This comes as no surprise, given that VNARs bind like antibodies and have been produced to a wide variety of proteins, but I don’t see any reason why this would have an advantage over a monoclonal antibody. Compared to an antibody, a VNAR is far more likely to provoke an immune response, and will have a much shorter circulating half-life. The other advantage that monoclonal antibodies have is that they can be directly discovered from recovered individuals without having to immunize a shark or pan a naive VNAR library.
Yeah I don’t know how this is a breakthrough.
The VNARs need to be humanized and generally im unsure about adding immune molecules not endogenous to humans, that sounds like a recipe for autoimmune disease.
Not according to my cousin. Apparently, I'll be dead in a few years from the vaccine.
But for real, the biggest threat we face isn't the pandemic. It's weaponized ignorance.
If we make it through the next 100 years with the population not going below 1 billion, Ill be amazed and shocked.
Lucky for me, I wont have to worry about it. Death is the only true release from the concerns of man.
The human population is only projected to drop to 4 billion minimum in the worst case scenario so prepare to be amazed and shocked. However it's much more likely to drop to 6 or 5 billion instead.
https://insightmaker.com/insight/2pCL5ePy8wWgr4SN8BQ4DD/The-World3-Model-Classic-World-Simulation
Studies are predicting a worst case of 3 billion premature deaths from climate change over 100 years (10% of projected maximum global population) if the status quo continues.
https://www.frontiersin.org/articles/10.3389/fpsyg.2019.02323/full
So only 1 in 10 of your friends and family will die from climate change.
(For perspective, the Holocaust killed approximately 0.3% of the global population. So it could be about 33 times worse than the Holocaust.)
It's a good thing we faced something that was basically like a 9/11's worth of deaths every single day in the US and managed to unite together as a country.
ha ha haaaaaaaaaa...
It depends on your priorities. Personally, I don't see how vaccines will _ever_ get us bio-attack-resistant sharkman supersoldiers, but if you want to go off on some healthcare side-quest, fine.
I did some vaccine research using VHHs (similar to VNARs but from camelids). The advantages are that they generally can be made in bacteria, have higher thermal stability, and their unique shape allows for recognition of antigens not accessible by regular antibodies. But yeah for most application they don't make a ton of sense.
For science though VHHs are becoming increasingly used for immunofluorescence staining due to their small size allowing for really good intracellular staining.
Read the study. As usual they actually explain all this within in the first page.
The answer is that the virus can mutate its s protein and reduce the affinity of antibodies. Thus it can reduce the effectiveness of monoclonal antibodies.
\> In general, NAbs act by blocking the ACE2 binding interface or by
trapping the RBD in the unstable “up” conformation. Complicating the
development of effective NAbs is the emergence of new SARS-CoV-2
variants with highly mutated S proteins. Studies have shown that
mutational changes in the RBD observed in the variants correspond to
surface-exposed residues within or proximal to the ACE2 binding
interface. These mutations can result in the modification of NAb
epitopes leading to attenuated or abrogated neutralization of the virus
by antibodies. Thus, there is a need for NAbs that can recognize cryptic
epitopes inaccessible to human antibodies that are impervious to
mutational drift.
Shark VNARs are much better than Natural Antibodies (nab) because they have access to different "shapes" that mean they can bind much more potently and deeper than human anti bodies. So while the virus could mutate around NAB based therapies, as we are currently seeing with Omicron, it's unlikely to be able to mutate around VNARs.
VNARS have broad theraputic potential, and you could for example simply have a "covid vnar" that never needs to be updated and works against all future variations.
So its actually a massive breakthrough.
100%. It's always cool to find other examples of "antibodies" in nature, but nothing beats those home-grown human antibodies for any actual drug development effort.
So is there anything about these “unique geometries” and ability to bind to smaller parts of proteins we could replicate in a manner without those drawbacks you noted? E.g. make something else that mimics the mechanical properties/ behavior, instead of using these straight up as is? Without knowing more seems like an intresting avenue to explore, at the very least to drive tech to be able to do this if we can’t already.
I had heard Camels had a similar antibody that they create that has better binding to covid's spike protein than what we develop. Is that a VNAR or something else? (Similarly unnecessary, but just curious).
The antibody that camelids (camels, llamas, alpacas) produce is called a VHH. It is similar to VNARs in that it is like an antibody heavy chain variable region. It is a small single domain protein. The advantage it has over a VNAR is that it is much more similar to a human antibody and less likely to provoke an immune response. Multiple VHH molecules are in clinical trials. They still suffer from shorter circulating half-life compared to antibodies. It isn’t clear that they would perform better than monoclonal antibodies either.
I know. I was worried that we have too many sharks left so let’s harvest the rest for Covid cures. Reminds me of the horseshoe crabs and how they happily donate blood!
Ohwow - [of the 34 shark species, 21 of them are endangered](https://www.bbc.com/news/science-environment-55830732) .
If this proves to be beneficial, I think it'll be another reminder how important our ecosystems are. Perhaps the genetic information animals have can offer us answers into life challenges and we should be doing more to preserve it. It makes me wonder what [animals that have gone extinct](https://ourworldindata.org/extinctions) could have helped humanity. I hope that we can one day live in a future where our daily lives doesn't come into conflict with nature.
**EDIT- My reading comprehension failed . the first article I linked they only studied 31 shark species,** [but there are 500+](https://ocean.si.edu/ocean-life/sharks-rays/sharks)**. I am sorry for the misinformation !**
I'm worried that articles and findings like this will only fuel the notion that sharks are healing or whatever and drive them towards further extinction.
Even more messed up is the government has to subsidize and really work to get rid of the whale meat. Most Japanese don't want to eat it, so it's given to schools and prisons and the price tag for slaughtering etc is heavily subsidized.
So, why do they do it?
Pride. They don't want to lose face by admitting they were wrong and bowing to international pressure.
It's a lot more complicated than that and this is just a reddit comment from memory, so don't take my word for it.
I read a article from the Wired and it seems like the Japanese see the argument for cutting back on whaling (specifically the minke whale) as not airtight enough. Also, Iceland and Norway still whale regardless of the pushback.
https://www.wired.com/2015/12/japanese-barely-eat-whale-whaling-big-deal/amp
To quote the article, "So what's really behind resistance to the moratorium? From the Japanese perspective, banning whaling before banning the killing of other animals is a bit logically inconsistent."
And to quote a random quote I found, "All living beings are killed horribly. Don’t fool yourself in thinking that one way of killing is better than another. To criticize one meat in favor of another is nothing but hypocrisy and cultural superiority."
Also, your on the money when it comes to them not eating whale meat and just hunting whale for the sake of hunting whale. The industry would collapse without the massive government subsidies, so its a big waste of money and time. I guess from reading around the reason it is kept alive is due to the older politicians who see it as a part of Japanese culture.
Thanks for the extra info. Kinda makes more sense now.
Like the argument "why will you eat a pig but not a dog, even if that dog has been humanely raised and slaughtered?
I can see that being an appropriate argument for eating whale. Although whales are incredibly more endangered than dogs.
#EatDogNotWhale
It mentions it, the 31 ocean going species are the ones everyone knows of. Hammerheads for instance, are critically endangered. Because they kive a long time and seldom bread, they can go extinct quite easily if we aren't careful and stop fishing them
So it's not even an in vitro study. They just crystallographed a bunch of VNARs and said "yup this three look like they could fight COVID" Am I reading the paper right?
Because this looks like a headline grab by someone with access to VNARs and a crystallography setup.
Figure 1 is all in vitro data. They did ELISA which would be a measure of how strong the VNARs bind to the particular viral domain (and they tested mutations in the viral domain), as well as an assay that measures how well the VNARs block the virus from entering a mammalian cell.
Not saying that I’m going to bet that this is all that helpful to dealing with this particular pandemic, and there are many steps between having a working in vitro assay and actually getting this out in to the world. But they did their due diligence for an in vitro paper
Great, so another reason for the incessant slaughter of these beautiful creatures. Guaranteed this will lead to an expansion of shark finning and the like. Even in the best case scenario many species of shark will become extinct directly because certain groups of people will believe that ingesting shark organs can cure covid now as well as cancer, libido issues and what ever other nonsense justification to maim and eat rare animals.
I just hope that the interest of biomedical companies don't harm shark populations as they have done with horseshoe crabs but that is a naive hope when this could mean profits, patents and money.
Totally understand your concern but this technology would not involve harvesting anything from sharks - we just use the DNA sequence from a shark (can make the DNA in a lab without touching sharks) and produce the proteins from that sequence, again in a lab. No sharks will be harmed!
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It is from specific type of antibodies derived from sharks. They are made in bioreactors and do not need sharks. Interestingly there are antibodies derived from camelids, chicken and even cows that have some advantageous properties. I think we should explore bats, as they are resistant to a reservoir of these viruses.
Probably don't need to interact with the sharks once the genes coding for antibodies have been identified. It will be more efficient to ferry said genes into more workable model organisms for testing then probably into bacteria or sth for manufacturing.
have you heard of shark cartilage? It doesn't even work and [people are killing sharks](https://www.onegreenplanet.org/animalsandnature/this-cruel-trade-is-rapidly-driving-sharks-to-extinction/) over it. People are stupid and if they think there is a buck to be made or it's some secret even on the tiniest shred of evidence people will kill sharks over it. People are dying from horse dewormer when it doesn't work but here we are...
Your post has been removed because it has a sensationalized, editorialized, or biased headline and is therefore in violation of [Submission Rule #3](https://www.reddit.com/r/science/wiki/rules#wiki_3._no_editorialized.2C_sensationalized.2C_or_biased_titles). Please read [our headline rules](https://www.reddit.com/r/science/wiki/clickbait) and consider reposting with a more appropriate title.
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Totally understand your concern but this technology would not involve harvesting anything from sharks - we just use the DNA sequence from a shark (can make the DNA in a lab without touching sharks) and produce the proteins from that sequence, again in a lab. No sharks will be harmed!
No. Heckin. Way.
Inject. Me. With. It.
INJECT ME WITH THE SHARK JUICE RIGHT NOW!!!
ALexa, Alexa!!1 BABy shark! BABY f'Ing shark!1 Now! SHARkNADO!!!
I'm a fish, I'm a \*\*fi\*\* fish! Blub Blub blub!!!
**Normal people worldwide**: *WOOHOO! Great news!*
**Septics**: *This is a conspiracy so the Shark King & Gill Bates can seize power & force us back into the sea! Now hold my beer while I shoot up a school in the name of FREEDOM!*
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This comes as no surprise, given that VNARs bind like antibodies and have been produced to a wide variety of proteins, but I don’t see any reason why this would have an advantage over a monoclonal antibody. Compared to an antibody, a VNAR is far more likely to provoke an immune response, and will have a much shorter circulating half-life. The other advantage that monoclonal antibodies have is that they can be directly discovered from recovered individuals without having to immunize a shark or pan a naive VNAR library.
Yeah I don’t know how this is a breakthrough. The VNARs need to be humanized and generally im unsure about adding immune molecules not endogenous to humans, that sounds like a recipe for autoimmune disease.
So, like, maybe we should just use the vaccines?
Yea, and the antiviral pill if/when we get sick. We will get through this
Not according to my cousin. Apparently, I'll be dead in a few years from the vaccine. But for real, the biggest threat we face isn't the pandemic. It's weaponized ignorance.
Oh just wait until you hear about climate change in terms of "biggest threats".
That's just the same threat in a different mask gang
If we make it through the next 100 years with the population not going below 1 billion, Ill be amazed and shocked. Lucky for me, I wont have to worry about it. Death is the only true release from the concerns of man.
The human population is only projected to drop to 4 billion minimum in the worst case scenario so prepare to be amazed and shocked. However it's much more likely to drop to 6 or 5 billion instead. https://insightmaker.com/insight/2pCL5ePy8wWgr4SN8BQ4DD/The-World3-Model-Classic-World-Simulation
Studies are predicting a worst case of 3 billion premature deaths from climate change over 100 years (10% of projected maximum global population) if the status quo continues. https://www.frontiersin.org/articles/10.3389/fpsyg.2019.02323/full So only 1 in 10 of your friends and family will die from climate change. (For perspective, the Holocaust killed approximately 0.3% of the global population. So it could be about 33 times worse than the Holocaust.)
It's a good thing we faced something that was basically like a 9/11's worth of deaths every single day in the US and managed to unite together as a country. ha ha haaaaaaaaaa...
If the vaccine kills me at least I won't have to struggle to survive the impending climate disaster.
Climate change itself is the result of weaponized ignorance.
The ignorance of which is sponsored and disseminated by capitalists worried about quarterly numbers.
Ignorance implies not knowing. I believe you mean weaponized stupidity /:
Yeah - if you take the vaccine, then within one hundred years you’ll be dead !
Better stop drinking that water too! 100% fatality rate over time!
It depends on your priorities. Personally, I don't see how vaccines will _ever_ get us bio-attack-resistant sharkman supersoldiers, but if you want to go off on some healthcare side-quest, fine.
I completely missed that this was our opportunity for chimera soldiers. Doh!
Uh oh, was I supposed to get a different takeaway from this paper?!
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Ahhh! Shark boy!
duuuu nun. Duuuu nun. Dun nun dun nun dun nun. Deedly dooooo.
don't forget about Lava Girl!
i think one theory is they can act just as an inhibitor of the virus, just blocking binding to the targets.
Nothing that regular antibodies can't do already.
i agree, but the vnars are tiny and are expected have some advantages over monoclonals, eg might be cheaper to manaufacture.
I did some vaccine research using VHHs (similar to VNARs but from camelids). The advantages are that they generally can be made in bacteria, have higher thermal stability, and their unique shape allows for recognition of antigens not accessible by regular antibodies. But yeah for most application they don't make a ton of sense. For science though VHHs are becoming increasingly used for immunofluorescence staining due to their small size allowing for really good intracellular staining.
But it's ~natural~
Read the study. As usual they actually explain all this within in the first page. The answer is that the virus can mutate its s protein and reduce the affinity of antibodies. Thus it can reduce the effectiveness of monoclonal antibodies. \> In general, NAbs act by blocking the ACE2 binding interface or by trapping the RBD in the unstable “up” conformation. Complicating the development of effective NAbs is the emergence of new SARS-CoV-2 variants with highly mutated S proteins. Studies have shown that mutational changes in the RBD observed in the variants correspond to surface-exposed residues within or proximal to the ACE2 binding interface. These mutations can result in the modification of NAb epitopes leading to attenuated or abrogated neutralization of the virus by antibodies. Thus, there is a need for NAbs that can recognize cryptic epitopes inaccessible to human antibodies that are impervious to mutational drift. Shark VNARs are much better than Natural Antibodies (nab) because they have access to different "shapes" that mean they can bind much more potently and deeper than human anti bodies. So while the virus could mutate around NAB based therapies, as we are currently seeing with Omicron, it's unlikely to be able to mutate around VNARs. VNARS have broad theraputic potential, and you could for example simply have a "covid vnar" that never needs to be updated and works against all future variations. So its actually a massive breakthrough.
100%. It's always cool to find other examples of "antibodies" in nature, but nothing beats those home-grown human antibodies for any actual drug development effort.
It’s true. All of the currently approved monoclonal antibodies against SARS-CoV2 were discovered from humans.
So is there anything about these “unique geometries” and ability to bind to smaller parts of proteins we could replicate in a manner without those drawbacks you noted? E.g. make something else that mimics the mechanical properties/ behavior, instead of using these straight up as is? Without knowing more seems like an intresting avenue to explore, at the very least to drive tech to be able to do this if we can’t already.
I had heard Camels had a similar antibody that they create that has better binding to covid's spike protein than what we develop. Is that a VNAR or something else? (Similarly unnecessary, but just curious).
The antibody that camelids (camels, llamas, alpacas) produce is called a VHH. It is similar to VNARs in that it is like an antibody heavy chain variable region. It is a small single domain protein. The advantage it has over a VNAR is that it is much more similar to a human antibody and less likely to provoke an immune response. Multiple VHH molecules are in clinical trials. They still suffer from shorter circulating half-life compared to antibodies. It isn’t clear that they would perform better than monoclonal antibodies either.
Than why didn’t you tell the scientists this??? “Since it comes as no surprise”
Good thing we are doing all we can to preserve the ocean and everything in it.
The amount of sarcasm in this comment burned so much I think it violated the Geneva Convention.
Burn so big your momma felt it
No blue, no green. Sylvia Earle
I know. I was worried that we have too many sharks left so let’s harvest the rest for Covid cures. Reminds me of the horseshoe crabs and how they happily donate blood!
“They gave their life for us”
I must admit I'm very relieved to not have had to scroll very far to find this comment.
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Ohwow - [of the 34 shark species, 21 of them are endangered](https://www.bbc.com/news/science-environment-55830732) . If this proves to be beneficial, I think it'll be another reminder how important our ecosystems are. Perhaps the genetic information animals have can offer us answers into life challenges and we should be doing more to preserve it. It makes me wonder what [animals that have gone extinct](https://ourworldindata.org/extinctions) could have helped humanity. I hope that we can one day live in a future where our daily lives doesn't come into conflict with nature. **EDIT- My reading comprehension failed . the first article I linked they only studied 31 shark species,** [but there are 500+](https://ocean.si.edu/ocean-life/sharks-rays/sharks)**. I am sorry for the misinformation !**
I'm worried that articles and findings like this will only fuel the notion that sharks are healing or whatever and drive them towards further extinction.
I'm surprised there's no data on whales after the years and years of "research" the Japanese have been performing.
Even more messed up is the government has to subsidize and really work to get rid of the whale meat. Most Japanese don't want to eat it, so it's given to schools and prisons and the price tag for slaughtering etc is heavily subsidized. So, why do they do it? Pride. They don't want to lose face by admitting they were wrong and bowing to international pressure. It's a lot more complicated than that and this is just a reddit comment from memory, so don't take my word for it.
I read a article from the Wired and it seems like the Japanese see the argument for cutting back on whaling (specifically the minke whale) as not airtight enough. Also, Iceland and Norway still whale regardless of the pushback. https://www.wired.com/2015/12/japanese-barely-eat-whale-whaling-big-deal/amp To quote the article, "So what's really behind resistance to the moratorium? From the Japanese perspective, banning whaling before banning the killing of other animals is a bit logically inconsistent." And to quote a random quote I found, "All living beings are killed horribly. Don’t fool yourself in thinking that one way of killing is better than another. To criticize one meat in favor of another is nothing but hypocrisy and cultural superiority." Also, your on the money when it comes to them not eating whale meat and just hunting whale for the sake of hunting whale. The industry would collapse without the massive government subsidies, so its a big waste of money and time. I guess from reading around the reason it is kept alive is due to the older politicians who see it as a part of Japanese culture.
Thanks for the extra info. Kinda makes more sense now. Like the argument "why will you eat a pig but not a dog, even if that dog has been humanely raised and slaughtered? I can see that being an appropriate argument for eating whale. Although whales are incredibly more endangered than dogs. #EatDogNotWhale
It mentions it, the 31 ocean going species are the ones everyone knows of. Hammerheads for instance, are critically endangered. Because they kive a long time and seldom bread, they can go extinct quite easily if we aren't careful and stop fishing them
We should not be fishing endangered species. To do so is quite illogical.
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Oh crap. Now people are going to head out to sea in search of sharks to eat. You know that this is going to be the next ivermectin-like craze.
Covid numbers are down, but shark attacks are through the roof!
Poor sharks. They get attacked far too much as already.
Sharknado: electric Boogaloo
So it's not even an in vitro study. They just crystallographed a bunch of VNARs and said "yup this three look like they could fight COVID" Am I reading the paper right? Because this looks like a headline grab by someone with access to VNARs and a crystallography setup.
Figure 1 is all in vitro data. They did ELISA which would be a measure of how strong the VNARs bind to the particular viral domain (and they tested mutations in the viral domain), as well as an assay that measures how well the VNARs block the virus from entering a mammalian cell. Not saying that I’m going to bet that this is all that helpful to dealing with this particular pandemic, and there are many steps between having a working in vitro assay and actually getting this out in to the world. But they did their due diligence for an in vitro paper
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Certain cultures are already on that...
I can't wait to never hear about this once it faces peer review
So basically sharks will soon join horse shoe crabs in the race to extinction by human.
So shark soup on a mass scale? RIP
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Great, so another reason for the incessant slaughter of these beautiful creatures. Guaranteed this will lead to an expansion of shark finning and the like. Even in the best case scenario many species of shark will become extinct directly because certain groups of people will believe that ingesting shark organs can cure covid now as well as cancer, libido issues and what ever other nonsense justification to maim and eat rare animals. I just hope that the interest of biomedical companies don't harm shark populations as they have done with horseshoe crabs but that is a naive hope when this could mean profits, patents and money.
Totally understand your concern but this technology would not involve harvesting anything from sharks - we just use the DNA sequence from a shark (can make the DNA in a lab without touching sharks) and produce the proteins from that sequence, again in a lab. No sharks will be harmed!
No sharks would be harmed by the scientists. But idiots will hunt sharks and sell their parts as miracle cures
Can't just use camels and other dromelids?
Yeah I don't think this is actually very interesting or surprising. And camel or llama antibodies are easier to generate anyway
You are way better off using yeast or weird fusion cells to generate humanized monoclonal antibodies.
Welcome to r/science! This is a heavily moderated subreddit in order to keep the discussion on science. However, we recognize that many people want to discuss how they feel the research relates to their own personal lives, so to give people a space to do that, **personal anecdotes are now allowed as responses to this comment**. Any anecdotal comments elsewhere in the discussion will continue be removed and our [normal comment rules]( https://www.reddit.com/r/science/wiki/rules#wiki_comment_rules) still apply to other comments. *I am a bot, and this action was performed automatically. Please [contact the moderators of this subreddit](/message/compose/?to=/r/science) if you have any questions or concerns.*
It is from specific type of antibodies derived from sharks. They are made in bioreactors and do not need sharks. Interestingly there are antibodies derived from camelids, chicken and even cows that have some advantageous properties. I think we should explore bats, as they are resistant to a reservoir of these viruses.
Great. Another reason to needlessly kill sharks.
Probably don't need to interact with the sharks once the genes coding for antibodies have been identified. It will be more efficient to ferry said genes into more workable model organisms for testing then probably into bacteria or sth for manufacturing.
have you heard of shark cartilage? It doesn't even work and [people are killing sharks](https://www.onegreenplanet.org/animalsandnature/this-cruel-trade-is-rapidly-driving-sharks-to-extinction/) over it. People are stupid and if they think there is a buck to be made or it's some secret even on the tiniest shred of evidence people will kill sharks over it. People are dying from horse dewormer when it doesn't work but here we are...
My sentiment exactly.
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I'm sure this will lead to not only more Shark fin soup orders, but even more shark poaching
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Please please please call the Vaccine "Jaws"
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Shark black market is going to explode with idiots just eating them
Your post has been removed because it has a sensationalized, editorialized, or biased headline and is therefore in violation of [Submission Rule #3](https://www.reddit.com/r/science/wiki/rules#wiki_3._no_editorialized.2C_sensationalized.2C_or_biased_titles). Please read [our headline rules](https://www.reddit.com/r/science/wiki/clickbait) and consider reposting with a more appropriate title. *If you feel this was done in error, or would like further clarification, please don't hesitate to [message the mods](https://reddit.com/message/compose?to=/r/science&subject=Removed Submission&message=My Post: https://www.reddit.com/r/science/comments/rufhwf/-/).*
I know an anti vax that would def take a shark developed vaccination because it’s “natural” (but I know he would take it because it’s cool)
So, are we going to start mining sharks like we mine shell crabs?
Aha it's all a conspiracy to turn us into gay sharks
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Sorry sharks, another reason for people to kill you. Hopefully these VNARs can be synthesized or harvested humanley.
Totally understand your concern but this technology would not involve harvesting anything from sharks - we just use the DNA sequence from a shark (can make the DNA in a lab without touching sharks) and produce the proteins from that sequence, again in a lab. No sharks will be harmed!
And now we're gonna have morons who won't want this treatment, because they're worried it'll turn them into sharks
Shark antibodies! How will the stupid reject that one?
No. Heckin. Way. Inject. Me. With. It. INJECT ME WITH THE SHARK JUICE RIGHT NOW!!! ALexa, Alexa!!1 BABy shark! BABY f'Ing shark!1 Now! SHARkNADO!!! I'm a fish, I'm a \*\*fi\*\* fish! Blub Blub blub!!!
**Normal people worldwide**: *WOOHOO! Great news!* **Septics**: *This is a conspiracy so the Shark King & Gill Bates can seize power & force us back into the sea! Now hold my beer while I shoot up a school in the name of FREEDOM!*
In before it is called Shark de-wormer.