5 ms·

When you say in 2023 that they have "new insights" as to why a common over the counter drug works it really doesn't instill great confidence in pharma. Seems l

When you say in 2023 that they have "new insights" as to why a common over the counter drug works it really doesn't instill great confidence in pharma. Seems like we're still grinding up rhino horns and tiger penis and hoping for the best outcome, just that we do it with extensive testing now so we get a statistically acceptable outcome viable for marketing.

selfmodruntime 4y ago
No. Science has all along been testing if something works and then finding out why. Often the „why“ is orders of magnitudes harder to find out than the „if“. For example, we can observe how the brain functions in some instances, but why it works like does will elude us perhaps forever. Highly complex systems like the inner biomechanical workings of our brains are essentially a black box.
- marginalia_nu 4y ago
  "Why" questions in general are pretty difficult question to answer in a satisfactory way. [1] https://www.youtube.com/watch?v=36GT2zI8lVA https://www.youtube.com/watch?v=36GT2zI8lVA
  - rcme 4y ago
    I think “how” is more appropriate in the GP’s comment.
    - thomastjeffery 4y ago
      We can understand a thousand instances "how", but it will always be "why" that ties them together. Like software incompatibility: every program is the story of "how", written explicitly, and translated into instructions. The only way to fit them together is to implement "why". If we could write both stories together, we could factor out incompatibility.
  - thisismyswamp 4y ago
    I knew it was the Feynman video!
  - jjeaff 4y ago
    Feynman doesn't disappoint. Although, I would have liked for him to make clear how quickly we (including physicists like him) get to "we have no idea". Sort of the overall arc of his answer made it seem that, well we know why but it would be impossible to explain it to you because it is incomparable to anything else you might know. But the reality is, we quickly arrive at the four fundamental forces (the we know of) for which we have no explanation, no further reducibility (that we know of). We know they exist because we can observe them or work them out mathematically. But we have to just accept them on their face as they are in order for the rest of the universe to make sense.
- Fragoel2 4y ago
  For an example in CS, we currently use machine-learning algorithms that work very well in practice. However, why they work so well is still unclear in many cases (although we are making progress).
  - selfmodruntime 4y ago
    I find it fascinating that describing an automated learning process is so much easier than manually teaching. Once trained, looking inside a model to gather information about how it comes up with an answer to a question is somewhat similar to doing exactly that with a real brain.
- chatmasta 4y ago
  I'm not sure that invalidates GP's point. Your comment is basically just repeating his premise. If we don't understand the why, we don't understand the how. We can spend years testing that "it works," but we're only testing for a specific outcome and checking for specific risks. Without understanding the how or why, we have little way of knowing what we don't know.
  - mulmen 4y ago
    We start with what then much later to how which finally leads us to why.
    - deleted 4y ago
      [deleted]
  - tinco 4y ago
    Ground rhino horn and tiger penis don't have measurable results, sure it's not ideal we might not understand how aspirin does what it does, but at least we know that it does something. That's not even in the same ballpark as Chinese medicine so comparing them just for that reason is disingenuous. We don't test medicine for marketing, we test them for results. If homeopathy and Chinese medicine would teach us one thing it's that testing only for marketing would be the greatest waste of time and money ever.
    - mrguyorama 4y ago
      Indeed, chinese medicine and homeopathy show us that spending a dime on testing that you could be spending on marketing instead is always a waste
    - russdill 4y ago
      Not only that, but it's based on a very certain, but false, idea of why it "works".
- PaulHoule 4y ago
  Not always in pharmacology. There are many cases in drug development where people decide to target a particular biological process and tailor a molecule to do that.
naijaboiler 4y ago
As a doctor, i can confidently tell you as much as we know, we know so damn little. I get headaches everytime a patent asks me to explain why. The truth is for most diseases at best we have some plausible mechanism that's sorta supported up with some biology, and some treatment that works and we think we have some idea why. The real answer is we don't know, we have some reasonable theories that may or may not be true
- carlmr 4y ago
  >I get headaches everytime a patent asks me to explain why. Maybe pop an aspirin!
  - ape4 4y ago
    I'm sure a doctor can make up jargon to assure the patient that its understood
- mistrial9 4y ago
  >a patent asks me to explain why Freudian slip of the week !! ex-computational pharmacology here .. EX- !
oldgradstudent 4y ago
If we could reliably show that ground rhino horns and tiger penises work, we'd be using them, or finding an easily mass produced derivatives.
- wongarsu 4y ago
  If they'd work we we would quickly start trying to find the one chemical in them that is responsible for that, and once successful find a way to synthesize it from cheaper to source ingredients. In the end you'd just have an ointment that says "active ingredient: acetylsalicylic acid" and it's up to the marketing department whether they want to mention rhinos or not.
  - borski 4y ago
    Gives new meaning to Tiger balm
  - oldgradstudent 4y ago
    That's skipping a few steps. When insulin was discovered in 1921-2, it was only known that a pancreatic extract that has gone through some specific chemical processes could lower blood sugar. International units of insulin were initially defined not by the quantity of material, but rather by their effect. An international unit was defined to be the amount of extract that once given to a 24-hour fasted 1 kg rabbit, would lower its blood glucose level to 45 mg/L. Only in the 1950s, it was discovered that insulin was a specific protein, and the definition was updated accordingly. We could use rhino horns well before the chemical is isolated and a synthesized.
- krisoft 4y ago
  Same as we did with willow bark and ended up with aspirin we have today. History of aspirin: https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.14520 https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.14520
  - deleted 4y ago
    [deleted]
cromulent 4y ago
This is not about "pharma" though, where "pharma" means pharmaceutical companies. There is nothing of any interest in aspirin for commercial pharmaceutical organizations - any money spent in research is not recoverable. They will of course focus their efforts on researching new drugs, as their shareholders would expect.
LinuxBender 4y ago
You joke but most drugs are made from interesting things. NAC's components for example are human hair and chicken feet.
atombender 4y ago
This might surprise you, but we don't actually fully understand how most drugs work. Not just common OTC drugs, either, but also complex synthetic drugs used for things like autoimmune disorders, preventing organ rejection, and so on. Not just drugs that have been in use since the inception of modern medicine, but also about brand new drugs. Often we have some idea how they work and what the internal end result appears to be, but the pathways that the drug seems to work on aren't fully understood. So we know the drug does something to that pathway, but it is to some extent a black box for us. But the fact that the drug operates on the pathway also opens new avenues for the scientists to gain a better understand of that pathway. Modern medicine is optimized for end results. If a drug appears to work, the "how" is of secondary importance. We can always figure that out later. Sometimes we find stuff in nature, for example, like chemicals produced by fungi or bacteria, and we discover that they have medicinal properties. They nevertheless get productized as drugs, even when we don't fully understand them or the pathways they target.
- mistrial9 4y ago
  > Modern medicine is optimized for end results except thousands of common herbal remedies are replaced by patent medicine with legal controls, because $MONEY
  - atombender 4y ago
    Which ones?
  - fundatus 4y ago
    > except thousands of common herbal remedies are replaced by patent medicine with legal controls, because $MONEY Except they are not being replaced? Just like in the good old days™ you can still get out and collect the herbs you're looking for. It's just that nowadays we know that component X of a herbal remedy actually does the job so you just buy that in tablet form (or whatever) instead eating of the whole thing.
    - mistrial9 4y ago
hprotagonist 4y ago
efficacy and safety are the benchmark targets for regulatory approval. mechanism of action isn’t even on the list. “it works, it won’t kill you faster than the thing it treats, we have no idea why” is totally legit. welcome to biology, the dance of control with non-engineered systems.
- lanstin 4y ago
  The dance of control with non-engineered systems. Nice summary. And the systems reuse hits for distinct purposes like mad. For a little while in lockdown I tried to understand the biology of ACE receptors and my god, I couldn’t even memorize all the different types and subtypes nor the tissues they were found in, much less what functions that might imply.
joshspankit 4y ago
We don’t even fully understand how cuts heal... The idea that doctors (or even the medical community) are standing on the top of a Mountain of Truth is a harmful fantasy.
deleted 4y ago
[deleted]
pfdietz 4y ago
If aspirin were introduced today it would be prescription-only drug, and might not even be approved for that.
hnbad 4y ago
Honestly, aspirin is really closer to "grinding up rhino horns" than to complex pharmaceuticals you have to make in a lab. It's literally "drink this tea made from willow bark" except we got better at isolating the active components and finding other ways to produce them and more reliably measuring the dosage. The difference is that empirical studies have demonstrated the effect of "willow bark tea" and the lack of an effect of "ground up rhino horn".
- roywiggins 4y ago
  That's not technically true, willow has salicin in it. Aspirin is intentionally a slight modification.
  - hnbad 4y ago
    Yes, penicilin is probably a better example.
acc_297 4y ago
Recently started working in pharma and this was somewhat of a surprise for me as well having never taken any biology in school - drug approval for bio equivalence has tolerance intervals of like 5-10% - on my first day I worked on some data for an aspirin generic that showed crazy high variance across subjects I think biochemistry might be one of those final frontier sciences we are such a long way from what physics has in the standard model (if the standard model is correct)
refurb 4y ago
Would you say if we had new insights into how electrons behaved that it doesn't instill great confidence in our understanding of physics?
allturtles 4y ago
Yes it's somewhat disheartening for those raised on illusions of our scientific supremacy to discover that we understand very little about the human body or how to correct its defects or failures. The illusion is quickly punctured once you start having any medical problems. The vast majority of the time the answer is "we don't know what it is, but it will probably get better on its own" or "we know what it is, but it's not going to get better and there's nothing we can do about it."
taf2 4y ago
Sorry gotta share but when we had my first daughter 13 years ago we got to take a tour of the doctors office . He walked us over to an antique cabinet that was full old dusty worn looking bottles… the doctor as I recall said: “these are all medicines from around 100 years ago they are all pretty much alcohol based and would reduce your pain - medicine really hasn’t improved much since… we can help you with pain but otherwise it’s pretty much up to you”. He went on to point out this is why he avoids keeping patients in the waiting room as he pointed to kids finger prints on the glass wall. So take this as you will his name was Dr. Jones so that was even cooler IMO but he did pass away sadly shortly after we started there… maybe his insight still applies today…
graypegg 4y ago
If I had to guess that’s probably a result of the incentives at play here: extending life and lowering suffering. Like everyone else has said, it’s normally easier to find out « if » something works before the « why » and only one of those questions needs a « yes » to stop someone suffering.
Broken_Hippo 4y ago
"When you say in 2023 that they have "new insights" as to why a common over the counter drug works it really doesn't instill great confidence in pharm" This isn't a problem with big pharma, but rather, an issue with your understanding of how little we know about medicine. We occasionally still find new body parts, and we've been dissecting bodies for centuries. We don't cure some diseases because we don't know the reasons they happen, but find out some medicines that seem to help. Others, we don't cure simply because we don't know how to prevent them. And this sort of thing isn't limited to medicine: We weren't sure the astronauts would survive. We did what we could to me reasonably sure, but... we weren't. This isn't new, nor is it contained to medicine. We've done a lot of things without understanding the underlying mechanisms.
gumby 4y ago
> When you say in 2023 that they have "new insights" as to why a common over the counter drug works it really doesn't instill great confidence in pharma. When you read of new work on friction in 2023 does it reduce your confidence in the field of physics? It is true that we are still just scratching at the surface of biology, but incrementally we (humanity) are making progress every day. It's not engineering.
- deleted 4y ago
  [deleted]
exq 4y ago
“Doctors are men who prescribe medicines of which they know little, to cure diseases of which they know less, in human beings of whom they know nothing.” – Voltaire
mock-possum 4y ago
Ironically, new discoveries and ongoing research is exactly what instills confidence for me.

selfmodruntime 4y ago

No. Science has all along been testing if something works and then finding out why. Often the „why“ is orders of magnitudes harder to find out than the „if“. For example, we can observe how the brain functions in some instances, but why it works like does will elude us perhaps forever. Highly complex systems like the inner biomechanical workings of our brains are essentially a black box.

marginalia_nu 4y ago
"Why" questions in general are pretty difficult question to answer in a satisfactory way. [1] https://www.youtube.com/watch?v=36GT2zI8lVA https://www.youtube.com/watch?v=36GT2zI8lVA
- rcme 4y ago
  I think “how” is more appropriate in the GP’s comment.
  - thomastjeffery 4y ago
    We can understand a thousand instances "how", but it will always be "why" that ties them together. Like software incompatibility: every program is the story of "how", written explicitly, and translated into instructions. The only way to fit them together is to implement "why". If we could write both stories together, we could factor out incompatibility.
- thisismyswamp 4y ago
  I knew it was the Feynman video!
- jjeaff 4y ago
  Feynman doesn't disappoint. Although, I would have liked for him to make clear how quickly we (including physicists like him) get to "we have no idea". Sort of the overall arc of his answer made it seem that, well we know why but it would be impossible to explain it to you because it is incomparable to anything else you might know. But the reality is, we quickly arrive at the four fundamental forces (the we know of) for which we have no explanation, no further reducibility (that we know of). We know they exist because we can observe them or work them out mathematically. But we have to just accept them on their face as they are in order for the rest of the universe to make sense.
Fragoel2 4y ago
For an example in CS, we currently use machine-learning algorithms that work very well in practice. However, why they work so well is still unclear in many cases (although we are making progress).
- selfmodruntime 4y ago
  I find it fascinating that describing an automated learning process is so much easier than manually teaching. Once trained, looking inside a model to gather information about how it comes up with an answer to a question is somewhat similar to doing exactly that with a real brain.
chatmasta 4y ago
I'm not sure that invalidates GP's point. Your comment is basically just repeating his premise. If we don't understand the why, we don't understand the how. We can spend years testing that "it works," but we're only testing for a specific outcome and checking for specific risks. Without understanding the how or why, we have little way of knowing what we don't know.
- mulmen 4y ago
  We start with what then much later to how which finally leads us to why.
  - deleted 4y ago
    [deleted]
- tinco 4y ago
  Ground rhino horn and tiger penis don't have measurable results, sure it's not ideal we might not understand how aspirin does what it does, but at least we know that it does something. That's not even in the same ballpark as Chinese medicine so comparing them just for that reason is disingenuous. We don't test medicine for marketing, we test them for results. If homeopathy and Chinese medicine would teach us one thing it's that testing only for marketing would be the greatest waste of time and money ever.
  - mrguyorama 4y ago
    Indeed, chinese medicine and homeopathy show us that spending a dime on testing that you could be spending on marketing instead is always a waste
  - russdill 4y ago
    Not only that, but it's based on a very certain, but false, idea of why it "works".
PaulHoule 4y ago
Not always in pharmacology. There are many cases in drug development where people decide to target a particular biological process and tailor a molecule to do that.

naijaboiler 4y ago

As a doctor, i can confidently tell you as much as we know, we know so damn little. I get headaches everytime a patent asks me to explain why. The truth is for most diseases at best we have some plausible mechanism that's sorta supported up with some biology, and some treatment that works and we think we have some idea why. The real answer is we don't know, we have some reasonable theories that may or may not be true

carlmr 4y ago
>I get headaches everytime a patent asks me to explain why. Maybe pop an aspirin!
- ape4 4y ago
  I'm sure a doctor can make up jargon to assure the patient that its understood
mistrial9 4y ago
>a patent asks me to explain why Freudian slip of the week !! ex-computational pharmacology here .. EX- !

oldgradstudent 4y ago

If we could reliably show that ground rhino horns and tiger penises work, we'd be using them, or finding an easily mass produced derivatives.

wongarsu 4y ago
If they'd work we we would quickly start trying to find the one chemical in them that is responsible for that, and once successful find a way to synthesize it from cheaper to source ingredients. In the end you'd just have an ointment that says "active ingredient: acetylsalicylic acid" and it's up to the marketing department whether they want to mention rhinos or not.
- borski 4y ago
  Gives new meaning to Tiger balm
- oldgradstudent 4y ago
  That's skipping a few steps. When insulin was discovered in 1921-2, it was only known that a pancreatic extract that has gone through some specific chemical processes could lower blood sugar. International units of insulin were initially defined not by the quantity of material, but rather by their effect. An international unit was defined to be the amount of extract that once given to a 24-hour fasted 1 kg rabbit, would lower its blood glucose level to 45 mg/L. Only in the 1950s, it was discovered that insulin was a specific protein, and the definition was updated accordingly. We could use rhino horns well before the chemical is isolated and a synthesized.
krisoft 4y ago
Same as we did with willow bark and ended up with aspirin we have today. History of aspirin: https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.14520 https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.14520
- deleted 4y ago
  [deleted]

cromulent 4y ago

This is not about "pharma" though, where "pharma" means pharmaceutical companies. There is nothing of any interest in aspirin for commercial pharmaceutical organizations - any money spent in research is not recoverable. They will of course focus their efforts on researching new drugs, as their shareholders would expect.

LinuxBender 4y ago

You joke but most drugs are made from interesting things. NAC's components for example are human hair and chicken feet.

atombender 4y ago

This might surprise you, but we don't actually fully understand how most drugs work. Not just common OTC drugs, either, but also complex synthetic drugs used for things like autoimmune disorders, preventing organ rejection, and so on. Not just drugs that have been in use since the inception of modern medicine, but also about brand new drugs. Often we have some idea how they work and what the internal end result appears to be, but the pathways that the drug seems to work on aren't fully understood. So we know the drug does something to that pathway, but it is to some extent a black box for us. But the fact that the drug operates on the pathway also opens new avenues for the scientists to gain a better understand of that pathway. Modern medicine is optimized for end results. If a drug appears to work, the "how" is of secondary importance. We can always figure that out later. Sometimes we find stuff in nature, for example, like chemicals produced by fungi or bacteria, and we discover that they have medicinal properties. They nevertheless get productized as drugs, even when we don't fully understand them or the pathways they target.

mistrial9 4y ago
> Modern medicine is optimized for end results except thousands of common herbal remedies are replaced by patent medicine with legal controls, because $MONEY
- atombender 4y ago
  Which ones?
- fundatus 4y ago
  > except thousands of common herbal remedies are replaced by patent medicine with legal controls, because $MONEY Except they are not being replaced? Just like in the good old days™ you can still get out and collect the herbs you're looking for. It's just that nowadays we know that component X of a herbal remedy actually does the job so you just buy that in tablet form (or whatever) instead eating of the whole thing.
  - mistrial9 4y ago

hprotagonist 4y ago

efficacy and safety are the benchmark targets for regulatory approval. mechanism of action isn’t even on the list. “it works, it won’t kill you faster than the thing it treats, we have no idea why” is totally legit. welcome to biology, the dance of control with non-engineered systems.

lanstin 4y ago
The dance of control with non-engineered systems. Nice summary. And the systems reuse hits for distinct purposes like mad. For a little while in lockdown I tried to understand the biology of ACE receptors and my god, I couldn’t even memorize all the different types and subtypes nor the tissues they were found in, much less what functions that might imply.

joshspankit 4y ago

We don’t even fully understand how cuts heal... The idea that doctors (or even the medical community) are standing on the top of a Mountain of Truth is a harmful fantasy.

deleted 4y ago

[deleted]

pfdietz 4y ago

If aspirin were introduced today it would be prescription-only drug, and might not even be approved for that.

hnbad 4y ago

Honestly, aspirin is really closer to "grinding up rhino horns" than to complex pharmaceuticals you have to make in a lab. It's literally "drink this tea made from willow bark" except we got better at isolating the active components and finding other ways to produce them and more reliably measuring the dosage. The difference is that empirical studies have demonstrated the effect of "willow bark tea" and the lack of an effect of "ground up rhino horn".

roywiggins 4y ago
That's not technically true, willow has salicin in it. Aspirin is intentionally a slight modification.
- hnbad 4y ago
  Yes, penicilin is probably a better example.

acc_297 4y ago

Recently started working in pharma and this was somewhat of a surprise for me as well having never taken any biology in school - drug approval for bio equivalence has tolerance intervals of like 5-10% - on my first day I worked on some data for an aspirin generic that showed crazy high variance across subjects I think biochemistry might be one of those final frontier sciences we are such a long way from what physics has in the standard model (if the standard model is correct)

refurb 4y ago

Would you say if we had new insights into how electrons behaved that it doesn't instill great confidence in our understanding of physics?

allturtles 4y ago

Yes it's somewhat disheartening for those raised on illusions of our scientific supremacy to discover that we understand very little about the human body or how to correct its defects or failures. The illusion is quickly punctured once you start having any medical problems. The vast majority of the time the answer is "we don't know what it is, but it will probably get better on its own" or "we know what it is, but it's not going to get better and there's nothing we can do about it."

taf2 4y ago

Sorry gotta share but when we had my first daughter 13 years ago we got to take a tour of the doctors office . He walked us over to an antique cabinet that was full old dusty worn looking bottles… the doctor as I recall said: “these are all medicines from around 100 years ago they are all pretty much alcohol based and would reduce your pain - medicine really hasn’t improved much since… we can help you with pain but otherwise it’s pretty much up to you”. He went on to point out this is why he avoids keeping patients in the waiting room as he pointed to kids finger prints on the glass wall. So take this as you will his name was Dr. Jones so that was even cooler IMO but he did pass away sadly shortly after we started there… maybe his insight still applies today…

graypegg 4y ago

If I had to guess that’s probably a result of the incentives at play here: extending life and lowering suffering. Like everyone else has said, it’s normally easier to find out « if » something works before the « why » and only one of those questions needs a « yes » to stop someone suffering.

Broken_Hippo 4y ago

"When you say in 2023 that they have "new insights" as to why a common over the counter drug works it really doesn't instill great confidence in pharm" This isn't a problem with big pharma, but rather, an issue with your understanding of how little we know about medicine. We occasionally still find new body parts, and we've been dissecting bodies for centuries. We don't cure some diseases because we don't know the reasons they happen, but find out some medicines that seem to help. Others, we don't cure simply because we don't know how to prevent them. And this sort of thing isn't limited to medicine: We weren't sure the astronauts would survive. We did what we could to me reasonably sure, but... we weren't. This isn't new, nor is it contained to medicine. We've done a lot of things without understanding the underlying mechanisms.

gumby 4y ago

> When you say in 2023 that they have "new insights" as to why a common over the counter drug works it really doesn't instill great confidence in pharma. When you read of new work on friction in 2023 does it reduce your confidence in the field of physics? It is true that we are still just scratching at the surface of biology, but incrementally we (humanity) are making progress every day. It's not engineering.

deleted 4y ago
[deleted]

exq 4y ago

“Doctors are men who prescribe medicines of which they know little, to cure diseases of which they know less, in human beings of whom they know nothing.” – Voltaire

mock-possum 4y ago

Ironically, new discoveries and ongoing research is exactly what instills confidence for me.