Updates on Lumina Probiotic
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Lumina, the genetically modified anti-tooth-decay bacterium that I wrote about in December, is back in the news after lowering its price from $20,000 to $250 and getting endorsements from Yishan Wong, Cremieux, and Richard Hanania (as well as anti-endorsements from Saloni and Stuart Ritchie). A few points that have come up:
1: What happened with the FDA testing?
In the original FAQ, I wrote:
Professor Hillman started a company “Oragenics” and applied for FDA approval. The FDA demanded a study of 100 subjects, all of whom had to be “age 18-30, with removable dentures, living alone and far from school zones”. Hillman wasn’t sure there even were 100 young people with dentures, but the FDA wouldn’t budge from requiring this impossible trial. Hillman gave up and switched to other projects.
I got this information from (company CEO) Aaron, who says he got it from (original inventor) Jeffrey Hillman.
Commenters (and Kevin Drum) searched publicly-available archives and found a slightly different story, with three trials:
A Phase 1 trial, scheduled April 2005, on 26 people, age <55, with dentures. The company couldn’t find enough people who met enrollment criteria, so they renegotiated with the FDA and switched to (2).
A second attempt at Phase 1 trial, scheduled October 2007, on 10 people, age 18-30, no dentures necessary, done in a hospital setting. This trial succeeded, escalating the process to (3)
A Phase 1b trial, scheduled January 2011. Nobody can find any details on this one, but Oragenics says it never took place because of “the very restrictive study enrollment criteria required by the FDA”.
Some people have tried to argue that someone must be lying, because I wrote about a 100 person trial age 18-30 with dentures, and this doesn’t match either of the two trials we know about.
I think two more likely explanations are:
This is Trial 3, the one we know nothing about
Or someone in the Dr. Hillman → Aaron → me chain mixed up details of the three trials into a mishmash with some characteristics of each.
2: What happened in the rat trials?
Several people including Natalia Coelho found an old rat study that Dr. Hillman had done.
The rats with the new strain (BCS3-L1) got only 1/3 the normal rats’ “caries score”. But they didn’t get a score of zero. So maybe claims like “BCS3 represents a complete cure for cavities” are overblown.
Why didn’t rats with the new strain get zero dental caries? Bacteria other than S. mutans can also cause cavities, so maybe it’s one of those.
Rat trials are famous for results that don’t replicate in human trials, so take these with a grain of salt.
3: What did the latest colonization studies show?
Aaron was able to retest six people who got free samples in December. Four of those people still have the bacterium. The other two don’t.
Of the two failures, one had an active cavity at the time the strain was applied (which interferes with the oral microbiome), and the other had his wisdom teeth removed (which involves rinsing the mouth with strong antiseptics).
Aaron hopes this shows the strain will stick around in most normal situations (though the failure in the presence of active cavities is disappointing).
4: Any new concerns about side effects?
In my original post, I mentioned the possibility that this would set off Breathalyzers. Lantern was able to test this, and proved that it wasn’t a problem.
Yesterday, Lao Mein suggested on Less Wrong that it might raise oral cancer risk - their post focused on people with ALDH deficiency (most common in Asians) but the calculations are too vague to be sure exactly which groups should and shouldn’t worry. This is less than 24 hours old, the company hasn’t replied yet, and is still developing. I’ll try to update people if anyone gets more clarity on this.
Someone on the post mentioned that they’ve gotten worse hangovers since using the product, maybe because the constant trickle of alcohol changed the way gut flora metabolize it.
5: Any other meaningful results since the samples?
Cremieux says his breath smells better.
Some people have objected to this claim on the grounds that it takes ~12 months before the bacterium has colonized your mouth. One of the figures in my earlier post suggested that the bacterium might start strong, retreat for a while, and then take 12 months to fully colonize, so that might potentially explain his findings. But also, is it biologically plausible that this prevents bad breath? My impression was that bad breath came from other bacterial byproducts besides lactic acid. It might be possible in theory that the same metabolic changes that switch lactic acid to alcohol disrupt these other byproducts, but it seems kind of unlikely.
An alternate explanation is that, in order to apply this product at all, you need to do a dentist-style teeth cleaning that kills your previous mouth bacteria. Maybe that improves the bad breath regardless of whether you add the Lumina afterwards?
Some other people have said their mouth feels fresher or something, but realistically all of this is overwhelmingly likely to be placebo.
6: Do I “endorse” Lumina?
Richard Hanania has a post about how he trusts Lumina because I’ve endorsed them. It’s extremely kind and I appreciate his respect.
But also, the most I said in the original post was that I was still debating whether or not to get the treatment.
My real opinion, as precisely as I can express it, is:
Advance of approximately the same magnitude as fluoride: 5%
Good on balance, comparable to other beneficial dental treatments: 35%
Doesn’t work in its current form, but could easily be modified into something that does: 10%
Doesn’t work at all and never will: 50%
Causes minor side effects for some people, same scale as Tylenol: 30%
Causes medium side effects, same scale as tricyclics: 5%
Causes disastrous side effects, same scale as thalidomide: <1%
Lots of people are going to round this off to “So you’re saying it hasn’t yet been proven to work? Doesn’t that mean it’s Not Real Science which means it’s a scam which means anyone who likes it is exactly as bad as LK-99 believers or ivermectin proponents?”
I will never get tired of posting this picture:
If there’s really an intervention with a 5% chance of being as good as fluoride, languishing in a file drawer somewhere, that’s a big deal!
Obviously the best course is to study it carefully and not do anything until you know more. The FDA has already closed off that route. Aaron’s taking the only option left - getting it out there where it can be mass tested by users. Soon we’ll have good data on colonization rates, retention rates, and (hopefully) mouth lactic acid levels. After a while, we’ll have at least some anecdotal evidence on cavities. If we’re really lucky, that will provoke a second round of interest from pharma companies, dentists, and scientists.
Just because testing things like this is +EV value for society, doesn’t mean it’s +EV value for every individual involved. The testing process has to pull together inventors, investors, manufacturers, and customers, using some mix of greed, delusion, altruism, technophilia, and goodwill. I think it’s fair to try to minimize the greed and delusion by reminding people that medical interventions which make biological sense and work in rats have a bad human track record. But having done that, I don’t think you also have to try to crush the goodwill and technophilia.
If you’re a poor person, spending your last $250 on this because you desperately want to cure your cavity problem, and you would be devastated if it didn’t work or if had any side effects - then you shouldn’t buy Lumina.
But if you have extra money, and you think biomedical innovation is cool, you want to be able to tell people you have genetically-modified bacteria in your mouth, and you want to contribute to the project of taking this out of the file drawer of discarded good ideas and back into the arena, and maybe get fewer cavities as a bonus - then yeah, I think it’s a prosocial thing to do, and probably won’t go too wrong - although this is not medical advice and really we have no way of knowing how wrong it will go (though maybe wait until people have had more time to look over the new oral cancer claims, especially if you’re Asian).
I would prefer not to be quoted as “endorsing” Lumina in any way more simplistic than this, lest people who think endorsement = “it definitely works” over-update on my supposed opinion.