6 ms·

100% response, zero side effects? This sounds like world changing news. Can anyone with domain expertise explain the catch, if any?

estearum 10mo ago
The catch is that there are thousands of promising therapies in animal models/pre-human testing. A very very tiny fraction of them will ever make it to market for a variety of both good and not-good reasons.
- colordrops 10mo ago
  What's the difference between a good and not-good reason to not go to market?
  - hyc_symas 10mo ago
    A lot of potential treatments are too easily available and can't be patented. If a big pharma company can't make massive profit from it, they won't bother bringing it to market. Consider that a not-good reason. Other treatments may eventually prove to have too many serious negative side effects. That's a good reason to abandon them.
    - megaman821 10mo ago
      Why would a China or India care if it were a viable treatment? Unless a country wants to use their population as lab rats, it takes money and scientists to actually confirm a treatment is safe and effective.
      - cluckindan 10mo ago
        Obviously you use the neighboring country’s population, or an ethnic minority, or prisoners, or orphans, or…
    - dboreham 10mo ago
      Kind of like open source software.
    - justinclift 10mo ago
      Wonder if some form of FOSS approach would work as an alternative development model for pharma?
      - ikawe 10mo ago
        These folks gave an interesting talk on producing pharmaceuticals at defcon a couple years ago. IIRC it was more about production methods than developing new treatments. https://fourthievesvinegar.org/ https://fourthievesvinegar.org/
      - vibrio 10mo ago
        This made me think of the "Institute for one world health" . It came out as a non-profit pharmaceutical company in the mid 2000's. Victoria Hale was the founder-it got her a MacArthur fellowship. It is focuses(focused?) on global health and populations underserved by for-profit models. I think they successfully developed a treatment for leishmaniasis. it's an adorable model and should be pushed but as usual it seems like the philantropy money is limiting.
    - Aurornis 10mo ago
      > A lot of potential treatments are too easily available and can't be patented. This isn’t really an obstacle, at least not as much as it’s made out to be. There are numerous examples of drugs being brought to market at high prices despite having been generic compounds. Even old drugs can be brought back at $1000/month or more at different doses or delivery mechanisms. One example: Doxepin is an old antidepressant that is extremely cheap. It was recently re-certified for sleep at lower doses and reintroduced at low doses at a much higher price, despite being “off patent”. This happens all the time. The drug companies aren’t actually abandoning usable treatments due to patent issues as much as journalists have claimed. If they couldn’t, for some reason, find a way to charge for it they could still use it as a basis for finding an improved relayed compound with more targeted effects, better pharmacokinetics, etc. They’re not just dropping promising treatments anywhere if there’s a market for them.
      - DivingForGold 10mo ago
        About Doxepin. As many seniors do, I also suffer from extreme inability to stay asleep at night. I have trialed through all the known prescription and non prescription possibilities, only eszopiclone and baclofen seem to show some promise, however, eszopiclone is DEA listed, requires higher and higher doses, and if I take it more than say 2 weeks, it has rather serious side effects attempting to withdraw, addictive, serious anxiety, trying to wean oneself off it. Doxepin is prescribed as an antidepressant in large doses, one of the most potent H1 histamine antagonists known. The H1 system in our bodies promotes wakefulness. In very low doses, doxepin acts against the H1 to promote sleep. To avoid the upcharges of low dose doxepin, I am prescribed the high dose version, which I have to break the capsules to administer about 5 to 10 mg. placed in an empty gelatin capsule (it's bitter). It really works well, however you are fairly tired and useless the next day.
        estearum 10mo ago
        Have you tried Cognitive Behavioral Therapy? I am a lifelong sufferer of insomnia (though mostly sleep onset) and tried all sorts of increasingly risky things. CBT cured me in ~2 months.
  - 3eb7988a1663 10mo ago
    Prevalence of the disease - if it only impacts 1/100 million, going to be hard to ever find sufficient patient population to test and recoup your investment. Existing quality of treatments - if there are already efficacious drugs on the market - how sure are you that this new therapy will be best in class? Only being as good as the status quo is not an ideal competitive position. Conversely, if there is an unmet need because a disease is so lethal/debilitating, regulatory agencies can give latitude in approvals. Likelihood patient compliance - if it is the most effective drug in the world, but requires intravenous infusion six times a day - nobody is going to adhere to that. GLP drugs are effective, but there is a needle-phobia that is preventing patients getting on board with the idea. Which is why there is an arms race for the first company to develop an oral version. Toxicity - all chemicals are poisonous. Yet some have a lower therapeutic window than others. If you drug does what it should, but if you take 2x as much and it gives you a heart arrhythmia that is going to be a tough approval for anything but the most deadly conditions.
    - z3t4 10mo ago
      Also the ethically in blind studies, can't just let some random patients die just to prove that your drug works.
      - Someone 10mo ago
        Yes, you can. The problem with testing is that a candidate treatment may make things worse for patients, not that it may improve things. If your treatment works, that’s an improvement of what you had before. Once you know that, you can treat all patients. For some, that will be too late, but without your tests, it would be too late for them, too. If your treatment doesn’t do anything at all, it keeps things the same, but the patients in the test group likely will have had some inconveniences (having to visit a doctor, getting an injection, etc), so you shouldn’t do the test. If your treatment makes things worse, you of course shouldn’t do the test. Problem is that you typically only can only know in hindsight which of these applies. So, you think carefully on whether a treatment could fall in category 3, and, if so, first do it on a group of patients who consent to be Guinea pigs and, often, are already terminally ill, as any negative outcomes will cause less harm to such patients. Then, as soon as during the test your stats tell the drug does or doesn’t work, you stop the test and either treat all patients or stop treating the test subjects.
  - estearum 10mo ago
    Good reasons: * Most drug candidates just don't work * Even among the drug candidates that do, figuring how to safely deliver them to their target is very hard (looks similar to "just doesn't work") Bad reasons: * It's too expensive to prove that a drug works * It's too difficult to differentiate the patients for whom a drug works and the patients for whom it does not * It is very hard to predict recruitment and to actually recruit patients for clinical trials * There aren't enough people with the disorder who are also rich enough to afford treatment to justify development
    - bawolff 10mo ago
      There is also the ole', drug works 20% of the time and kills the patient 80% of the time.
    - kevincox 10mo ago
      > It's too expensive to prove that a drug works I'm not sure that is necessary a bad reason. You need to factor in a lot of concerns to determine what "too expensive" means. But if you are going to spend billions of dollars to develop a drug that only treats about 2 people a year it is likely too expensive even if it is 100% effective. That money would be better spent on treatments that have wider applicability. Of course this is not simple to measure. Costs aren't known upfront and the research may end up proving invaluable to more widely applicable treatments. So it is a judgment call and not necessarily a bad reason.
      - estearum 10mo ago
        Agreed it isn't necessarily a bad reason. In some cases it's a good reason for failure (like the one you describe). In other cases it's a bad reason for failure: it's also incredibly expensive to prove your drug works even if it does work for a lot of people. That's bad! It'd be better if it were cheaper. Actually counterintuitively, due to a weird drug approval and payor reimbursement policy arbitrage, pharma companies are highly incentivized to produce drugs for tiny populations. One of my hobby horses is railing against this specific dynamic.
  - pants2 10mo ago
    In the early 2010s I had a couple friends working at a biotech startup with a moonshot cancer cure. They had amazing results in animal testing, and had raised just enough funding to do a first human trial on a terminal patient. That patient was hit and killed by a car two days after finishing their treatment. Along with the CEO's stubborn refusal to give up any more equity in the company, they went under, and the world will never know if that treatment worked.
- deleted 10mo ago
  [deleted]
- d--b 10mo ago
  From what I saw, there are very few experimental therapies that claim 100% efficacy, no side effect, no patent on complex engineering process to produce the drug. I agree with GP that it is very notable. I mean if it works on humans, which is not a stretch, colorectal cancer is done. It's huge.
  - estearum 10mo ago
    Yes there are few that claim 100% efficacy and no side effect at this stage, but there are far, far, far fewer who make it to human availability. I wouldn't describe it working in humans as "a stretch" per se. I'm not identifying a specific reason it shouldn't work in humans. I'm just saying that's true of thousands and thousands of really great looking treatments (per year!) that, nonetheless, end up not working in humans, or not being convincing enough to even warrant putting them in humans once.
    - d--b 10mo ago
      If it is the case that there are such treatments (easy to produce, 100% efficacy, no side effect) that cure fairly common deadly disease such as colorectal cancer in mice, and that never make it to human trial, there is something seriously broken about medical research...
      - estearum 10mo ago
        No, the issue is that mice are very different from humans. The only thing such a state of affairs clearly indicates is broken is using mice as proto-human test subjects. Which of course, when you state it like that, is obviously suboptimal. But no one knows what to do about it.
        d--b 10mo ago
        Right, yes, at least that study proved that some bacteria eat cancerous cells in at least one mammal. If that particular bacteria doesn't work in humans it may still trigger a search for a bacteria that does. Still being optimistic about this :)
deleted 10mo ago
[deleted]
barrenko 10mo ago
I hesitate to link directly to a single podcast dealer, but if you search for Dave Ricks, CEO of Eli Lilly's podcast with Stripe brothers, there's some alpha in there.
rwmj 10mo ago
Certainly good news for mice. I wonder if anyone has tried to engineer a mouse that lives forever by applying all these life enhancing mouse therapies at once.
- wvlia5 10mo ago
  Yes, Mathuselah Mouse Price
somedude89897 10mo ago
Very small sample size and only in mice. Most experimental treatments don't make it to the clinic, and this could be another in a long list of exciting early results that don't lead to anything. However... These results seem too good to be true, but the paper actually seems pretty good. There have been other attempts to use anaerobic bacteria to treat cancer (as solid tumors tend to be hypoxic environments), this is the first I've seen that interacts with PD-1/PD-L1 pathway. This is the most promising cancer treatment I've seen in quite a while. Maybe we can be cautiously optimistic!
throw9393848449 10mo ago
A few years ago we also had 100% effective medication with zero side effects. Now birth rates are down, mortality up, and young people misteriosly die from cancer and hearth attacks.
citrate05 10mo ago
It looks like they screened 45 strains of bacteria to find 9 that passed their safety tests, and then only one of those had a 100-percent response. The sample size is also small: 5/5 sounds a lot less impressive than 100%. I'd expect the true response rate to be substantially lower ("winner's curse"). The bar for an acceptable side effect profile in an FDA-approved drug would also be a lot higher than "five genetically near-identical mice did not show evidence of pathology in a single study." I'm not saying this work is bad (skimming, it seems fine for what it is, though haven't read in detail), but it's quite preliminary if we're talking about developing a medical treatment that could eventually be deployed in humans. There's a reason it ended up in a mid-tier microbiome journal.

estearum 10mo ago

The catch is that there are thousands of promising therapies in animal models/pre-human testing. A very very tiny fraction of them will ever make it to market for a variety of both good and not-good reasons.

colordrops 10mo ago
What's the difference between a good and not-good reason to not go to market?
- hyc_symas 10mo ago
  A lot of potential treatments are too easily available and can't be patented. If a big pharma company can't make massive profit from it, they won't bother bringing it to market. Consider that a not-good reason. Other treatments may eventually prove to have too many serious negative side effects. That's a good reason to abandon them.
  - megaman821 10mo ago
    Why would a China or India care if it were a viable treatment? Unless a country wants to use their population as lab rats, it takes money and scientists to actually confirm a treatment is safe and effective.
    - cluckindan 10mo ago
      Obviously you use the neighboring country’s population, or an ethnic minority, or prisoners, or orphans, or…
  - dboreham 10mo ago
    Kind of like open source software.
  - justinclift 10mo ago
    Wonder if some form of FOSS approach would work as an alternative development model for pharma?
    - ikawe 10mo ago
      These folks gave an interesting talk on producing pharmaceuticals at defcon a couple years ago. IIRC it was more about production methods than developing new treatments. https://fourthievesvinegar.org/ https://fourthievesvinegar.org/
    - vibrio 10mo ago
      This made me think of the "Institute for one world health" . It came out as a non-profit pharmaceutical company in the mid 2000's. Victoria Hale was the founder-it got her a MacArthur fellowship. It is focuses(focused?) on global health and populations underserved by for-profit models. I think they successfully developed a treatment for leishmaniasis. it's an adorable model and should be pushed but as usual it seems like the philantropy money is limiting.
  - Aurornis 10mo ago
    > A lot of potential treatments are too easily available and can't be patented. This isn’t really an obstacle, at least not as much as it’s made out to be. There are numerous examples of drugs being brought to market at high prices despite having been generic compounds. Even old drugs can be brought back at $1000/month or more at different doses or delivery mechanisms. One example: Doxepin is an old antidepressant that is extremely cheap. It was recently re-certified for sleep at lower doses and reintroduced at low doses at a much higher price, despite being “off patent”. This happens all the time. The drug companies aren’t actually abandoning usable treatments due to patent issues as much as journalists have claimed. If they couldn’t, for some reason, find a way to charge for it they could still use it as a basis for finding an improved relayed compound with more targeted effects, better pharmacokinetics, etc. They’re not just dropping promising treatments anywhere if there’s a market for them.
    - DivingForGold 10mo ago
      About Doxepin. As many seniors do, I also suffer from extreme inability to stay asleep at night. I have trialed through all the known prescription and non prescription possibilities, only eszopiclone and baclofen seem to show some promise, however, eszopiclone is DEA listed, requires higher and higher doses, and if I take it more than say 2 weeks, it has rather serious side effects attempting to withdraw, addictive, serious anxiety, trying to wean oneself off it. Doxepin is prescribed as an antidepressant in large doses, one of the most potent H1 histamine antagonists known. The H1 system in our bodies promotes wakefulness. In very low doses, doxepin acts against the H1 to promote sleep. To avoid the upcharges of low dose doxepin, I am prescribed the high dose version, which I have to break the capsules to administer about 5 to 10 mg. placed in an empty gelatin capsule (it's bitter). It really works well, however you are fairly tired and useless the next day.
      - estearum 10mo ago
        Have you tried Cognitive Behavioral Therapy? I am a lifelong sufferer of insomnia (though mostly sleep onset) and tried all sorts of increasingly risky things. CBT cured me in ~2 months.
- 3eb7988a1663 10mo ago
  Prevalence of the disease - if it only impacts 1/100 million, going to be hard to ever find sufficient patient population to test and recoup your investment. Existing quality of treatments - if there are already efficacious drugs on the market - how sure are you that this new therapy will be best in class? Only being as good as the status quo is not an ideal competitive position. Conversely, if there is an unmet need because a disease is so lethal/debilitating, regulatory agencies can give latitude in approvals. Likelihood patient compliance - if it is the most effective drug in the world, but requires intravenous infusion six times a day - nobody is going to adhere to that. GLP drugs are effective, but there is a needle-phobia that is preventing patients getting on board with the idea. Which is why there is an arms race for the first company to develop an oral version. Toxicity - all chemicals are poisonous. Yet some have a lower therapeutic window than others. If you drug does what it should, but if you take 2x as much and it gives you a heart arrhythmia that is going to be a tough approval for anything but the most deadly conditions.
  - z3t4 10mo ago
    Also the ethically in blind studies, can't just let some random patients die just to prove that your drug works.
    - Someone 10mo ago
      Yes, you can. The problem with testing is that a candidate treatment may make things worse for patients, not that it may improve things. If your treatment works, that’s an improvement of what you had before. Once you know that, you can treat all patients. For some, that will be too late, but without your tests, it would be too late for them, too. If your treatment doesn’t do anything at all, it keeps things the same, but the patients in the test group likely will have had some inconveniences (having to visit a doctor, getting an injection, etc), so you shouldn’t do the test. If your treatment makes things worse, you of course shouldn’t do the test. Problem is that you typically only can only know in hindsight which of these applies. So, you think carefully on whether a treatment could fall in category 3, and, if so, first do it on a group of patients who consent to be Guinea pigs and, often, are already terminally ill, as any negative outcomes will cause less harm to such patients. Then, as soon as during the test your stats tell the drug does or doesn’t work, you stop the test and either treat all patients or stop treating the test subjects.
- estearum 10mo ago
  Good reasons: * Most drug candidates just don't work * Even among the drug candidates that do, figuring how to safely deliver them to their target is very hard (looks similar to "just doesn't work") Bad reasons: * It's too expensive to prove that a drug works * It's too difficult to differentiate the patients for whom a drug works and the patients for whom it does not * It is very hard to predict recruitment and to actually recruit patients for clinical trials * There aren't enough people with the disorder who are also rich enough to afford treatment to justify development
  - bawolff 10mo ago
    There is also the ole', drug works 20% of the time and kills the patient 80% of the time.
  - kevincox 10mo ago
    > It's too expensive to prove that a drug works I'm not sure that is necessary a bad reason. You need to factor in a lot of concerns to determine what "too expensive" means. But if you are going to spend billions of dollars to develop a drug that only treats about 2 people a year it is likely too expensive even if it is 100% effective. That money would be better spent on treatments that have wider applicability. Of course this is not simple to measure. Costs aren't known upfront and the research may end up proving invaluable to more widely applicable treatments. So it is a judgment call and not necessarily a bad reason.
    - estearum 10mo ago
      Agreed it isn't necessarily a bad reason. In some cases it's a good reason for failure (like the one you describe). In other cases it's a bad reason for failure: it's also incredibly expensive to prove your drug works even if it does work for a lot of people. That's bad! It'd be better if it were cheaper. Actually counterintuitively, due to a weird drug approval and payor reimbursement policy arbitrage, pharma companies are highly incentivized to produce drugs for tiny populations. One of my hobby horses is railing against this specific dynamic.
- pants2 10mo ago
  In the early 2010s I had a couple friends working at a biotech startup with a moonshot cancer cure. They had amazing results in animal testing, and had raised just enough funding to do a first human trial on a terminal patient. That patient was hit and killed by a car two days after finishing their treatment. Along with the CEO's stubborn refusal to give up any more equity in the company, they went under, and the world will never know if that treatment worked.
deleted 10mo ago
[deleted]
d--b 10mo ago
From what I saw, there are very few experimental therapies that claim 100% efficacy, no side effect, no patent on complex engineering process to produce the drug. I agree with GP that it is very notable. I mean if it works on humans, which is not a stretch, colorectal cancer is done. It's huge.
- estearum 10mo ago
  Yes there are few that claim 100% efficacy and no side effect at this stage, but there are far, far, far fewer who make it to human availability. I wouldn't describe it working in humans as "a stretch" per se. I'm not identifying a specific reason it shouldn't work in humans. I'm just saying that's true of thousands and thousands of really great looking treatments (per year!) that, nonetheless, end up not working in humans, or not being convincing enough to even warrant putting them in humans once.
  - d--b 10mo ago
    If it is the case that there are such treatments (easy to produce, 100% efficacy, no side effect) that cure fairly common deadly disease such as colorectal cancer in mice, and that never make it to human trial, there is something seriously broken about medical research...
    - estearum 10mo ago
      No, the issue is that mice are very different from humans. The only thing such a state of affairs clearly indicates is broken is using mice as proto-human test subjects. Which of course, when you state it like that, is obviously suboptimal. But no one knows what to do about it.
      - d--b 10mo ago
        Right, yes, at least that study proved that some bacteria eat cancerous cells in at least one mammal. If that particular bacteria doesn't work in humans it may still trigger a search for a bacteria that does. Still being optimistic about this :)

deleted 10mo ago

[deleted]

barrenko 10mo ago

I hesitate to link directly to a single podcast dealer, but if you search for Dave Ricks, CEO of Eli Lilly's podcast with Stripe brothers, there's some alpha in there.

rwmj 10mo ago

Certainly good news for mice. I wonder if anyone has tried to engineer a mouse that lives forever by applying all these life enhancing mouse therapies at once.

wvlia5 10mo ago
Yes, Mathuselah Mouse Price

somedude89897 10mo ago

Very small sample size and only in mice. Most experimental treatments don't make it to the clinic, and this could be another in a long list of exciting early results that don't lead to anything. However... These results seem too good to be true, but the paper actually seems pretty good. There have been other attempts to use anaerobic bacteria to treat cancer (as solid tumors tend to be hypoxic environments), this is the first I've seen that interacts with PD-1/PD-L1 pathway. This is the most promising cancer treatment I've seen in quite a while. Maybe we can be cautiously optimistic!

throw9393848449 10mo ago

A few years ago we also had 100% effective medication with zero side effects. Now birth rates are down, mortality up, and young people misteriosly die from cancer and hearth attacks.

citrate05 10mo ago

It looks like they screened 45 strains of bacteria to find 9 that passed their safety tests, and then only one of those had a 100-percent response. The sample size is also small: 5/5 sounds a lot less impressive than 100%. I'd expect the true response rate to be substantially lower ("winner's curse"). The bar for an acceptable side effect profile in an FDA-approved drug would also be a lot higher than "five genetically near-identical mice did not show evidence of pathology in a single study." I'm not saying this work is bad (skimming, it seems fine for what it is, though haven't read in detail), but it's quite preliminary if we're talking about developing a medical treatment that could eventually be deployed in humans. There's a reason it ended up in a mid-tier microbiome journal.