Because this has to get done!
(FTX Future Fund awarded us $120k for this project, but they went bankrupt before we actually received it.)
Dental cavities cost about $45 billion per year in America alone, disproportionately affecting lower-income persons. BCS3-L1 is a genetically engineered streptococcus mutans bacteria which does not secrete lactic acid, and thereby doesn't cause cavities in teeth. After a single application, this strain persists in the mouth indefinitely, hedging out cavity-causing bacteria. (See our FAQ and safety review at https://docs.google.com/document/d/1mDJCTO2QySmQOZQcajYReDCA1MFpKs-EZ5E0VNu50Fo/)
This passed animal trials back in 2003 (under the brand name SMaRT, Streptococcus Mutans associated Replacement Therapy) and tested flawlessly in human volunteers, but the developing company declined to go to market, and instead pivoted to selling once-daily probiotic mouthwash.
Eventually, to cure cavities for everyone forever.
BCS3-L1 isn't under patent, but possession remains a significant part of the law. Although I have the blessing of the original inventor Dr. Jeffrey Hillman, he and his former company Oragenics have parted ways, and as far as we can tell, they're the only holders of the organism.
But, there's nothing preventing us from recreating BCS3-L1 ourselves from commercially available precursor bacteria.
-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, it certainly isn't great for our Weirdness Points budget.
-Fewer than 15 people have actually had this in their mouths already, and success is not guaranteed. Animal studies do not always translate to human efficacy, regardless how compelling.
Lantern Bioworks has also applied to Lightspeed Grants for a different phase of this project.
5 months ago
Matching Austin's commitment. I think this is ambitious and feasible. It's just awesome to cure caries forever, and also to serve as an inspiration of projects that are simultaneously ambitious, altruistic, and potentially self-sustaining companies. I don't mind whether this is an investment or a grant.
Putting down $20k of my regrantor budget for now (though as mentioned, we'll likely structure this as a SAFE investment instead of a grant, once we've finished getting commitments from regrantors)
Technically speaking, it probably does raise the risk some, but I don't actually predict it to be a problem; see the Safety Review section "Will I get drunk?"
Oh, the odds of it successfully colonizing the gut seem very low to me. Humans are constantly swallowing wild S mutans without issue, so I don't expect it to gain a foothold on its own. The mutacin 1140 could be an issue, but mutacin isn't very stable through the stomach acid, and the half-life/pharmokinetics are pretty bad; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6256755/.
BCS3L1 contains JH1140's knockouts for genetic stability, too, so I expect it to mutate much less than standard S mutans. A year of rat testing didn't indicate disruption to their gut microbiota.
Additionally, the people who self-colonized with strains like JH1005 haven't reported any issue ¯\_(ツ)_/¯
If everyone on earth colonized with this, I suppose I do expect someone to get autobrewery, because multiplying a very small number by a very big number does yield a number, but I don't expect to see that failure state in the first million people.
(See the safety review section, "How might this disrupt the microbiome", subheading, "In the gut"
Thanks for submitting this, Aaron! We really like this kind of concrete object-level proposal, which is ambitious yet starts off affordable, and you have quite the track record on a variety of projects. A few questions:
As this is a project for Lantern Bioworks, would you be open to receiving this as an investment (eg a SAFE) instead of grant funding?
If funded, what do you think your chances of success are, and where are you most likely to fail? (I've set up a Manifold Market asking this question)
Could you link to your Lightspeed application as well?
Conflict of interest note, Aaron was an angel investor in Manifold Market's seed round.
I think our odds are very good. I'm working with the original inventors, Drs. Hillman and Smith, who made it the first time.
I'm not sure that I can link to my Lightspeed application? The link they sent me is an edit link, and I don't want to post that on the public internet.