A genetically modified bacterium that outcompetes bacteria causing tooth decay
astralcodexten.com
astralcodexten.com
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.
> 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.
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
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.
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.That alone isn’t enough for long term colonization as it’s not the only bacteria resistant to mutacin-1140.
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.
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.
Wonder if it could in a different direction, giving rise to other oral bacteria also unaffected by mutacin-1140?
However it is likely that, since this one strain managed to evolve this trait, that others have as well.
It'll be interesting to see if it works.
What does this mean exactly?
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?)
I’m curious to see whether my dental hygienist notices any improvement next visit.
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=()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.
I'm with this science guy!
Interesting that the FDA can request such things. Would be a good way to block disruptive products that larger companies wouldn’t like.
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 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.
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.
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.
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
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?"
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.
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.
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.
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).
My great grandma loved jello “salad”s (eg jello with fruit in it). It’s just genetics.
Of course if your teeth are decaying due to cavities and this is left untreated, halitosis is also a common result.
Maybe it’s the balance of regular coffee intake for lowering pH but a naturally higher pH?
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?
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.
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.
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".
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.
But I think this is the same in a 50ml bottle. https://www-apodiscounter-de.translate.goog/myrrhentinktur-h...
What's the purpose of the myrrh? It seems to appear a bit out of nowhere in the recipe
Also why not try getting it approved elsewhere first like in the EU if FDA is making it harder to approve?
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://journals.asm.org/doi/10.1128/microbiolspec.cm-0008-2...
https://drive.google.com/file/d/1744h_8sozZJ2wMR9X-j1GbsXXON...
what happens if someone, ahem, takes a dim view of the process and denies entry on biosecurity grounds?
https://www.aclunc.org/our-work/know-your-rights/know-your-r...
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.
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.
> 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?
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.
Has ProBiora3 helped?
[1] https://www.amazon.com/Sunstar-6505A-Soft-Picks-Advanced-Pac...
how do you know your gingivitis levels?
> 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.
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.
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?
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!
I'm not about to give it a go in my mouth.
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)
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.
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.)
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.
https://www.astralcodexten.com/p/selection-bias-is-a-fact-of...
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".
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".
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.
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.
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.
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.)
"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.
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.