The lottery of the snakebite antivenom industry
theguardian.com
theguardian.com
This is expensive, and many people develop allergies to the antibodies.
A cool practical application of DeepMind's AlphaFold is that it allows one to "design" proteins because it is now possible to predict how they will fold. [0]
This means it is possible to create synthetic protein antibodies that neutralise snake venom, specifically designed for humans [1].
There is a recent Veritasium video [2] that contains a great explanation. The whole video is worth a watch!
[0]: https://ui.adsabs.harvard.edu/abs/2023Natur.620.1089W/abstra...
A big reason why the antivenon for those snakes is rare is because one needs to keep a population of the snakes to produce them. If you don't need the snakes anymore, just the minimum amount countries have on hand for dealing with exotic fauna is enough to justify manufacturing them, and once you are manufacturing them, there's no reason not to do a larger batch and export some.
But if you optimize it for full in-vitro manufacturing, then anybody will be able to make it. And there's plenty of demand for somebody to do it, because lots of countries want small amounts of it.
> scam
Probably not completely, but making the venom more accessible and affordable means less people are likely to fall for it and thus less people are likely to run a scam for it
> african countries not receiving antivenom designed for local snakes
A more abundant antivenom would mean more can be shipped to wherever it's needed most.
> shortages, delay to get to treatment centers, and expensive products.
Again, more abundance = easier to get, cheaper to make, etc.
If that is not being done, then it's surely because there is too little demand and the hurdles to get FDA to accept a new, obviously better serum, are too expensive to overcome.
Protein folding is incredibly complex. Imagine a string of 1,000 beads, each bead being made up of 6 different magnets all with the poles aligned in a different orientation.
Now predict if you suspended it in zero gravity, how would it fold upon itself?
Pretty complex? Well, it gets more complex.
Now add millions of smaller magnets (water molcules) to the mix, each of which can attach to each magnet on the beads. Some will block the interactions that drive folding, others will enhance it.
Pretty complex? It gets more complex.
Now add a mixture of other magnets, some small (ions) some large (small molecules or other proteins) to the mix. Some have a single magnet pole, others have dozens.
Now predict the structure and the resulting binding sites.
AI can do a decent job of predicting the macro folding of proteins, but fails when it comes to accurately predicting all of the inter- and intra-molecular interactions.
And if you can't predict all the interactions, you can't accurately predict what the actual activity of the molecule will be.
At best, AI can highlight potential protein structures that might have activity.
The designed protein does not necessarily have to be an antibody or nanobody, where only part of the protein is involved in antigen binding. The example you cite shows how smaller, single-domain proteins can also block and neutralize the venom.
Unless there are some breakthrough recently, Looks like we can't really do it at scale. Doing a few in lab setting is possible, but you can't really use them in drug.
Quite good actually. Recombinant insulin is one example.
Is this a common form of insulin and how does the price compare to the old pig insulin?
For something like an antivenom that hardly matters. But just curious on what it means for a daily protein dose.
The $25 vials at Walmart are a human insulin. More recent formulations modify the insulin to act faster or last longer, but they are based on human insulin.
Though I'm probably missing a few steps here. A large part of this seems to be possible though, given the success of mRNA vaccines. Though using humans rather than animals to produce the actual protein is less than ideal.
I imagine the harder part is finding the most effective ones to manufacture, as it is still quite costly. Harvesting serum from a live animal has the benefit of harvesting whatever antibodies have been produced, rather than a single specific one, so an effective antivenom might need to be composed of a number of monoclonal antibodies.
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.
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.
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"?
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?
They have been subjected to some very negative experiences, most likely.
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
... and the antivenoms have an expiration date, plus you'll need to keep the antivenoms distributed around the country at least enough to be able to fly it via a chopper anywhere it might be needed fast enough to be actually useful. The process for spider toxins is pretty similar with similar challenges.
And on top of that, at least for snakes, even in a specific region the composition of what is in the snake venom might differ between local snake populations based on what the snakes eat.
Well. Interesting article, unfortunately ending with the dumbest sentence.
Ebola presents a real threat to become a pandemic. Snake bites do not. Hence, the difference.
- What did you do with all those money we funded you?!
- Well, we spent them on snake bites. So in the event you get both Ebola and a snake bites you, you'll die, but it won't be the snake bite that killed you.
Take you to the place where the Healing flow, oh ho
Weak in Spirit? We got The Juice!
Won't save your Soul; It'll Shine Your Shoes."
https://en.m.wikipedia.org/wiki/Bothrops_asper
(As I understood the story, it had been lying unseen on top of a branch he grabbed.) He immediately, as in within seconds, laid his finger against a tree and whipped it off at the root with his machete. No one questioned the correctness of his decision, because he subsequently survived a 45-minute walk to the trail-head, and a 2-hour drive to the clinic, without any sign of further envenomation. (Indeed, the clinic didn't keep any anti-venom, so he'd have had a further 40 minutes to go to the hospital in the nearest small city.) His chances of living would have been dicy at best, and the loss of at least his entire arm a certainty.
The local (Maya-language) slang for the Fer-de-lance translated to something like "fifteen-steps", because that was supposedly how far you'd walk before you'd die from a bite. Brave, quick-thinking dude.
Or would that not count as antivenom regulation since they weren't actually selling antivenom?
Was this the sentence you were referring to?
What a sad situation, I can't imagine the stress of being disabled and unable to provide for my young children.