[HN Gopher] The lottery of the snakebite antivenom industry
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       The lottery of the snakebite antivenom industry
        
       Author : n1b0m
       Score  : 68 points
       Date   : 2025-02-13 15:04 UTC (4 days ago)
        
 (HTM) web link (www.theguardian.com)
 (TXT) w3m dump (www.theguardian.com)
        
       | molf wrote:
       | > The first snakebite antivenom was made in the mid-1890s and the
       | method has changed little since: snakes are "milked" for their
       | venom, which is injected into horses or sheep and the antibodies
       | that their immune systems then produce are extracted via the
       | animals' blood.
       | 
       | 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...
       | 
       | [1]: https://www.nature.com/articles/s41586-024-08393-x
       | 
       | [2]: https://www.youtube.com/watch?v=P_fHJIYENdI&t=20m36s
        
         | mschuster91 wrote:
         | > This is expensive
         | 
         | ... 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.
        
         | perching_aix wrote:
         | 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 wrote:
           | > 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
        
           | gus_massa wrote:
           | > _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.
        
           | gosub100 wrote:
           | 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.
        
         | j16sdiz wrote:
         | AlphaFold helps the _design_ problem. ... but, How good are we
         | at synthesizing the actual protein?
         | 
         | 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.
        
           | shiandow wrote:
           | In theory at least you could produce the mRNA and duplicate
           | it and use it to produce the proteins.
           | 
           | 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.
        
             | afthonos wrote:
             | In theory, the difference between theory and practice is
             | zero.
        
               | aaronmdjones wrote:
               | I've heard this phrased as "In theory, there's no
               | difference between theory and practice. In practice,
               | there is."
        
             | maxerickson wrote:
             | The methods for producing antibodies are well understood.
             | There were several different monoclonal antibodies produced
             | for use in treating Covid infections.
             | 
             | 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.
        
           | flobosg wrote:
           | > How good are we at synthesizing the actual protein?
           | 
           | Quite good actually. Recombinant insulin is one example.
        
             | cogman10 wrote:
             | TIL. I didn't realize insulin was being produced like this.
             | 
             | 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.
        
               | maxerickson wrote:
               | In richer countries, essentially all insulin on the
               | market uses recombinant insulin.
               | 
               | 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.
        
         | zosima wrote:
         | There has been well-known processes for many years, to produce
         | the relevant antibodies from industrial fermentation processes.
         | 
         | 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.
        
         | pyrale wrote:
         | Technology won't fix the issues described in the article, which
         | include scam, african countries not receiving antivenom
         | designed for local snakes, shortages, delay to get to treatment
         | centers, and expensive products.
        
           | noah_buddy wrote:
           | Maybe, maybe not. Cheapening costs can improve access,
           | especially if it's possible to perform a new cheap technique
           | more widely.
        
           | marcosdumay wrote:
           | It most likely will.
           | 
           | 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.
        
             | krisoft wrote:
             | I don't understand what you are saying. Part of the problem
             | is that the african country is buying snake venom specific
             | to snakes in india. This is a problem which is not going to
             | be solved by someone manufacturing a larger batch of snake
             | venom and exporting some. In fact it is caused by that
             | practice at least in part.
        
               | marcosdumay wrote:
               | Nobody is going to make antivenom for their snakes is
               | large amounts because doing that would risk introducing
               | their snakes on the local fauna.
               | 
               | 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.
        
           | squigz wrote:
           | Why wouldn't 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.
        
         | flobosg wrote:
         | > This means it is possible to create synthetic protein
         | antibodies that neutralise snake venom, specifically designed
         | for humans [1].
         | 
         | 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.
        
       | hoseja wrote:
       | Paragraph sixteen, second sentence.
        
         | rybosome wrote:
         | > The father of five children under 10, who made his living
         | from fixing, building and digging, can no longer work and so
         | his children no longer go to school.
         | 
         | 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.
        
       | AStonesThrow wrote:
       | "Covered wagon Medicine Show!
       | 
       | 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."
        
       | wavemode wrote:
       | Evaluating the quality of snakebite antivenom feels like a
       | classic example of: https://xkcd.com/937/
        
       | RecycledEle wrote:
       | If there is insufficient supply of antivenom, is it wise to
       | reduce the supply further with regulation?
        
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       (page generated 2025-02-17 23:01 UTC)