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.
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.
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.
FMT was the topic of my dissertation. Donor stool is heavily screened, and there's pushes both to use the patient's own stool where possible, or creating synthetic stool that is pathogen free.
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.
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.
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.
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.
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.
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"
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.
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.
> 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.
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?
it's shocking that it hasn't been mentioned (ok, except by me in another comment) but flouridating municipal water systems through/after the 1960's at least in the US had a huge impact on the number of cavities/caries among children. Yuge. There are suspicions that fouride isn't good for us, and I mean beyond our precious bodily essences too, but in terms of teeth, it's been miraculous.
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.
The problem is that nobody keeps the toothpaste on their teeth after brushing, like they should. Putting it in drinking water is an unacceptable alternative given the potential risks.
Yeah there is a very straight forward to reap all the rewards with almost none of the risks… but the problem is nobody is disciplined enough to actually follow the correct procedure.
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 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?
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.
> There are suspicions that fouride isn't good for us, and I mean beyond our precious bodily essences too, but in terms of teeth, it's been miraculous.
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.
too much flouride is actually really bad for your teeth; brown spots/pits I think. It's why children's toothpaste has minimal flouride, because they swallow a lot of it.
White spots is mild fluorosis. The brown stuff comes in when you live next to a coal mine so your water is filled with fluoride (at concentrations way over what any reasonable water-fluoridizer wants to add) and other nasty stuff.
People talk about how the fluoride in tea can help prevent cavities, but on the darker side... just imagine having all your food come from that sort of fluoride-rich soil.
It always amazes me how awful and toxic the earth can be once you get below the surface that's been rinsed with rain, biological acids, and otherwise weathered and covered up with thoroughly processed particles for millions of years.
I was curious as to where the fluoride was coming from, and this report: https://sci-hub.ee/https://link.springer.com/article/10.1007... seems to indicate that the mines increase fluoride in grounderwater due to exposing carbonates which then can dissolve, kicking off a change in pH and various other reactions that release fluoride from the minerals it's otherwise locked in.
That we have not migrated to hydroxyapatite from fluoride is a mystery to me. It actually remineralizes the enamel rather than protecting it. It lacks the toxicity of fluoride as well. It’s more expensive, but I suspect that’s because it hasn’t scaled yet.
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
We had to buy special toothpaste with high amount of fluoride for our kid after a year of experimenting with non-fluoride toothpaste, and we had to pay for fixing caries in 6 teeth too (done under sedation). Hence I do NOT recommend leaving out the fluoride at least from the toothpaste
> the developing company declined to go to market, and instead pivoted
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.
Another commenter posted that going through FDA trials could be ruinously expensive for the company,
which made more sense to me than just looking for recurring revenue.
Cavities are a ridiculously huge market without the recurring revenue imo.
The thing is, perhaps the researchers were getting more and more coincidental evidence that the treatment didn't actually work ('I snuck some out of the lab and gave it to my whole family, but it didn't really seem to make much difference').
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".
Well, how much money did they make selling probiotic mouth wash?
I'm pretty sure if they had gone with curing all the world's cavities I would have heard of them. The brand recognition alone would be worth more than a probiotic mouth wash company.
Very unlikely there was a miracle cure that was left on the table because founders wanted to sell mouthwash.
It isn’t that simple. Say you believe that you have a miracle cure, but it will take a billion dollars to go through all the medical trials. And at the end, you could find out that it isn’t a miracle cure or could end up having too many side effects, then you are out a billion dollars. You just might not have the pockets deep enough to risk it. A probiotic mouthwash may have the potential for a fraction of the returns, but may only cost 5 million to bring to market.
If the cure is powerful enough to self replicate and resource starve the cavity causing bacteria, there is literally no business model. You could in theory swab a treated persons mouth and grow your own cultures.
If you can make money off open source, you can make money off curing every cavity in the world... But the company decided instead.... To sell mouthwash?
But you know how money is made off open source? Usually by support subscriptions (which, to be fair, is also how money was/is made on low-volume, high-value proprietary software, like e.g. SDKs for obscure and ancient industrial protocols). Beyond that, there is no general way to turn open source into money. Instead, open source is used by companies:
- To lower their costs - by outsourcing a chunk of development and testing to free volunteers; also by improving quality and reducing on-boarding costs of new hires (as you can select for those who already spent significant personal time learning your tech stack);
- For marketing purposes - mostly in terms of marketing to prospective employees, but for companies targeting technical audience, also marketing to customers;
- As a weapon against competition - the code you open-source is code your competitors can't sell; this is useful both in breaking into a legacy market, as well as restricting the kind of competition you'll get from those who started after you;
Where does the money come from then? Usually some combination of venture capital, rent-seeking and advertising. Open source destroyed the viability of the simple, honest model of providing value in exchange for payment. The alternative business models are much worse for end-users and society at large.
Assuming the bacteria story is true, your open source analogy is wrong. Anyone can copy the bacteria (similar to open source) but there's no maintenance needed once the bacteria is released to the public. Anyone in any country can offer to give you the bacteria. It's naive to think that anyone but a non-profit would release something like this.
Apples entire business model goes against that philosophy. Reoccurring revenue is where it’s at. Unless you actually want to make things better, in which case you’re shouldn’t be in business. (Which these guys blessedly aren’t!)
It’s not but it is also a) a selected example of many to illustrate a point with clarity, b) a widely emulated model, c) essentially what the company who pivoted pivoted towards. Rather than a one time solution, a reoccurring subscription model, so is salient and likely it or a similar model was considered in that switch.
I agree. Sadly most investors risking capital don’t. That’s why I love these guys and hope they get their funding. I imagine they fall outside some kickstarted T&C prohibiting bioengineering for use in humans, and likely Patreon too, but I would definitely kick over some bucks to help them if there were a channel.
I love the spirit of this grant but it has big "programmer knows better then pharma" vibes. At a first glance:
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.
Yeah, agreed that the proposal has a whiff of "too good to be true". The applicant's track record looks fairly good, though (he's previously invested in my startup, Manifold Markets, and otherwise has an interesting history in many different domains).
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 am a drug developer working on identifying novel therapeutics from human skin, oral, and intestinal bacteria.
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.
Curious what those would be. Again, too good to be true, but if we could vaccinate against cavities, that seems like an enormous amount of human misery eliminated for a one time investment.
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/or death seems just like a major flaw we should be trying a lot harder to fix.
It's a flaw with an agrarian diet, not intrinsic to human anatomy. Archaeological remains of hunter-gatherers show extremely few cavities. They begin in earnest once people start eating domesticated cereal grains as a primary food source.
> It's a flaw with an agrarian diet, not intrinsic to human anatomy.
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).
Are these really good counter examples - they all have common explanations of this sort (whether or not true idk)? We have glasses because modern society requires focusing on close objects like books and screens causing eye strain. Cars are great for modern society but pretty poor and hunting an animal in the middle of a forest, etc.
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.
>We have glasses because modern society requires focusing on close objects like books and screens causing eye strain.
This doesn't make sense. This only explains why people use reading glasses or bifocals over the age of 40.
Most people needing vision correction are near-sighted (myopia), not far-sighted (hyperopia). We have glasses because we need to be able to see things and read signs at distances greater than our arm reach.
There's something else going on causing SO many people to need vision correction.
>Cars are great for modern society
As someone who lives in a walkable city with excellent public transit, I completely disagree. Cars are a disaster and a cancer on society.
>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.
I think this is a big thing, though I think it's more complicated because some people eat plenty of sugar and still don't have cavities, so I think sugar affects different peoples' bacteria differently, or different people have someone acquired or evolved different bacteria that respond differently to sugars. But yeah, sugar seems to be a central issue.
I would argue it is more to do with the amount of sugars and the frequency these sugars are in contact with the teeth than anything. Sipping HFCS the entire day seems to be much more common these days..
It's amazing how much your vision improves by simply focusing at the edge of your eye resolution level. Don't squint, just focus. A month later you will be blown away.
This becomes difficult for someone whose eyes are mismatched.
Would practicing with one eye properly covered, to have low enough lux to prevent the natural feedback mechanism which causes myopia[1], seem impractical?
[1] Extended or frequent exposure to low-contrast input causes lengthening of the eye, and can be irreversible after two weeks[2]. Seems to involve eye and visual cortex, and to not occur if the eye has no connection to the visual cortex. I'm not aware of any similar mechanism to account for far-sightedness.
[2] Consequently, nightlights and other light sources which shine into a sleeping area may be counter-indicated.
Modern hunter gatherers are a lot more modern than one might imagine. Usually wearing T-shirts and sometimes, as in this case smoking cigarettes. Their diet is different in many ways than hunter gatherers of the past, along with many other parts of their lifestyle.
It’s probably a good demonstration of the “Paleo fantasy“- if these groups that are still playing by some of the hunter gatherer groups are getting very different results on these important markers, then we are likely to as well when we try to incorporate parts of the hunter gather diet or lifestyle into our very different lives.
Mostly fresh food- eating things they day they were picked or killed as the default. But generally in an environment of abundance with generational wisdom about what is nutrient dense. The group in the study may be eating lots of honey because they are more marginalized today by territorial pressure and others hunting and hunting restrictions, etc.
"The unexpected discovery of high caries incidences for men in the bush is likely explained by heavy reliance on honey, and perhaps differential access to tobacco and marijuana. "
I'd also expect a high fruit diet in certain tropical regions where fruit is available more constantly also shows similar effects.
I think we can maybe all move on from this awful quote.
But, no I'm specifically referring to cultures like the Efé where men gather honey full time during a season, Yao honey-hunters who work with birds to find honey, or other forest cultures where honey is gathered from especially tall trees as a show of masculinity and bravery.
Not long, but actually longer than the first agricultural societies is my understanding. With the agrarian transition, population density and family sizes went up (a lot) but life expectancy went down a bit and infant mortality and disease rates (zoonotic diseases + higher concentration of population to spread through) went up.
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.
> With the agrarian transition, population density and family sizes went up (a lot) but life expectancy went down a bit and infant mortality and disease rates (zoonotic diseases + higher concentration of population to spread through) went up.
Infant mortality going up is the same thing as life expectancy going down. Neither one tells you much about whether people die before or after you'd expect to start seeing problems in their teeth. After ignoring infant mortality, it's mostly afterward, but "remains" are not a representative selection.
> Hunter gatherers are/were constrained by wild food source densities but also tended to have smaller families
This conflicts with the idea that they had lower infant mortality.
I gave you the reason right there above, but you cared not to read it: longer breastfeeding period.
Plus the fact that in a hunter-gatherer society people choose not too have too many children for the same reason people make that choice in advanced capitalist economies. Children become a resource burden.
In an agrarian economy, your children are extra hands for farm work. In a hunter gatherer society they are mouths to feed in an environment with intrinsically limited resources.
> 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.
Aren't there parts of rural China still living in that mixed model today? And Africa too iirc...
The bacteria which cause cavities also evolved alongside us. The problem worsened as we introduced more food for the bacteria (from the agrarian diet).
Even if you only eat meat (or whatever else besides grains), bits of food will still get wedged between into your gums and then rot away with your teeth.
It's not the fact that there is food stuck in your teeth that causes cavities, it's what pH results from the bacteria metabolizing that food. Bacteria breaking down carbs produces acidic conditions, but when they break down protein or fat the reaction products from that are much closer to neutral pH.
Yes. But is that a result of not eating meat? Or a result of paying close attention to your diet?
A lot of inexperienced vegetarians/vegans end up with nutrient deficiencies because they don't ensure that they are properly getting all essential vitamins or amino acids in their meatless diets. I'm not a dietician, but it's pretty safe to say that these people are not going to be the ones with reduced mortality rates. You cannot simply remove an entire food group from your diet without putting in effort into paying attention to the rest of your diet.
Some studies[1] show that pescetarian diets offer the lowest mortality rates. This diet still requires paying close attention to what you eat, but you are far less likely to have nutrient deficiencies.
This is one of the huge issues I have with diet-mortality studies. During the gluten-free trend a while back, there were many that suggested gluten-free diets provided health benefits. However, for the vast majority of people, gluten isn't really that special as far as proteins go. It turned out those "health benefits" were just the result of people with gluten intolerances actually paying attention to their diet.
Just to reiterate, I am not a dietician. Everything above is just my cynicism for studies that constantly fail to take into account that most people just don't care what they're eating. I would absolutely love to be proven wrong.
> A lot of inexperienced vegetarians/vegans end up with nutrient deficiencies because they don't ensure that they are properly getting all essential vitamins or amino acids in their meatless diets
While that certainly happens, its not like you have to maintain constant vigilance. Most popular vegetarian diets are nutrionally complete (major exception being vitamin b12 for vegans is something to be very careful about).
Like yes, if you decide to only eat rice and nothing else it will be bad, but its not like you have to meticulously record what you eat every meal. Getting all essential amino acids is pretty easy if you eat like a sane person.
Where did I imply you need to 'meticulously record every meal'? I explicitly added the "inexperienced" tag to try to avoid this kind of extreme contrarian argument.
> major exception being vitamin b12 for vegans is something to be very careful about
Add to that list iodine, omega-3, zinc, iron, calcium, and vitamin D. All of these are essential nutrients that vegetarians need to include in their diet. Sure, they're easier to get than B12, but they can still be pitfalls if you're careless.
> Getting all essential amino acids is pretty easy if you eat like a sane person.
Yes. That's basically the entire point I'm making. Most vegetarians eat 'like a sane person' because if they don't then they will have issues very quickly. Having a diet with meat means you can eat more carelessly because you're less likely to have immediate issues compared to eating carelessly as a vegetarian.
What I'm asking for are studies that take this into account. Studies that aren't just asking people if their diet includes something. Studies that actually take into account the fact that most people that don't care what they are eating tend to eat meat.
Are vegetarians typically 'inexperienced' long enough to lose lifespan, though?
Fwiw, I've been vegetarian for like twenty years, don't really track much of anything in terms of vitamin intake, and am doing just fine according to the last time I had blood work done. I eat eggs and beans and rice for protein, and cook on a cast iron for iron... And that's the sum of my thought on vitamin intake. My partner takes b12 supplements, though.
I do think there's a certain over estimation of how hard it is to not eat meat. It's really not.
> Are vegetarians typically 'inexperienced' long enough to lose lifespan, though?
No, because they find out really quickly what they're deficient in when symptoms show up (or they revert back to their previous diet). I admit I worded that paragraph poorly though, that wasn't my intention.
> Fwiw, I've been vegetarian for like twenty years, don't really track much of anything in terms of vitamin intake, and am doing just fine according to the last time I had blood work done. I eat eggs and beans and rice for protein, and cook on a cast iron for iron... And that's the sum of my thought on vitamin intake. My partner takes b12 supplements, though.
So you get blood work done regularly, ensure you have certain things in your diet, and you intentionally try to make up for a common nutrient deficiency?
You may not see that as a lot of effort, but for people that don't really care about their health, every one of those things can make a significant difference in terms of lifespan.
I got blood work done once last year because it's a reasonable thing to do when you turn 40. Not regular at all, and I was feeling fine at the time.
I'm not sure why you're so invested in the idea that eating protein is hard when one doesn't eat meat. It's really not harder to eat other protein sources - eggs, rice, and beans are common foods. It's not a thing I think about, more a consequence of... eating.
Mostly in jest, let's turn this around:
Eating meat, by contrast, seems to require significant mental gymnastics to justify. The impossible cruelty of the industrial meat production system and massive environmental impacts of eating meat create a lot of cognitive dissonance, so people need to fabricate justifications for their decision to eat meat. I'm honestly not sure how you keep up your meat-eating lifestyle when you have to work so hard to create an argument not to be vegetarian, and defend your psyche from all the evidence of the moral bankruptcy of your food choices. It seems like it would create a lot of anxiety, which could be a factor in the reduced lifespan of meat eaters.
> I'm not sure why you're so invested in the idea that eating protein is hard when one doesn't eat meat.
I'm not sure why you're so invested in misrepresenting my argument. You're conflating my use of the word "effort" with some specific amount of difficulty. Would it be more accurate to use the word "willpower" instead? I personally do not believe changing any part of your diet is "hard". I have done it myself multiple times, and even now the only meat I eat regularly is fish on occasion.
The point I am making though, is that health studies don't ever seem to take into account that most people who don't put any willpower at all to have a healthy diet also tend to also eat meat. And to demonstrate that point further, here's a study on some amazing health benefits of a meat-only diet[1]. Notice how the reported health benefits are oddly similar to those that are common with vegan or vegetarian diets? My argument is that this is because this study also fails to take into account the type of people who don't put any effort into having a healthy diet (granted, at least this study acknowledges those shortcomings in their methodology as part of their conclusion).
I am not making an argument to not be vegetarian. Just as I am not making an argument to not be a carnivore. And I am certainly not trying to "defend my psyche" from being "morally bankrupt" or whatever that last paragraph of yours was suppose to be about. I honestly don't even know where you pulled that from.
> Add to that list iodine, omega-3, zinc, iron, calcium, and vitamin D
Common nutrients that even non-vegetarians do not generally get from meat.
Iodine is usually from salt, Omega-3 is often vegetable oil and nuts, zinc is commonly in beans and grains, calcium and D3 is in milk (you said vegetarian not vegan), and more to the point, most people do not get vit D exclusively from diet.
These are all things that non-vegetarians get in sufficient quantity from non-meat sources. So why would someone becoming a vegetarian suddenly stop eating these things.
> Having a diet with meat means you can eat more carelessly because you're less likely to have immediate issues compared to eating carelessly as a vegetarian.
While i agree in general, your definition of "careless" is so ridiculous that I think meat eaters would rapidly be in trouble if they were this level of careless.
I want to preface this with the fact that I never said you can't have a well-balanced vegetarian or vegan diet, because I feel like that's what you're thinking I'm implying.
> Common nutrients that even non-vegetarians do not generally get from meat.
Other than Vitamin D3, meat is objectively an excellent source of all of those nutrients. Fish is an excellent source of iodine and omega-3, and saying people do not get zinc, iron, or calcium from meat is just incorrect.
> These are all things that non-vegetarians get in sufficient quantity from non-meat sources. So why would someone becoming a vegetarian suddenly stop eating these things.
Maybe because they never started eating those to begin with? I do not know, and I can only speculate on the different reasons. Each person is different, but all we know is that it does happen[1]. Some people just don't have those in their diet.
Anecdotally, I don't think I ever ate beans until I was in my early 20s because my parents just never cooked with them. We also pretty much only had sea salt available, and most of our food was cooked with butter instead of vegetable oil. We weren't unhealthy, but if I immediately dropped meat from my diet at that time without changing anything else, I would have started to have issues.
> While i agree in general, your definition of "careless" is so ridiculous that I think meat eaters would rapidly be in trouble if they were this level of careless.
I'm not going to argue semantics. My argument is about the statistics and how these dietary studies tend to fail to account for extremes in behavior. Vegans, vegetarians, and pescetarians are just less likely to have these extremes.
To reiterate the results from the previous study I linked[2], semi-vegetarians (people who only occasionally had meat) have a fairly worse mortality rate than vegetarians, yet strictly speaking their diet only varies by having meat once or twice a month. The only way this makes sense in my mind is either there's a huge behavior difference in these two groups (less care put into their diet), or that meat is so incredibly unhealthy that just eating it occasionally will knock years off your lifespan. Considering the standard deviation of those results are larger for both non-vegetarians and semi-vegetarians (and that pescetarians have a significantly lower mortality rate than even the vegan group), I would bet on the former.
And if you don't think there's a lot of people that are completely careless about their diets, just remember how much soda the average American drinks in a single day[3], despite half of the population not drinking soda at all. And nearly a quarter of Europeans don't get regular checkups at a doctor[4], despite their access to healthcare. It's safe to say that a lot of people that just flat out don't care if they have a balanced diet (or exercise, regular healthcare, etc), and when you don't care you tend to eat meat.
When we get health studies that don't take this into account, we end up with fad diets because those studies essentially just show that those who pay attention to their diet tend to be healthier. To demonstrate the issues with those studies, this one[5] concludes a meat-only diet has very good health benefits compared to the general population.
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.
So... is the existence, or non-existence, of a certain bacteria why some people never get cavities? I'm sure there can be multiple factors, but I'm 51 and never had a cavity, but don'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.
I grew up without fluoridated water and have no cavities (I am over 40). I have gum disease, though, so apparently I am still susceptible to the bacteria that causes it.
While evidence for temporary benefit from fluoride in toothpaste is somewhat positive, evidence for similar benefit from fluoridated water is mixed and has not been isolated from numerous confounding factors. Ingested fluoride at has some small potential for mildly adverse health effects. Whether common levels in municipal water supplier are a net benefit, harm, or neither remains debatable.
However, there is significant variation of thickness of tooth enamel, seemingly due to genetics.
Not OP but I'm a similar age and never had a cavity either. I grew up in a rural area and drank well water as a kid. They did occasionally provide topical flouride in the schools.
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.
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.
I'm happy to go for regular cleanings, but I don't know how you could construct a well designed study to get data showing objectively what interval of cleanings results in better outcomes over many years. There's just too many uncontrolled variables. And, I don't think you can glean it from population studies either, because again, there are too many variables.
Routine dental visits are essentially cargo culted.
There is some robust evidence indicating that routine plaque removal does not improve outcomes for cavity prevention or gingivitis [0].
Routine consultation with dentists otherwise may be beneficial, maybe not, but it hasn't really been studied much yet. The studies that exist are insufficient to form any conclusions. [1]
My post was downvoted by those who feel going to the dentist is important. I should state clearly avoiding the dentist should not be considered medical advice from me, and YMMV. I did the research myself and determined that routine dentistry was unlikely to improve my health outcomes, this is a personal decision that people should make on their own.
The fact that these were published in 2018, implying before then it was never really studied, is sort of crazy.
The cost of biannual dentist visits for life is huge across the entire population. I would have thought there was strong evidence for this a long time ago. If nothing else, I would have thought insurance companies would stop paying for the bi-annual visits if there wasn't good evidence it works.
Then again, maybe I'm giving insurance companies to much credit since they've been paying for acupuncture for decades.
for many years, i went for cleanings every 6 months. zero problems, usually in and out without any pain.
i didn't go for a couple years and just had one of the worst experiences at a cleaning in quite some time. super painful, a lot of build up.
i haven't changed my brushing/flosing habits at all, but i did switch toothpastes to non-flouride.
now, i'm back on the 6 month schedule and back to flouride. i also switched to a tablet based toothpaste (tidalove). you chew it (don't swallow) and then brush. the pill has a bunch of other good stuff in it too. kind of neat cause it is also zero waste packaging.
I’ve never had a cavity. Still like to go to the dentist and get the plaque scraped off. I also cracked a tooth from grinding my teeth at night and he fixed that up for me.
The primary purpose of cleanings is not to prevent cavities. It's to remove the biofilm that exists at and below the gumline containing facultative anaerobes which cause periodontal disease. You can have gorgeous, cavity-free teeth that fall out because the supporting structures have been resorbed and destroyed by these anaerobes.
I think the section about why we should trust the project founder is quite funny. Something like "I did video games and stuff". 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'd love to see this happen, but this doesn't help their case imho.
-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 isn't even really AI; it's a pet project from that insane, sex-pest-filled movement in the US that calls itself "effective altruism" (that and their dozens of even-more-insane offshoots). IIRC originally funded by the pitiful creature that Yudkowsky had by then become.
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.
"value" not "valuation". It has a value of hundreds of billions, if not trillions, of dollars. It would require enforceable patents to have that value funnel to one company.
Lets see, are there any parallels?
Is there a solution to soil eriosion thats been supressed for 60 years, like perrenial agricultur
If only there was a solution to climate change thats been supressed for 60 years, like nuclear power!
Supressed is not the right term- not developed. Marker settles on a local optimum and does not make the huge investment needed to go to the global optimum. Also all the current market leaders lobby against the transition.
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.
* 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.
> My routine includes brushing my teeth 3x per day for 3 minutes
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?
I usually eat 3 meals a day or two meals and a snack and I brush my teeth about 20-30 minutes after that so I guess it mostly due to my wish to get my mouth feel fresh and prevent staining if I had something like kimchi. 2 minutes twice per day is probably sufficient most of the time but the amount of abrasion and gum damage will probably also heavily depend on the hardness of the brush, the specific toothpaste and and the of course how vigorously you brush. I asked my dentist about this last year and he said it's fine and my gum health and enamel seem to confirm that.
Newbie question: Can someone help me understand how adding a new benign bacteria helps prevent infection by the other cavity-causing bacteria? Do they "fight" each other?
That's a good point they may not have even considered... if they are "recreating from precursor" why wouldn't you just 1. Check the status of the test subjects e.g. any new cavities
2. Get the supposed indefinite strain from one or several of the 15
Nowhere on the page does it explain how will this grant be used. It asserts that there's nothing preventing them from recreating BCS3-L1 ourselves from commercially available precursor bacteria but it doesn't say if that's the plan.
My guess is this funding will be used to look into the different approaches, and then they will come back with a real project.
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 won't smell bad.
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).
Happy to answer any questions!