Happy to answer any questions!
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.
> 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
https://www.cnbc.com/2018/04/11/goldman-asks-is-curing-patie...
This shit should just be taken by the state for the benefit of everyone, because really it's insane not to.
Plenty of ways to make a profit.
My bet is that it was never tested and the claim is entirely a prediction.
https://news.ycombinator.com/item?id=17095954
> The product was being developed by Oragenics, but was shelved in 2014, citing regulatory concerns and patent issues.
A few HN commenters seem to think that there's a nefarious explanation where a cavity wonder treatment would be unprofitable to develop; I think that's possible, but also it could just be that the company dropped the ball. Hanlon's razor: "never attribute to malice that which is adequately explained by stupidity"
It's clear they couldn't raise $10b to fund trials on a timely basis for something that was far from a sure thing - it worked in a couple cases, but imagine if it caused increased heart disease or "no clinical benefit" and you'd poured billions into it.
Don't forget about Hanlon's handgun: don't attribute to stupidity that which can be adequately explained by systemic incentives promoting malice.
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.
I mean - you know how there’s pills you only need to take once a week - but they come in sequential packs, to be opened daily? Resulting in one real pull and six placeholder placebos per week? Because it’s easier to get in the habit of taking a pill once daily, than it is to get in the habit of once weekly?
It’s stuff like that. Fluoride in water is a hack to get around humans’ naturally poor performance.
I haven't seen any pills exactly like this, though I guess some may exist.
The most famous real world example is "the pill", contraceptive hormonal treatment which is usually prescribed as complete cycles with some "dummy" pills which roughly simulate a 28 day "typical" female ovulation cycle. That choice is somewhat arbitrary, some people do perfectly well just taking the "live" pills every day whereupon their body just suppresses ovulation and they don't experience periods. A sympathetic doctor may be able to prescribe this actual treatment (which avoids discarding the "dummy" pills in a pack) if it suits you, so you just get "live" pills to take daily, typically for a year or so at a time. On the other hand, at the far end of the spectrum my mother was unrecognisable, basically completely psychotic on the pill, whereas it turns out she's fine when pregnant (fortunately for me and my sister) or after solving the problem in a more drastic way†. The choice of 28 days is basically because they had to pick something as most people aren't in either of the prior categories, their bodies will tolerate hormonal intervention to a point, and 28 days felt sort of like the natural ovulation cycle.
[None of this is medical advice. Ask your doctor about what you should do, don't interpret something from some HN poster as advice for your own medical treatment]
† My mother had her uterus removed, so, no more pregnancies.
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.
adults: don't swallow your toothpaste.
So does fluoride. (It replaces the hydroxyl group. Your saliva already contains calcium and phosphate.) Enamel remineralized with fluoride yields fluorapatite, which has a critical PH of 4.5 vs 5.5. of hydroxyapatite: https://en.wikipedia.org/wiki/Fluorapatite
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.
Cavities are a ridiculously huge market without the recurring revenue imo.
At that point, it looks much better on your CV to say "we made this miracle treatment, but the FDA put up hurdles to us getting it to market" rather than "we spent many years but the treatment we made didn't work".
> pivoted to selling once-daily probiotic mouthwash.
Businesses love recurring revenue streams
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.
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.
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.
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).
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.
And we have toothbrushes…
I'd also expect a high fruit diet in certain tropical regions where fruit is available more constantly also shows similar effects.
How long did they live before becoming remains?
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.
So did the tapeworms. Or fleas
- 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.
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.
However, there is significant variation of thickness of tooth enamel, seemingly due to genetics.
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.
Then you don’t know if you have cavities. Not all cavities are painful. Good luck.
You don’t know if you have cavities. I was similar. No issues so I stopped going for 15 years. Needed multiple fillings when I finally got a checkup, one of which was quite deep and has caused tonnes of issues since. If I’d gone regularly it would have been caught early. I wish I’d kept going when I had no issues so things would have been caught earlier. Cavity != pain a lot of the time. Typically when you get pain it’s a bad cavity which could have been caught sooner and treated more easily.
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.
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...
-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.
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.
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.
Is it plausible a company would choose to sell mouth wash instead and that the cure would remain undeveloped for 20 years?
* 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.
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?
Wouldn't there be patent problems with reproducing this? Unless Oragenics is willing to license/give up their patent?
Also how does this compare to bacteria like s. salivarius ?
My guess is this funding will be used to look into the different approaches, and then they will come back with a real project.
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?
Is BSL1 even certified or self attested?
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).
