There may be a third factor, and that is our "awareness" of what's in our mouth. After I eat food, I can't stand for any food that is lingering or stuck anywhere on my teeth. It gets picked out with my tongue, water, or something else. It could be that a lot of people that have bad oral "health" are unaware of the amount of food they're letting float around in their mouth because they never became aware or able to "sense" the insides of their mouth.


It would be cool if you would submit your DNA to a public database. It could be useful at some future time.


How's your breath? Frequently you either have a mouth microbiome that ends up acidic and prone to cavities, or you end up with a high pH mouth which lends itself to tartar buildup and halitosis.

Of course if your teeth are decaying due to cavities and this is left untreated, halitosis is also a common result.


Not OP but this is how it is for me.

Also, anecdotally, from people I've spoken to, it seems they get either caries or tartar. It's a decent sample size, more than a dozen.

Yet the last time I went to a dentist, 2010 or so, she claimed to have never heard of this, and I couldn't find any good studies either. Do you know of any?


I don’t get negative reviews to my knowledge :)

Maybe it’s the balance of regular coffee intake for lowering pH but a naturally higher pH?


What is your diet ? I am assuminf there is no processed sugar or refined wheat/gluten ?


Not OP, but in a similar situation. I'm 39, the last time a dentist looked in my mouth I was probably 16 or so* and I brush only once a day (after breakfast, which is the least effective over doing it before going to sleep). Never had a cavity. I don't think I have halitosis, at least the people I have kissed over the years never complained to me.

Being Italian, I eat pasta literally every day, and my daily breakfast is chocolate chip cookies.

My impression is that mouth health is 100% genetics and biome lottery.

* I have extreme mistrust in their profession, due to bad experiences. When I was a kid, I injured a milk tooth which turned black. The dentist shrugged and said that it would fall normally. It didn't and it fucked up all permanent teeth that sprouted in random directions in the area. Every single dentist surveyed to fix the problem requested gigantic payments (to the tune of tens thousands of dollars, this was in the 90s in Italy, so adjust for inflation and cost of living to know how crazy this was) without providing any result guarantees, so I kept my crooked teeth. It doesn't help dentistry in Italy is that profession where you mainly do tax evasion, and occasionally look into people mouths to pass the time.


41 here, and also not seen by a dentist since I was around 16. No cavities for now, that I know of. If I have any, they don't hurt, at least for now. Fingers crossed.

My diet is rather unremarkable, I don't consume a lot of sugar or sweets but don't refrain from them either. I brush 3 times a day. I do have occasional halitosis but it seems to be related to acid reflux, my breath seems to be fine when I have no reflux.


37 and same here. I brush twice a day with an electric toothbrush. I also brush my tongue well and rinse and gargle vigorously with water afterwards. I find I need to an electric toothbrush or I can't brush my wisdom teeth properly.

Last time I went to the dentist they removed 4 teeth because my mouth was crowded. Then I had braces. They came out when I was 16 or so and haven't been since.

I also spit several times a day. I don't know if this is relevant, but it seems to me it might be. At some point in my life I developed a habit, whenever I go to the toilet, I spit. My mouth actually salivates to get ready for it. I feel like it might do something to keep my mouth fresh.

I don't eat fruit. Very little sugar. I only eat within an 8 hour window each day. Lots of cheese. Every meal is balanced (plenty of fat to accompany any carbs, protein is incidental, I don't think about it).


Anecdata: all members of my nuclear family have crowded, crooked teeth. We all have a penchant for sweets across the day. My mom is 93 and has no cavities, but her A1c started reading for 6 in the last few years. I'm 61 and have one filling. FWIW, offer the years, lots of dentists have found other cavities in my mouth, but no two dentists have ever found the same cavities... Between the four of us in my family, there aren't even 5 fillings in our ugly teeth.


Diet doesn't do much if you have bad genetics, I eat and brush the same as my gf, we don't smoke/drink, exercise the same, we basically have the same exact lifestyle. She has teeth issues multiple times a year, I never had a single problem


Are you sure? My girlfriend says one thing but I observe the daily unaccounted for consumption of fruit and sweets. Fair enough if you also consume lots of sweets, though.


100% sure, first because I trust her and second because there is no way I wouldn't notice given our current work/life situation


Sorry to say but you're naive to think you can trust someone when it comes to diet. There's a reason human diet studies are considered very difficult if not impossible (given ethical requirements, although of course it can be done unethically like making people afraid of saturated fats for no good reason). Fair enough on the second point, though, I believe you.


idk what kind of relationships you have but I can assure you this isn't a problem here


Nothing that severe. I have beer, toast, sandwiches and burgers. I don't do a ton of sweets / soda but I do some (and if I do my teeth definitely get a fuzz that motivates brushing!).

My great grandma loved jello “salad”s (eg jello with fruit in it). It’s just genetics.


I just rinse my mouth every night with sugar, in addition to brushing. Have not had problems since. Effect of three-year consumption of erythritol, xylitol and sorbitol candies on various plaque and salivary caries-related variables https://pubmed.ncbi.nlm.nih.gov/24095985/

Xylitol and erythritol inhibit real-time biofilm formation of Streptococcus mutans https://pubmed.ncbi.nlm.nih.gov/32600259/

And, what I always expected, it is better to rinse with two sugars:

Exploration of singular and synergistic effect of xylitol and erythritol on causative agents of dental caries https://pubmed.ncbi.nlm.nih.gov/32286378/

two tablespoons and 50 ml of handwarm water (the stuff does not really dissolve good), a few drops of this: https://www.apodiscounter.de/myrrhentinktur-hetterich-30ml-p...

This tincture might not be available in the US due to alcohol content. I saw only oil based versions in the US.


Sugar alcohols*. You certainly should not rinse your mouse with sucrose as your first sentence implies would be fine.


I rinse my mouth regularly with coffee and chocolate containing sugar. I always thought it was a bad thing. Bring on the donuts!


I eliminated regular sugar to a bare minimum in my diet.

https://en.wikipedia.org/wiki/Pure,_White_and_Deadly


Pure carbs (so anything with white flour) is pretty close to pure sugar. I increased my fiber intake by trying to make sure that anything with carbs has a higher % daily value of fiber than carbohydrates.

I've been feeling a lot better, and have been slowly losing weight ever since.

Calorie counting worked OK for me in the past, but then I gained the weight back.

Anyway, from what I can tell, when health studies show that "processed foods" are unhealthy, they invariably just mean foods that have had the fiber replaced with sugar and salt.

Of course, studies show that not doing what I just said to do causes heart disease, diabetes, obesity, gastrointestinal ailments, and many other health problems.

I wish some whole foods competitor would pop up that only sold low-salt, high-fiber foods with no added sugar. Most grocery stores stock such things, but it's less than 5% of the selection, so finding it is always like looking for a needle in a haystack. The hypothetical store could even have a sign out front saying "shopping here will significantly increase your life expectancy".


> low-salt, high-fiber foods with no added sugar

Only half tongue-in-cheek, but if you stick to the produce and dried goods sections, this is pretty much every grocery store!

In all seriousness, yes it's a problem. But unfortunately it's an unholy trinity of consumers (give me flavor!), grocers (give me shelf life!) and producers (give me lower costs!) that is practically impossible to dislodge beyond generational shifts in preferences (which are, indeed, happening ime).

Short of that, the best thing we can do is to do as much "processing" ourselves as possible, and gradually expand one brand/product at a time as you gain trust and do your research.


You last link returned no results.

But I think this is the same in a 50ml bottle. https://www-apodiscounter-de.translate.goog/myrrhentinktur-h...


Two tablespoons of which? One of each? Two of each?

What's the purpose of the myrrh? It seems to appear a bit out of nowhere in the recipe


Ah, I've been doing the same but only with xylitol. Maybe I should by both, erythritol and xylitol, and make cavity killing cocktail.


Is there a way to determine if FDA actually set this requirement for the study? Is it on public record? Or do we just have to rely on what they claim.

Also why not try getting it approved elsewhere first like in the EU if FDA is making it harder to approve?


I can only add that I wrote Dr. Hillman over a decade ago and he wasn't specific about it, only that the FDA's requirements were not reasonable.


Related:

Story out of Japan that has been getting attention in the last year around here

Japan pharma startup to begin human trials of tooth regrowth drug in 2024

https://news.ycombinator.com/item?id=37638956


This specific product aside, it seems to me there could be huge future potential in therapies involving genetically engineered bacteria. We can modify bacteria far more easily than we can our own genomes. And we're just beginning to develop an understanding of the gut microbiome. As that understanding improves, surely there will be opportunities to make beneficial changes.


Cheesemakers take advantage of something similar. Good mold on cheese makes it harder for bad mold to gain a foothold.


yes indeed, it’s actually safer to use the wooden barrels than the new stainless ones for this exact reason.

https://journals.asm.org/doi/10.1128/microbiolspec.cm-0008-2...


Blessed are the cheese makers for they shall see the good mold


Here is the recipe (linked from the article), it appears they opensourced it?

https://drive.google.com/file/d/1744h_8sozZJ2wMR9X-j1GbsXXON...


So, in order to bypass the FDA, you plan to produce a bacterium, export it, go somewhere outside the US, pass it to people and then everybody returns to the US?

what happens if someone, ahem, takes a dim view of the process and denies entry on biosecurity grounds?


People aren't tested for any contagious illnesses when entering the country.


Not since SARS anyway when they did take temps on entry.


I forgot about that.


Unless there is a reason to.


> U.S. citizens cannot be denied entry to the U.S. for any reason

https://www.aclunc.org/our-work/know-your-rights/know-your-r...


I use a similar product, LEF Florassist Oral

https://www.lifeextension.com/vitamins-supplements/item02120...

That has BLIS M18™ and Immuno-LP20®

BLIS M18: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9012604/

I have not noticed any difference.


Does this help with morning breath?


No :(


The question missing there is: do small amounts of lactic acid fulfill a function, and if so, what happens when there's no more of it in our mouths? Will this have consequences on our digestive system? It sounds to me like they're focusing on one thing only and not thinking systemically enough.


Swap spit/kiss someone who gets this. Cheaper than dental insurance. Time to bring back the kissing booth.


See section 5.2, "Can’t people transfer the bacterium among themselves without paying Lantern?"


If this is true and approved it will probably be sold over the counter. Similar to how you buy yoghurt or probiotic pills today.


I'd want to know a lot more about that antibiotic these bacteria produce. If there is no natural immunity it will be developed very shortly if doses produced are low (and how can they possibly control for the dose). Then on the other hand if doses are really high, what about consuming an antibiotic for the rest of your life? What will it do to your gut flora?

It seems very implausible to me.

If I was working for FDA and someone was trying to bring such an obviously flawed product to the market I too would've asked them for very robust testing.


This is already answered in TFA:

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


Bonus points for launching it in the anarcho capitalist wonderland /s "Prospera", a Charter City.

https://www.vice.com/en/article/k7a7ae/foreign-investors-are...

> A controversial law allows these experimental cities, known as “charter” or “model” cities, to use a legal right to land known as “eminent domain”, which permits a government, or in this case charter cities, to take over private property. The community is worried that it could be forced from its ancestral lands.

Of course, the model of Charter Cities is one the Tories wish to take to the UK - areas where laws and regulations would no longer apply, except the ones companies want.


The idea that they've engineered a bacterium that will successfully outcompete naturally selection indefinitely seems overly optimistic. They blocked the most obvious failure mode with the horizontal gene transfer pathway, sure, but considering how quickly antibiotics become ineffective I'm just not sold that their modified bacteria will be as untouchable as they seem to think. Certainly not 20 grand effective.


I've just started using ProBiora3 to try to reduce my gingivitis levels. I would love a one-application solution and will be watching this closely.


Have you tried just using interdental brushes, like these[1]? Using these once a day did wonders for my gingivitis levels.

[1] https://www.amazon.com/Sunstar-6505A-Soft-Picks-Advanced-Pac...


> did wonders for my gingivitis levels

how do you know your gingivitis levels?


Less gum inflammation / bleeding / odor.


I used this one for a little while and I regret it. I'm pretty sure it messed up my mouth microbiome -- been having worse breath, more deposits on teeth/tooth pain, and a lot of gum bleeding. All once I stopped taking it.


My understanding is that bacteria that cause gingivitis thrive in a different pH level than the ones that cause cavities. I have no cavities but I am in a constant battle with gum disease. I don't think this specific strain will help us, but it can obviously lead the way.

Has ProBiora3 helped?


I use lactibiane buccodental pills, it's the only one I could find in my local pharmacies. I also regularly use curaprox moutwash with chlorhexidine.


What are you gingivitis levels?


I have to say that releasing genetically modified organisms that can permanently colonize our bodies and potentially spread from person to person sounds like something that should be incredibly restricted.


This quote seems like it can't possibly be true—is it? One would imagine that even if you avoided kissing anyone your entire life, you'd still get cavities.

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


It would be nice to see some positive examples of where species (GM or otherwise) have been artificially introduced to an ecosystem and not ended up doing more harm than good.

Otherwise, this kind of thing makes me sceptical, as there are always unintended consequences.

I would only use this treatment if (amongst other things) the strain was engineered to be very sensitive to a very specific narrow-spectrum antibiotic, that is NOT produced by the same company offering the bacterial strain.


Faecal matter transplants.


Thanks for the example. I'm not sure that this is the same, as I don't think the gut microbiome introduced via a fecal transplant is likely to spread throughout a population without further intervention, though (i.e. more transplants).


It's insane to voluntarily colonize your body with a virtually untested genetically engineered bacteria. The article claims it occurs naturally but they have no good data on its natural prevalence and they added two additional mutations to the natural strain they found.

Even if it's safe, is it effective? The only way to tell is to enroll the people who are colonized in a long-running study. Are they doing that?


As the article points out: genetically engineered probiotics are already a thing. Everyone's risk tolerance is different, but this doesn't seem that big a deal to me personally. If it was already available for a more reasonable price, I'd probably get it tomorrow.


Really? Aren't you curious if it actually works?

Feels like there's an attitude here along the lines of "we know exactly where cavities come from, so we don't need empirical evidence that our treatment works". Seems dubious to me!


Introducing poorly understood and tested invasive species rarely goes well i.e. the cane toad https://en.wikipedia.org/wiki/Cane_toads_in_Australia

I'm not about to give it a go in my mouth.


This was my "Mr. Hilltop"* style instantaneous reaction

https://eandt.theiet.org/2018/05/24/top-10-invasive-species-...

My favorite move, in God's** (actual) 4D chess game (playing off our ... tendencies, say), is when we try to introduce a species to get some benefit / value from it ...

https://fyi.extension.wisc.edu/spongymothinwisconsin/history...

... then, think - "gee, that worked so well, let's introduce a different species to try and undo the damage!" ...

https://www.science.org/content/article/biological-control-b...

There are plenty of further examples where attempts to remove invasive species have backfired in other ways as well...

But, ya gotta admire that indefatigable optimism!

To be fair and try for a degree of accuracy, we have obviously benefited, in the short term, greatly from technology, engineering, science, etc. ... But, there are certain areas where we do have an abysmal track record. Just about anything abstractly related to the so-called "gray goo" scenario being a prime example. Just like that recursive function you're SURE is limited no matter preconditions ... that takes down one of the main university computer systems the first time it's run... (back in the ol' days when there were fewer 'protectives' [codpieces being out of style even at that time ;)])

* https://youtu.be/DJ976Eb31qw

** For a suitable value of "God" (i.e., insert whatever term you use for everything ... the universe, the matrix, whatever... the relative personification of that particular word works better here, I think)


Signed up for the longer term offering, I'm super intrigued by it.


With good hygiene and dental checkups twice a year, you can reasonably expect to avoid cavities altogether.


That's not true for everybody: people have very different mouth chemistry/ecosystem that depends on diet, genetics and god knows what. Some people can live with brushing teeth once in a blue moon, others will get their teeth eaten by cavities no matter what they do. Your advice is probably OK for the median person, but really does not apply to everyone.


I used to believe this. Then I got a Girlfriend who I know brushes twice a day. Yet got cavities relatively often. I don't know why this is but there is a very large factor(or factors) that just makes some people much more vulnerable to cavities.


> With good hygiene and dental checkups twice a year, you can reasonably expect to avoid cavities altogether.

Your comment is self-contradicting. The only thing that dental checkups do is allow cavities to be flagged before they progress very far.

Also, I feel that in this context "good hygiene" is a weasel word, in the sense that implies that any occurrence of a cavity can only be explained by the absence of good hygiene. There are many factors to cavities that aren't addressed by hygiene, such as vulnerable teeth and cavity types such as root cavities, whose primary risk factor is decreased salivary flow.



Just chiming in to mention that xylitol seems to have a beneficial effect, similar to what this sounds like, though very different mechanism.


We always hear good news in medical field but never actually see them in real life bunch of clowns who only want attention


Eat meat. Cut carbs. That's how you outcompete tooth decay.


I'm going off on a tangent here, but whenever I read about progress in dentistry I always get the feeling they are just sugarcoating medieval practices. In an era where mankind routinely flies people into space, the primary tools leveraged by orthodontists is still drilling and pulling teeth, and teeth replacement is still implemented as lodging metal spikes onto the jawbone. It sounds like the only progress that we had since the 17th century is clever ways to numb pain and how finer materials ended up replacing wood for dental prosthetics.


"In an era where mankind routinely flies people into space ... replacement is still implemented as lodging metal spikes"

Osseo-integration of titanium was first observed in the 1940s, so the technology for modern dental implants is approximately of the same age as space rockets. (Wernher von Braun designed the first A4/V2 at almost precisely the same time.)


Capitalism does not allow this.


This seems like a scam...

The author claims that the FDA set impossible standards for getting this approved when it was originally discovered and that those same standards prevent them from seeking FDA approval now....but further down acknowledges that probiotics like this product are actually subject to much more lenient standards.


I think you misunderstood the author.

The treatment was proposed to the FDA decades ago as a drug. The drug approval process yielded the impossible ask. Those same standards prevent them from seeking FDA approval now as a drug.

That this could be approved as a probiotic is a recent idea. The impossible standards are not the probiotic lenient standards.


For a product supposedly being pushed by a bunch of rationalists, nothing about this drug or the underlying story is actually rational if you know anything about how the FDA approval process works.

The approval process supposedly required an impossible ask. Oddly enough, I could find no record of this impossible ask anywhere except in this company's website or on other "rationalist" websites, all of whom cite this company as the sole source.

And in fact...this impossible ask doesn't actually take into account how the FDA approval process works...or has ever worked...

It's the kind of story someone make ups when they're trying to explain why their miracle invention failed.

(And note that oral probiotics have been approved by the FDA for human use for several decades, including back when this supposed miracle bacteria was discovered. And Japan and Europe have much more lenient standards, now and then, for oral treatments and yet no attempt was made to launch the product there. And China and much of South East Asia don't even bother regulating this type of product, so why wasn't this launched in Asia? Why is the only market they're launching this product in a jurisdiction in which "biohacking" products are completely exempted from regulationo)

Nothing about this product adds up, and it bares multiple hallmarks of being a scam. (See the currently top-ranked comment on this post.)


Here's a discussion of this in the New York Times - https://www.nytimes.com/2004/11/30/health/bacteria-enlisted-...

"Dr. Hillman has been working on this therapy for 25 years and first applied to the F.D.A. for permission to begin a clinical trial in 1998. The agency, the company said, has demanded change upon change to make sure the modified bacteria would not run amok, cause undesirable changes in the mouth, or revert to a cavity-producing form. To win approval, Oragenics has agreed that the 15 volunteers in the first trial will not even have teeth -- they will have dentures."

This differs from the version I heard from Aaron in that Aaron said 100 people and NYT says 15 people, but NYT says the FDA demanded "change after change", so the 100 might be either an earlier or a later version of this.

Hopefully this changes your opinion of whether or not this is a scam, and of how much you understand about the FDA approval process.


Given that this version from the NYT is very different from the one in the post, and far more reasonable in its requirements, it makes it even more apparent that the linked product is a scam.

Exaggerating details the way the linked post does is one of the major red flags of almost every scam. Especially dangerous is the way it attempts to make the regulator the enemy based on a fraudulent retelling of actual events.


I really hate to appeal to authority but Scott Alexander is the single last person on earth, and I am not exaggerating, who I would accuse of analyzing a topic in bad faith.


Scott absolutely analyses topics in bad faith, particularly when it comes to politics or movements/people he personally supports. Here's one where he essentially says 'no study is ever fully representative, therefore my friends twitter polls are exactly as good evidence as a scientific study':

https://www.astralcodexten.com/p/selection-bias-is-a-fact-of...


Your comment is an example of analyzing in bad faith.

In the linked article there is a whole section that starts with "Selection bias is disastrous if". He definitely does not says anything remotely close to "twitter polls are exactly as good evidence as a scientific study".


It's essentially the thesis of the post. I will say the "exactly" part was a bit hyperbolic.

He starts by stating that people say his surveys and Aella's Twitter polls (which he calls surveys) have selection bias, meaning the conclusions don't count.

He then goes on to say (paraphrasing): "people say surveys have selection bias, but don't think real scientific studies have selection bias" and in the next paragraph says "but scientific studies do have selection bias and that's ok." Note that in this section, he is implictly relating scientific studies with his and aellas surveys.

In the section that starts with "selection bias is disasterous if", he gives a narrow view of why and when it's bad: "only if you're doing a poll or census that should include everyone". He neglects to say the ways in which it's bad for literally all science (it's a massive problem in drug RCTs, but he literally uses RCTs as a point for why selection bias isn't so bad later on).

In the next few paragraphs he says that selection bias is fine for correlations, and gives some examples of when scientific studies have selection bias that we accept (I'm not going into details here because the post is long, and I'm on my phone).

So he's said why selection bias is present in science, and that it's only really bad for census's and polls. He then concludes, "hey guys stop saying surveys are bad because selection bias, science is also biased".

In this post he starts by bringing up a critism of Aella's 'research', which she uses data from Twitter polls for. He then implicitly equates surveys and scientific studies, and says "look, science is biased too, so selection bias isn't bad". He then concludes, "so stop saying surveys are a bad because of selection bias".

He might not literally say "twitter polls are exactly as good evidence as a scientific study", but the point of the post was to detract from the valid criticisms against his and Aella's posts that use survey/twitter poll data by saying "science does it too".


His thesis is “you should not discount twitter polls with large sample sizes out of hand as totally meaningless, or if you’re going to, you need a better reason than this long list of issues that twitter polls share with RCTs.”

The contrapositive of his thesis is “there is some interesting signal worth paying attention to in large twitter polls, selection bias is in many unexpected places so be skeptical about sweeping conclusions even in RCTs”.

Your characterization of this as “so twitter polls are just as good as RCTs” seems wildly uncharitable to me.


I'll definitely admit to some bias here, I've been reading Scott's content for 7ish years and I've gone from loving his content to being increasingly skeptical about his writings.

Something I feel Scott (and rationalists in general) tend to do is obfuscate their points in large walls of text, that allude to their actual reasons for writing without directly stating it. Aside from the beginning and end of the post, he never mentions the context or specifics, and just talks about broad counterarguments against selection bias in general. He doesn't bring up relevant specifics like "Aella does polls about sex to an audience she cultivated by doing porn", which seems like an obvious source of bias to me. Instead he gets the best of both worlds, if someone criticizes internet surveys he can point them to the post, without including any specifics that can be easily argued against. It requires a similarly sized wall of text to respond, which most people won't bother with. I personally used to argue that's just how he writes and it's not intentional, but stuff like the email leaks made me change my mind on that [1].

I do wish I'd picked a better example though, what I'm really trying to say is that Scott is definitely capable of analyzing a topic in bad faith. He has his biases like the rest of us, and they get infused into his writing.

[1] https://imgur.com/a/gWeIK6c




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