Of course, there is another option: raise funds to perform a private double-blind study. The FDA is a “nice to have” not a necessity for doing the science.
As a small child in the 1960s, I had a lot of cavities -- I recall the dentist finding seven in one session. But I haven't had any in at least 50 years, which I attribute to flouride in toothpaste and water, as well as more recent improvements in toothbrush technology. Why would I want this Lumina Probiotic?
Gallant is being an idiot, though, and will fall for speculative junk. There are an infinite number of interventions that do not help but have bad data that is compatible with there being a small positive effect. A susbtantial proportion of these will also do net harm, but this has not been proven either and will thus not be put forward by the proponents of this months flavour of lifestyle garbage. Such is the nature of confidence intervals, and to soften your standards for recommending medical intervention based on this faulty reasoning is a form of soft thinking. Pandemic reasoning made this error time and again and I guess it is only logical that it now infects other areas of science. Only question is how long it will take for the next EBM revolution to rid us of this nonsense.
I don’t plan to get this soon. My reasoning is, my current microflora is probably fine given that i have had zero cavities in my life, despite brushing on average 0,6–0,8 times daily. I doubt it’s genetic given my sibling has had several cavities.
So either this helps a little bit for me (I would still need to brush AIUI, but i might half my already very low cavity risk) or it makes things worse by making my microflora worse. Of course, if it’s shown to be widely safe, or it reduces bad breath, then I’d be more likely to get it’
What prevents bacteriophage from exploiting the new ecological conditions of the Lumina oral microbiome? I haven't seen anything about modifications to the bacteria that address this, nor have I seen any mention of this potential problem in any of the marketing done for this product. Can someone please enlighten me?
A lot of the opinion on LK=99 was, try to replicate the experiment nd then we'll know. Then the replication attempts failed, and for most people that was that. Still, it was very cool to watch science being done by e.g. Andrew McAlip.
I guess this is similar .. $250 to be a guinea pig in a cool science experiment that might or might not work out,
I will totally admit to spending more than $250 of my own money on doing a cool experiment.
And i'll also admit to spending way, way more than that of DARPA's money on doing a cool experiment. (My magagement tells me my research group's published papers cost more than a million dollars each, so there's that.._)
Relevant tweet showing a table where the control group has about as much caries as the BCS3-L1-infected group. People should be free to try this, but Cremieux's post reminded me of podcasts hosts shilling supplements, which was fun and unusual to see in this sphere.
I wouldtrust the company more, if they publicly released the data of their ongoing testing. My trust already increased a little because they admit to failed colonisation in two cases.
I think it is worth it. First of all, just as a non-FDA intervention it has a huge potential market. That's kind of how PRP
gained traction-- and even now, while it is not usually paid by insurance, it is incredibly common.
Once it's on the market with use in large enough numbers, there will be sufficientl data to establish its efficacy and then possibly go for FDA approval.
I've pre-ordered, though I'm not sure how effective it will be for me.
I've had a lot, *a lot*, of cavities. I don't think I have single tooth that hasn't had something done to it. (My wife, who has had zero cavities, joke that it's a good thing we go to the dentist as a pair, so we average out to a normal patient.) With less real-tooth surface area, will that impact the ability of this new bacteria to strive and thrive and drive out the old bacteria?
I don't know. But I've got $250 to spare and I'm willing to give it a shot. I've spent $250 on a lot worse.
> I think two more likely explanations are: This is Trial 3, the one we know nothing about
That would make sense, because trial #3 is where he gave up, and also, the sample sizes usually go up the later the trial - it would be odd if trial #3 were planned to have fewer than 26 or 10 people, after all, and 100 is a nice round number.
Goofus and Gallant - Wow, what a time machine! My parents got me a subscription to Highlights For Children when I was six. JFK would remain President for another few weeks.
IIRC, there was another feature called The Timbertoes, about people made of wood.
A reader's letter asked if the editor was a man or a woman, and the response was "yes", which young me found quite funny.
I saw a copy a few years ago, I think at the library, and it looked virtually unchanged from my childhood.
My feeling is that disastrous results - comparable to thalidomide - are well-nigh impossible. It's just a bacterium that colonises a rare niche in the mouth. It doesn't spread aggressively, so presumably won't infect other people by kissing etc. (it being hard to establish is not all a bad thing.) So really people should have at it, and if enough try then even anecdotal data will be good enough that a proper trial will be easy to arrange, and others will do studies anyway.
Personally I have no interest as whether it is due to mouth microflora, saliva, or sugar avoidance, I don't really get cavities any more. [EDIT: or fluoride, as mentioned by Steve Sailer. I too got lots of cavities when I was young. Now I have fillings that are over four decades old. My dentist at the time noted that I had a interesting amount of 'arrested decay', so something changed. But wouldn't dentists / public health scientists have noticed if fluoridation had a sudden massive effect on new cavity formation?]
I legitimately do not understand why so many people treat the LK-99 hype with such scorn. It's a good thing to be able to be excited and hopeful about potential breakthroughs. It's not a big deal if it doesn't pan out.
But for some very large subset of people, it is just infuriating and shameful to take these announcements with anything other than heaping skepticism, and I cannot wrap my mind around it.
Uh, what does a "constant trickle of alcohol" do to developing baby brains? Since you mentioned in a previous post, your kids might get this bacteria from your wife...
I think Yishan Wong's implication that "because Pfizer offered to buy the IP it must be safe" is very sloppy reasoning. Big pharma is VERY familiar with reasoning under uncertainty and VERY comfortable paying for drugs that they know further trials might show are unsafe or ineffective.
I agree that the Pfizer offer is indeed some evidence that some experts thought there was promise. But all that shows is that they thought it had a decent expected value. Given the gigantic potential market here that expected value could easily be justified with a very small probability of actually making it to market.
On balance for me the cancer risk is the marginal factor. I had thought of this before Lao Mein's post, but without the genetic factor. My (lay person's) reasoning goes: alcoholics get oral/throat cancer at higher rates because they put large amounts of ethanol into their mouths and throats on a regular basis. Do we know if there is a similar increase in risk of these cancers if you have a low amount of ethanol in your mouth 100% of the time?
If I could get good evidence that this risk is negligible I would be good with trying this - but I'm not there now.
Probably too expensive to do irl, but I’m 39 and have never had a cavity and I’m wondering if I already have some natural version of this and if there’s a way to test for it.
Best correlational test I can think of:
Test a bunch of people like myself who have hit middle age without having a cavity. Are we much more likely to have this?
Test a bunch of people with a lot of cavities in the same age bracket. Are they less likely/completely missing this bacteria?
Best causal test I can think of (but is too expensive):
Give each of the above groups the intervention, keep a control group, and track how they progress over the next x period of time.
That seems totally good as an experiment and I don’t know why the FDA would want young people with dentures. Is it because of possible hazard of this causing some extreme negative effect? Just the fact that this is bacteria makes me think you could probably eat this and get rid of it if you really needed to. I mean, I eat day old food that’s been left on the counter all the time. Or cheese. Or milk. Or what have you.
In the comments of the previous post on this subject, I mentioned that it probably won't work. I want to expand on a few reasons why.
Suppose a patient applies Lumina as directed, and it works exactly as well as anyone could hope. Within eighteen months, the Lumina strain has successfully outcompeted all other strains of S. Mutans, and for that matter all other bacteria within its ecological niche.
It still won't work forever. And probably not for very long. And the reason why is pretty obvious once you ask yourself why the grad student in whom the Lumina predecessor was found had other bacteria in his mouth as well.
There is a metabolic cost to producing M-1140. Once all the bacteria in the mouth have the make M-1140 gene and the immune to M-1140 gene, the evolutionary advantage goes to those bacteria that (through inevitable natural mutation) are immune, but don't produce the antibiotic.
Over time, ceteris paribus, Lumina's descendants will evolve away from the M-1140 producing gene. And if non-immune bacteria don't colonize the mouth before the producing gene goes extinct, the immunity gene will go extinct too (since there's no benefit to being immune to an antibiotic you're not exposed to).
The most likely outcome is a semi-stable yoyoing between immune + producing bacteria, and neither immune nor producing bacteria.
And this all assumes that there is no net evolutionary disadvantage to the other two genes that are essential in Lumina, which is doubtful.
For example, if a bacteria colonizes the mouth which produces a different antibiotic, to which Lumina is not immune, then lumina can only obtain immunity through natural mutation, not horizontal-gene-transfer, and will very swiftly be outcompeted by bacteria that can obtain beneficial mutations horizontally.
With all that said, I think your probabilities are pretty close to my own, although there is one outcome that I would add.
Lumina has a statistically significant benefit, but due to the evolutionary pressures outlined above, it must be reapplied on a regular basis: ~35%
There were two attempted trials, not 3. Numbers 2 and 3 in your list are the same trial, and it didn’t succeed. It looks like it didn’t even get started.) Oragenics has described the process in detail in each year’s Form 10-KSB/Form 10-K, which they have been filing since 2003. All those forms are available on their website. I think it was in the 2012 form that they said they had given up.
None of the forms mention anywhere near 100 people required in a trial, or people under 30.
[Update: the second trial did require people under 30 (ten of them, with teeth), and it looks like it did get started (but didn't succeed).]
I preordered it, partly because I think they'll get shut down at some point and I wanted to maximize my chances of getting this cool thing. But I'll probably keep it in my freezer for a few months to a year to see more analysis before committing.
And I don't really get cavities, my main dental concern is gingivitis and bad breath. It seems there's a good chance this will not help with those, so there's that.
It's not a good deal if you actually need ior want the benefit of the product. The opportunity cost of ending up on placebo for months might mean forestalling other steps you could take to mitigate against decay. And if it were structured as it should be for a true DB trial, you would never know which group you were in, and so potentially take no other positive action while using a placebo.
Is every other western drug approval process as horrible as the FDA, or would it make sense to seek regulartory approval in a less broken (if less lucrative) market?
Shot in the dark here, but does anybody know anything about how this product might interact with liver function? This sounds great, but I don’t want to mess with my liver enzymes.
This is helpful, thanks. I was one of the first fifty people in the West Coast to get the SMiLE surgery (in the LASIK family but newer; no flap, and fixes astigmatism) in 2017. Seven years later, I still haven't grown any horns, and I see 20/20. No more excuses not to train. Now, I am looking into Lumina.
So does it actually exist? Your post and the comments make it seem like it's available in the wild, but the linked website says pre-orders won't ship until June 2024. I'm happy to spend $250 to apply a potentially dangerous bacterial treatment to my mouth, but I'm not prepaying to a biotech startup long before a ship date.
Among the Swartzentruber Amish, it is common to get dentures by age 21 because most in the community do not practice oral hygiene. Of course, the Swartzentruber Amish community is uncommonly insular, so getting them to participate in this study might be a challenge.
Of course, there is another option: raise funds to perform a private double-blind study. The FDA is a “nice to have” not a necessity for doing the science.
As a small child in the 1960s, I had a lot of cavities -- I recall the dentist finding seven in one session. But I haven't had any in at least 50 years, which I attribute to flouride in toothpaste and water, as well as more recent improvements in toothbrush technology. Why would I want this Lumina Probiotic?
Gallant is being an idiot, though, and will fall for speculative junk. There are an infinite number of interventions that do not help but have bad data that is compatible with there being a small positive effect. A susbtantial proportion of these will also do net harm, but this has not been proven either and will thus not be put forward by the proponents of this months flavour of lifestyle garbage. Such is the nature of confidence intervals, and to soften your standards for recommending medical intervention based on this faulty reasoning is a form of soft thinking. Pandemic reasoning made this error time and again and I guess it is only logical that it now infects other areas of science. Only question is how long it will take for the next EBM revolution to rid us of this nonsense.
I don’t plan to get this soon. My reasoning is, my current microflora is probably fine given that i have had zero cavities in my life, despite brushing on average 0,6–0,8 times daily. I doubt it’s genetic given my sibling has had several cavities.
So either this helps a little bit for me (I would still need to brush AIUI, but i might half my already very low cavity risk) or it makes things worse by making my microflora worse. Of course, if it’s shown to be widely safe, or it reduces bad breath, then I’d be more likely to get it’
What prevents bacteriophage from exploiting the new ecological conditions of the Lumina oral microbiome? I haven't seen anything about modifications to the bacteria that address this, nor have I seen any mention of this potential problem in any of the marketing done for this product. Can someone please enlighten me?
What did the Company do with the test animals when done with them?
A lot of the opinion on LK=99 was, try to replicate the experiment nd then we'll know. Then the replication attempts failed, and for most people that was that. Still, it was very cool to watch science being done by e.g. Andrew McAlip.
I guess this is similar .. $250 to be a guinea pig in a cool science experiment that might or might not work out,
I will totally admit to spending more than $250 of my own money on doing a cool experiment.
And i'll also admit to spending way, way more than that of DARPA's money on doing a cool experiment. (My magagement tells me my research group's published papers cost more than a million dollars each, so there's that.._)
https://twitter.com/natalia__coelho/status/1779610061658325461
Relevant tweet showing a table where the control group has about as much caries as the BCS3-L1-infected group. People should be free to try this, but Cremieux's post reminded me of podcasts hosts shilling supplements, which was fun and unusual to see in this sphere.
I wouldtrust the company more, if they publicly released the data of their ongoing testing. My trust already increased a little because they admit to failed colonisation in two cases.
Coincidentally I just read about the biblical Hananiah, who was a false prophet. Doesn't seem to have said anything about teeth, though.
Thank you for finally acknowledging that caries can come from bacteria besides for S. mutans
I think it is worth it. First of all, just as a non-FDA intervention it has a huge potential market. That's kind of how PRP
gained traction-- and even now, while it is not usually paid by insurance, it is incredibly common.
Once it's on the market with use in large enough numbers, there will be sufficientl data to establish its efficacy and then possibly go for FDA approval.
I've pre-ordered, though I'm not sure how effective it will be for me.
I've had a lot, *a lot*, of cavities. I don't think I have single tooth that hasn't had something done to it. (My wife, who has had zero cavities, joke that it's a good thing we go to the dentist as a pair, so we average out to a normal patient.) With less real-tooth surface area, will that impact the ability of this new bacteria to strive and thrive and drive out the old bacteria?
I don't know. But I've got $250 to spare and I'm willing to give it a shot. I've spent $250 on a lot worse.
It seem still no shipping to Europe :/
> I think two more likely explanations are: This is Trial 3, the one we know nothing about
That would make sense, because trial #3 is where he gave up, and also, the sample sizes usually go up the later the trial - it would be odd if trial #3 were planned to have fewer than 26 or 10 people, after all, and 100 is a nice round number.
Goofus and Gallant - Wow, what a time machine! My parents got me a subscription to Highlights For Children when I was six. JFK would remain President for another few weeks.
IIRC, there was another feature called The Timbertoes, about people made of wood.
A reader's letter asked if the editor was a man or a woman, and the response was "yes", which young me found quite funny.
I saw a copy a few years ago, I think at the library, and it looked virtually unchanged from my childhood.
The V in EV stands for value, think it should just be “+EV for society”
Tyler Cowen is doubtful. https://marginalrevolution.com/marginalrevolution/2024/04/saturday-assorted-links-453.html
I am ready to try, but too far away
Looking forward to the "Dentists HATE this one oral bacteria colonization treatment" ads.
My feeling is that disastrous results - comparable to thalidomide - are well-nigh impossible. It's just a bacterium that colonises a rare niche in the mouth. It doesn't spread aggressively, so presumably won't infect other people by kissing etc. (it being hard to establish is not all a bad thing.) So really people should have at it, and if enough try then even anecdotal data will be good enough that a proper trial will be easy to arrange, and others will do studies anyway.
Personally I have no interest as whether it is due to mouth microflora, saliva, or sugar avoidance, I don't really get cavities any more. [EDIT: or fluoride, as mentioned by Steve Sailer. I too got lots of cavities when I was young. Now I have fillings that are over four decades old. My dentist at the time noted that I had a interesting amount of 'arrested decay', so something changed. But wouldn't dentists / public health scientists have noticed if fluoridation had a sudden massive effect on new cavity formation?]
I like the categories and odds you laid out! Care to bet on them?
https://manifold.markets/Joshua/lantern-bioworks-lumina-probiotic-d?r=Sm9zaHVh
I legitimately do not understand why so many people treat the LK-99 hype with such scorn. It's a good thing to be able to be excited and hopeful about potential breakthroughs. It's not a big deal if it doesn't pan out.
But for some very large subset of people, it is just infuriating and shameful to take these announcements with anything other than heaping skepticism, and I cannot wrap my mind around it.
Uh, what does a "constant trickle of alcohol" do to developing baby brains? Since you mentioned in a previous post, your kids might get this bacteria from your wife...
I think Yishan Wong's implication that "because Pfizer offered to buy the IP it must be safe" is very sloppy reasoning. Big pharma is VERY familiar with reasoning under uncertainty and VERY comfortable paying for drugs that they know further trials might show are unsafe or ineffective.
I agree that the Pfizer offer is indeed some evidence that some experts thought there was promise. But all that shows is that they thought it had a decent expected value. Given the gigantic potential market here that expected value could easily be justified with a very small probability of actually making it to market.
Re. "and the other had his wisdom teeth removed (which involves rinsing the mouth with strong antiseptics).":
Would taking a 2 week course of amoxicillin or keflex kill the anti- cavity bacteria?
On balance for me the cancer risk is the marginal factor. I had thought of this before Lao Mein's post, but without the genetic factor. My (lay person's) reasoning goes: alcoholics get oral/throat cancer at higher rates because they put large amounts of ethanol into their mouths and throats on a regular basis. Do we know if there is a similar increase in risk of these cancers if you have a low amount of ethanol in your mouth 100% of the time?
If I could get good evidence that this risk is negligible I would be good with trying this - but I'm not there now.
Probably too expensive to do irl, but I’m 39 and have never had a cavity and I’m wondering if I already have some natural version of this and if there’s a way to test for it.
Best correlational test I can think of:
Test a bunch of people like myself who have hit middle age without having a cavity. Are we much more likely to have this?
Test a bunch of people with a lot of cavities in the same age bracket. Are they less likely/completely missing this bacteria?
Best causal test I can think of (but is too expensive):
Give each of the above groups the intervention, keep a control group, and track how they progress over the next x period of time.
That seems totally good as an experiment and I don’t know why the FDA would want young people with dentures. Is it because of possible hazard of this causing some extreme negative effect? Just the fact that this is bacteria makes me think you could probably eat this and get rid of it if you really needed to. I mean, I eat day old food that’s been left on the counter all the time. Or cheese. Or milk. Or what have you.
My problem with lumina is the constant lying. Combined with trying to charge 20k it just screams "scam" -- totally unethical.
In the comments of the previous post on this subject, I mentioned that it probably won't work. I want to expand on a few reasons why.
Suppose a patient applies Lumina as directed, and it works exactly as well as anyone could hope. Within eighteen months, the Lumina strain has successfully outcompeted all other strains of S. Mutans, and for that matter all other bacteria within its ecological niche.
It still won't work forever. And probably not for very long. And the reason why is pretty obvious once you ask yourself why the grad student in whom the Lumina predecessor was found had other bacteria in his mouth as well.
There is a metabolic cost to producing M-1140. Once all the bacteria in the mouth have the make M-1140 gene and the immune to M-1140 gene, the evolutionary advantage goes to those bacteria that (through inevitable natural mutation) are immune, but don't produce the antibiotic.
Over time, ceteris paribus, Lumina's descendants will evolve away from the M-1140 producing gene. And if non-immune bacteria don't colonize the mouth before the producing gene goes extinct, the immunity gene will go extinct too (since there's no benefit to being immune to an antibiotic you're not exposed to).
The most likely outcome is a semi-stable yoyoing between immune + producing bacteria, and neither immune nor producing bacteria.
And this all assumes that there is no net evolutionary disadvantage to the other two genes that are essential in Lumina, which is doubtful.
For example, if a bacteria colonizes the mouth which produces a different antibiotic, to which Lumina is not immune, then lumina can only obtain immunity through natural mutation, not horizontal-gene-transfer, and will very swiftly be outcompeted by bacteria that can obtain beneficial mutations horizontally.
With all that said, I think your probabilities are pretty close to my own, although there is one outcome that I would add.
Lumina has a statistically significant benefit, but due to the evolutionary pressures outlined above, it must be reapplied on a regular basis: ~35%
I appreciate this. My question on whether I would recommend this to a grandchild seems to be answered.
As an aside, wish someone would have done this with the covid vaccine.
Can we just rinse our mouths with an alkaline solution twice a day?
There were two attempted trials, not 3. Numbers 2 and 3 in your list are the same trial, and it didn’t succeed. It looks like it didn’t even get started.) Oragenics has described the process in detail in each year’s Form 10-KSB/Form 10-K, which they have been filing since 2003. All those forms are available on their website. I think it was in the 2012 form that they said they had given up.
None of the forms mention anywhere near 100 people required in a trial, or people under 30.
[Update: the second trial did require people under 30 (ten of them, with teeth), and it looks like it did get started (but didn't succeed).]
I preordered it, partly because I think they'll get shut down at some point and I wanted to maximize my chances of getting this cool thing. But I'll probably keep it in my freezer for a few months to a year to see more analysis before committing.
And I don't really get cavities, my main dental concern is gingivitis and bad breath. It seems there's a good chance this will not help with those, so there's that.
It's not a good deal if you actually need ior want the benefit of the product. The opportunity cost of ending up on placebo for months might mean forestalling other steps you could take to mitigate against decay. And if it were structured as it should be for a true DB trial, you would never know which group you were in, and so potentially take no other positive action while using a placebo.
Is every other western drug approval process as horrible as the FDA, or would it make sense to seek regulartory approval in a less broken (if less lucrative) market?
I have chronic heartburn and can't tolerate alcohol... Sounds too risky to be worth trying in my particular case, otherwise I'd be interested.
Shot in the dark here, but does anybody know anything about how this product might interact with liver function? This sounds great, but I don’t want to mess with my liver enzymes.
This is helpful, thanks. I was one of the first fifty people in the West Coast to get the SMiLE surgery (in the LASIK family but newer; no flap, and fixes astigmatism) in 2017. Seven years later, I still haven't grown any horns, and I see 20/20. No more excuses not to train. Now, I am looking into Lumina.
So does it actually exist? Your post and the comments make it seem like it's available in the wild, but the linked website says pre-orders won't ship until June 2024. I'm happy to spend $250 to apply a potentially dangerous bacterial treatment to my mouth, but I'm not prepaying to a biotech startup long before a ship date.
I haven't been this enthusiastic about new tech in a long time.
What countries qualify as Asian fit the purposes of the aldh concern. Is it just east Asian or south Asian as well
Among the Swartzentruber Amish, it is common to get dentures by age 21 because most in the community do not practice oral hygiene. Of course, the Swartzentruber Amish community is uncommonly insular, so getting them to participate in this study might be a challenge.
https://ideaexchange.uakron.edu/cgi/viewcontent.cgi?article=1281&context=amishstudies
Would these bacteria help with tooth decay in dogs? My dog won't let me brush his teeth and he's already had to hava a lot of teeth pulled.
(I've just spent about US $1000 on dental work...)
If this product works, it would be an incredible win. I mean, look at how much people are paying for dental work at the moment.
I wish them the best of luck, and hope it works.