"No, the FDA is not a perfect institution, and yes, it can be improved in many, many ways. But the history of health product regulation is written in blood."
"But the history of health product regulation is written in blood" is a very broad phrase, and this entire article is part of a debate about whether the FDA should be ignored or worked around.
So OP is directly on target, and for me at least it is easy to say we should not work around the FDA with purportedly-anti-cavity bacteria, and also to agree with Jake Seliger's point.
I imagine Trevor would agree that there are trade-offs between trying to stop unscrupulous snake-oil salesmen from luring desperate people into blowing their life savings and then going into debt, in the hope of surviving, versus letting people participate in experiments when they don't seem to have much to lose. I tend to agree that right now the dial is turned too far towards restriction -- by and large, bureaucrats are more afraid of getting pilloried for approving a drug that causes problems (see: thalidomide) than they are of stories about people who died because they missed out on an experiment that, a priori, had a low-probability-of-helping anyways. There _are_ FDA exceptions for experimental treatment, but I think those should probably be much broader than they are, as long as the experimenter is not in any way charging the study participants -- they should be _compensating_ the participant for any expenses associated with participating.
Get rid of the FDA. It is responsible for a huge number of deaths and a vast amount of suffering. At the very least cut its power back to where it was before 1962. Use liability law to hold drug companies accountable. That balances risks and rewards. Given the litigious culture in the USA (and the lack of loser pays), this will still be too restrictive but an improvement.
Probably true, but not me. I studied economic history, have a degree in Economics from Oxford, and have studied the history of regulation. Some people need to read Free to Choose (read chapter 7, "Who Protects the Consumer?") and Sam Peltzman.
The dangers of unregulated patent medicines was exaggerated by muckraking journals, led by Upton Sinclair. "Baptist" groups such as The Women's Christian Temperance Union and the National Temperance Society (which combined to create the National Pure Food and Drug Congress) joined with "bootlegger" groups such as the meatpackers (who wanted to restrict "diseased" meat imports that increased competition. This led to the 1906 act which, inevitably, was later applied to prescription drugs.
a degree in economics disqualifies u from most sane conversations, but rest assured we will call on u when an expert in making shit up and mathematical "models" based on nothing but conjecture is required.
This was an informative post, but I found it frustrating. It admixes arguments from three different levels: 1) personal attacks, 2) appeals to scientific authority/process/conservatism, and 3) object-level scientific arguments. I found only level 3 enlightening, with level 2 being obvious and level 1 distracting and, frankly, hypocritical.
Aaron's qualifications so closely match Trevor's (both are web entrepreneurs repurposing other people's drugs) that level 1 should never have come up in the first place. Meanwhile the references to Aella are irrelevant and come across as sexual shaming. Trevor tries to wave both objections away in Footnote 4, but this is praeteritio. If you don't mean the smears, don't put them in your blog post.
You see? It's distracting. I am now distracted and angry. Instead of making me write that last paragraph, the post should have skipped the gossip and focused on the argument that 1) probiotics carry risks both known and unknown and 2) FDA approval and GMP would have addressed these risks. That's a clear thesis that stands best on its own.
I first heard about this from Aella, and I didn’t realize how connected she was to the people driving this. So I think it’s relevant to include her. Re: sex shaming, this article mentions her sex work (relevant as the source of her public prominence and her connection to Lumina’s team) but doesn’t say anything bad about sex work or sex workers. Assuming that bringing it up must be intended as shaming reminds me of this: https://x.com/TitaniaMcGrath/status/1478741009974669312
I tend to think that the risk/reward for Lumina is not good.
But I 100% agree that the bizarre sex-shaming-via-innuendo undermined the whole pieces so thoroughly that I was unable to actually absorb any of the potentially enlightening arguments that followed.
Are you so irritated on aellas behalf that you are unable to follow the far more significant story of a potentially harmful genetically engineered bacteria being mass marketed, possibly to your friends? That seems odd.
Nice post Trevor - I appreciate someone from the actual pharma development side taking the time to review this. I tried to write something similar several times, but just couldn't find the time.
I also tried to reach out to Aaron when I first saw the Lumina pitch deck. My company is developing a antimicrobial peptide (in a class related to the mutacins) for immune modulation. What I wanted to warn him about was the fact that a lot of these molecules traditionally classed as antibiotics have profound immune modulating properties that might end up doing adverse things in a mucus membrane.
Hey, I do microbial process engineering and bioproduction at Lumina and would like to clarify some misinformation.
I’ve been working in biopharmaceutical development, GMP manufacturing, fermentation, sterile operations, and leading technology transfers to contract manufacturing organizations worldwide for over the last 25 years. You seem like you’re genuinely trying to help people, which I am totally behind.
But you're mistaken about our production standards, and microbial and chemical contamination control practices. We abide by GMP, Good Manufacturing Practices, which involves building quality into the process along with analytical and release testing.
Many people hear “cosmetics” and think it’s the absolute Wild West. I can't speak for other companies, but we are abiding by the same process controls that I’ve used in biopharma companies.
We haven't explicitly talked about our QA processes because we hadn't anticipated people might think we're not doing it. I’ll nudge Aaron about writing up a FAQ about manufacturing and how to maintain purity.
Thank you for clarifying. As a Lumina customer, I'd like to see that manufacturing FAQ. The argument about manufacturing was the part of this that most concerned me.
You may be right that this is a bad idea to try, but also, your argument for the FDA in general is crappy. It’s like you’ve never even heard of the unseen.
Appreciate you pointing out Scott and Aaron's association with promoting the work of pornographers - an irrelevant detail to those with lax morality, but for those of us who care about integrity and ethical standards, that's a significant mark against their trustworthiness.
The sex industry is absolutely horrid, and pornographers have a well-deserved reputation for being among the most abusive and amoral participants in that business.
Aaron being a pornographer is absolutely relevant to his willingness to sacrifice the health and well being of others for profit. If you read Aella regularly, the deep tragedy of her life comes through her writings, and this guy is personally profiting off her misery.
Not sure how that contradicts the cited line? Sometimes people accidentally cultured something bad in their milk, and got sick. Yes, the techniques they developed over time had good statistics on producing safe yogurt, rather than "spoiled milk with something that will make you sick", and probably the methods also made it likely that if you cultured the wrong thing, it would be _noticeable_ -- the batch would look or smell wrong, so you could toss it. But getting sick from traditionally cultured products is a thing!
Random relatively recent incident that was the first hit on a Google search:
An awful lot of people have reached the reasoned conclusion that the FDA’s mandate to prove *efficacy* kills more people than it helps. Thalidomide *was* effective, it just wasn’t (for certain users) safe. Adding alongside “first prove it’s safe” the additional FDA requirement “prove it works” was *not* justified by thalidomide; regulators seem to have done that anyway due to the “something” rule:
1. Something must be done!
2. This is something.
3. Therefore, this must be done!
We know why the fence was put there and we know its net effect is to kill lots of people; Chesterton would support repairing or removing that fence. There’s nothing wrong with a world in which the FDA only looks at safety and leaves establishing efficacy up to other, more voluntary, institutions.
Early adopters who try out new drugs or drug-like products that *might* help solve big problems are providing a public service to everyone else. Over time it should eventually become clear from the *results* whether it works. Meanwhile, so long as something seems pretty safe but we can’t yet know for sure if it works, an equilibrium in which a few people informally try it anyway (so DATA CAN BE GATHERED - even informally - to gradually DISCOVER if it works) is much better than an equilibrium in which nobody ever does that because you have to first burn half a billion dollars to satisfy the gods of the FDA so in cases where it’d be hard to recoup that cost the money never gets spent.
Informal data is pretty useless in determining drug efficacy, especially if the endpoint isn't obvious. To take Lumina for example, the endpoint would be a significant reduction in cavities. But Lumina is a relatively expensive product, so you've essentially self-selcted for people with a large amount of disposal income - who can afford regular dental care and would likely take good care of their teeth.
In this situation, how would you distinguish between "Lumina reduces cavities", and "People wealthy enough to afford Lumina can afford good dental care". In a clinical trial you can attempt to control for this kind of bias, or at least collect a large amount of minimally biased data. With gradual informal data collection you can't really control for anything.
On a broad level, I'd argue that making sure that medications are effective before they're sold is important because it:
1. Maintains public trust in medicine.
2. Prevents people from wasting their time and money on treatments that don't work.
If a treatment’s effect is *so subtle* that you need a big RCT to verify efficacy then it’s probably not a huge improvement to have people start using that treatment - it might not matter very much.
In this case, the expected endpoint is going from a normal amount of cavities/fillings to essentially NO cavities/fillings. That should be pretty obvious - once the treatment is an available option out in the world you could pick it up from a survey. A survey of dentists, or of dental patients, better yet one run by a dental insurance firm of its customers - the firm expects to *save money* if it works by encouraging use so they have an incentive to find that out and customers of the same dental insurance company should have similar access to dental care, no?
Come to think of it, the selection effect you’re suggesting might even go the other way - people with “regular dental care” are having their teeth *inspected* more often so might plausibly have more cavities *found* and *filled* over some period of time given that dental insurance and wealth make us less sensitive to the cost so we’re less inclined to “wait and see” in borderline cases. (Though a complicating factor is kids getting a “dental sealant” for their first permanent teeth.)
On the broad level, what is the *mechanism* by which you think the FDA's stranglehold on drug development "Maintains public trust in medicine"? For context, a couple of the most obvious FDA reform options include:
(1) make a short list of other countries whose regulators we trust and establish a policy that any drug approved for use in other countries gets automatically approved here 10 years later with no additional testing required. The delay means we have a decade for thalidomide-like effects and/or general-population effectiveness data/stories to show up. Put the country name on the label - this drug was EU or Japan-approved - so if individuals don't personally trust that country they don't have to use those drugs.
(2) make FDA approval OPTIONAL but require an "UNAPPROVED BY FDA" label. Then people who only trust the FDA have the OPTION to take only FDA-approved drugs, but people who want something else can do that first.
How would either of THOSE options "reduce trust in medicine"?
More generally, I'm not sure our goal SHOULD be to "maintain public trust in medicine". Rather our goal should be for medicine to ACTUALLY BE TRUSTWORTHY. If some product clearly says on the label "we're not yet sure if this works" and it later turns out it didn't work, why would that reduce trust in stuff that IS FDA-certified for effectiveness? Let's just be clear about what we're doing - what we know and with what certainly level - and let overall "trust in medicine" take care of itself.
The social value in "preventing people from wasting their time and money on treatments that don't work" ought to be balanced against the social value of "allow people to organically discover treatments and/or improvements that DO work", does it not? "Early adopters" in every industry - not just medicine - voluntarily choose to waste their own time and money on stuff that only *might* work; in so doing they provide a public service to the rest of us who can wait and see how they fare. Why give that up?
I mostly agree with you about the FDA -- I think there's a very strong argument for reform. But I can't get behind the conclusion that "Undermining the FDA is good, actually." That's more or less the equivalent of "defund the police". Saying that police abuse problems are real, and the institution of policing needs reform, does not mean we don't need police to deal with crime, or that folks should engage in petty crime if they can get away with it to "undermine the police", even if in some cases civil disobedience and protest seems justifiable.
I also think our process for building public infrastructure is a catastrophe, and "guerrilla public works" sometimes seem justifiable ( https://99percentinvisible.org/episode/guerrilla-public-service/ ), but I wouldn't want LOTS of people randomly changing signs or modifying streets.
If somebody is a snake oil salesman, _of course_ they're going to claim that their product belongs in the category of justifiable evasion of the existing rules. But assuming that everyone who's "Fighting the Man!" is in the right is just as silly as assuming that "the Man" (here embodied by the FDA) is always right.
Also, technically speaking, the Chesterton's Fence concept is about tearing down a fence, not just jumping it:
<blockquote>
There exists in such a case a certain institution or law; let us say, for the sake of simplicity, a fence or gate erected across a road. The more modern type of reformer goes gaily up to it and says, “I don’t see the use of this; let us clear it away.” To which the more intelligent type of reformer will do well to answer: “If you don’t see the use of it, I certainly won’t let you clear it away. Go away and think. Then, when you can come back and tell me that you do see the use of it, I may allow you to destroy it.”
</blockquote>
It's fine to say, "the reason this rule was put in place no longer applies" or that the cost-benefit trade-off of the rule has changed. But just trashing a rule because you don't instantly understand it is arrogant and reckless.
I have met some hardcore libertarians who want to scrap the FDA entirely (and other consumer product regulation), who will say clearly they think anyone should be able to sell anything, and the only remedy if you buy something from them and it poisons you is to sue them for fraud. They are convinced that even in the absence of anything like the Consumer Product Safety Commission, we'll all be fine, you won't get fly-by-night brands selling cheap toasters that burst into flame, and then when that brand-name is mud, reconstituting under a new name.
I basically agree with a lot of the critiques of the FDA, I think the existing process is too onerous, and entirely rules out certain categories of trial (like vaccine challenge trials) that we should allow. But I can't go along with folks who basically imagine that normal people are going to be able to navigate a world full of snake-oil salesmen. (The supplements industry is already demonstration of that, with people buying stuff that, when anyone bothers to check, contains wildly varying amounts of the ingredients it's supposed to contain, sometimes none at all, and sometimes contaminated with molds, heavy metals, and other fun things.)
> But the history of health product regulation is written in blood.
It sure is! Want to count how many people have died while waiting for the FDA to approve treatments that could have helped them? Do you think it’s less than a million? Less than ten million? Hard to say. The FDA may or may not be worse than the Third Reich, in other words.
If you want to read about the details, the best source I know is, well… you know the punchline.
What does this mean: "those treatments"? Yes, if you choose a random treatment for cancer -- rubbing nickels on your face, howling at the moon -- it will likely not work. Thus, we must ban chemotherapy, to protect the public from quackery!
I advocate a system in which patients and doctors are free to try treatments that they have researched and have good reason to believe may be effective, rather than be barred by law from performing such treatments.
I think you are a bit misleading when you say Scott Alexander has promoted this. He says it is very interesting, might or might not work, and isn’t taking it himself. As endorsements go it’s not knocking it out of the park. I don’t quite know what to make of this - careless or what?
You make two arguments that seem to be in tension. Firstly that mutacin-1140 producing and resisting bacteria are already naturally present in some people's mouths, and therefor would not be killed by BCS3L-1, and secondly that having mutacin-1140 producing bacteria in ones mouth might nuke all other bacteria in one's body and therefor cause medical problems, particularly for infants and imunocompromised people. How can both of these be true? If mutacin-1140 producing bacteria are already in some mouths, and we aren't seeing negative outcomes from it, doesn't that show that mutacin-1140, in the quantities mouth bacteria will produce, is harmless?
It's an inductor of that, but not necessarily conclusive. It's (probably) not a 'dead in 10 years' kind of harmful, but there's no way of knowing if it's not a 'more cancer in 20 years' type of harmful.
I'd guess that no one has actually measured the outcomes of people with these mouth bacteria, so theres no actual evidence one way or another.
You misleadingly cite its one-and-only failed human trial as evidence against it, but that trial was intended only to measure its effectiveness in preventing gum disease, also known as periodontal disease or periodontitis, not tooth decay, cavities, or caries.
The only two measures correlated with cavity/cary formation, salivary Prevotella intermedia counts and % of sites with plaque, both showed *significant improvement* in the probiotic group following 12 weeks of twice-daily use as well as 12 weeks after cessation of use (i.e., at the 24-week mark).
From the paper:
> Results: The primary and secondary outcome measures were significantly (p < 0.05) improved at the 12- and the 24-week evaluation in both groups. However, no significant inter-group differences could be detected at any time point, except from the % of sites with plaque that were significantly lower in the probiotic group than in the control group at the 24-week evaluation. In addition, at the 12-week time point, the salivary Prevotella intermedia counts were significantly lower in the probiotic group.
"In exchange for positive reviews"? This and the strange mentioning of porn connections doesn't make the rest more valuable (and may cost you a lot if the people in question bother to bother their lawyers).
I'm seeking some clarification on your final point that I may be misunderstanding.
Your concern seems to be that the presence of a Mutacin-1140 producing bacteria could cause systemic problems due to its ability to survive long periods in the digestive tract and bind to blood.
What I can't resolve is that you also assent earlier in the section about what BCS3L-1 is, that plenty of wild S. mutans naturally produces the same Mutacin-1140. So why the special concern for colonizing a person's mouth with Mutacin-1140 producing bacteria, when similar bacteria already exists naturally in the population with no known ill effects?
been waiting for someone with enough eyes and feet in this area to say what i've been feeling about this product. Not only will this impact people who take it, the bacterium may infect anyone who they make out with, making this a contagious bacterium, and possibly a pathogenic one at that.
Which makes this a biological weapon and Lumina a terrorist organization, just like ecohealth alliance.
But rationalist progressivism cannot possibly have dire consequences!
"No, the FDA is not a perfect institution, and yes, it can be improved in many, many ways. But the history of health product regulation is written in blood."
This is a vast understatement and I'm dying in large part due to the FDA's torpor and intransigence: https://jakeseliger.com/2023/07/22/i-am-dying-of-squamous-cell-carcinoma-and-the-treatments-that-might-save-me-are-just-out-of-reach/
Persons like me, with fatal diagnoses, should be allowed to try any treatment that has passed phase 1a safety trials. Instead, the FDA lets people like me fill the invisible graveyard, and that's a tragedy: https://jakeseliger.com/2024/01/29/the-dead-and-dying-at-the-gates-of-oncology-clinical-trials/
"But the history of health product regulation is written in blood"
Yeah—the blood of people like me, who die because the FDA has zero sense of urgency.
"Persons like me, with fatal diagnoses, should be allowed to try any treatment that has passed phase 1a safety trials."
I mostly agree with this, but it also seems like an irrelevant point to make on post about a tooth decay drug.
"But the history of health product regulation is written in blood" is a very broad phrase, and this entire article is part of a debate about whether the FDA should be ignored or worked around.
So OP is directly on target, and for me at least it is easy to say we should not work around the FDA with purportedly-anti-cavity bacteria, and also to agree with Jake Seliger's point.
I imagine Trevor would agree that there are trade-offs between trying to stop unscrupulous snake-oil salesmen from luring desperate people into blowing their life savings and then going into debt, in the hope of surviving, versus letting people participate in experiments when they don't seem to have much to lose. I tend to agree that right now the dial is turned too far towards restriction -- by and large, bureaucrats are more afraid of getting pilloried for approving a drug that causes problems (see: thalidomide) than they are of stories about people who died because they missed out on an experiment that, a priori, had a low-probability-of-helping anyways. There _are_ FDA exceptions for experimental treatment, but I think those should probably be much broader than they are, as long as the experimenter is not in any way charging the study participants -- they should be _compensating_ the participant for any expenses associated with participating.
I also think we should have a process for challenge trials. ( https://www.slowboring.com/p/the-case-for-vaccine-challenge-trials )
Regardless, I'm very sorry for what you're going through, that sucks.
Get rid of the FDA. It is responsible for a huge number of deaths and a vast amount of suffering. At the very least cut its power back to where it was before 1962. Use liability law to hold drug companies accountable. That balances risks and rewards. Given the litigious culture in the USA (and the lack of loser pays), this will still be too restrictive but an improvement.
It’s useful to read up on the history of pre-FDA patent medicines to get some balance here. Very few if any cancer cures, lots of straight up poisons
Probably true, but not me. I studied economic history, have a degree in Economics from Oxford, and have studied the history of regulation. Some people need to read Free to Choose (read chapter 7, "Who Protects the Consumer?") and Sam Peltzman.
The dangers of unregulated patent medicines was exaggerated by muckraking journals, led by Upton Sinclair. "Baptist" groups such as The Women's Christian Temperance Union and the National Temperance Society (which combined to create the National Pure Food and Drug Congress) joined with "bootlegger" groups such as the meatpackers (who wanted to restrict "diseased" meat imports that increased competition. This led to the 1906 act which, inevitably, was later applied to prescription drugs.
Also, learn about "the invisible graveyard".
a degree in economics disqualifies u from most sane conversations, but rest assured we will call on u when an expert in making shit up and mathematical "models" based on nothing but conjecture is required.
This was an informative post, but I found it frustrating. It admixes arguments from three different levels: 1) personal attacks, 2) appeals to scientific authority/process/conservatism, and 3) object-level scientific arguments. I found only level 3 enlightening, with level 2 being obvious and level 1 distracting and, frankly, hypocritical.
Aaron's qualifications so closely match Trevor's (both are web entrepreneurs repurposing other people's drugs) that level 1 should never have come up in the first place. Meanwhile the references to Aella are irrelevant and come across as sexual shaming. Trevor tries to wave both objections away in Footnote 4, but this is praeteritio. If you don't mean the smears, don't put them in your blog post.
You see? It's distracting. I am now distracted and angry. Instead of making me write that last paragraph, the post should have skipped the gossip and focused on the argument that 1) probiotics carry risks both known and unknown and 2) FDA approval and GMP would have addressed these risks. That's a clear thesis that stands best on its own.
I first heard about this from Aella, and I didn’t realize how connected she was to the people driving this. So I think it’s relevant to include her. Re: sex shaming, this article mentions her sex work (relevant as the source of her public prominence and her connection to Lumina’s team) but doesn’t say anything bad about sex work or sex workers. Assuming that bringing it up must be intended as shaming reminds me of this: https://x.com/TitaniaMcGrath/status/1478741009974669312
I tend to think that the risk/reward for Lumina is not good.
But I 100% agree that the bizarre sex-shaming-via-innuendo undermined the whole pieces so thoroughly that I was unable to actually absorb any of the potentially enlightening arguments that followed.
Are you so irritated on aellas behalf that you are unable to follow the far more significant story of a potentially harmful genetically engineered bacteria being mass marketed, possibly to your friends? That seems odd.
I think that part is just meant to be funny.
Nice post Trevor - I appreciate someone from the actual pharma development side taking the time to review this. I tried to write something similar several times, but just couldn't find the time.
I also tried to reach out to Aaron when I first saw the Lumina pitch deck. My company is developing a antimicrobial peptide (in a class related to the mutacins) for immune modulation. What I wanted to warn him about was the fact that a lot of these molecules traditionally classed as antibiotics have profound immune modulating properties that might end up doing adverse things in a mucus membrane.
Hey, I do microbial process engineering and bioproduction at Lumina and would like to clarify some misinformation.
I’ve been working in biopharmaceutical development, GMP manufacturing, fermentation, sterile operations, and leading technology transfers to contract manufacturing organizations worldwide for over the last 25 years. You seem like you’re genuinely trying to help people, which I am totally behind.
But you're mistaken about our production standards, and microbial and chemical contamination control practices. We abide by GMP, Good Manufacturing Practices, which involves building quality into the process along with analytical and release testing.
Many people hear “cosmetics” and think it’s the absolute Wild West. I can't speak for other companies, but we are abiding by the same process controls that I’ve used in biopharma companies.
We haven't explicitly talked about our QA processes because we hadn't anticipated people might think we're not doing it. I’ll nudge Aaron about writing up a FAQ about manufacturing and how to maintain purity.
Thanks, man
Thank you for clarifying. As a Lumina customer, I'd like to see that manufacturing FAQ. The argument about manufacturing was the part of this that most concerned me.
You may be right that this is a bad idea to try, but also, your argument for the FDA in general is crappy. It’s like you’ve never even heard of the unseen.
Appreciate you pointing out Scott and Aaron's association with promoting the work of pornographers - an irrelevant detail to those with lax morality, but for those of us who care about integrity and ethical standards, that's a significant mark against their trustworthiness.
Don't forget to ask your priest, rabbi, or mullah for their learned medical opinions.
I'm pretty sure he was tongue in cheek
What association does Scott Alexander have with Aella? As far as I know none whatsoever.
They're friends, in the same community, and Scott met his wife at one of Aella's parties:
https://www.astralcodexten.com/p/theres-a-time-for-everyone
The sex industry is absolutely horrid, and pornographers have a well-deserved reputation for being among the most abusive and amoral participants in that business.
Aaron being a pornographer is absolutely relevant to his willingness to sacrifice the health and well being of others for profit. If you read Aella regularly, the deep tragedy of her life comes through her writings, and this guy is personally profiting off her misery.
> As the links above suggest, even “safe” probiotics like yogurt or kombucha can make you incredibly sick or kill you if improperly manufactured.
Yogurt and kombucha have been manufactured by traditional societies long before the FDA existed.
Not sure how that contradicts the cited line? Sometimes people accidentally cultured something bad in their milk, and got sick. Yes, the techniques they developed over time had good statistics on producing safe yogurt, rather than "spoiled milk with something that will make you sick", and probably the methods also made it likely that if you cultured the wrong thing, it would be _noticeable_ -- the batch would look or smell wrong, so you could toss it. But getting sick from traditionally cultured products is a thing!
Random relatively recent incident that was the first hit on a Google search:
https://japantoday.com/category/national/students-hospitalized-after-eating-teacher%E2%80%99s-homemade-yogurt-in-nagoya
An awful lot of people have reached the reasoned conclusion that the FDA’s mandate to prove *efficacy* kills more people than it helps. Thalidomide *was* effective, it just wasn’t (for certain users) safe. Adding alongside “first prove it’s safe” the additional FDA requirement “prove it works” was *not* justified by thalidomide; regulators seem to have done that anyway due to the “something” rule:
1. Something must be done!
2. This is something.
3. Therefore, this must be done!
We know why the fence was put there and we know its net effect is to kill lots of people; Chesterton would support repairing or removing that fence. There’s nothing wrong with a world in which the FDA only looks at safety and leaves establishing efficacy up to other, more voluntary, institutions.
Early adopters who try out new drugs or drug-like products that *might* help solve big problems are providing a public service to everyone else. Over time it should eventually become clear from the *results* whether it works. Meanwhile, so long as something seems pretty safe but we can’t yet know for sure if it works, an equilibrium in which a few people informally try it anyway (so DATA CAN BE GATHERED - even informally - to gradually DISCOVER if it works) is much better than an equilibrium in which nobody ever does that because you have to first burn half a billion dollars to satisfy the gods of the FDA so in cases where it’d be hard to recoup that cost the money never gets spent.
In short: undermining the FDA is good, actually.
Informal data is pretty useless in determining drug efficacy, especially if the endpoint isn't obvious. To take Lumina for example, the endpoint would be a significant reduction in cavities. But Lumina is a relatively expensive product, so you've essentially self-selcted for people with a large amount of disposal income - who can afford regular dental care and would likely take good care of their teeth.
In this situation, how would you distinguish between "Lumina reduces cavities", and "People wealthy enough to afford Lumina can afford good dental care". In a clinical trial you can attempt to control for this kind of bias, or at least collect a large amount of minimally biased data. With gradual informal data collection you can't really control for anything.
On a broad level, I'd argue that making sure that medications are effective before they're sold is important because it:
1. Maintains public trust in medicine.
2. Prevents people from wasting their time and money on treatments that don't work.
If a treatment’s effect is *so subtle* that you need a big RCT to verify efficacy then it’s probably not a huge improvement to have people start using that treatment - it might not matter very much.
In this case, the expected endpoint is going from a normal amount of cavities/fillings to essentially NO cavities/fillings. That should be pretty obvious - once the treatment is an available option out in the world you could pick it up from a survey. A survey of dentists, or of dental patients, better yet one run by a dental insurance firm of its customers - the firm expects to *save money* if it works by encouraging use so they have an incentive to find that out and customers of the same dental insurance company should have similar access to dental care, no?
Come to think of it, the selection effect you’re suggesting might even go the other way - people with “regular dental care” are having their teeth *inspected* more often so might plausibly have more cavities *found* and *filled* over some period of time given that dental insurance and wealth make us less sensitive to the cost so we’re less inclined to “wait and see” in borderline cases. (Though a complicating factor is kids getting a “dental sealant” for their first permanent teeth.)
On the broad level, what is the *mechanism* by which you think the FDA's stranglehold on drug development "Maintains public trust in medicine"? For context, a couple of the most obvious FDA reform options include:
(1) make a short list of other countries whose regulators we trust and establish a policy that any drug approved for use in other countries gets automatically approved here 10 years later with no additional testing required. The delay means we have a decade for thalidomide-like effects and/or general-population effectiveness data/stories to show up. Put the country name on the label - this drug was EU or Japan-approved - so if individuals don't personally trust that country they don't have to use those drugs.
(2) make FDA approval OPTIONAL but require an "UNAPPROVED BY FDA" label. Then people who only trust the FDA have the OPTION to take only FDA-approved drugs, but people who want something else can do that first.
How would either of THOSE options "reduce trust in medicine"?
More generally, I'm not sure our goal SHOULD be to "maintain public trust in medicine". Rather our goal should be for medicine to ACTUALLY BE TRUSTWORTHY. If some product clearly says on the label "we're not yet sure if this works" and it later turns out it didn't work, why would that reduce trust in stuff that IS FDA-certified for effectiveness? Let's just be clear about what we're doing - what we know and with what certainly level - and let overall "trust in medicine" take care of itself.
The social value in "preventing people from wasting their time and money on treatments that don't work" ought to be balanced against the social value of "allow people to organically discover treatments and/or improvements that DO work", does it not? "Early adopters" in every industry - not just medicine - voluntarily choose to waste their own time and money on stuff that only *might* work; in so doing they provide a public service to the rest of us who can wait and see how they fare. Why give that up?
I mostly agree with you about the FDA -- I think there's a very strong argument for reform. But I can't get behind the conclusion that "Undermining the FDA is good, actually." That's more or less the equivalent of "defund the police". Saying that police abuse problems are real, and the institution of policing needs reform, does not mean we don't need police to deal with crime, or that folks should engage in petty crime if they can get away with it to "undermine the police", even if in some cases civil disobedience and protest seems justifiable.
I also think our process for building public infrastructure is a catastrophe, and "guerrilla public works" sometimes seem justifiable ( https://99percentinvisible.org/episode/guerrilla-public-service/ ), but I wouldn't want LOTS of people randomly changing signs or modifying streets.
If somebody is a snake oil salesman, _of course_ they're going to claim that their product belongs in the category of justifiable evasion of the existing rules. But assuming that everyone who's "Fighting the Man!" is in the right is just as silly as assuming that "the Man" (here embodied by the FDA) is always right.
Typo in fn 8: "if you don’t get why the fence isn’t there" -- should be "is there".
Also, technically speaking, the Chesterton's Fence concept is about tearing down a fence, not just jumping it:
<blockquote>
There exists in such a case a certain institution or law; let us say, for the sake of simplicity, a fence or gate erected across a road. The more modern type of reformer goes gaily up to it and says, “I don’t see the use of this; let us clear it away.” To which the more intelligent type of reformer will do well to answer: “If you don’t see the use of it, I certainly won’t let you clear it away. Go away and think. Then, when you can come back and tell me that you do see the use of it, I may allow you to destroy it.”
</blockquote>
It's fine to say, "the reason this rule was put in place no longer applies" or that the cost-benefit trade-off of the rule has changed. But just trashing a rule because you don't instantly understand it is arrogant and reckless.
nobody says "drug regulation never had a reason".
what everyone says "those guys are more trouble than value. more die due to fda intransigence than saved by their added 'safety'"
there is a graph showing drug development over the 20th century.
it crashes about the time fda laws got strict.
I have met some hardcore libertarians who want to scrap the FDA entirely (and other consumer product regulation), who will say clearly they think anyone should be able to sell anything, and the only remedy if you buy something from them and it poisons you is to sue them for fraud. They are convinced that even in the absence of anything like the Consumer Product Safety Commission, we'll all be fine, you won't get fly-by-night brands selling cheap toasters that burst into flame, and then when that brand-name is mud, reconstituting under a new name.
I basically agree with a lot of the critiques of the FDA, I think the existing process is too onerous, and entirely rules out certain categories of trial (like vaccine challenge trials) that we should allow. But I can't go along with folks who basically imagine that normal people are going to be able to navigate a world full of snake-oil salesmen. (The supplements industry is already demonstration of that, with people buying stuff that, when anyone bothers to check, contains wildly varying amounts of the ingredients it's supposed to contain, sometimes none at all, and sometimes contaminated with molds, heavy metals, and other fun things.)
yeah. the FDA isn't only killing. it does also has various positives.
the libertarian arguments are stupid nonsense.
the real question is comparing costs and benefits.
any analysis that focuses on one aspect of the FDA will not be right. focusing illusion.
we need to fully calculate current FDA Vs abolishing or other systems.....
You're right. We need Daddy to take of us.
> But the history of health product regulation is written in blood.
It sure is! Want to count how many people have died while waiting for the FDA to approve treatments that could have helped them? Do you think it’s less than a million? Less than ten million? Hard to say. The FDA may or may not be worse than the Third Reich, in other words.
If you want to read about the details, the best source I know is, well… you know the punchline.
https://www.astralcodexten.com/p/adumbrations-of-aducanumab
You have to remember those treatments have like a 1% of working so far less than you think.
What does this mean: "those treatments"? Yes, if you choose a random treatment for cancer -- rubbing nickels on your face, howling at the moon -- it will likely not work. Thus, we must ban chemotherapy, to protect the public from quackery!
I advocate a system in which patients and doctors are free to try treatments that they have researched and have good reason to believe may be effective, rather than be barred by law from performing such treatments.
Here's a story of absolutely indefensible FDA dysfunction, just today: https://marginalrevolution.com/marginalrevolution/2024/05/the-left-on-fda-peer-approval.html
Please, please explain to me the rationale behind this FDA policy. I am all ears.
Here’s another one — not new, but evergreen, the FDA’s ludicrous position on sunscreen that kills how many people every year?
https://marginalrevolution.com/marginalrevolution/2024/05/deadly-precaution.html?utm_source=rss&utm_medium=rss&utm_campaign=deadly-precaution
“Written in blood”, indeed!
I think you are a bit misleading when you say Scott Alexander has promoted this. He says it is very interesting, might or might not work, and isn’t taking it himself. As endorsements go it’s not knocking it out of the park. I don’t quite know what to make of this - careless or what?
You make two arguments that seem to be in tension. Firstly that mutacin-1140 producing and resisting bacteria are already naturally present in some people's mouths, and therefor would not be killed by BCS3L-1, and secondly that having mutacin-1140 producing bacteria in ones mouth might nuke all other bacteria in one's body and therefor cause medical problems, particularly for infants and imunocompromised people. How can both of these be true? If mutacin-1140 producing bacteria are already in some mouths, and we aren't seeing negative outcomes from it, doesn't that show that mutacin-1140, in the quantities mouth bacteria will produce, is harmless?
It's an inductor of that, but not necessarily conclusive. It's (probably) not a 'dead in 10 years' kind of harmful, but there's no way of knowing if it's not a 'more cancer in 20 years' type of harmful.
I'd guess that no one has actually measured the outcomes of people with these mouth bacteria, so theres no actual evidence one way or another.
You missed your best argument against Lumina:
You can already buy ProBiora for $20 at CVS.
You misleadingly cite its one-and-only failed human trial as evidence against it, but that trial was intended only to measure its effectiveness in preventing gum disease, also known as periodontal disease or periodontitis, not tooth decay, cavities, or caries.
The only two measures correlated with cavity/cary formation, salivary Prevotella intermedia counts and % of sites with plaque, both showed *significant improvement* in the probiotic group following 12 weeks of twice-daily use as well as 12 weeks after cessation of use (i.e., at the 24-week mark).
From the paper:
> Results: The primary and secondary outcome measures were significantly (p < 0.05) improved at the 12- and the 24-week evaluation in both groups. However, no significant inter-group differences could be detected at any time point, except from the % of sites with plaque that were significantly lower in the probiotic group than in the control group at the 24-week evaluation. In addition, at the 12-week time point, the salivary Prevotella intermedia counts were significantly lower in the probiotic group.
Source: https://pubmed.ncbi.nlm.nih.gov/26427036/
"In exchange for positive reviews"? This and the strange mentioning of porn connections doesn't make the rest more valuable (and may cost you a lot if the people in question bother to bother their lawyers).
I'm seeking some clarification on your final point that I may be misunderstanding.
Your concern seems to be that the presence of a Mutacin-1140 producing bacteria could cause systemic problems due to its ability to survive long periods in the digestive tract and bind to blood.
What I can't resolve is that you also assent earlier in the section about what BCS3L-1 is, that plenty of wild S. mutans naturally produces the same Mutacin-1140. So why the special concern for colonizing a person's mouth with Mutacin-1140 producing bacteria, when similar bacteria already exists naturally in the population with no known ill effects?
been waiting for someone with enough eyes and feet in this area to say what i've been feeling about this product. Not only will this impact people who take it, the bacterium may infect anyone who they make out with, making this a contagious bacterium, and possibly a pathogenic one at that.
Which makes this a biological weapon and Lumina a terrorist organization, just like ecohealth alliance.
But rationalist progressivism cannot possibly have dire consequences!
butlerian jihad when?