[akrolsmir]

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

Happy to answer any questions!

[rudyfink]

Why do you think the company never took it to market past testing?

And thank you for looking into this. I recall reading about experiments on the modified bacteria years ago, but then I forgot about it. Until I read your page, I had not realized it died on the vine.

[hrkfmud50k]

> After a single application, this strain persists in the mouth indefinitely, hedging out cavity-causing bacteria

> but the developing company declined to go to market, and instead pivoted to selling once-daily probiotic mouthwash.

sounds like they preferred to sell a recurring subscription vs a one-time sale

[0cVlTeIATBs]

"Goldman Sachs asks in biotech research report: ‘Is curing patients a sustainable business model?’"

https://www.cnbc.com/2018/04/11/goldman-asks-is-curing-patie...

[pmarreck]

This attitude is so stupid. You could:

1) milk a dumb problem you've already solved, making very moderate profit, or

2) solve it and move onto more interesting problems, continuing to make money

[ASalazarMX]

It's a legitimate question. The article is about gene theraphy, and its potential to cure chronic genetic diseases.

If you create a startup that after a decade creates an affordable and effective gene theraphy for type II diabetes, and most of people recover, will your startup survive curing only new cases of it? Will it be able to tackle another disease before your coffers dry up?

The question can be viewed as greedy companies wanting to milk diseases forever, or as a sustainability issue. Being able to cure chronic diseases affordably will probably become a new socioeconomic challenge.

[fsckboy]

"I wonder if the one-time sale can be "resold" through snogging?" - Phil MacAvity

[totetsu]

Probiotic kissing booth?

[TeMPOraL]

Well, why not? Compared to fecal matter transplants, which are already a thing, tickets to a kissing booth will sell out like hot cakes.

(Can I pay for a monthly pass up front? It's for medical purposes!)

[klyrs]

> Well, why not?

Herpes.

And other viruses, probably, but one incurable STI (KTI?) is all the reason I need to say hell no.

[autoexec]

Here's hoping that someday someone who cares more about promoting health than padding wallets will take this idea and use it to bring the masses something they can apply once at a low price.

[DropInIn]

So once again we doom the species to eternal torment for the sake of one company's profits....

This shit should just be taken by the state for the benefit of everyone, because really it's insane not to.

[Llamamoe]

Welcome to virtually all of healthcare.

[cellularmitosis]

Why doesn't the state just purchase the IP from them?

[TeMPOraL]

Unfortunately, states these days rarely do anything on their own. So even if they bought or took the IP, they'd still have to lend it to some private manufacturer, who will quickly ensure the government itself ends up locked into a subscription. Either way, some private company gets fat, and society gets shafted: you'll be paying a subscription for this, whether directly to a vendor, or hidden as part of your taxes.

Like usual, the problem isn't whose name is on the box. The problem is the subscription-based business model, which can easily turn into pure rent seeking.

[jaggederest]

Why purchase the IP at all? The proposed funding is for parallel reconstruction - we know it's possible, we have enough details to recreate it, it's a "simple matter of funding" at that point.

[DropInIn]

What is the IP doing now? If it's abandoned what value does it actually have in the marketplace?

Theres no real reason to reward squatting on world changing tech, is there?

[_Algernon_]

While there is some work and capital that goes in to developing the IP, it also builds up on decades of fundamental research that is funded by the public (standing on the shoulders of giants and all that). Therefore, I'd say that a big discount should be had for such a purchase.

[diffeomorphism]

What is the difference? When something is "taken" they still get ample compensation.

[NotYourLawyer]

Yeah, THAT will incentivize people to come up with more stuff like this!

[ajuc]

If free market can't get this done, maybe we should just pay people from our taxes to do such research?

[DropInIn]

The IP is effectively valueless if there is no intent to monetize it.

Really....

[Clent]

It would incentivize them to use or lose it.

The government is protecting their discovery via patent law, why is it not allowed to remove this protection.

Patents and copyright are very recent inventions. Not everyone is motivated by profit. People were inventing things before capitalism consumed the world.

[ImHereToVote]

The employers of politicians would never pay them to do it.

[refurb]

There are plenty of one time therapies in healthcare. Hell, cancer therapies are one course of therapy.

Plenty of ways to make a profit.

My bet is that it was never tested and the claim is entirely a prediction.

[ralfd]

These comments from 2018 say FDA approval was to complicated:

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.

[akrolsmir]

I don't have any special insight into what happened at Oragenics (my full context on this application includes what's listed at the link, plus a short call with Aaron about his fundraising plans). There's a little more color on the Wikipedia page for the cavity vaccine: https://en.wikipedia.org/wiki/Caries_vaccine

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"

[jaggederest]

I've looked at it pretty extensively over the years and the explanation is pretty obvious: the cost to run the trials would have been ruinous for the return. Look at the clinical requirements for the stage 1 and 2 trials - IRB specified only people without teeth and some other requirement which was prohibitive, like a clean room, or only terminal patients, or something.

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.

[jansan]

Hello billionaires, how about becoming known by future generation as "the person who eradicated cavities"?

[brookst]

I’ve got my checkbook here but I am scared of being remembered as “the person who eradicated teeth”

[jaggederest]

Yeah that would probably get your name on a lot of high schools, if that's your thing.

On the other hand, it wouldn't eliminate oral hygiene, for both the obvious olfactory and comfort reasons, as well as gingivitis and other non-caries oral health issues.

[justinclift]

It'd be funny if it accidentally eliminated Alzheimer's disease as a side effect though. ;)

[petra]

Does anybody has access for the document with the clinical requirements ? It seems like an interesting problem.

[jaggederest]

Here's a related document, not sure if this is where I first read it though

https://www.sec.gov/Archives/edgar/data/1174940/000156459019...

Relevant portion excerpted:

> Replacement Therapy

>

> Our SMaRT Replacement Therapy is based on the creation of a genetically modified strain of bacteria that colonizes in the oral cavity and replaces native bacteria that cause tooth decay. Our SMaRT Replacement Therapy product candidate is designed to be a painless, one-time, five-minute topical treatment applied to the teeth that has the potential to offer lifelong protection against dental caries, or tooth decay. While we commenced a Phase 1b clinical trial for SMaRT Replacement Therapy during the first quarter of 2011, the very restrictive trial enrollment criteria required by the FDA made the enrollment of candidates meeting the restrictive criteria difficult. This enrollment difficulty was also present in our Phase 1a clinical trial. Due to the enrollment difficulties we encountered with our initial Phase 1a clinical trial and with our Phase 1b clinical trial, we determined to discontinue pursuit of our Phase 1b clinical trial. Our focus for the SMaRT Replacement Therapy technology is on possible partnering opportunities that may exist.

[another2another]

For something that could benefit all of humanity (and the sugar industry), we have a whole planet we could utilize for trials. Couldn't we outsource at least the initial stages somewhere where the cost would be less for the same clinical criteria?

[mkmk]

$10b?!

[TeMPOraL]

> Hanlon's razor: "never attribute to malice that which is adequately explained by stupidity"

Don't forget about Hanlon's handgun: don't attribute to stupidity that which can be adequately explained by systemic incentives promoting malice.

[ClumsyPilot]

exactly, playing dumb cant be a free get-out-of-jail card

[RomanHauksson]

Hey Austin, nice seeing you here!