14 ms·

Recreate the cavity-preventing GMO bacteria BCS3-L1 from precursor

266 points by flaque 3y ago

NoMoreNicksLeft 3y ago
Which state is this company located in? We should go to our state legislators and demand they use eminent domain on it. Maybe first after having the AG go to a judge for an injunction against destroying it (out of spite).
KingMachiavelli 3y ago
I would try this in a heartbeat, cavities IME seem to be mostly genetic or per-person microbiome environmental thing. The fact that without daily maintenance our teeth can just rot away to a point where severe infection and/or death seems just like a major flaw we should be trying a lot harder to fix.
- cmrdporcupine 3y ago
  It's a flaw with an agrarian diet, not intrinsic to human anatomy. Archaeological remains of hunter-gatherers show extremely few cavities. They begin in earnest once people start eating domesticated cereal grains as a primary food source.
  - pineconewarrior 3y ago
    The bacteria which cause cavities also evolved alongside us. The problem worsened as we introduced more food for the bacteria (from the agrarian diet).
    - ClumsyPilot 3y ago
      > bacteria which cause cavities also evolved alongside us. So did the tapeworms. Or fleas
  - ch4s3 3y ago
    It seems like modern hunter gatherers get cavities[1]. [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5351833/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5351833/
    - cmrdporcupine 3y ago
      "The unexpected discovery of high caries incidences for men in the bush is likely explained by heavy reliance on honey, and perhaps differential access to tobacco and marijuana. " I'd also expect a high fruit diet in certain tropical regions where fruit is available more constantly also shows similar effects.
      - ch4s3 3y ago
        Access to and a cultural appreciation for honey probably plays/ed a factor in some societies.
        fsckboy 3y ago
        you think honey appreciation is cultural? that's ... sweet, my sweet summer honeychild.
        ch4s3 3y ago
        > sweet, my sweet summer honeychild I think we can maybe all move on from this awful quote. But, no I'm specifically referring to cultures like the Efé where men gather honey full time during a season, Yao honey-hunters who work with birds to find honey, or other forest cultures where honey is gathered from especially tall trees as a show of masculinity and bravery.
    - gregwebs 3y ago
      Modern hunter gatherers are a lot more modern than one might imagine. Usually wearing T-shirts and sometimes, as in this case smoking cigarettes. Their diet is different in many ways than hunter gatherers of the past, along with many other parts of their lifestyle. It’s probably a good demonstration of the “Paleo fantasy“- if these groups that are still playing by some of the hunter gatherer groups are getting very different results on these important markers, then we are likely to as well when we try to incorporate parts of the hunter gather diet or lifestyle into our very different lives.
  - teryasdasd 3y ago
    Even if you only eat meat (or whatever else besides grains), bits of food will still get wedged between into your gums and then rot away with your teeth.
    - cmrdporcupine 3y ago
      Sure, but it's a matter of degrees.
    - EGreg 3y ago
      Don’t vegetarians live 10 years longer, though? Seems like a net win for them
      - slabity 3y ago
        Yes. But is that a result of not eating meat? Or a result of paying close attention to your diet? A lot of inexperienced vegetarians/vegans end up with nutrient deficiencies because they don't ensure that they are properly getting all essential vitamins or amino acids in their meatless diets. I'm not a dietician, but it's pretty safe to say that these people are not going to be the ones with reduced mortality rates. You cannot simply remove an entire food group from your diet without putting in effort into paying attention to the rest of your diet. Some studies[1] show that pescetarian diets offer the lowest mortality rates. This diet still requires paying close attention to what you eat, but you are far less likely to have nutrient deficiencies. This is one of the huge issues I have with diet-mortality studies. During the gluten-free trend a while back, there were many that suggested gluten-free diets provided health benefits. However, for the vast majority of people, gluten isn't really that special as far as proteins go. It turned out those "health benefits" were just the result of people with gluten intolerances actually paying attention to their diet. Just to reiterate, I am not a dietician. Everything above is just my cynicism for studies that constantly fail to take into account that most people just don't care what they're eating. I would absolutely love to be proven wrong. [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4191896/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4191896/
        bawolff 3y ago
  - thaumasiotes 3y ago
    > Archaeological remains of hunter-gatherers show extremely few cavities. How long did they live before becoming remains?
    - cmrdporcupine 3y ago
      Not long, but actually longer than the first agricultural societies is my understanding. With the agrarian transition, population density and family sizes went up (a lot) but life expectancy went down a bit and infant mortality and disease rates (zoonotic diseases + higher concentration of population to spread through) went up. Ag gives more calories per square km, so more people. But also more vulnerability to disease, periodic famine, and in some cases malnutrition from over reliance on cereal crops (e.g. Pellagra). Hunter gatherers are/were constrained by wild food source densities but also tended to have smaller families, breast feed longer (so fewer pregnancies), and could sometimes migrate when local wild animal populations were exhausted. If you have a bad crop year you can't migrate to the next valley and find a new field of wheat waiting for you. However there were likely many millennia of societies that mixed agriculture with hunting/gathering. Eastern woodland native Americans were like that pre-contact; maize agriculture + hunting game + fish etc. Seems like a good overall strategy.
      - DropInIn 3y ago
        > However there were likely many millennia of societies that mixed agriculture with hunting/gathering. Eastern woodland native Americans were like that pre-contact; maize agriculture + hunting game + fish etc. Seems like a good overall strategy. Aren't there parts of rural China still living in that mixed model today? And Africa too iirc...
        thaumasiotes 3y ago
        As described, everyone in the world is living that mixed model today. Fish mostly come from the ocean.
      - thaumasiotes 3y ago
        > With the agrarian transition, population density and family sizes went up (a lot) but life expectancy went down a bit and infant mortality and disease rates (zoonotic diseases + higher concentration of population to spread through) went up. Infant mortality going up is the same thing as life expectancy going down. Neither one tells you much about whether people die before or after you'd expect to start seeing problems in their teeth. After ignoring infant mortality, it's mostly afterward, but "remains" are not a representative selection. > Hunter gatherers are/were constrained by wild food source densities but also tended to have smaller families This conflicts with the idea that they had lower infant mortality.
  - guy98238710 3y ago
    Dogs don't get cavities. Human saliva is more acidic.
    - mlyle 3y ago
      Dogs absolutely get cavities. Yes, somewhat fewer, because: - Dogs eat fewer carbs and don't really eat acidic foods (no soda, fruit) - Dogs live a much shorter time and so there is much less time for damage to accumulate to enamel.
  - KingMachiavelli 3y ago
    > It's a flaw with an agrarian diet, not intrinsic to human anatomy. We don't accept anthropological arguments for any more human anatomy limitations. We have contacts and glasses to correct our eyes and cars and planes to travel farther and faster then we ever could on our legs alone. I just think compared to the other recurring hygiene tasks, teeth seem to be the most labor intensive and accumulate damage continuously while most other hygiene tasks can be technically be ignored for days/weeks (like camping with no shower).
    - bawolff 3y ago
      Are these really good counter examples - they all have common explanations of this sort (whether or not true idk)? We have glasses because modern society requires focusing on close objects like books and screens causing eye strain. Cars are great for modern society but pretty poor and hunting an animal in the middle of a forest, etc. While i doubt its the only factor, diets higher in sugar than what hunter/gathers would have eaten seems plausibly linked to there being more cavities in modern times.
      - themitigating 3y ago
        Fruit?
      - doubleg72 3y ago
        I would argue it is more to do with the amount of sugars and the frequency these sugars are in contact with the teeth than anything. Sipping HFCS the entire day seems to be much more common these days..
      - jamilton 3y ago
        They're good counterexamples in they show solutions of the form "use technology" can work instead of "change the root behavior".
      - ImHereToVote 3y ago
        It's amazing how much your vision improves by simply focusing at the edge of your eye resolution level. Don't squint, just focus. A month later you will be blown away.
at_a_remove 3y ago
Dr. Hillman, I was right! I had written him well over a decade ago, I want to say 2008. He has long since retired, but the gist of the hints in our correspondence was that this was something the FDA just didn't have a conceptual slot for, and that was creating a great deal of impedance. I believe he had gotten as far as Phase IB in testing.
- mmaunder 3y ago
  Interesting use of 'impedance' as opposed to 'impediment'. I feel like you just birthed a neologism.
  - at_a_remove 3y ago
    I was thinking more in line of electrical impedance matching.
bilsbie 3y ago
Is the link wrong? I don’t see any details. Also how does this compare to bacteria like s. salivarius ?
modeless 3y ago
> the developing company declined to go to market, and instead pivoted I'd want to hear a lot more about why this happened before I invested in this. I've been hearing about this bacteria for years and the story gives me strong "miracle carburetor" vibes.
- downWidOutaFite 3y ago
  You cut off the answer to your question > pivoted to selling once-daily probiotic mouthwash. Businesses love recurring revenue streams
  - heydemo 3y ago
    Curing all the cavities in the world is likely to be more profitable than selling mouthwash.
    - spullara 3y ago
      Probably not? Especially if anyone can take anyone's mouth biome and copy it.
    - fnordpiglet 3y ago
      Apples entire business model goes against that philosophy. Reoccurring revenue is where it’s at. Unless you actually want to make things better, in which case you’re shouldn’t be in business. (Which these guys blessedly aren’t!)
      - jdiff 3y ago
        Apple's business model existing isn't an argument against other business models.
        fnordpiglet 3y ago
        It’s not but it is also a) a selected example of many to illustrate a point with clarity, b) a widely emulated model, c) essentially what the company who pivoted pivoted towards. Rather than a one time solution, a reoccurring subscription model, so is salient and likely it or a similar model was considered in that switch.
wolpoli 3y ago
Is the plan to cultivate the bacteria from the 1 of the 15 test subjects?
- khaki54 3y ago
  That's a good point they may not have even considered... if they are "recreating from precursor" why wouldn't you just 1. Check the status of the test subjects e.g. any new cavities 2. Get the supposed indefinite strain from one or several of the 15
  - wolpoli 3y ago
    Nowhere on the page does it explain how will this grant be used. It asserts that there's nothing preventing them from recreating BCS3-L1 ourselves from commercially available precursor bacteria but it doesn't say if that's the plan. My guess is this funding will be used to look into the different approaches, and then they will come back with a real project.
Hizonner 3y ago
It "persists in the mouth indefinitely". It's "been in the mouths of fewer than 15 people". This was in 2003, so I'm guessing they're not all dead. I'll stake 'em a box of cotton swabs...
- mlyle 3y ago
  Indefinitely may not be 20 years. That's a long time for selective pressure and rare events causing winnowing of mouth bacterial amounts.
- cdchn 3y ago
  Saliva transplant.
  - nayaketo 3y ago
    yum
heydemo 3y ago
A product that permanently cures all cavities would have a valuation of hundreds of billions, if not trillions, of dollars. Is it plausible a company would choose to sell mouth wash instead and that the cure would remain undeveloped for 20 years?
- hanniabu 3y ago
  Why sell a one time cure if you can sell a daily cure
  - heydemo 3y ago
    This is obviously a scam. There's no miracle cavity cure that's been suppressed for 20 years so a company could sell mouthwash
    - ClumsyPilot 3y ago
      Lets see, are there any parallels? Is there a solution to soil eriosion thats been supressed for 60 years, like perrenial agricultur If only there was a solution to climate change thats been supressed for 60 years, like nuclear power! Supressed is not the right term- not developed. Marker settles on a local optimum and does not make the huge investment needed to go to the global optimum. Also all the current market leaders lobby against the transition.
- throwaway829 3y ago
  "value" not "valuation". It has a value of hundreds of billions, if not trillions, of dollars. It would require enforceable patents to have that value funnel to one company.
teaearlgraycold 3y ago
This would be a huge win for humanity! But I suppose the downside is many people might stop brushing their teeth - and I doubt this new bacteria won't smell bad.
akrolsmir 3y ago
Oh wow -- totally didn't expect one of our grant proposals to be trending on HN! I'm Austin, cofounder at Manifund; we just launched our regranting program last week (https://forum.effectivealtruism.org/posts/RMXctNAksBgXgoszY/announcing-manifund-regrants https://forum.effectivealtruism.org/posts/RMXctNAksBgXgoszY/...) and are currently looking out for cool grants (like this one!) to fund. Happy to answer any questions!
- rudyfink 3y ago
  Why do you think the company never took it to market past testing? And thank you for looking into this. I recall reading about experiments on the modified bacteria years ago, but then I forgot about it. Until I read your page, I had not realized it died on the vine.
  - hrkfmud50k 3y ago
    > After a single application, this strain persists in the mouth indefinitely, hedging out cavity-causing bacteria > but the developing company declined to go to market, and instead pivoted to selling once-daily probiotic mouthwash. sounds like they preferred to sell a recurring subscription vs a one-time sale
    - fsckboy 3y ago
      "I wonder if the one-time sale can be "resold" through snogging?" - Phil MacAvity
      - totetsu 3y ago
        Probiotic kissing booth?
        TeMPOraL 3y ago
        Well, why not? Compared to fecal matter transplants, which are already a thing, tickets to a kissing booth will sell out like hot cakes. (Can I pay for a monthly pass up front? It's for medical purposes!)
wdwvt1 3y ago
I love the spirit of this grant but it has big "programmer knows better then pharma" vibes. At a first glance: 1) The original strain (BCS3-L1) is a clinically derived isolate with who knows what properties. Why not just take the well characterized ATCC/DSMZ strain and knock out the lactate dehydrogenase? I am sure the FDA would look more kindly on a better characterized strain - especially since you don't need whatever wild type mutations it has to keep it in the dental microbiome (the lantibiotic does that). 2) Who pays for this? Why? Finding the appropriate payer for a pharmaceutical intervention is difficult. Getting this through FDA trial costs (let's say) $200 million dollars. At the point of sale (PCP, dentist) the competitive product will be...toothpaste and a toothbrush. Getting a patient or insurance to purchase this under current models of care is going to be extremely difficult.
- akrolsmir 3y ago
  Yeah, agreed that the proposal has a whiff of "too good to be true". The applicant's track record looks fairly good, though (he's previously invested in my startup, Manifold Markets, and otherwise has an interesting history in many different domains). I think if there's even a 1% chance that the intervention looks as good as promised, it'd be worth further study for the proposed costs.
  - wdwvt1 3y ago
    I am a drug developer working on identifying novel therapeutics from human skin, oral, and intestinal bacteria. I love the idea of Manifund - but I think this may not be the best project for it. This proposal needs some review by a biologist. In its current form, I think this is a much less impactful use of money than other things on Manifund.
    - fbdab103 3y ago
      Curious what those would be. Again, too good to be true, but if we could vaccinate against cavities, that seems like an enormous amount of human misery eliminated for a one time investment.
PlunderBunny 3y ago
Wikipedia article on carries vaccines: https://en.wikipedia.org/wiki/Caries_vaccine# https://en.wikipedia.org/wiki/Caries_vaccine#
superqd 3y ago
So... is the existence, or non-existence, of a certain bacteria why some people never get cavities? I'm sure there can be multiple factors, but I'm 51 and never had a cavity, but don't really know the specifics of what might be different about the environment of my mouth that seems to discourage, or not encourage, the formation of cavities.
- toomuchtodo 3y ago
  https://pubmed.ncbi.nlm.nih.gov/12369203/ https://pubmed.ncbi.nlm.nih.gov/12369203/ (2002)
- fsckboy 3y ago
  lemme ask you a question, I'm guessing you grow up with flouridated water?
  - JeremyNT 3y ago
    Not OP but I'm a similar age and never had a cavity either. I grew up in a rural area and drank well water as a kid. They did occasionally provide topical flouride in the schools. I stopped going to dentists in my mid 20s. Routine cleanings are not actually shown to improve outcomes, and the lack of cavities leaves me no other reason to go. I couldn't say why I'm so lucky in this respect, but the bacterial explanation seems plausible.
    - htss2013 3y ago
      Mind expanding on the lack of data for cleanings? I got busy, then pandemic, next thing I know it's been like 7 years since I've seen a dentist. No problems or discomfort whatsoever. It occurred to me that bi annual cleanings are the SaaSification of dentistry, but I've never seen any real evidence.
      - toast0 3y ago
        I'm happy to go for regular cleanings, but I don't know how you could construct a well designed study to get data showing objectively what interval of cleanings results in better outcomes over many years. There's just too many uncontrolled variables. And, I don't think you can glean it from population studies either, because again, there are too many variables.
anandvc 3y ago
Newbie question: Can someone help me understand how adding a new benign bacteria helps prevent infection by the other cavity-causing bacteria? Do they "fight" each other?
- BestGuess 3y ago
  Something like this I think https://en.wikipedia.org/wiki/Competitive_exclusion_principle https://en.wikipedia.org/wiki/Competitive_exclusion_principl...
obblekk 3y ago
If I wanted to buy an atcc bacteria, what’s the easiest way to get access to a BSL1 lab that they’ll agree to ship to? Is BSL1 even certified or self attested?
fsckboy 3y ago
it's shocking that it hasn't been mentioned (ok, except by me in another comment) but flouridating municipal water systems through/after the 1960's at least in the US had a huge impact on the number of cavities/caries among children. Yuge. There are suspicions that fouride isn't good for us, and I mean beyond our precious bodily essences too, but in terms of teeth, it's been miraculous. I'm just mentioning it because people are talking about bacteria being "the deciding factor" to account for differences in outcomes, and there's a flouride elephant in that room.
- deleted 3y ago
  [deleted]
- mike_d 3y ago
  > There are suspicions that fouride isn't good for us, and I mean beyond our precious bodily essences too, but in terms of teeth, it's been miraculous. Fluoride is weird. Everyone just assumes some is good so more must be better, and any research into dental fluorosis (over exposure) is shunned. I believe primarily because prior to dumping it into the water and every dental product imaginable fluoride was expensive to dispose of and we produce a ton of it as a byproduct of making fertilizer.
  - fsckboy 3y ago
    too much flouride is actually really bad for your teeth; brown spots/pits I think. It's why children's toothpaste has minimal flouride, because they swallow a lot of it. adults: don't swallow your toothpaste.
    - latchkey 3y ago
      i had white spots (Dental Fluorosis) as a kid from too much flouride... they eventually went away.
      - arthur2e5 3y ago
        White spots is mild fluorosis. The brown stuff comes in when you live next to a coal mine so your water is filled with fluoride (at concentrations way over what any reasonable water-fluoridizer wants to add) and other nasty stuff. People talk about how the fluoride in tea can help prevent cavities, but on the darker side... just imagine having all your food come from that sort of fluoride-rich soil.
jimnotgym 3y ago
> After a single application, this strain persists in the mouth indefinitely, In which case you only need to find a person from the original trial and get it from them. You don't need to recreate it?
Escapado 3y ago
Super exciting stuff and it got me thinking: could we genetically engineer bacteria to get rid of morning breath? I would like to think (and so does my dentist) I have very good oral hygiene* and I get regular checkups where everything is fine but when I wake up the taste in my mouth and my breath are really unpleasant. The last time I had to be on antibiotics for a longer time I noticed it was severely lessened but came back just as strong after. * My routine includes brushing my teeth 3x per day for 3 minutes with an ultrasonic toothbrush, I use an interdental brush at night, I use a tongue scraper in the morning and at night and I do an occasional chx mouthwash and semi-regular salt water rinses.
- arthur2e5 3y ago
  Could be something deeper down (tonsils, esophagus, nose), or... mouth breathing, which can become a habit if your nose is clogged often.
- an_aparallel 3y ago
  tonsil stones contribute a lot to bad breath in general (if you have them) - hazard a guess folks have no clue wtf they are :P
- austinjp 3y ago
  > My routine includes brushing my teeth 3x per day for 3 minutes I appreciate that you may have specific reasons for this routine, but is that a typical routine generally? I've heard 2 minutes twice per day, so 3x3 seems excessive, and might cause gum/tooth damage through abrasion?
  - Escapado 3y ago
    I usually eat 3 meals a day or two meals and a snack and I brush my teeth about 20-30 minutes after that so I guess it mostly due to my wish to get my mouth feel fresh and prevent staining if I had something like kimchi. 2 minutes twice per day is probably sufficient most of the time but the amount of abrasion and gum damage will probably also heavily depend on the hardness of the brush, the specific toothpaste and and the of course how vigorously you brush. I asked my dentist about this last year and he said it's fine and my gum health and enamel seem to confirm that.
PeterStuer 3y ago
As with everything in biology there are tradeoffs. What is the tradeoff here?
RamblingCTO 3y ago
I think the section about why we should trust the project founder is quite funny. Something like "I did video games and stuff". And MIRI is AI, operations lead sounds like administration? So no relevant experience. While I can respect someone doing a moonshot, really I do, but maybe, just maybe get someone with relevant experience on board? I'd love to see this happen, but this doesn't help their case imho. -I spent five years at MIRI as Operations Lead. -I produce a video game that's #42 in category on Patreon, with an 11-person team, making six-figures with >1,000,000 downloads. -I run Heist and Geist and Heist: Sunlit Forge; welcometotheheist.com -I'm nominated for the Nebula for fiction, and was published in Asterisk three days ago under the name Jamie Wahls. -I run Aella's media empire.
- TeMPOraL 3y ago
  > -I run Aella's media empire. Well, that is a unique thing to put on your resume. But you're right, and I'm saying this as a person who'd easily fall for the halo problem after the MIRI mention. Pausing for a moment, all the list you quoted tells me is that the person is most likely clearer-thinking and smarter than average, is likely to be "nerdy" in exactly the way I'd hope people running a biotech project like this, and hangs out with people even smarter and nerdier in the way I like[0] -- alas, it also tells me he has little to offer in terms of relevant scientific, technological, or product qualifications. Sure, he seems qualified for a leader/manager (and he's definitely not afraid of holding a PR equivalent of a live grenade), but the first step I'd expect of him is, as you say, to "get someone with relevant experience on board". Preferably more than one. Being a certain type of nerd may help to inspire people, but vision is no substitute for actual experience in biotech. -- [0] - Which I realize may be less of an indicator of domain competence, and more of my bias towards like-minded people.
- duozerk 3y ago
  MIRI isn't even really AI; it's a pet project from that insane, sex-pest-filled movement in the US that calls itself "effective altruism" (that and their dozens of even-more-insane offshoots). IIRC originally funded by the pitiful creature that Yudkowsky had by then become. MIRI hasn't produced or published anything of scientific value. In fact seeing the person this fundraiser is about putting it as a high point in their references is a major red flag.
swader999 3y ago
They should pursue vet market first, less regulatory hurdles.
londons_explore 3y ago
http://www.oragenics.com/news-media/press-releases/detail/35/oragenics-receives-new-patent-for-improved-replacement http://www.oragenics.com/news-media/press-releases/detail/35... Wouldn't there be patent problems with reproducing this? Unless Oragenics is willing to license/give up their patent?

266 points by flaque 3y ago

Which state is this company located in? We should go to our state legislators and demand they use eminent domain on it. Maybe first after having the AG go to a judge for an injunction against destroying it (out of spite).

KingMachiavelli 3y ago

I would try this in a heartbeat, cavities IME seem to be mostly genetic or per-person microbiome environmental thing. The fact that without daily maintenance our teeth can just rot away to a point where severe infection and/or death seems just like a major flaw we should be trying a lot harder to fix.

cmrdporcupine 3y ago
It's a flaw with an agrarian diet, not intrinsic to human anatomy. Archaeological remains of hunter-gatherers show extremely few cavities. They begin in earnest once people start eating domesticated cereal grains as a primary food source.
- pineconewarrior 3y ago
  The bacteria which cause cavities also evolved alongside us. The problem worsened as we introduced more food for the bacteria (from the agrarian diet).
  - ClumsyPilot 3y ago
    > bacteria which cause cavities also evolved alongside us. So did the tapeworms. Or fleas
- ch4s3 3y ago
  It seems like modern hunter gatherers get cavities[1]. [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5351833/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5351833/
  - cmrdporcupine 3y ago
    "The unexpected discovery of high caries incidences for men in the bush is likely explained by heavy reliance on honey, and perhaps differential access to tobacco and marijuana. " I'd also expect a high fruit diet in certain tropical regions where fruit is available more constantly also shows similar effects.
    - ch4s3 3y ago
      Access to and a cultural appreciation for honey probably plays/ed a factor in some societies.
      - fsckboy 3y ago
        you think honey appreciation is cultural? that's ... sweet, my sweet summer honeychild.
        ch4s3 3y ago
        > sweet, my sweet summer honeychild I think we can maybe all move on from this awful quote. But, no I'm specifically referring to cultures like the Efé where men gather honey full time during a season, Yao honey-hunters who work with birds to find honey, or other forest cultures where honey is gathered from especially tall trees as a show of masculinity and bravery.
  - gregwebs 3y ago
    Modern hunter gatherers are a lot more modern than one might imagine. Usually wearing T-shirts and sometimes, as in this case smoking cigarettes. Their diet is different in many ways than hunter gatherers of the past, along with many other parts of their lifestyle. It’s probably a good demonstration of the “Paleo fantasy“- if these groups that are still playing by some of the hunter gatherer groups are getting very different results on these important markers, then we are likely to as well when we try to incorporate parts of the hunter gather diet or lifestyle into our very different lives.
- teryasdasd 3y ago
  Even if you only eat meat (or whatever else besides grains), bits of food will still get wedged between into your gums and then rot away with your teeth.
  - cmrdporcupine 3y ago
    Sure, but it's a matter of degrees.
  - EGreg 3y ago
    Don’t vegetarians live 10 years longer, though? Seems like a net win for them
    - slabity 3y ago
      Yes. But is that a result of not eating meat? Or a result of paying close attention to your diet? A lot of inexperienced vegetarians/vegans end up with nutrient deficiencies because they don't ensure that they are properly getting all essential vitamins or amino acids in their meatless diets. I'm not a dietician, but it's pretty safe to say that these people are not going to be the ones with reduced mortality rates. You cannot simply remove an entire food group from your diet without putting in effort into paying attention to the rest of your diet. Some studies[1] show that pescetarian diets offer the lowest mortality rates. This diet still requires paying close attention to what you eat, but you are far less likely to have nutrient deficiencies. This is one of the huge issues I have with diet-mortality studies. During the gluten-free trend a while back, there were many that suggested gluten-free diets provided health benefits. However, for the vast majority of people, gluten isn't really that special as far as proteins go. It turned out those "health benefits" were just the result of people with gluten intolerances actually paying attention to their diet. Just to reiterate, I am not a dietician. Everything above is just my cynicism for studies that constantly fail to take into account that most people just don't care what they're eating. I would absolutely love to be proven wrong. [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4191896/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4191896/
      - bawolff 3y ago
- thaumasiotes 3y ago
  > Archaeological remains of hunter-gatherers show extremely few cavities. How long did they live before becoming remains?
  - cmrdporcupine 3y ago
    Not long, but actually longer than the first agricultural societies is my understanding. With the agrarian transition, population density and family sizes went up (a lot) but life expectancy went down a bit and infant mortality and disease rates (zoonotic diseases + higher concentration of population to spread through) went up. Ag gives more calories per square km, so more people. But also more vulnerability to disease, periodic famine, and in some cases malnutrition from over reliance on cereal crops (e.g. Pellagra). Hunter gatherers are/were constrained by wild food source densities but also tended to have smaller families, breast feed longer (so fewer pregnancies), and could sometimes migrate when local wild animal populations were exhausted. If you have a bad crop year you can't migrate to the next valley and find a new field of wheat waiting for you. However there were likely many millennia of societies that mixed agriculture with hunting/gathering. Eastern woodland native Americans were like that pre-contact; maize agriculture + hunting game + fish etc. Seems like a good overall strategy.
    - DropInIn 3y ago
      > However there were likely many millennia of societies that mixed agriculture with hunting/gathering. Eastern woodland native Americans were like that pre-contact; maize agriculture + hunting game + fish etc. Seems like a good overall strategy. Aren't there parts of rural China still living in that mixed model today? And Africa too iirc...
      - thaumasiotes 3y ago
        As described, everyone in the world is living that mixed model today. Fish mostly come from the ocean.
    - thaumasiotes 3y ago
      > With the agrarian transition, population density and family sizes went up (a lot) but life expectancy went down a bit and infant mortality and disease rates (zoonotic diseases + higher concentration of population to spread through) went up. Infant mortality going up is the same thing as life expectancy going down. Neither one tells you much about whether people die before or after you'd expect to start seeing problems in their teeth. After ignoring infant mortality, it's mostly afterward, but "remains" are not a representative selection. > Hunter gatherers are/were constrained by wild food source densities but also tended to have smaller families This conflicts with the idea that they had lower infant mortality.
- guy98238710 3y ago
  Dogs don't get cavities. Human saliva is more acidic.
  - mlyle 3y ago
    Dogs absolutely get cavities. Yes, somewhat fewer, because: - Dogs eat fewer carbs and don't really eat acidic foods (no soda, fruit) - Dogs live a much shorter time and so there is much less time for damage to accumulate to enamel.
- KingMachiavelli 3y ago
  > It's a flaw with an agrarian diet, not intrinsic to human anatomy. We don't accept anthropological arguments for any more human anatomy limitations. We have contacts and glasses to correct our eyes and cars and planes to travel farther and faster then we ever could on our legs alone. I just think compared to the other recurring hygiene tasks, teeth seem to be the most labor intensive and accumulate damage continuously while most other hygiene tasks can be technically be ignored for days/weeks (like camping with no shower).
  - bawolff 3y ago
    Are these really good counter examples - they all have common explanations of this sort (whether or not true idk)? We have glasses because modern society requires focusing on close objects like books and screens causing eye strain. Cars are great for modern society but pretty poor and hunting an animal in the middle of a forest, etc. While i doubt its the only factor, diets higher in sugar than what hunter/gathers would have eaten seems plausibly linked to there being more cavities in modern times.
    - themitigating 3y ago
      Fruit?
    - doubleg72 3y ago
      I would argue it is more to do with the amount of sugars and the frequency these sugars are in contact with the teeth than anything. Sipping HFCS the entire day seems to be much more common these days..
    - jamilton 3y ago
      They're good counterexamples in they show solutions of the form "use technology" can work instead of "change the root behavior".
    - ImHereToVote 3y ago
      It's amazing how much your vision improves by simply focusing at the edge of your eye resolution level. Don't squint, just focus. A month later you will be blown away.

at_a_remove 3y ago

Dr. Hillman, I was right! I had written him well over a decade ago, I want to say 2008. He has long since retired, but the gist of the hints in our correspondence was that this was something the FDA just didn't have a conceptual slot for, and that was creating a great deal of impedance. I believe he had gotten as far as Phase IB in testing.

mmaunder 3y ago
Interesting use of 'impedance' as opposed to 'impediment'. I feel like you just birthed a neologism.
- at_a_remove 3y ago
  I was thinking more in line of electrical impedance matching.

bilsbie 3y ago

Is the link wrong? I don’t see any details. Also how does this compare to bacteria like s. salivarius ?

modeless 3y ago

> the developing company declined to go to market, and instead pivoted I'd want to hear a lot more about why this happened before I invested in this. I've been hearing about this bacteria for years and the story gives me strong "miracle carburetor" vibes.

downWidOutaFite 3y ago
You cut off the answer to your question > pivoted to selling once-daily probiotic mouthwash. Businesses love recurring revenue streams
- heydemo 3y ago
  Curing all the cavities in the world is likely to be more profitable than selling mouthwash.
  - spullara 3y ago
    Probably not? Especially if anyone can take anyone's mouth biome and copy it.
  - fnordpiglet 3y ago
    Apples entire business model goes against that philosophy. Reoccurring revenue is where it’s at. Unless you actually want to make things better, in which case you’re shouldn’t be in business. (Which these guys blessedly aren’t!)
    - jdiff 3y ago
      Apple's business model existing isn't an argument against other business models.
      - fnordpiglet 3y ago
        It’s not but it is also a) a selected example of many to illustrate a point with clarity, b) a widely emulated model, c) essentially what the company who pivoted pivoted towards. Rather than a one time solution, a reoccurring subscription model, so is salient and likely it or a similar model was considered in that switch.

wolpoli 3y ago

Is the plan to cultivate the bacteria from the 1 of the 15 test subjects?

khaki54 3y ago
That's a good point they may not have even considered... if they are "recreating from precursor" why wouldn't you just 1. Check the status of the test subjects e.g. any new cavities 2. Get the supposed indefinite strain from one or several of the 15
- wolpoli 3y ago
  Nowhere on the page does it explain how will this grant be used. It asserts that there's nothing preventing them from recreating BCS3-L1 ourselves from commercially available precursor bacteria but it doesn't say if that's the plan. My guess is this funding will be used to look into the different approaches, and then they will come back with a real project.

Hizonner 3y ago

It "persists in the mouth indefinitely". It's "been in the mouths of fewer than 15 people". This was in 2003, so I'm guessing they're not all dead. I'll stake 'em a box of cotton swabs...

mlyle 3y ago
Indefinitely may not be 20 years. That's a long time for selective pressure and rare events causing winnowing of mouth bacterial amounts.
cdchn 3y ago
Saliva transplant.
- nayaketo 3y ago
  yum

heydemo 3y ago

A product that permanently cures all cavities would have a valuation of hundreds of billions, if not trillions, of dollars. Is it plausible a company would choose to sell mouth wash instead and that the cure would remain undeveloped for 20 years?

hanniabu 3y ago
Why sell a one time cure if you can sell a daily cure
- heydemo 3y ago
  This is obviously a scam. There's no miracle cavity cure that's been suppressed for 20 years so a company could sell mouthwash
  - ClumsyPilot 3y ago
    Lets see, are there any parallels? Is there a solution to soil eriosion thats been supressed for 60 years, like perrenial agricultur If only there was a solution to climate change thats been supressed for 60 years, like nuclear power! Supressed is not the right term- not developed. Marker settles on a local optimum and does not make the huge investment needed to go to the global optimum. Also all the current market leaders lobby against the transition.
throwaway829 3y ago
"value" not "valuation". It has a value of hundreds of billions, if not trillions, of dollars. It would require enforceable patents to have that value funnel to one company.

teaearlgraycold 3y ago

This would be a huge win for humanity! But I suppose the downside is many people might stop brushing their teeth - and I doubt this new bacteria won't smell bad.

akrolsmir 3y ago

Oh wow -- totally didn't expect one of our grant proposals to be trending on HN! I'm Austin, cofounder at Manifund; we just launched our regranting program last week (https://forum.effectivealtruism.org/posts/RMXctNAksBgXgoszY/announcing-manifund-regrants https://forum.effectivealtruism.org/posts/RMXctNAksBgXgoszY/...) and are currently looking out for cool grants (like this one!) to fund. Happy to answer any questions!

rudyfink 3y ago
Why do you think the company never took it to market past testing? And thank you for looking into this. I recall reading about experiments on the modified bacteria years ago, but then I forgot about it. Until I read your page, I had not realized it died on the vine.
- hrkfmud50k 3y ago
  > After a single application, this strain persists in the mouth indefinitely, hedging out cavity-causing bacteria > but the developing company declined to go to market, and instead pivoted to selling once-daily probiotic mouthwash. sounds like they preferred to sell a recurring subscription vs a one-time sale
  - fsckboy 3y ago
    "I wonder if the one-time sale can be "resold" through snogging?" - Phil MacAvity
    - totetsu 3y ago
      Probiotic kissing booth?
      - TeMPOraL 3y ago
        Well, why not? Compared to fecal matter transplants, which are already a thing, tickets to a kissing booth will sell out like hot cakes. (Can I pay for a monthly pass up front? It's for medical purposes!)

wdwvt1 3y ago

I love the spirit of this grant but it has big "programmer knows better then pharma" vibes. At a first glance: 1) The original strain (BCS3-L1) is a clinically derived isolate with who knows what properties. Why not just take the well characterized ATCC/DSMZ strain and knock out the lactate dehydrogenase? I am sure the FDA would look more kindly on a better characterized strain - especially since you don't need whatever wild type mutations it has to keep it in the dental microbiome (the lantibiotic does that). 2) Who pays for this? Why? Finding the appropriate payer for a pharmaceutical intervention is difficult. Getting this through FDA trial costs (let's say) $200 million dollars. At the point of sale (PCP, dentist) the competitive product will be...toothpaste and a toothbrush. Getting a patient or insurance to purchase this under current models of care is going to be extremely difficult.

akrolsmir 3y ago
Yeah, agreed that the proposal has a whiff of "too good to be true". The applicant's track record looks fairly good, though (he's previously invested in my startup, Manifold Markets, and otherwise has an interesting history in many different domains). I think if there's even a 1% chance that the intervention looks as good as promised, it'd be worth further study for the proposed costs.
- wdwvt1 3y ago
  I am a drug developer working on identifying novel therapeutics from human skin, oral, and intestinal bacteria. I love the idea of Manifund - but I think this may not be the best project for it. This proposal needs some review by a biologist. In its current form, I think this is a much less impactful use of money than other things on Manifund.
  - fbdab103 3y ago
    Curious what those would be. Again, too good to be true, but if we could vaccinate against cavities, that seems like an enormous amount of human misery eliminated for a one time investment.

PlunderBunny 3y ago

Wikipedia article on carries vaccines: https://en.wikipedia.org/wiki/Caries_vaccine# https://en.wikipedia.org/wiki/Caries_vaccine#

superqd 3y ago

So... is the existence, or non-existence, of a certain bacteria why some people never get cavities? I'm sure there can be multiple factors, but I'm 51 and never had a cavity, but don't really know the specifics of what might be different about the environment of my mouth that seems to discourage, or not encourage, the formation of cavities.

toomuchtodo 3y ago
https://pubmed.ncbi.nlm.nih.gov/12369203/ https://pubmed.ncbi.nlm.nih.gov/12369203/ (2002)
fsckboy 3y ago
lemme ask you a question, I'm guessing you grow up with flouridated water?
- JeremyNT 3y ago
  Not OP but I'm a similar age and never had a cavity either. I grew up in a rural area and drank well water as a kid. They did occasionally provide topical flouride in the schools. I stopped going to dentists in my mid 20s. Routine cleanings are not actually shown to improve outcomes, and the lack of cavities leaves me no other reason to go. I couldn't say why I'm so lucky in this respect, but the bacterial explanation seems plausible.
  - htss2013 3y ago
    Mind expanding on the lack of data for cleanings? I got busy, then pandemic, next thing I know it's been like 7 years since I've seen a dentist. No problems or discomfort whatsoever. It occurred to me that bi annual cleanings are the SaaSification of dentistry, but I've never seen any real evidence.
    - toast0 3y ago
      I'm happy to go for regular cleanings, but I don't know how you could construct a well designed study to get data showing objectively what interval of cleanings results in better outcomes over many years. There's just too many uncontrolled variables. And, I don't think you can glean it from population studies either, because again, there are too many variables.

anandvc 3y ago

Newbie question: Can someone help me understand how adding a new benign bacteria helps prevent infection by the other cavity-causing bacteria? Do they "fight" each other?

BestGuess 3y ago
Something like this I think https://en.wikipedia.org/wiki/Competitive_exclusion_principle https://en.wikipedia.org/wiki/Competitive_exclusion_principl...

obblekk 3y ago

If I wanted to buy an atcc bacteria, what’s the easiest way to get access to a BSL1 lab that they’ll agree to ship to? Is BSL1 even certified or self attested?

fsckboy 3y ago

it's shocking that it hasn't been mentioned (ok, except by me in another comment) but flouridating municipal water systems through/after the 1960's at least in the US had a huge impact on the number of cavities/caries among children. Yuge. There are suspicions that fouride isn't good for us, and I mean beyond our precious bodily essences too, but in terms of teeth, it's been miraculous. I'm just mentioning it because people are talking about bacteria being "the deciding factor" to account for differences in outcomes, and there's a flouride elephant in that room.

deleted 3y ago
[deleted]
mike_d 3y ago
> There are suspicions that fouride isn't good for us, and I mean beyond our precious bodily essences too, but in terms of teeth, it's been miraculous. Fluoride is weird. Everyone just assumes some is good so more must be better, and any research into dental fluorosis (over exposure) is shunned. I believe primarily because prior to dumping it into the water and every dental product imaginable fluoride was expensive to dispose of and we produce a ton of it as a byproduct of making fertilizer.
- fsckboy 3y ago
  too much flouride is actually really bad for your teeth; brown spots/pits I think. It's why children's toothpaste has minimal flouride, because they swallow a lot of it. adults: don't swallow your toothpaste.
  - latchkey 3y ago
    i had white spots (Dental Fluorosis) as a kid from too much flouride... they eventually went away.
    - arthur2e5 3y ago
      White spots is mild fluorosis. The brown stuff comes in when you live next to a coal mine so your water is filled with fluoride (at concentrations way over what any reasonable water-fluoridizer wants to add) and other nasty stuff. People talk about how the fluoride in tea can help prevent cavities, but on the darker side... just imagine having all your food come from that sort of fluoride-rich soil.

jimnotgym 3y ago

> After a single application, this strain persists in the mouth indefinitely, In which case you only need to find a person from the original trial and get it from them. You don't need to recreate it?

Escapado 3y ago

Super exciting stuff and it got me thinking: could we genetically engineer bacteria to get rid of morning breath? I would like to think (and so does my dentist) I have very good oral hygiene* and I get regular checkups where everything is fine but when I wake up the taste in my mouth and my breath are really unpleasant. The last time I had to be on antibiotics for a longer time I noticed it was severely lessened but came back just as strong after. * My routine includes brushing my teeth 3x per day for 3 minutes with an ultrasonic toothbrush, I use an interdental brush at night, I use a tongue scraper in the morning and at night and I do an occasional chx mouthwash and semi-regular salt water rinses.

arthur2e5 3y ago
Could be something deeper down (tonsils, esophagus, nose), or... mouth breathing, which can become a habit if your nose is clogged often.
an_aparallel 3y ago
tonsil stones contribute a lot to bad breath in general (if you have them) - hazard a guess folks have no clue wtf they are :P
austinjp 3y ago
> My routine includes brushing my teeth 3x per day for 3 minutes I appreciate that you may have specific reasons for this routine, but is that a typical routine generally? I've heard 2 minutes twice per day, so 3x3 seems excessive, and might cause gum/tooth damage through abrasion?
- Escapado 3y ago
  I usually eat 3 meals a day or two meals and a snack and I brush my teeth about 20-30 minutes after that so I guess it mostly due to my wish to get my mouth feel fresh and prevent staining if I had something like kimchi. 2 minutes twice per day is probably sufficient most of the time but the amount of abrasion and gum damage will probably also heavily depend on the hardness of the brush, the specific toothpaste and and the of course how vigorously you brush. I asked my dentist about this last year and he said it's fine and my gum health and enamel seem to confirm that.

PeterStuer 3y ago

As with everything in biology there are tradeoffs. What is the tradeoff here?

RamblingCTO 3y ago

I think the section about why we should trust the project founder is quite funny. Something like "I did video games and stuff". And MIRI is AI, operations lead sounds like administration? So no relevant experience. While I can respect someone doing a moonshot, really I do, but maybe, just maybe get someone with relevant experience on board? I'd love to see this happen, but this doesn't help their case imho. -I spent five years at MIRI as Operations Lead. -I produce a video game that's #42 in category on Patreon, with an 11-person team, making six-figures with >1,000,000 downloads. -I run Heist and Geist and Heist: Sunlit Forge; welcometotheheist.com -I'm nominated for the Nebula for fiction, and was published in Asterisk three days ago under the name Jamie Wahls. -I run Aella's media empire.

TeMPOraL 3y ago
> -I run Aella's media empire. Well, that is a unique thing to put on your resume. But you're right, and I'm saying this as a person who'd easily fall for the halo problem after the MIRI mention. Pausing for a moment, all the list you quoted tells me is that the person is most likely clearer-thinking and smarter than average, is likely to be "nerdy" in exactly the way I'd hope people running a biotech project like this, and hangs out with people even smarter and nerdier in the way I like[0] -- alas, it also tells me he has little to offer in terms of relevant scientific, technological, or product qualifications. Sure, he seems qualified for a leader/manager (and he's definitely not afraid of holding a PR equivalent of a live grenade), but the first step I'd expect of him is, as you say, to "get someone with relevant experience on board". Preferably more than one. Being a certain type of nerd may help to inspire people, but vision is no substitute for actual experience in biotech. -- [0] - Which I realize may be less of an indicator of domain competence, and more of my bias towards like-minded people.
duozerk 3y ago
MIRI isn't even really AI; it's a pet project from that insane, sex-pest-filled movement in the US that calls itself "effective altruism" (that and their dozens of even-more-insane offshoots). IIRC originally funded by the pitiful creature that Yudkowsky had by then become. MIRI hasn't produced or published anything of scientific value. In fact seeing the person this fundraiser is about putting it as a high point in their references is a major red flag.

swader999 3y ago

They should pursue vet market first, less regulatory hurdles.

londons_explore 3y ago

http://www.oragenics.com/news-media/press-releases/detail/35/oragenics-receives-new-patent-for-improved-replacement http://www.oragenics.com/news-media/press-releases/detail/35... Wouldn't there be patent problems with reproducing this? Unless Oragenics is willing to license/give up their patent?