Gene-Engineered Mouth Bacteria | Hacker News Reader

Gene-Engineered Mouth Bacteria

lanternbioworks.com

416 pointsapsec112296 comments

This is certainly an interesting idea, but there's absolutely no way for anyone to judge whether the claim on this page is bulletproof true, something plausible worth researching more, or just total nonsense.

But the fact that there isn't a single link to any scientific paper or evidence whatsoever, or even a single person's name linked to the site (or source of funding or anything), makes me assume this is just spam or a scam.

Apsec112, why did you submit this? How did you find it? Can you give us any context to suggest that anything about this is legit?

And anybody else -- are there actual published results from legit scientists on this? Is this a real thing, or just make-believe?

Because this is an extraordinary claim, and extraordinary claims require extraordinary evidence. Not just 11 sentences.

Edit: I missed that at the very bottom of the page there's a link to a... Google Drive folder? [1] But it's disorganized and not exactly, well, professional. I can't make heads or tails of anything in it, or find anything that suggests credibility.

[1] https://drive.google.com/drive/u/0/folders/18ZDSe92LgLmS0sUb...

Hi! These are friends of mine. There is much more detail in the Google Drive (linked from the About page): https://drive.google.com/drive/u/2/folders/18ZDSe92LgLmS0sUb...

Sorry, but we don't know you either, so a word-of-mouth referral doesn't tell us much here. The Google Drive link doesn't provide anything substantive, like links to peer-reviewed, published research.

This comment describes the research: https://news.ycombinator.com/item?id=37635401

If your friends are looking for feedback, you can pass on that at least one person on the internet finds it in very bad taste for them to describe the delay in treatment as a "civilizational embarrassment" while planning to charge $20k for a dose. The pricing point seems equally a civilizational embarassment to me.

Not just embarrassing. A disgusting example of the worst parts of humanity.

I can easily imagine someone who don't brush their teeth ever to spend like $1000 a year for cavity repairs (because, well, I did).

So I guess $20k is near to the market price you could expect people to pay for a lifetime (with refills and no cavities guarantee) for this product.

If $20k it too much for you, just wait for cheaper generics.

That's not the point — the critique (as I understand it) is about the way in which it's presented.

Capitalism at its finest. A civilization should be measured at how it treats the poorest. By selling such an incredible cure (if it's really working) for thousands of dollars makes it impossible for the low-income class to purchase.

https://www.bizapedia.com/ca/lantern-bioworks-inc.html has something:

"LANTERN BIOWORKS, INC. is a California Non-Profit Corporation - Ca - Public Benefit filed on January 4, 2023. The company's filing status is listed as Active and its File Number is 5412825.

The Registered Agent on file for this company is Tovella Dowling, PC and is located at 501 W Broadway Suite 1310, San Diego, CA 92101. The company's principal address is 501 W Broadway Ste 1310, San Diego, CA 92101 and its mailing address is 501 W Broadway Ste 1310, San Diego, CA 92101.

The company has 3 contacts on record. The contacts are Aaron Silverbook from San Diego CA, Connor Flexman from San Diego CA, and Nick Mossakowski from San Diego CA.

It seems hard to believe the ethanol producing bacterial strain would dominate your oral microbione for life from one application. But I’m willing to have an open mind and see some data.

They need to get the data off of the Google drive and presented in a better way. I don’t click unknown Google drive links if I can avoid it.

Brushing your teeth and using mouthwash wipes out the majority of the micro biome. Application of the new strain shortly after could totally replace it wholesale.

That said, I can’t imagine there’s not other side effects that just aren’t known yet. The sample size and reporting (as far as we know) is just too small and meaningless.

Does brushing and mouthwash really eliminate your microbiome? I heard it does precious little. Most of the microorganisms live below the gumline and surfaces. If that were true it would eliminate caries! Please post links

Mouthwash (WITH alcohol) daily almost completely eliminates the need for daily brushing and flossing. This was later retracted by demand of the ADA to only say "as good or better than flossing"; from here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894074/ "mouth rinses would be considered to be “at least as good as” daily flossing if the upper limit of the 90% confidence interval" there are a number of studies on this topic and they all seem to generally be in agreement. Mouthwash even once a week is really good for dental hygiene. They make alcohol free mouthwash but it's hard to argue with the antimicrobial properties of alcohol and the price difference is neglible.

That would get rid of all the good bacteria too, which can't be… good.

No thanks. I'll not be using alcohol-based mouthwash. https://drugfree.org/drug-and-alcohol-news/australian-study-...

You should stop drinking diet soda too, a byproduct of metabolizing aspartame is formaldehyde which is also a carcinogen.

This definitely can’t be true. There are too many spaces that cannot be reached mechanically.

In one of their articles they claim that the microbiome is stable over 15 years, but this is categorized as "unpublished work" which leaves me with a large sense of doubt. I don't mind research that is in preliminary stages (as in conference abstracts, technical papers, etc), but the fact they are very naïve in how they approach scientific evidence makes me highly doubtful.

Yeah, if it's in "patent hell and FDA hell" there should be applications and evidence of that online, right?

Patent hell should be over if this was invented in 1985.

who knows. maybe invented as a concept and then developed as a concrete dentistry protocol, which then got parented recently?

Good point. But that would be odd then to present it as solved in 1985 if only recently was figured out how to put it into a protocol. That would be a new innovation rather than “been around forever but never used.”

I didn’t look at that Google drive, but Google search gave me:

https://pubmed.ncbi.nlm.nih.gov/12369203

https://en.wikipedia.org/wiki/Caries_vaccine

As a layman, I would be concerned about trying to control a bacterium called Streptococcus mutans, as that, to me, signals “this thing mutates rapidly”.

Mutations trend towards stable states. Stable states further trend towards states where fast mutation becomes disabled because it's in a "good" stable zone.

Symbiosis is the ultimate stable state.

You can get stable states in intermediate zones like hiv infections, but these zones are not as good as symbiosis. They have potential to kill off a weak population, additionally humans are actively combatting the virus. In symbiosis there's no negative for either side.

There is no evolutionary pressure to "mutate" in symbiosis. Mutations will occur in the beginning. Those will die off fast and eventually the strain will become more and more stable as the gene starts mutating towards a configuration that has slow mutations.

As I understand it you left off the key reason why symbiosis is a stable state for a parasite/symbiote: because other states tend to destroy the host, causing the mutated strain to (usually) have a harder time propagating. That's all well and good when you're looking at evolutionary theory writ large, it's less appealing when you're talking about sticking a new bacteria in a specific person's mouth.

>because other states tend to destroy the host

No untrue. That is the most extreme case. A parasite can make a host less healthy and less likely to reproduce. This all lives on a gradient where parasitic relationship move the likelihood of reproduction down a little while symbiosis is the most extreme state where reproductive success is only positively effected.

>it's less appealing when you're talking about sticking a new bacteria in a specific person's mouth.

What does appeal have to do with anything? Much of our medical treatments were unappealing at one point in time. Colonoscopy? Sticking a camera up your ass to prevent cancer. Surgery? Cutting you open to fix something. None of it appealing but all of it necessary and worth it in the end.

Also keep in mind we live in times where much of the food we eat is bioengineered to live in symbiosis with us. The difference is instead of directly manipulating the gene, we indirectly manipulate it through artificial offspring selection. All domesticated animals and plants have been manipulated this way at a macro level for eons. The difference here is that the manipulation is happening on the molecular level rather then the macro level.

Your aversion to it is just instinctive and habitual but it's no different to much of the things we already do.

> A parasite can make a host less healthy and less likely to reproduce. This all lives on a gradient where parasitic relationship move the likelihood of reproduction down a little while symbiosis is the most extreme state where reproductive success is only positively effected.

Whether or not the host is destroyed, that symbiosis is the end game is not reassuring to someone whose mouth has gotten worse as a result of the treatment.

I'm not saying it won't work and isn't worth a large scale trial, I'm just saying your arguments based on evolutionary theory aren't a sound basis for medicine. I would not take a tapeworm into me on the grounds that someday tapeworms might evolve into a symbiotic relationship with humans.

>Whether or not the host is destroyed, that symbiosis is the end game is not reassuring to someone whose mouth has gotten worse as a result of the treatment.

That is the point of clinical trials. No treatment can be released until it has been verified to be safe.

>I'm not saying it won't work and isn't worth a large scale trial, I'm just saying your arguments based on evolutionary theory aren't a sound basis for medicine.

I never said it was a sound basis in it's current form. It's a sound basis to move forward rahttps://news.ycombinator.com/newspidly to change the current theory into a sound basis.

> I would not take a tapeworm into me on the grounds that someday tapeworms might evolve into a symbiotic relationship with humans.

one average guy who literally did the opposite of you. Against all medical advice, he infected himself with hookworms:

https://www.theguardian.com/lifeandstyle/2010/may/23/parasit...

podcast on the same guy who infected himself with hookworms: https://www.thisamericanlife.org/404/enemy-camp-2010/act-thr...

The innovative risk takers are the ones that try things out and move things forward. I'm not recommending you become one, but I recommend you support people who have the drive and willingness to do this because you and I only stand to benefit.

The other problem with science is that it's slow. Will science produce a verified treatment in your lifetime? Clinical trials cost millions. Maybe they'll do one, maybe not. In those cases if you have no other option, take a risk.

Another guy who did it: https://www.npr.org/sections/goatsandsoda/2016/08/12/4896190...

But here, we move this organism to a state of which we don’t know whether it’s stable. If it isn’t, it may take a while to get back to a stable state and, in-between, it could be nasty.

Also, I would think the Spanish flu, the Hongkong flu, COVID-19, etc. are examples of cases where “trending towards stable states” had fairly dire consequences.

>But here, we move this organism to a state of which we don’t know whether it’s stable.

We have to test the stability in experiments. Logically though we can assume it's stable as all the macro evolutionary pressures make sense here. When a virus kills, it's almost always a fluke one off mutation.

>Also, I would think the Spanish flu, the Hongkong flu, COVID-19, etc. are examples of cases where “trending towards stable states” had fairly dire consequences.

Yes they are trending towards stable states. But these are huge anomalies of conditions involving death. Likely instable states of mouth bacteria basically involve the newly introduced bacteria dying off or having new side effects. Again this has to be measured. I think it can be easily done with primates getting fed human diets.

I think you're just reacting to the fear mongering headlines of killer virus. What's going on here isn't living at those extremities and is ultimately a different topic. Cavities in our mouths are also stable states, the goal is to push it out of this zone into the ultimate stable state of symbiosis.

As I layman, I am more concerned that drastic alterations to the oral microbiome could have many negative downstream effects on health, from everything to digestion (naturally) to heard disease and neurodegenerative disorders. All of which show some correlation to an altered oral microbiome. We barely understand the connections, but that is obviously an argument in favor of caution.

I'm grateful that there are people out there willing to be guinea pigs for stuff like this, but I definitely wouldn't touch this kind of product until there are years (ideally decades) of usage with systemic scientific investigation into immediate complications as well as long term health impacts.

S. mutans was named in 1924, long before the idea of genetic mutations was established. It was likely named that because it converts sugars to acid.

I take very significant issue with the fact their appendix A and B do not link to the original literature. When I was skimming the pitch deck, I thought they had done the experiments themselves, but it just looks like they copy pasted the results without proper citation. At best this appears as miscommunication, at worst misrepresentation of the work they have accomplished.

I work in medical startup space and the evidence we develop to prove our technology works typically has a higher threshold than what I've seen presented. I would want to see significantly more work done to demonstrate the scientific validity of this research. Do they intend to carry out any additional pre-clinical research (in vitro/in vivo)? Do they intend to do a clinical trial? It appears from their slide deck that they don't?

>I work in medical startup space and the evidence we develop to prove our technology works typically has a higher threshold than what I've seen presented.

Like what?

>I would want to see significantly more work done to demonstrate the scientific validity of this research.

Like what?

Educate the layman instead of saying this is no good, please.

>are there actual published results from legit scientists on this?

The main papers referenced by document on the page are by JD Hillman on 1987[0] (et al) and 2002[1]. A layman review was done few years later by PopSci[2]. This specific site and company appear to have no relation to Hillman or Oragenics (co-founded by Hillman) that holds a patent on this[3,4].

[0]: https://journals.sagepub.com/doi/abs/10.1177/002203458706600...

[1]: https://link.springer.com/article/10.1023/A:1020695902160

[2]: https://www.popsci.com/scitech/article/2008-01/germ-could-sa...

[3]: https://www.oragenics.com/news-media/press-releases/detail/3...

[4]: https://patents.google.com/patent/US9260488B2/en

Thanks! They have a deal with Hillman for use of the tech, it's in the slides:

https://docs.google.com/presentation/d/1OqDqFYMQdcS0XM4hORqN...

A conversation with my friend who was a dentistry student, ~2013.

  > [The friend, let's call her L, trying to dissuade me from drinking some fizzy drink]
  > J: But I won't get a cavity if the liquid doesn't touch my teeth.
  > L: Cavities are caused by the ensuing low ph environment, not by contact with teeth
  > J: Does that mean I can drink as much of it as I want as long as I rinse my mouth with water afterwards?
  > L, with a hint of defeat in her voice: yes.

After this conversation, I started the practice of rinsing my mouth with water after eating anything sugary or associated with tooth decay, as well as using interdental toothbrushes. My rate of cavities dropped from one on most years to zero - I haven't had a cavity since. Even the one noticed by my dentist at the time and left untreated for being too small hasn't developed yet, and that was ~ten years ago.

On a sidenote, I have yet to find interdental toothbrushes whose use doesn't lead to ingesting nylon.

> I have yet to find interdental toothbrushes whose use doesn't lead to ingesting nylon.

Use the interdental toothpicks made of wood.

Very bad advice, as the brushes need to have specific sizes suitable for the spaces and the bristles actually reach more spaces and remove plaque. However, someone could manufacture the brushes from natural hair, e.g. from pigs as with other kinds of brushes.

Water also just dissolves the sugar and reduces the amount sitting in and on our teeth. I do this same thing and haven’t had a cavity in a very long time.

Is the rinsing needed, strictly speaking? Is there something special about spitting the water out afterwards instead of e.g. swallowing it?

Who said they spat it out? Rinse doesn’t necessarily imply spitting something out. You spit out mouth wash after rinsing because you can’t drink mouth wash. But sugary water is something you can drink.

Yeah I don't necessarily spit it out. It's getting it off of your teeth that is the important thing.

Your stomach is already full of whatever it is you just ate. 0.1% more from whatever remains in your mouth is not going to hurt it.

You should rinse and spit it out in the morning, don't swallow as you will be swallowing significantly more plaque from the over night build up. After initial morning cleaning swallowing should be fine.

Why would swallowing the plaque be significant?

It destroys your heart, possibly. Plaque builds up in arteries, etc. I just don't know if dietary plaque gets into the bloodstream. Don't think there are many studies. But plaque left on the teeth is known to cause heart problems and be lethal so I imagine trying to keep it out of our systems has to be better than not.

> I have yet to find interdental toothbrushes whose use doesn't lead to ingesting nylon.

Isn't that all toothbrushes, or are interdentals unique? (I haven't used them.)

I always assumed that toothbrushes would shed microplastics during brushing.

Also, avoid flossers, as they usually have PFAS. I use a water flosser instead.

There is floss made from silk without any PFAS. One brand is called RADIUS. Floss does a better job than water flossers.

It would apply to all to some extent, but when you make the wrong move with an interdental toothbrush it can lose a quarter of its bristles in one session.

You could make the bristles from pigs hair or similar as with other kinds of brushes probably. It would just be really expensive and probably isn't worth it. If you can, do use the correct interdental brushes as they are way more effective. You should consult a dental hygienist for proper sizing. Should you come to Prague, you should contact fulldent.cz as far in advance as you can and arrange an appointment.

(Disclaimer, my GF works there however I and my whole family and some friends who attend there have since then the best dental hygiene possible. They also don't mind English at all.)

The research that found this didn’t identify PFAs in any dental floss but instead found a correlation in blood levels in the (small number of) participants.

They detected fluorine in the floss and assumed that meant PFAs (Perfluoroalkoxy). This is a really bizarre leap because the floss is made of PTFE (Polytetrafluoroethylene), which has fluorine, but is unrelated to PFAs even if you squint, despite both being fluropolymers.

PTFE is safe unless heated to over 300C, which doesn’t happen in your mouth. At one point in history the manufacturing process used PFOA, which is not an awesome chemical, but has not been used since 2013.

However it carries a reputational stigma from that time to this day. It’s otherwise chemically stable and non reactive. It’s also important to note that the study that everyone is basing these conclusions on was in the range of time that PFOA was used to produce PTFE, possibly explaining the PFOA detected in higher amounts.

https://www.nature.com/articles/s41370-018-0109-y

I mean these: https://www.amazon.co.uk/Interdental-Original-0-4-1-5mm-effe... The problem is that when they encounter a sharp edge, they get torn or cut off. I doubt there has been any research on the ingestion of nylon cuttings, which is why I would prefer to find something as effective but known to be safe.

Yeah sorry I was referring to the dental floss comment I responded to. There’s a lingering belief that PTFE is bad for you, which had more to do with its original production method than the substance itself. Modern PTFE is safe.

I pretty much stopped getting cavities when about 10 years ago I stopped enjoying sweet foods and drinks. (Dessert, pastries, juice, soda, etc)

Yes I understand that refined breads, such as white bread on sandwiches, will still cause tooth decay; but I found simply drastically cutting down sugary foods & drinks was enough.

I drink a lot of acidic sodas, but I've never had a cavity as an adult.

You could be lucky but you could also just have a bad dentist who does not x-ray or the x-ray might be old and with insufficient picture quality. (Source, GF is a highly specialized dental hygienist and we talk a lot about some cases. I was even at Euro Perio with her...)

Holy shit man you used to get one new cavity a year??

> one on most years

What?! Did you never brush your teeth or something? That's an insane rate.

Genetics seems to be weird when it comes to teeth.

I (foolishly) stopped seeing a dentist at all after college. I finally managed to force myself to go around 15 years later. My enamel was worn down, my teeth discolored (not terribly, but noticeably), and my gums were not in great shape, but I ended up with only two cavities that needed to be drilled and filled. After resuming regular dental visits, my teeth are fine. My general oral hygiene prior to that was ok, but not great (2x daily brushing most of the time & mouthwash, very occasional flossing).

A friend of mine does everything right: mostly avoids sugary foods, brushes after meals), mouthwash, flossing, and he goes to the dentist every 4 or 6 months for a cleaning. But he still has many dental issues to deal with, and has had quite a few cavities filled.

Yes! Rinsing your mouth REGULARLY after meals does a lot to prevent further cavities. Also a diet high in animal meat and fats (cheese, butter etc.) helps strengthen teeth https://www.healthygoods.com/blogs/news/dr-weston-prices-die...

And cutting out sugars - especially fructose - avoids diabetes. Some people who are lactose intolerant cut out lactose, and some people prone to celiac disease cut out gluten. Sometimes the simplest solutions, done consistently, are best:

https://aeon.co/essays/sugar-is-a-toxic-agent-that-creates-c...

As for toothbrushes — if you are worried about microplastics you can get this:

https://www.amazon.com/Bamboo-Toothbrush-Adult-Size-Pack/dp/...

> Yes! Rinsing your mouth REGULARLY after meals does a lot to prevent further cavities.

So basically drinking water?

Not drinking

Rinsing your mouth, like sloshing it around to make sure it gets rid of all the gunk. Maybe flossing too.

I've done everything the experts have said, we were too poor for sweets, but they have continued to prove themselves wrong.

Something I find interesting is the role zinc plays in the oral cavity, a sufficiently high intake see's an increase of zinc in the saliva, which in turn reduces the oral bacteria levels, zinc will appear in the enamel of the teeth, and zinc has a similar oesteoblastic effect with bones where its also stored for quick release. The effect it has on bone marrow, increasing stem cell numbers, and people will be familiar with the idea of taking zinc at the start of a cold to half the duration, I'm left wondering if zinc is deliberately ignored by medical experts for fear of being put out of work!

I've found them to be pretty correct. I brush and floss before I got to bed and I haven't had a cavity in over 15 years. In the past few years I've switched to using hydroxyapatite toothpaste, but that's the only big change.

This conflicts with some advice I have previously heard, so would be interested in any hard research for or against.

I was told that if you vomit, you should not brush or rinse your mouth. You are only moving the low pH stomach acid around your mouth and exposing more teeth to the acidic environment. Instead you should try to neutralize the acid (baking powder or similar).

On one hand, I could believe you are just spreading the damage around. On the other, it feels hard to believe that some residual ~2 pH stomach acid would remain when massively diluted by a mouthful of ~7 pH tap water.

That doesn't sound like a conflict to me. People actively resist allowing vomit to touch most of their mouth. We tend to do the opposite with soda. So swishing with water after vomiting puts vomit where it otherwise wouldn't have been, while swishing with water after drinking soda only dilutes the places that soda already was.

The brushing thing has to do with the effect acid has on enamel.

I doubt you could find a dentist that wouldn't recommend swishing with water after drinking soda.

Perhaps I am an explosive vomit-er, but mid-act, I have little concern to what area of my mouth is being exposed. I would consider my entire mouth to be vomit coated. Whereas soda would be mostly concentrated to the bottom fraction of my mouth, predominantly on my tongue.

Acidic vomit or acidic soda seem like roughly the same thing. Either it should be diluted and swished or not.

Not sure that I understood what you're saying...

You drink fizzy drinks during the day, and each time that you drink you rinse your mouth with water without brushing your teeth.

And you only brush, say, before sleep, and this has reduced your cavities to zero?

thanks

The FDA requirements for the original clinical trial were wild: "...the FDA required them to find a cohort of 300 healthy 18-30 year olds who lived alone, not near a school zone, and had fully removable teeth."

I can see why this makes sense, but no wonder they failed at enrolling the cohort.

Why the "not near a school zone"?

Because of ethanol?

Maybe. You could possibly now fall foul of certain alcohol production laws....

Maybe some attempt to prevent a contagion that would rapidly spread to many households through the children?

That is a good question. I couldn't find a citation for the original comment, but my guess would be either that they want an unbiased cohort OR, since its a bacterial treatment, they wouldn't want to risk the spread and possibly contaminating children after the trial was done.

"fully removable teeth"?

For FDA, never permitting it is a completely acceptable outcome, and that's why it probably will never be permitted in the US. Unless somebody will find a reason to spend many billions of dollars to make it happen, which I don't foresee happening. I wonder if there's a chance in other countries, or they have their own FDAs?

Doing a couple Google/Twitter searches for this company it's pretty obvious it's coming out of the Berkeley-area EA/rationalist cluster, which automatically makes me pretty skeptical. These people don't exactly have a stellar track record of medical startups (recall all the hype around MetaMed, which delivered precisely nothing).

Longevity biotech came from a similar milieu and has been doing very well: https://english.elpais.com/economy-and-business/2023-07-17/t...

(along with AI companies of course)

> Longevity biotech came from a similar milieu and has been doing very well

They're doing well numerically when it comes to funding but is there anyone who has actually lived materially longer as a result of the field?

Ray Kurzweil will outlive us all, if taking 200 pills a day works:

https://www.wired.com/2008/03/ff-kurzweil/#:~:text=He%20is%2....

I just cant take this seriously. Why are Americans so afraid of death?

Almost everyone is afraid of death. Like, if you point a gun at someone, most people will feel fear. The main exceptions are people who are so sick with age-related diseases that they can't live happy lives anymore, but, of course, aging interventions would help with that.

I don't subscribe to his belief system, but logically if you enjoyed life, why wouldn't you want to prolong it?

I have no problem with prolonging life but trying to become immortal is dumb (and you will fail)

I will spend my time living instead of trying to avoid death.

I can’t that you seriously - what other fear could possibly be more valid?

Death is the end of EVERYTHING for an individual. What could be worse than that?

Everything else, we can figure out for ourselves, given time - pushing back death gives us more time.

Death is the beginning and end of everything. There is more to existence than your ego.

More time is fine but don't waste it by trying to avoid death (protip: you can't)

I honestly can’t think of a dumber take.

Longevity isn’t really about adding more years. No one wants to live another 10,20,30 more years how we currently do. But, if you can improve everyone’s health span, the amount of healthy, able bodies years, why wouldn’t you? It would be a great relief to our health care system. People can spend more time doing what they love without worrying about their body giving out on them.

Being someone who lost two immediate family members before 30, I’d do anything to have had them live longer and healthy instead of watching the slow and fast decline of the human body.

I'll raise my hand and say I'll gladly live another 30, 300, or 3,000 years longer than we currently do. Why in the hell would I want to cease existing?

I was referring to how a lot of the elderly live where they have no community, their body is shot, their mind is going, and modern medicine just keeps them in pain longer (if you were commenting directly to me)

Yeah - I don't get this take. Always rings a bit fanatical where you believe in some heaven, or suicidal at worst. I enjoy my neurons firing, because if they weren't, i wouldn't know it.

As a big science fiction fan who has been reading his whole life about fantastical possible futures for humanity, I'm not so much afraid of death as just super bummed that I'm going to miss out on things like exploring the solar system and hopefully beyond. The universe is such a mind-bogglingly fascinating place, and we know so little about it. I'm intensely curious to know how that's all going to pan out.

That is, if humanity doesn't destroy itself before then.

Not sure if you are kidding, but death is bad. I assume you don't want to die now, so why would you want to any other time? And don't say 'because I'm old', because obviously aging is part of the problem. Being 20-30 forever is the goal.

Death is not bad - without it life makes no sense. Being 30 forever and immortal would be my definition of hell. Death is doing a great job, leave it alone.

Chugging 300 pills per day - you will still die.

It is inevitable.

It is sad that you are insécable of finding joy and meaning in life without death. Go touch some grass.

you are reading something into my comment that is not there - I was saying immortal life would be a meaningless existence and no panacea to the human condition. Trying to escape death is not only futile, it is a waste of life. You are right of course, we should all touch grass more (I.e. really live) instead of trying to "solve" the human condition.

You misunderstood me too. Go touch grass and see what is so great about living. Then I don’t think you can fairly say we should have less years to live.

Can't wait to be a perpetually 20-year-old immortal Wal-Mart cashier because all the good jobs have already been taken by the other immortal 20-year-olds. Cleaning public toilets for the rest of eternity.

That is, if he doesn't get clubbed with a barbell by Nassim Taleb.

https://omniorthogonal.blogspot.com/2013/06/the-anti-kurzwei...

We'll let you know in 20 to 30 years...

If it takes 20-30 years to show any measure of success on what's supposed to be $600B of investment, it's a grift.

> These people don't exactly have a stellar track record of medical startups (recall all the hype around MetaMed, which delivered precisely nothing).

I can only think of one other medical startup coming out of the Berkeley-area EA/rationalist cluster, which would be Equator Therapeutics. They're working on an anti-obesity drug, and my understanding is it's going pretty well. But maybe you have others in mind?

(MetaMed came out of the NYC-area rationalist cluster and ~predates EA, and Alvea came out of the Boston-area EA group and shut down after their vaccine candidate gave disappointing results in human trials.)

Their org chart includes "Aella", who is apparently acting as their "media advisor" [0]. That tells you just about everything you need to know about this organization.

[0] https://nitter.net/Aella_Girl/status/1705772547781140541

So... people who are into sex work, fetishism, etc. aren't capable of being competent professionals?

Not saying this company is or is not legit, but this doesn't seem like a reasonable vector for criticism.

Where did I say any of that? What a weird response.

"This has, to our knowledge, caused no ill effects since."

That's the kicker. Damn near everything has side effects. How and why the FDA approves some things but not others is a quagmire, but the truth is that almost everything has side effects. Sometimes it feels like every approved drug ad you see on TV will have some lawsuit 20-30 years later. Look at where we are right now with ozempic. We know one of the side effects is thyroid cancer and doctors are prescribing it left and right while there is money to be made. In 10 years there will be a multi-billion dollar settlement for "misrepresenting the risks".

Ozempic, aka Semaglutide, the antidiabetic drug also being sold for weight loss. (For those like me who didn't know)

https://en.m.wikipedia.org/wiki/Semaglutide

Ozempic and thyroid cancer? Not really.

https://healthnews.com/news/possible-thyroid-cancer-risks-wi...

Source on Ozempic causing thyroid cancer?

Only thing I could find was a study in mice (which you should always take with a heap of salt) showing an increased incident, and a modest correlation in human studies but with a lot of caveats and a disclaimer that the study was in no way conclusive.

> Damn near everything has side effects.

Maybe that's true, I don't know. But it's worth noting they did not say it had no side effects, it was that they weren't aware of any ill effects.

You also need to weigh cost/benefit though. Everything may have side effects, but the mere presence of side effects is not alone grounds to not use something. For the particular case of ozempic, the effectiveness appears so strong, and obesity causes so many complications and such a massive loss of QALYs, it's probably worth it even if there is an increased risk of thyroid cancer, unless that increase is really huge.

> doctors are prescribing it left and right while there is money to be made

I think that's painting with a broad brush the motivations of doctors. Case in point: when diagnosed with diabetes, my doctor suggested attempting a modified diet before she'd prescribe medications (such as ozempic). She got no money from a modified diet.

Furthermore, I don't think she would've gotten any money had she prescribed medication; in the US, there's a "Medicaid/Medicare anti-kickback statute" [0]

I suspect that those motivated by money would be more inclined to pursue a lucrative career in finance rather than the long, arduous, and expensive path of becoming a doctor.

[0] https://journalofethics.ama-assn.org/article/it-legal-physic...

Thyroid cancer is one of the least dangerous cancers being easily treated and not generally life threatening. Obviously it would be nice not to get it, but a small increase to the risk of thyroid cancer for a substantially reduced risk of cardiovascular issues and complications from diabetes seems like a very sound medical decision.

The question I always have with this type of stuff is: why is it not _already_ huge. Cavities were a big thing already in 1985. If this was a miracle cure in 1985 then I do not believe that this study would have ended in 'ok that was fun, back to normal life'. This has huge commercial potential if true, so the apparently implications is that there is something blocking that commercial application.

Was it FDA? Was it side effectives? Is it impossible to scale this up? What is it that made this "miracle cure" just stop.

Don't want to get too conspiratorial, but dentists make their money on cavities, not cleanings.

Why are they not pushing against fluoride en masse, then?

Because they can charge $40-$80 (or more) for a fluoride treatment. It's actually how they make money on cleanings. If you don't opt for the fluoride treatment it's a wash.

> they can charge $40-$80 (or more) for a fluoride treatment. It's actually how they make money on cleanings

This is nonsense. Many dentists, mine included, don’t apply fluoride. (They trust you to use toothpaste.)

It's not nonsense. Perhaps many don't, but most ask (at least where I am). They literally ask you when you go in for a cleaning if you want fluoride and then charge you. My current dentist charges $40. My last dentist (Orange County) charged $80, which was a total scam place I only went to once.

Some years ago, maybe 25, no dentists in the USA applied fluoride. Yet somehow they stayed in business.

I don't think it's inconceivable that the economics of running a dental practice have changed over that time period.

Hell, my dentist doesn't ask: they just assume I want it ($80, SF bay area) unless I tell them otherwise.

I'm honestly kinda meh on my dentist, but getting me to go to the dentist at all is a slog (and I very much appreciate that they make me a new appointment for next time while I'm still there); the idea of expending the effort to find a new dentist feels paralyzing.

I end up just letting them do it. My teeth aren't exactly in the best shape. Unclear if the fluoride treatment actually does all that much, but it certainly doesn't hurt, and I don't want to look back when I'm older and regret not spending $160/yr for better teeth. I'd much rather look back and regret (but in reality not particularly care) that I wasted $160/yr.

And fluoride treatments likely don't do much. The main benefit of fluoride is from ingestion by children, while their teeth are forming.

That is absolutely not true. Flouride varnish helps prevent cavities and remineralize enamel in all ages.

Here's a meta analysis for you: https://www.ncbi.nlm.nih.gov/books/NBK401516/

It's the exact opposite

There are no benefits from ingestion - it's actually harmful and linked to a series of terrible stuff (cognitive development issues and neurological problems in primis). The only benefits are from topical application.

Source: my parents fed me fluoride pills for my entire childhood

My old dentist would give me a pump of it and have me swish for a minute. Billed insurance $20. Insurance always said "$5," then they "forgave" the rest, probably because I'd be asking some questions about how that costs them $20.

I think that's something else, just a fluoridated mouthwash? At my dentist it's something they "paint" on my teeth with a q-tip, and then tell me not to eat or drink for a few hours.

I’ve never heard of fluoride treatment. I never had it, I don’t think that’s common in Europe.

I was referring to fluoride in water and toothpaste.

Yes, sometimes it takes time, like in Japan the birth control pill ..

"Campaigners here joke that it took the country 30 years to approve the contraceptive or birth control pill, but just six months to approve the Viagra pill for male impotence. Both became available in 1999, but the latter came first."

https://www.bbc.com/news/world-asia-62515356

Well you have to take birth control constantly and a lot of very young women end up having it. You could easily wipe out a generation of fertile women if you didn’t do it correctly. On the flip side, old men (usually) that sometimes need to use a pill doesn’t seem all that dangerous.

Yes but, Women in the whole world took the pill since decades.

US dentists make their money on cavities.

Some other countries have healthcare systems where the primary goal is the patient outcome, and lowering the need for treatment is considered a win. If this were a thing, you'd expect that it might have been picked up and trialled in one of those places.

I don't know any place in the world where that's the case.

I can tell you publicly funded eu hospitals all want more treatments so they can justify bigger budgets. Rinse and repeat.

Universal healthcare systems very often don't extend to dentists. This is part of the reason British and Japanese stereotypically have bad teeth.

Meanwhile in the capitalist US, I haven't seen mine in months because her husband does her bookings and seems to be unable to remember to call me back. Small business owners usually don't profit maximize, and unfortunately it'd be better if they did.

If you want to more or less permanently stop gum bleeding pre-brush with a dilute (50 to 200 ppm) solution of hypochlorous acid generated from vinegar acidified salt water (0.8-2%) with salt concentration (saline is 0.8-0.9%) then hit it with a $5 Aliexpress USB electrolyzer for about 30 seconds. The biofilms come right off, your toothbrush ceases to accumulate biological matter, and hypochlorous acid does not begin to show toxicity in keratinocytes until 10,000 ppm. It is extremely unpleasant in the mouth above 200 ppm so it is relatively easy to guesstimate.

Any thoughts on brushing with a concoction of peroxide and baking soda as recommended in this yt video?

https://www.youtube.com/watch?v=Cow6wNRJqoo

Yeah, hydrogen peroxide is more toxic than hypochlorous acid.

Or just rinse (water pick even better) with a dilute bleach solution (0.25%). Make the solution fresh each time or every 24 hours, since sodium hypochlorite tends to decompose easily.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9292655/

Don't use bleach when you can easily make hypochlorous acid. Hypochlorous acid is bleach but acidified and much safer to the human body than bleach. Bleach is thousands of times more toxic to humans at the same HOCl concentration. You suggest using an OCl- concentration of 2500 ppm which would be extremely high for an equivalent therapeutic use of hypochlorous acid. You can easily use a 10 times lower concentration of hypochlorous acid for the same purpose, and it would still be total overkill. You can easily make hypochlorous acid with electrolysis safely or by mixing highly dilute bleach with highly dilute acid (vinegar) with a target pH range of 4-6. If your solution pH falls below about 4 there may be chlorine gas evolution which is generally undesirable. Above pH 4 it is not significant. Given the desired HOCl dilution hardly any chlorine gas will be emitted even if working in a confined space and using an excessively low pH. I recommend the electrolysis route for use in and around the body because the route is generally free from potentially harmful contaminants which may be in your bleach products. The bleach and acid method is useful to make a general purpose deodorant and disinfectant or if you trust your bleach to be free from harmful contaminants. https://www.dstec.com.my/wp-content/uploads/2020/04/pH-for-H...

Hypochlorous acid is hundreds of times more effective than bleach as a biocide because it is uncharged and can far more readily diffuse past the lipid bilayer of microbes to wreak havoc. Somehow, humans are generally much more immune to these effects. Whereas 0.1 ppm HOCl can kill most bacteria it takes approximately 10,000 ppm to damage most human cells. It is not recommended to use much over a handful of ppm in the nose and eyes.

Do you have any research papers supporting those assertions? At least with low-concentration bleach, it's been tested numerous times in RCTs without any harmful effects, besides bad taste. It's also proven effective, or at least as effective as prescription-based chlorhexidine mouthwash.

I'm interested in reading more, because I find diluting the bleach solution to be annoying and would obviously damage dyed fabrics if spilled.

I just brush and floss once a day before heading off to bed and have none of these problems...

A different generalization is that dentists make more money on treatments, and less on diagnosis or preventive care. It's hard to say if this is really a conspiracy theory since the diagnoses from different dentists aren't always consistent.

https://news.ycombinator.com/item?id=37022911

You're just an anti-dentite! :)

But it wouldn't be surprising that there's pushback against any technological breakthrough where established industries had something to lose. The FDA is not a stranger to corruption[1,2], so it wouldn't be far-fetched for lobbyists in the dentist industry to grease a few palms in their favor. Big Pharma is an ugly business.

[1]: https://www.businessinsider.com/fda-chief-approved-oxycontin...

[2]: https://www.science.org/content/article/hidden-conflicts-pha...

The average time from scientific discovery to commercial success in biotech is measured in decades. Barry Werth's book The Antidote goes into why it's so slow and complicated: https://www.amazon.com/Antidote-Inside-World-New-Pharma/dp/1...

Ok its been just about 4 decades. There appears to be 0 progress on this front.

It costs a ton of money to bring a treatment to market, and this one has roughly zero commercial value. Presumably once in the world it would naturally spread just by people kissing or whatever.

I don't think it's totally impossible that this really works and everyone gave up on it.

But I'd probably still put my money on this not really working (or having unwelcome side effects) and people quietly shutting down the project without publicly documenting the issues.

They say it was because of FDA approval. As it was GM, in order to prove it is safe they wanted a study done on healthy people who are completely isolated from the human race so that they can't spread it. As nobody lives in a place where they are completely isolated from the human race it wasn't a very realistic. Then the patent ran out so it wasn't worth it for any drug company to proceed with approval because everyone else would just wait until they've paid the fee and then sell it too.

A one time cure for cavities is just bad for business!

Same with RISUG, a cheap semi-permanent reversible male contraceptive made with a tiny piece of plastic (which would destroy condoms and female hormonal pill - never got to the western world) or ocumetics, the bionic eyes promising 20/20 for everyone with a simple cataract surgery (which seems to be stuck in a endless cycle of getting bought, and doing trials).

No, that hardly ever matters.

1. There's always new people.

2. If you don't do it, someone else will, because they'd rather be paid once than not have any business.

Now this topic has a huge grain of salt, but imagine something that one cheap treatment of basically wipes out an entire industry do you think that industry and associated ones wouldn't fight tooth and nail to buy it an bury it? I know it's been said the same thing about various engine designs, but just for the sake of argument I believe that's what they're saying here.

So within the existing population today there exist individuals who essentially never get cavities. The hypothesis for this has been 1. they don't eat sugar, or only fibrous foods, etc. 2. They have a genetic difference that builds stronger enamel or similar.

I have never heard of anyone discussing bacteria in the mouth as a possible difference. Be interested to see if there is a natural strand that some people have present that could also be a culprit.

There has been modest support for this concept in term of gut bacteria, i.e. thin people who donate their excrement to fat people seem to inoculate them with a gut biome that helps them lose weight, or deal with digestive issues.

I'm 40 years old. Never had cavities.

I eat plenty of sugar.

Yeah, it's always baffled me. Growing up I ate snacks and sugar fiendishly, but only ever had maybe one or two cavities in 2nd grade or so.

I had another friend who got cavities on an almost yearly basis. What was really fascinating was how boring her diet was; I never saw her eat anything more complex than a peanut butter sandwich or cheese pizza. She brushed, flossed and mouthwashed every day but could never get ahead of it. Meanwhile I went through all of middle and high school without any major dental work besides getting my wisdom teeth pulled.

It's all very odd, and my personal experiences have also led me to believe that diet plays a smaller role than we might think. I could be wrong though, I'm willing to defer to the most reasonable explanation.

It's genetic, some people just have thicker and strong enamel and salivary activity. Just like some people are scrawny and others are naturally strong without really trying

Are you good about brushing your teeth and flossing on the regular? Having lots of sugar isn't what causes cavities, it's not keeping up your dental hygiene. So if you eat a lot of sugar but brush well on a regular basis, I would expect you to not get cavities.

Genetics play a role as well. My mom never got cavities despite never brushing her teeth, whereas my dad could brush pretty regularly and still have a cavity or two when he got checked up. Sadly I inherited my dad's genes, not my mom's.

Depends. Nowadays yes, but younger no. I lived 2 years in west africa where clean water was a premium: I didn't brush my teeth much and drunk a lot of coke.

Yeah basically the same for me - I had a couple in my baby teeth, but I’ve never had a cavity as an adult.

Scientist lurkers in the thread take note. We have a couple for the first cohort for testing to see if their mouth biome differs from base population. Inquiring minds want to know!

Anecdotally, none of my girlfriends seem to have developped any similar immunity. If the article is right, my flora should have replace theirs on the long run, no?

I'd be willing to bet you drink a lot of water and also brush regularly. Am I right? Because that's what I do and I've 2 cavities in 40 years of life.

I am one of those people who naturally are more or less immune to cavities. My dentist tells me it is because of the pH in my mouth.

I _do_ have to brush my teeth etc... though, because i tend to have a lot of plaque if i don't.

Apparently either it is cavities, or plaque. You must take care of your teeth!

I have very strong (and ugly) teeth. The few "cavities" that I had, were actually made by dentists (they do that, y'know), and have resulted in a couple of crowns.

Otherwise, my teeth are great. I now have a dentist that doesn't make cavities, and she seems almost disappointed, when she checks me.

But gum care is every bit as important as tooth care (take it from me, you don't want a gum-scraping), and that is why I need to brush, floss, and mouthwash, twice a day.

> The few "cavities" that I had, were actually made by dentists (they do that, y'know)

You are the only person I have ever heard entertain this idea, so it would be better to spell out how this happened than assume everyone knows it.

Fair ‘nuff, but I’m not gonna bother getting into it. Life’s too short.

Let’s just say that there has been a fair bit of press, over the years on the matter, so it may not be as singular an event as you might think.

I can certainly attest that I've had dentists damage my teeth on more than one occasion.

A dental hygienist (those people who do maintenance cleaning at dentist’s offices) told me that saliva quality is key to cavity and periodontal health. The ability of keep all teeth moist prevents plaque/tartar build up. I don’t know how true that is, but this at least provide an alternative hypothesis to the two that you listed.

I have a surfeit of saliva and get many cavities:(

You should assume that everything related to digestion is caused by gut bacteria.

Nerds love saying things is "genetics" because they think it'd make humanities types mad if something was genetics. But it's like lupus. It's never genetics. (Except celiac.)

Probiora seems similar, but less sticky (it recommends a daily dissolvable tablet instead a once a decade tablet) and instead of producing ethanol, produces hydrogen peroxide.

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

What happens when these get into the esophagus and produce oxide species? Extra free radicals can't be great for your DNA. I wonder what the long term cancer outcomes would be.

Hydrogen peroxide producing bacteria are far more of a known factor than ethanol producing bacteria where it comes to long-term interactions with human mucosa, the former being a natural part of human vaginal flora.

Interesting product, but the site has one of the worst GDPR controls ive seen - silently redirects to Google if you attempt to view the site from an EU IP address. Thought my computer is going nuts

Not just EU, Switzerland too.

That tells me everything I need to know, the site owner simply wants to steal my personal data and use it against me.

Surely that’s the reason and not the EU penalty for simply storing cookies “without consent” being so severe as to practically negate the value of EU citizens on the internet.

There's no reason for that site to use cookies in the first place.

There's a lot more nuance to the GDPR. It's perfectly possible to use cookies and not need a banner. Our industry's use of banners is just a passive aggressive reaction to being told to respect our users.

At this point, isn't consent compliance a solved problem? That they can't find a canned solution to suit their needs is eyebrow-raising.

Cookies needed for a functional site can be used without notice.

The permission popups are only needed if you want to gather and store data. And why do that if you don't want to use it?

If you're really worried you can write a simple privacy policy stating your server stores some stuff like the client IP etc. (so you can do something like, block abuse) and then follow that policy to the letter by not doing anything else with the data you gather.

It's not hard.

Now imagine you don't give a shit about EU customers and just having to think of what our idiotic rules are is a waste of money. And all of this because I want to use google analytics and see how many people my landing page is getting? I would redirect us as well.

I did the same for VATMOSS when I was not in Europe: if I need to spend 5 days implementing VAT rules and collecting proof, I need to evaluate what I'll make from EU customers and if that's not likely to be significantly more than implementation cost you can all go and buy stuff somewhere else.

I just blame our idiot EU politicians for restricting freedom on the internet.

GDPR doesn't make it illegal to use cookies without consent.

It's also happening for Australian IP addresses, so it's unlikely to be GDPR related.

Australia as well.

Oral bacteria are a complex system of delicate balance. There are second-order effects that can arise which undermine the benefits of the first-order effects. https://www.medicalnewstoday.com/articles/324621

They have a pitch deck lamenting 90% of US adults have cavities, and they are 2x likely to get untreated if you are poor, then propose to market this for 20k$/dose. Saving the world, again, startup style.

$20k per dose Jesus H Christ. Rent seeking galore. Hopefully the patent has run out by now and others can get in on the action and make it affordable. There’s no way in hell this could possibly cost $20k. Is capitalism ever going to produce innovation that’s affordable to regular people again and not just benefiting the profiteering VC parasite class?

The patent has expired. The whole pitch here is to modify the tech a bit so they can patent it again and charge 20k/dose.

I'm not going to say I buy any of this or that I think it's a good pitch, but you see these numbers for new treatments because the math doesn't work out for the go-to-market without them. When the product is established, the price goes down.

> Hopefully the patent has run out by now and others can get in on the action and make it affordable.

The patent has run out, and in the ~20y since it expired no one has tried to revive the idea. Why are you faulting the people who are finally picking the idea back up instead of all the people who could have but didn't over the last ~20y?

I’m faulting them because it’s nothing more than a get rich quick scheme. Another comment even noted they are slightly tweaking it so they can get another patent for it.

The government should be funding this and making it available to the general population at an affordable price instead of just having the free market “figure it out” and making something affordable only to the ultra rich. But the US is a country where the government isn’t allowed to do anything and everything has to be left to the free market which nowadays is nothing more than a bunch of hyper capitalistic rent seekers that are only interested in maximizing profit at the expense of everyone else.

The impression I have from your comment is that you think that the US is unusually bad at this? Which seems a bit hard to square with no other country having sorted out a caries vaccine either. Including many rich countries with socialized medicine.

If they want to pay for it they can, but the most effective way for public healthcare to reduce costs is by not paying for expensive things.

> Is capitalism ever going to produce innovation that’s affordable to regular people again and not just benefiting the profiteering VC parasite class?

No way, those capitalist parasites will never make anything affordable.

Sent from my iPhone

On an IKEA sofa

Drinking coffee from another hemisphere

Hardware sales are not the primary revenue stream for Apple, it's services. Would iPhone be the same if there was no need to sell iCloud and iTunes?

This is a well established route for new tech: first start by selling to the early adopters who have extra motivation and extra money, then use those funds to lower the costs by increasing scale then reach a bigger market.

but they say this is old tech, with exprired patents, with some confusing 'Pfizer offered to buy it' and no extra details. To me it seems they mostly want VC money from those who would bet on something unproven if the potential market is huge. For a lot of non-software new tech you at least have a visible research group and at least some attempts at presenting peer reviewed papers.

It’s only 20k$/dose for the first family member. Once they establish the new biome you can borrow their toothbrush for a dose.

> stuck in patent hell […] for decades

Patents only last for 20 years.

So a patent that predates their work could, at most, frustrate them for 20 years, or two decades. I have no idea who these guys are or what patents they're referring to, but the use of the word "decades" here is not obviously deceptive.

Technically yes, but there are caveats to this. Drug companies regularly create new variants with no distinguishing characteristics but which reset the patent clock, using litigation, trademarks, secrets, and other tactics to prevent the original variants being used.

...which is exactly what the folks at the link are proposing. From their Investment Proposal doc:

> However, we can create a new, derivative strain of SMaRT, which would be under new IP protections, and therefore, would very likely be of interest to a large pharma company.

That’s the freedom-to-operate side. But “Patent hell” could also be the lack of clear IP that would allow a commercializer to capture a return on developing this. Not much incentive to spend tens of millions on trials if at the of the process the product can be sold by anyone.

What if you spit it out? Or what about french-kissing someone, can you give this bacteria to the other person that way?

Yes I believe that would happen if it outcompetes “native” non-gmo bacteria.

Good luck selling it for 20k/dose then.

The FAQ in the google drive linked on the page tries to answer these questions.

  Will this spread to everyone I kiss? 
  It’s very unlikely in non-immunocompromised adults. However, if you’re concerned, you should avoid kissing anyone taking oral antibiotics, or children. 
  [...]

https://docs.google.com/document/d/1mDJCTO2QySmQOZQcajYReDCA...

The company that made the bacteria gets less money and any ill-effects will need active management going forward.

The key is whether the unknown active management of this bacteria is preferable to the immense expense and problems of tooth decay.

I can see how this would have trouble attracting development funding. If your product is successful, people need one dose, ever. After some number have bought it the natural spread is likely to wipe out the rest of the market. It might be "pirated" with a kiss or a shared lollipop?

Against that, you have the entire dental industry, an established market of i dunno how much per year but substantial. They're already well versed in selling people intangibles packaged with inert ingredients. They've got a long history of "science to order" (9 out of 10 dentists agree!). They've got a large body of known sadists to call on for the less civil dispute resolution processes they might choose to employ.

I salute the folks behind this effort. Even if its all fairy dust you've put your lives on the line.

This sounds like great additional protection, but I would still like to brush and floss to get the remaining food grime out of my mouth. Meaning it really doesn’t change my life all that much.

It would certainly be a game changer for lower income families.

Good choice. Gingivitis is a deeper problem than cavities. Without your gums you lose not just your teeth, but it can become a systemic infection. And it's much harder to fix than a cavity.

I don't think anyone is suggesting this would replace brushing and flossing.

Plenty of people still have problems with cavities, despite taking good care of their teeth (seems genetics plays an outsized role in tooth/gum health). Not having to worry about cavities would likely be of great value to them.

Call to action is to give them my email to learn more, but no description of what I'd actually get.

I'd love to see links to papers, news articles, or some description of what they plan to do next.

From the pitch deck in their linked Google Drive it looks like the patent on the original strain expired and their whole idea is to create a slightly different strain they can patent again and sell for 20k/dose.

Not quite as altruistic as their initial framing makes it seem...

Cool concept though!

Now just to engineer them to produce menthol instead.

It's easy enough to test this without investor money, you just need a simple kit and some dentures (not literally, I meant teeth essentially). The design of the experimental protocol is key.

Alternatively, a non-intrusive supplement with DIM has recently been found effective against the Streptococcus Mutans bacteria.

3,3′-Diindolylmethane (DIM) decreased the Streptococcus mutans biofilm, a leading contributor to plaque and cavities, by 90%.

Source: https://scitechdaily.com/90-reduction-scientists-discover-na...

Adding live organisms to complex living systems tends to have unpredictable and destabilizing consequences. Invasive species being introduced to ecosystems can have knock-on effects that go far beyond their immediate biome. The human body is a complex living system, and the consequences of perturbing that system are difficult to predict.

There are probably also lots of "good" bacteria in the mouth and gut using salivary lactate. I could not begin to guess at the number of additional metabolic pathways happening that are related to this. Not to mention the mutacin production that they mention, that they think may also kill off some of the bacteria in the mouth, that hopefully isn't replaced with nasty S. aureus, C. difficile, Candida.

The gut flora angle is just a whole other rabbit hole.

In light of the potential benefits, the "reasons not to" might fall by the wayside, hopefully none of the cautions end up being a big deal. But the status quo doesn't suck that much, if you look at how bad it could be.

Personally, I would like to see more resources go to diagnosis, study and understanding, rather than seeing people try to jump straight to the silver bullet and test on volunteers. Is it moral because they are "volunteers"? Are they really volunteers given that they would most likely get paid?

More importantly - and I cannot emphasize this enough: If this was such a great and simple solution, evolution would have already given this mechanism to us to and other animals. There is (or was at some point) a very, very good reason that our bodies don't already do this.

Michael Laufer from the Four Thieves Vinegar Collective gave a talk that included a bit about this at a 2018 Defcon talk at the bio-hacking village. You can watch it here https://www.youtube.com/watch?v=FzqEJM8B0h4&t=1935s. Entire talk is quite entertaining but this segment always stuck with me since I get cavities fairly frequently.

He gave a SkyTalk at DC30 on the same topic with a few more years of knowledge

> "to produce ethanol instead of cavity-causing lactic acid"

So, brush your teeth and have ethanol in your mouth forever? I'm curious if this would be of high enough concentrations to show up on a breathalyzer, or if it would cause problems for people in recovery from alcohol or drugs.

Don't forget alcohol is also a carcinogenic.

Charging $20,000 for a dose? Really?

What’s a fair price? Spending well over $20k on dental work over a lifetime is easy for many people. Adjust for inflation and it’s a steal. Cavities often lead to eventual root canals which require a crown which one day will probably require an extraction and a dental post and prosthetic tooth. That is probably around $8k or more for a single tooth at todays rates.

The time-value of money means the adjustment goes the other way. $20k is absolutely insane. That’s three times the cost of a full orthodontic treatment. They’ll get a handful of customers, if that.

$2k is more likely as a price point for mass adoption.

$20k is likely the price for early adopters, while production rates are low. Within a year or three the price would likely fall to some stable long-term rate. $2k indeed sounds about right.

Healthcare (including dental) costs have outpaced inflation though. The price of all those procedures is likely to increase more than inflation.

Similar to how it would be a bargain to have paid for a college education today 20 years ago.

The average American probably spends about 20k in their lifetime, that's probably where they got their pricing from. They get a check-up a year and a handful of fillings with some prosthetics if they live long enough. Which totals to around 20k.

The average American also cannot afford 20k in one shot they can't even afford 2k.

If this is such a revolutionary technology and it is cheap to mass produce, it should be like water fluoridation and similar state funded measures that increase overall population health. I am not arguing that $20k is more than regular dental work's cost over a lifetime, in the US at least, but that it's because dental work is so expensive is why oral health is so bad worldwide,Lifestyle, sugar consumtion and the like notwithstanding.

Maybe it ought to be that way. But we believe in property rights and government confiscation of property isn’t something I support.

Might be the pols manage to find a way to buy the tech to give away freely to the people. Until then it’s theirs to distribute as they please until their exclusive rights expire.

I wasn't talking about confiscation, although expropriation and similar measure are common when done for a public good. Anyway in this case I think the whole product is bogus and it's mostly VC bait.

thats not the way this works. Paying $20k over a lifetime vs an up front $20k payment means the up front $20k payment also includes the opportunity cost of the interest made - your up front payment of $20k is much more valuable than $20k over 60 or 70 years. That same $20k might be a large part of a downpayment on a mortgage and you'd get back many more times the value than if you spent it on your teeth all at once.

Right but the price of dental work goes up in price over time too. And healthcare has dramatically outpaced inflation.

Sure, but you're literally throwing an opportunity to own property which historically is the best possible return to get preventive work done on your teeth. And not all healthcare is the same, so I'm not even sure dental costs are rising at the same rate as "healthcare".

You can engineer something yourself using a kit like the one they give to iGEM participants. If the business model relies on exorbitant pricing, then there's something off somewhere.

As soon as you've had a dose you can just start kissing people and they will get it too. Or do what the government does in bioweapon simulations and just start spraying cities with it to see how easily it spreads.

If the bacteria is in the public domain, is there a way we could just order some and try it out ourselves? I'd be interested in being a test subject. They've got decades of evidence showing it had no side effects so it's not even a risky thing.

Wonder if they're able to follow up with most of the people inoculated back in 1985, and find out how they're going now?

Seems like an obvious thing to try, but am not seeing anything along those lines.

Great except for the ethanol thing...

No I haven't been drinking boss... it's the bacteria in my mouth!

> It is possible to genetically engineer Streptococcus mutans, the dominant human mouth bacteria, to produce ethanol instead of cavity-causing lactic acid

I hope it's in such small quantities that it wouldn't cause any alcoholic effects?

Nonetheless, such a simple website with short and concise copy. Wasn't expecting that for a biotech startup. Hope it works, cavities suck!

Auto-brewery syndrome! https://www.cbc.ca/radio/quirks/oct-26-2019-world-s-loudest-...

This is hilarious. "a walking brewerey".

https://i0.wp.com/thebeerthrillers.com/wp-content/uploads/20...

Plus, the first sentence.

  >Michelle Giannotto knew something was wrong with her husband Donato after he had an infection following a simple nose surgery.

The guy's name is Donato Giannotto.

Not being mean, just fun to say.

Edit: not at all funny and irrelevant, apparently.

Probably not going to generate more ethanol than you already get in your morning cup of orange juice

The amounts produced are tiny. See the safety FAQ here:

https://docs.google.com/document/d/1mDJCTO2QySmQOZQcajYReDCA...

The quantities are too small to make you drunk, but does it increase your risk of mouth cancer to have this in your mouth all day every day?

Better question: do any increased risks from this outweigh the risks incurred from poorer dental health and procedures to address these? (particularly at high age)?

It's pretty unlikely to cause an intoxicating effect: it's surrounded by the mouth, so it'll be taken up almost instantly. It never gets to accumulate, so I'd expect the impact is far less than even something like kombucha.

I wonder what the religious implications might be.

Unless the bacteria makes it past the stomach and inoculates the intestines. Then you get nice and drunk every time you have cake.

Yeah, sure. A milliliter of etanol a month versus pain and drop of quality of life. Who would choose that!

I'd be willing to give it a shot.

Pun intended? If so, nicely done!

>The average human digestive system produces approximately 3 g of ethanol per day through fermentation of its contents.

https://en.wikipedia.org/wiki/Ethanol_metabolism

Where we not here before? GMO bacteria producing alcohol...

https://www.cracked.com/article_18503_how-biotech-company-al...

https://www.youtube.com/watch?v=PtPNaMphl04

Also lactic-acid keeps other mouth bacteria under control, do we really want to mess with the balance?

And there is little reason to believe that ethanol producing bacteria have a selective advantage. Why would they be maintained in someone's mouth microbiome?

My worries are with translocation of oral bacteria.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6427756/

Once it is in the gut you have Small intestinal bacterial overgrowth (SIBO) issues. (could have ;)

https://www.youtube.com/watch?v=wMWy2Rg6Ul4

So its patent encumbered? If there was a time for the “bio-hackers” this would be it. I heard everyone can perform some basic CRISPR so could we make this bacteria at home?

patent hell = our patent applications keep getting rejected for prior art from an expired existing patent, general ineligibility, and we have no moat and no capital

So wait, will this let me micro-dose alcohol at the same time?

That happens all the time anyway, and your liver has no trouble keeping up. It’s a poison your body always knew how to handle, so long as you don’t reach megadoses of the stuff.

I saw this in popular mechanics magazine like 15 ish years ago as a kid and I haven't stopped thinking about what ever happened to it. I hope this happens!

This seems like a pretty huge caveat (from the "Methodology for Inoculation, and Caveats" doc in their linked GDrive):

> Do not expose children under the age of five to this strain, including by sharing food or liquids with them. Disruptions to early microbiome development can carry through someone’s entire life.

Seems like a product that would be difficult to monetize even with a patent as the bacteria outcompetes other oral microbiota. Which would make it just as possible to be treated via a nice deep tongue kiss. (Or you know, less grossly rinsing then getting swabbed with a sample from someone else).

I wonder why it does not happen naturally if they outcompete normal bacteria, though.

Bacteria has great speed of evolution.

The added genetic factors may, themselves, be exogenous and genetically modified. Your argument does make sense over thousands of years, however.

Because there's no downside to the current system they use. They only out-compete if you modify them in other ways to make them more successful in addition to the change you want.

Evolution is all about optimising tradeoffs. So what is the downside of this "miracle cure"?

> what is the downside of this "miracle cure"?

The strain is probably less tough than its wild type.

There's a lot of thoughtful speculation and salesmanship, but no clinical data.

Create a prototype product, get some volunteers, and after that is successful, raise some money to go through clinical trials with the FDA.

Looks interesting but too good to be true. No one knows what is the catch? Or why the patent or technology would be stuck for so long if so good?

Also, would it really be safe to change the chimical equilibrium of the mouth?

> Estimated price point: > $20,000/dose

Dammit, this will make Martin Shkreli feel like a petty shoplifter. I hope biohackers will soon pirate those bacteries and sell to everyone in need.

A related question is if the same idea can be used for a deodorant: make a type of skin bacteria that does not produce odour and can outcompete other types of bacteria.

The rat/postrat scene is full of scams. Look up Rheos Propulsion lol - they’ve flipped to ‘muon weapons’ now and still desperate chasers throw money at them.

isn't that basically a one person show. chasers?

Patent hell? Yes, I'd generally believe that, but given that it's been 38 years since 1985, any related patents should have expired years ago, no?

Isn't gum disease more of a long term problem that cavities ( assuming you don't have a ridiculously sugary drink diet ).

Small price to pay

Tooth decay or brain and liver damage? Or reducing sugar?

Our body can assimilate 1 Alcoholic Unit per day without any problems. I doubt those bacteria would produce anything in that order of magnitude so I truly don't understand your reply. Did you just blindly write: "alcohol therefore bad"?

Not sure why this was downvoted. The dose makes the poison here

>The average human digestive system produces approximately 3 g of ethanol per day through fermentation of its contents https://en.wikipedia.org/wiki/Ethanol_metabolism

Unless it gets past the stomach, into the intestine and ferments most of the carbs you eat instead of traces of the carbs ingested

Hmm I remember this from Omni magazine. Their claim was that people got icked out with "mutated bacteria".

Fascinating stuff.

The price is est $20k. Would you pay that to never get cavities? Seems a bit high given avg cost of cavities

Replacing bacteria in your mouth with genetically engineered ones. What could possibly go wrong?

Probably nothing.

Unless you have an antacid then swallow the bacteria.

Then the bacteria, that transforms sugars and carbs into ethanol, gets past the stomach acid, populates the gut and you get a free buzz with no cavities everytime you eat a cracker.

That's actually a thing! https://en.wikipedia.org/wiki/Auto-brewery_syndrome

After 40 years this should have spread to some of the population via kissing. ;-)

Why anyone would want to host bacteria that produce ethyl alcohol 24/7?

I would like to clear some things up about how cavities/ caries come to be. Source: my GF is an experienced dental hygienist with her own office in Prague, Czechia. You can assume that nobody is immune so the whole genetic resistance angle is a myth. With that cleared up, how does a cavity/ caries come to be?

When we eat or drink the bacteria gets nutrients (any form of sugar) and builds up plaque and the bacteria create an acid. Because the plaque stays on our teeth above and even slightly bellow the gums (gingiva) and the bacteria likes to live there the effects are strongest where the plaque is. The bacteria and the resulting acid over time cause demineralisation, dissolves the calcium in the teeth. After some time this leads to decay which we describe as cavity/ caries. Also, the plaque can solidify into a build-up of tartar/ calculus which further provides a nice habitat for bacteria, causing gingivitis (inflamation of the gums - they become red and swollen) spreads the sulcus, basically splitting gums from the teeth over time which results in periodontitis, which is basically loss of the bone and other problems below the gums. Periodontitis can also exacerbate other illnesses such as diabetes, cardiovascular illnesses, possibly some allergies (active research). This can really only be fixed by a professional dentist or dental hygienist since removing the tartar, especially under the gums, is a precise and demanding. The procedure can be painful without local anesthetics.

If you don't want all that do brush your teeth correctly each day. The 2 minutes number is myth again - do brush until the teeth are free from plaque. It is easier with a sonic/electric toothbrush, e.g. by Phillips or Oral B iO should be ok too. The brushing technique is very important, most people do this wrong. The brush should be at 45° to the sulcus (half of the bristles is on the gums the other on the tooth). Obviously also brush the top of the teeth. Each tooth basically has 5 surfaces, top and 4 sides. Don't forget to use correctly sized interdental brushes. Your dentist or dental hygienist should be able to help you find the correct sizes for specific spaces between teeth. (You will probably end up with TePe or Curaprox and probably more than one size.) You can use a solo brush too, which brushes exactly one tooth at a time. The bristles of the brush should be as soft as possible and removal of bigger amounts of plaque are done by spending more time instead of force/ pressure/ hardness/ abrasiveness. In addition to not replacement of interdental brushes, you can also use a super floss (the middle is made of a fluffy material) but learn a good technique so you don't hurt your gums, throw the thin waxed floss in the trash especially if you are not super handy/ careful as to not cut your gums. Also, the floss does not clean premolars and molars properly because of the shape of the teeth in interdental space (because of their concavity, imagine that the surface is basically made of two pillars).

Do have a regular appointment with your dentist and dental hygienist. 2x a year should be enough with good hygiene. If you have more problems, the frequency of appointments will of course vary. They should definitely do at least intraoral x-rays each preventive appointment and a OrthoPantomoGraph in ~2 years.

Doesn’t that lactic acid play a role in digestion?

This a quick way to get auto-brewery syndrome.

So are you just drunk all the time instead?

The amounts produced are tiny. See the safety FAQ here:

https://docs.google.com/document/d/1mDJCTO2QySmQOZQcajYReDCA...

Alas, no.

Good luck at the check stop after this.

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