3 ms·

I did see Veritasium's video on this, and have been generally familiar with AlphaFold, but it remains unclear to me how the safety and efficacy of the antivenom

I did see Veritasium's video on this, and have been generally familiar with AlphaFold, but it remains unclear to me how the safety and efficacy of the antivenoms' designed with its help would be ensured short of a regular clinical trial gauntlet, which I understand continues to be extremely costly and long on its own. This isn't comparing it to the animal antibody harvesting approach, but on its own. Like I'm sure it's great and all, but I can definitely see it both mispredicting (mistakenly missing suitable proteins as well as mistakenly considering proteins suitable) and not having the predictive power to know how a given protein will interact with the countless atoms and molecules in the countless, somewhat arbitrary, random human bodies.

mschuster91 2y ago
> I did see Veritasium's video on this, and have been generally familiar with AlphaFold, but it remains unclear to me how the safety and efficacy of the antivenoms' designed with its help would be ensured short of a regular clinical trial gauntlet, which I understand continues to be extremely costly and long on its own. Well that one will have to be done for any medicine, the problem is snake and spider bites are rare in the Global North countries [1], but pretty prevalent in Global South countries. That means that there isn't much money in getting antivenins through certifications, there are dozens of majorly relevant species and hundreds of lesser importance which means a ton of expenses even if the antivenins share superstructures, and we'd run into the same issue as with the Covid vaccines - the accusation of local populations that they will be used as testbeds. [1] https://en.wikipedia.org/wiki/Epidemiology_of_snakebites https://en.wikipedia.org/wiki/Epidemiology_of_snakebites
gus_massa 2y ago
> and not having the predictive power to know how a given protein will interact with the countless atoms and molecules in the countless, somewhat arbitrary, random human bodies. You test it first in mice. If the new drug has not nasty side effects, you try it in other animals, then in monkeys, then voluntairs and then in pilot trial with humans.
- perching_aix 2y ago
  > short of a regular clinical trial gauntlet
- AStonesThrow 2y ago
  Nah you just make a Russian Roulette menu out of pharmaceutical offerings and continually parade new chemicals through the marketing machine as the patent granting/expiration cycle chews through them. You run costly ad campaigns and multimedia commercials, and you send salesmen out with imprinted pens and fancy notepads and they hand those things to the physician, then they purchase a nice lunch for the clinicians and explain how they treat all the weird nouveau conditions that were coined specifically for this drug. Do not Taunt Happy Fun Ball Then the insurance companies get on board with "fail-first step therapy" and the physicians start writing the cheapest prescriptions possible in hopes that the patient will go away or so totally fuckin' placebo'd that they were so busy filling scrips that they wouldn't bother complaining about the same thing twice. Can you tell that I immensely enjoyed Hank Azaria, Jake Gylenhaal, and Anne Hathaway in "Love & Other Drugs"?
  - gus_massa 2y ago
    Mice are cheaper. And in case of a problem the family doesn't sue you and the press doesn't pretend to be angry for a week.
gosub100 2y ago
In rare situations, they can test on non-consenting patients. A few years back, there was a trial of "synthetic blood" intended to save trauma patients who were bleeding to death. They got a special permit to administer it to said patients without consent, because there is effectively no other way to test it. I don't recall the brand name or whatever came out of it. But something similar might be possible for this antivenom.
- perching_aix 2y ago
  I suppose that's a fair point, didn't think of that indeed.
- AStonesThrow 2y ago
  In the bigger picture, "Informed Consent" is a complete legal fiction. Anyone admitted to a hospital or clinic typically signs a blanket-consent form that says "I agree to be treated here [in whatever manner is laid down by your policies and regulations]." Physicians have a song-and-dance about explaining the condition or diagnosis, and then proposing a treatment, in terms of a drug, procedure, course of action, equipment, or whatever, but in my limited experience, the staff makes every effort to keep those conversations off paper, out of the record, not in the charts, and solely verbal; they always couch it in layperson's simple terms and not precise medical jargon; and while they're contractually obligated to rattle off a million risks and adverse outcomes, they really can't explain all the details of the proposed treatment, because the patients/family wouldn't understand the concepts, science, research, or outcomes anyway. Providers are far too overworked to document anything that doesn't earn them money, particular if that thing is an untreatable condition or a fact that may remove the patient from the workforce. 3/3 times I asked a physician for a respite from work, they told me to fuck off, but my supervisor said I'd ironically need to ride the bus and wait in a waiting room to procure a doctor's note to document my infectious cold, or I'd need to ride another bus and commute to the office while also sneezing on everyone, instead of pragmatically staying home for a day or two and resting until the viral load drops on its own? HIPAA is designed not to protect patients: HIPAA is designed to protect "vendor lock-in", it limits liability from malpractice suits, it keeps Western Medicine as an opaque black box where actual on-the-ground treatents and outcomes can never be known at all. HIPAA is copyright and patent law on steroids, literally. HIPAA forces patients and customers to run a gauntlet of forms and filings and expiration dates in order to keep third parties informed about their treatment. Providers often refuse to accept or act upon ROI authorizations unless there is a demonstrated need to know/disclose. It's impossible to test whether a third party can obtain the authorized PHI until they actually try. It's been impossible for me to go to the backend and request a list or manifest of all open, current ROIs. They all just disappear into black holes. Consider the white-hot fury rage when I reveal that I often record the audio of clinical encounters---because I need to review them to UNDERSTAND what was actually SAID and perhaps transcribe it, because my Eustachian Tubes completely disconnect from my Intellect and Reason when a doctor is flapping her officious expensive lips. My experience, for example: I'm in the hospital, with my glasses off, and a stranger rocks up at the worst possible time, with badge flipped over backwards, can't tell you which Crack Jack box conveyed their Board Certification, but rattles off a lot of well-rehearsed words without regard for understanding or definitions from first principles, and then consent is assumed by a nod of the head, a blurted out "OK?" or any lack of a definitive refusal or questioning whether any other course of action is possible, or what the hell sort of condition/diagnosis are you really describing in those dumbed-down shitty layman's terms that are ambiguous, colloquial, or worse? It's indistinguishable from tactics used by call-center scammers when they catch a vulnerable adult at 3am, or dinnertime, and obtain consent for financial transactions, by means of pressure tactics and fear or "keeping them in the ether" panic mode. Recall, of course, that American medicine operates with a "do it now, bill it later" paradigm where, unless the insurance carriers balk or require a preauth/pre-notify, the provider will hit you with every possible billable service/product throughout a hospital stay or clinic visit, and worry about the denied claims or patient responsibilities in 89 days from now. Consent for treatment of an unconscious person without PoA on file, would be simply a matter of "what can we get away with that's laid down by our standards and practices?" and it's utterly routine that experimental treatments are "on the table". Unfortunately, physicians are often wrong about a prognosis of death, even if it's just the time frame. "Bleeding to Death" is a subjective and colloquial diagnosis, isn't it? A physician can only work with probabilities, statistics, telemetry and professional experience to make educated guesses when the chances for survival are bleak. Can you tell that I was just reading about the Karen Ann Quinlan case?

mschuster91 2y ago

> I did see Veritasium's video on this, and have been generally familiar with AlphaFold, but it remains unclear to me how the safety and efficacy of the antivenoms' designed with its help would be ensured short of a regular clinical trial gauntlet, which I understand continues to be extremely costly and long on its own. Well that one will have to be done for any medicine, the problem is snake and spider bites are rare in the Global North countries [1], but pretty prevalent in Global South countries. That means that there isn't much money in getting antivenins through certifications, there are dozens of majorly relevant species and hundreds of lesser importance which means a ton of expenses even if the antivenins share superstructures, and we'd run into the same issue as with the Covid vaccines - the accusation of local populations that they will be used as testbeds. [1] https://en.wikipedia.org/wiki/Epidemiology_of_snakebites https://en.wikipedia.org/wiki/Epidemiology_of_snakebites

gus_massa 2y ago

> and not having the predictive power to know how a given protein will interact with the countless atoms and molecules in the countless, somewhat arbitrary, random human bodies. You test it first in mice. If the new drug has not nasty side effects, you try it in other animals, then in monkeys, then voluntairs and then in pilot trial with humans.

perching_aix 2y ago
> short of a regular clinical trial gauntlet
AStonesThrow 2y ago
Nah you just make a Russian Roulette menu out of pharmaceutical offerings and continually parade new chemicals through the marketing machine as the patent granting/expiration cycle chews through them. You run costly ad campaigns and multimedia commercials, and you send salesmen out with imprinted pens and fancy notepads and they hand those things to the physician, then they purchase a nice lunch for the clinicians and explain how they treat all the weird nouveau conditions that were coined specifically for this drug. Do not Taunt Happy Fun Ball Then the insurance companies get on board with "fail-first step therapy" and the physicians start writing the cheapest prescriptions possible in hopes that the patient will go away or so totally fuckin' placebo'd that they were so busy filling scrips that they wouldn't bother complaining about the same thing twice. Can you tell that I immensely enjoyed Hank Azaria, Jake Gylenhaal, and Anne Hathaway in "Love & Other Drugs"?
- gus_massa 2y ago
  Mice are cheaper. And in case of a problem the family doesn't sue you and the press doesn't pretend to be angry for a week.

gosub100 2y ago

In rare situations, they can test on non-consenting patients. A few years back, there was a trial of "synthetic blood" intended to save trauma patients who were bleeding to death. They got a special permit to administer it to said patients without consent, because there is effectively no other way to test it. I don't recall the brand name or whatever came out of it. But something similar might be possible for this antivenom.

perching_aix 2y ago
I suppose that's a fair point, didn't think of that indeed.
AStonesThrow 2y ago
In the bigger picture, "Informed Consent" is a complete legal fiction. Anyone admitted to a hospital or clinic typically signs a blanket-consent form that says "I agree to be treated here [in whatever manner is laid down by your policies and regulations]." Physicians have a song-and-dance about explaining the condition or diagnosis, and then proposing a treatment, in terms of a drug, procedure, course of action, equipment, or whatever, but in my limited experience, the staff makes every effort to keep those conversations off paper, out of the record, not in the charts, and solely verbal; they always couch it in layperson's simple terms and not precise medical jargon; and while they're contractually obligated to rattle off a million risks and adverse outcomes, they really can't explain all the details of the proposed treatment, because the patients/family wouldn't understand the concepts, science, research, or outcomes anyway. Providers are far too overworked to document anything that doesn't earn them money, particular if that thing is an untreatable condition or a fact that may remove the patient from the workforce. 3/3 times I asked a physician for a respite from work, they told me to fuck off, but my supervisor said I'd ironically need to ride the bus and wait in a waiting room to procure a doctor's note to document my infectious cold, or I'd need to ride another bus and commute to the office while also sneezing on everyone, instead of pragmatically staying home for a day or two and resting until the viral load drops on its own? HIPAA is designed not to protect patients: HIPAA is designed to protect "vendor lock-in", it limits liability from malpractice suits, it keeps Western Medicine as an opaque black box where actual on-the-ground treatents and outcomes can never be known at all. HIPAA is copyright and patent law on steroids, literally. HIPAA forces patients and customers to run a gauntlet of forms and filings and expiration dates in order to keep third parties informed about their treatment. Providers often refuse to accept or act upon ROI authorizations unless there is a demonstrated need to know/disclose. It's impossible to test whether a third party can obtain the authorized PHI until they actually try. It's been impossible for me to go to the backend and request a list or manifest of all open, current ROIs. They all just disappear into black holes. Consider the white-hot fury rage when I reveal that I often record the audio of clinical encounters---because I need to review them to UNDERSTAND what was actually SAID and perhaps transcribe it, because my Eustachian Tubes completely disconnect from my Intellect and Reason when a doctor is flapping her officious expensive lips. My experience, for example: I'm in the hospital, with my glasses off, and a stranger rocks up at the worst possible time, with badge flipped over backwards, can't tell you which Crack Jack box conveyed their Board Certification, but rattles off a lot of well-rehearsed words without regard for understanding or definitions from first principles, and then consent is assumed by a nod of the head, a blurted out "OK?" or any lack of a definitive refusal or questioning whether any other course of action is possible, or what the hell sort of condition/diagnosis are you really describing in those dumbed-down shitty layman's terms that are ambiguous, colloquial, or worse? It's indistinguishable from tactics used by call-center scammers when they catch a vulnerable adult at 3am, or dinnertime, and obtain consent for financial transactions, by means of pressure tactics and fear or "keeping them in the ether" panic mode. Recall, of course, that American medicine operates with a "do it now, bill it later" paradigm where, unless the insurance carriers balk or require a preauth/pre-notify, the provider will hit you with every possible billable service/product throughout a hospital stay or clinic visit, and worry about the denied claims or patient responsibilities in 89 days from now. Consent for treatment of an unconscious person without PoA on file, would be simply a matter of "what can we get away with that's laid down by our standards and practices?" and it's utterly routine that experimental treatments are "on the table". Unfortunately, physicians are often wrong about a prognosis of death, even if it's just the time frame. "Bleeding to Death" is a subjective and colloquial diagnosis, isn't it? A physician can only work with probabilities, statistics, telemetry and professional experience to make educated guesses when the chances for survival are bleak. Can you tell that I was just reading about the Karen Ann Quinlan case?