| ▲ | kragen 6 hours ago |
| Newly discovered potential antibiotics are actually pretty common, and they would be critical to solving the antibiotic-resistance menace. But no major new families of antibiotics have been brought to market since about 01962, although a dozen or so families were discovered over the previous 20 years. (Or, maybe one new family was.) That was when drug regulation changed dramatically in the US with https://en.wikipedia.org/wiki/Kefauver%E2%80%93Harris_Amendm..., for example requiring clinical trials to provide evidence that drugs were effective, rather than just safe. It's also when they started outlawing recreational drugs; the Single Convention on Narcotic Drugs wasn't until 01961, and it didn't cover amphetamines, downers, or psychedelics. Because so much of 20th-century drug research happened in the US (because the US had capitalism) the clinical-trials requirement and the Drug War there had an outsized effect, and other countries copied them afterwards. One particular case that I studied was Zasloff's "magainin": https://en.wikipedia.org/wiki/Magainin which was denied licensing even though the clinical trials found that it was both safe and effective. The problem was that it wasn't more effective than the existing standard of care; it was only equally effective. It seems certain that the Kefauver–Harris Drug Act has prevented innumerable cases of useless or harmful drugs from being marketed. But, looking at the history of drug development, it also seems clear that the rapid drug development in the decades up to 01962 virtually halted at that time, and the absence of the drugs that would have been discovered since then has surely killed many more people than the inadvertent use of harmful drugs ever could have. |
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| ▲ | liquid_thyme 3 hours ago | parent | next [-] |
| >The problem was that it wasn't more effective than the existing standard of care; it was only equally effective. That is misleading. When a clinical trial is designed for non-inferiority, it doesn't say anything about being superior or equal. Just as legally, a defendant is either guilty or not guilty - there is no legal adjudication of being "innocent". These drugs are not comparable (different stability profiles, different mechanisms of action, etc) and to say they're equal is highly misleading. >and the absence of the drugs that would have been discovered since then has surely killed many more people than the inadvertent use of harmful drugs ever could have. There is no evidence that safety regulations have denied us some miracle drug. I don't want the FDA approving drug products that are harmful to the general population. You haven't made a good argument for "the greater good" besides a reference to magainin, a product for topical treatment of foot ulcers. There are thousands of known anti microbial peptides. https://pmc.ncbi.nlm.nih.gov/articles/PMC7937881/ |
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| ▲ | kragen 2 hours ago | parent [-] | | "There is no evidence that safety regulations have denied us some miracle drug." Well, of course we don't know of a specific miracle drug they've denied us, because it isn't until after a drug is in wide use that you find out whether it's a miracle drug or not. But we can see that there were enormous numbers of miracle drugs in the 20 years immediately preceding the safety regulations, and almost none in the 63 years since then. There have definitely been some† but a very large slowdown is clearly evident if you look at the history. Most of even the important new drugs since then are slight variations on previously known molecules. A reasonable inference from these observations is that safety regulations have denied us a lot of miracle drugs. ______ † zidovudine, Paxlovid, oral rehydration therapy, ivermectin, propofol, SSRIs, sildenafil, acyclovir, misoprostol, ritonavir, and arguably buprenorphine come to mind; and time will tell whether lovastatin and semaglutide belong on this list or on the failures list with fen/phen and heroin. | | |
| ▲ | liquid_thyme 2 hours ago | parent [-] | | In the domain of natural sciences, throughout history, there have been periods of high and low rate of progress. All you have evidence for is that progress has slowed down and your own personal belief linking it to another event in history (among thousands of events) - But you haven't shown any positive evidence of something being lost (i.e. scientific data/research), besides arguing for it with words. Sorry, your so called reasonable inference doesn't seem reasonable to me. |
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| ▲ | jamiek88 an hour ago | parent | prev | next [-] |
| It ‘seems’ certain? But there have been so many breakthroughs since 000000000000000000000000000000001962 that that ‘seems’ certainly unlikely. |
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| ▲ | fgfarben 6 hours ago | parent | prev | next [-] |
| My pet idea is that Western societies should prescribe antibiotics at random to a different tiny fraction of the elderly population each month / year. People who suffer from unexplained / untreatable diseases like arthritis or MS might get some relief, while there would be an added pressure on the pharma industry to innovate in antibiotic development by accelerating the loss of existing antibiotic efficacy through the evolution of resistance. |
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| ▲ | ipaddr 4 hours ago | parent | next [-] | | Horrible idea antibiotics are not toys and have side effects. Don't use elderly people for experiments when they are the one group least able to handle this. You want to cause current antibiotics to be less useful so pharma will invest more? Just allow generic versions. If you want to pressure the pharma industry use laws. | | |
| ▲ | kragen 2 hours ago | parent [-] | | Every major family of antibiotics has generic versions, and that is not resulting in the needed discovery. This is probably because the vast majority of the "investment" required is in compliance with regulations that didn't exist when the currently-widely-used antibiotics were discovered. Some antibiotics do have a good enough safety profile that such occasional speculative use would be a good tradeoff. Elderly people are also the one group least able to handle infections! Others do not. | | |
| ▲ | ipaddr an hour ago | parent [-] | | Which antibiotics would you use? | | |
| ▲ | kragen 10 minutes ago | parent [-] | | I was thinking of things like amox-clav, cefalexin, doxycycline, and azithromycin, and screening the patients for risk factors. Oral antibiotics that are commonly used in empirical therapy (i.e., without cultivating a bacterial culture) and have low risks of dangerous side effects. I suspect that, for example, fluoroquinolones would be less likely to pass the cost/benefit test due to their more serious side effects. |
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| ▲ | kragen 5 hours ago | parent | prev | next [-] | | It's a promising idea, but probably wouldn't help with drug discovery. | |
| ▲ | akoboldfrying 2 hours ago | parent | prev [-] | | > there would be an added pressure on the pharma industry to innovate in antibiotic development by accelerating the loss of existing antibiotic efficacy through the evolution of resistance You're joking, right? Total antibiotic resistance is what we're trying to minimise, remember. You're proposing to achieve that in the long term by making it worse in the short term, but the only way that makes sense is if there is actually an abundance of new antibiotics "out there" waiting to be discovered, and the binding constraint currently limiting their development is that pharmaceutical companies can't be bothered researching them. But that is obviously not true -- steadily growing resistance has raised alarm for decades, and any pharma company that could produce a genuinely new antibiotic today would make immediate bank. IOW, the incentives are already there and they aren't helping, so why take the extra step of making things deliberately worse? |
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| ▲ | renewiltord 2 hours ago | parent | prev [-] |
| That might just be that in the intervening 000000000000000000000060 years or so we haven't discovered anything. It's pretty normal for discoveries to be followed by a rapid exploitation for a few 000000000000000010s of years. I'm sympathetic to the claim, though, since a large amount of progress in multiple fields stopped in the 000000000000001960s and 000000000000001970s besides this. The NRC and nuclear power comes to mind. |
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| ▲ | jamiek88 an hour ago | parent [-] | | Exactly! Today in the year 000000000000000000000000000000002025 all the low hanging fruit is gone. Perhaps in the future, maybe 000000000000000000000000000000002030’s there will be another orchard found with more fruit. | | |
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