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

Oh wow -- totally didn&#x27;t expect one of our grant proposals to be trending on HN! I&#x27;m Austin, cofounder at Manifund; we just launched our regranting program last week (<a href="https:&#x2F;&#x2F;forum.effectivealtruism.org&#x2F;posts&#x2F;RMXctNAksBgXgoszY&#x2F;announcing-manifund-regrants" rel="nofollow noreferrer">https:&#x2F;&#x2F;forum.effectivealtruism.org&#x2F;posts&#x2F;RMXctNAksBgXgoszY&#x2F;...</a>) and are currently looking out for cool grants (like this one!) to fund.<p>Happy to answer any questions!

it&#x27;s shocking that it hasn&#x27;t been mentioned (ok, except by me in another comment) but flouridating municipal water systems through&#x2F;after the 1960&#x27;s at least in the US had a huge impact on the number of cavities&#x2F;caries among children. Yuge. There are suspicions that fouride isn&#x27;t good for us, and I mean beyond our precious bodily essences too, but in terms of teeth, it&#x27;s been miraculous.<p>I&#x27;m just mentioning it because people are talking about bacteria being &quot;the deciding factor&quot; to account for differences in outcomes, and there&#x27;s a flouride elephant in that room.

&gt; the developing company declined to go to market, and instead pivoted<p>I&#x27;d want to hear a lot more about why this happened before I invested in this. I&#x27;ve been hearing about this bacteria for years and the story gives me strong &quot;miracle carburetor&quot; vibes.

I love the spirit of this grant but it has big &quot;programmer knows better then pharma&quot; vibes. At a first glance:<p>1) The original strain (BCS3-L1) is a clinically derived isolate with who knows what properties. Why not just take the well characterized ATCC&#x2F;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&#x27;t need whatever wild type mutations it has to keep it in the dental microbiome (the lantibiotic does that).<p>2) Who pays for this? Why? Finding the appropriate payer for a pharmaceutical intervention is difficult. Getting this through FDA trial costs (let&#x27;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 would try this in a heartbeat, cavities IME seem to be mostly genetic or per-person microbiome environmental thing. The fact that without daily maintenance our teeth can just rot away to a point where severe infection and&#x2F;or death seems just like a major flaw we should be trying a lot harder to fix.

Dr. Hillman, I was right!<p>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&#x27;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.

So... is the existence, or non-existence, of a certain bacteria why some people never get cavities? I&#x27;m sure there can be multiple factors, but I&#x27;m 51 and never had a cavity, but don&#x27;t really know the specifics of what might be different about the environment of my mouth that seems to discourage, or not encourage, the formation of cavities.

It &quot;persists in the mouth indefinitely&quot;.<p>It&#x27;s &quot;been in the mouths of fewer than 15 people&quot;.<p>This was in 2003, so I&#x27;m guessing they&#x27;re not all dead.<p>I&#x27;ll stake &#x27;em a box of cotton swabs...

I think the section about why we should trust the project founder is quite funny. Something like &quot;I did video games and stuff&quot;. And MIRI is AI, operations lead sounds like administration? So no relevant experience. While I can respect someone doing a moonshot, really I do, but maybe, just maybe get someone with relevant experience on board? I&#x27;d love to see this happen, but this doesn&#x27;t help their case imho.<p>-I spent five years at MIRI as Operations Lead. -I produce a video game that&#x27;s #42 in category on Patreon, with an 11-person team, making six-figures with &gt;1,000,000 downloads. -I run Heist and Geist and Heist: Sunlit Forge; welcometotheheist.com -I&#x27;m nominated for the Nebula for fiction, and was published in Asterisk three days ago under the name Jamie Wahls. -I run Aella&#x27;s media empire.

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

Super exciting stuff and it got me thinking: could we genetically engineer bacteria to get rid of morning breath? I would like to think (and so does my dentist) I have very good oral hygiene* and I get regular checkups where everything is fine but when I wake up the taste in my mouth and my breath are really unpleasant. The last time I had to be on antibiotics for a longer time I noticed it was severely lessened but came back just as strong after.<p>* 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.

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

<a href="http:&#x2F;&#x2F;www.oragenics.com&#x2F;news-media&#x2F;press-releases&#x2F;detail&#x2F;35&#x2F;oragenics-receives-new-patent-for-improved-replacement" rel="nofollow noreferrer">http:&#x2F;&#x2F;www.oragenics.com&#x2F;news-media&#x2F;press-releases&#x2F;detail&#x2F;35...</a><p>Wouldn&#x27;t there be patent problems with reproducing this? Unless Oragenics is willing to license&#x2F;give up their patent?

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

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

&gt; After a single application, this strain persists in the mouth indefinitely,<p>In which case you only need to find a person from the original trial and get it from them. You don&#x27;t need to recreate it?

This would be a huge win for humanity! But I suppose the downside is many people might stop brushing their teeth - and I doubt this new bacteria <i>won&#x27;t</i> smell bad.

They should pursue vet market first, less regulatory hurdles.

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

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

Which state is this company located in?<p>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).

Wikipedia article on carries vaccines:<p><a href="https:&#x2F;&#x2F;en.wikipedia.org&#x2F;wiki&#x2F;Caries_vaccine#" rel="nofollow noreferrer">https:&#x2F;&#x2F;en.wikipedia.org&#x2F;wiki&#x2F;Caries_vaccine#</a>