Disappearing Polymorphs
en.wikipedia.org
en.wikipedia.org
If someone told me this entire article was fabricated I would believe them. I would never have thought that such trace amounts of… everything one has ever shared a room with, essentially follow them everywhere dispersing as they go. Chemistry is wild.
Once the badly folding protein is introduced there is no way back.
https://www.hopkinsmedicine.org/health/conditions-and-diseas...
https://en.wikipedia.org/wiki/Scrapie
> In Iceland in 1978, a program was implemented to eradicate scrapie, and affected flocks were culled, premises were disinfected, and sheep houses were burnt; after two to three years, the premises were restocked with lambs from scrapie-free areas. Between 1978 and 2004, scrapie recurred on 33 farms. Nine recurrences occurred 14–21 years after culling as a result of persistent environmental contamination with PrPSc.
A human variant transmissible through cannibalism is Kuru (against which the locals have developed some resistance):
https://en.wikipedia.org/wiki/Kuru_(disease)
> In 2009, researchers at the Medical Research Council discovered a naturally occurring variant of a prion protein in a population from Papua New Guinea that confers strong resistance to kuru. [...] G127 polymorphism is the result of a missense mutation, and is highly geographically restricted to regions where the kuru epidemic was the most widespread. Researchers believe that the PrnP variant occurred very recently, estimating that the most recent common ancestor lived 10 generations ago.
> Culinary preparations include scrambling the brains with eggs or putting them in a meat and vegetable stew referred to as “burgoo”.
More interestingly it's rare - you have to eat infected brains that have a variation that side steps not one but two prion defence mechanisms that most humans have ... which suggests that almost all humans have ancestors that engaged in enough cannabalism to develop layered defences against brain transmitted diseases.
FIV is not the same as HIV (Feline, Human, but they're similiar) and so to with prion diseases.
Mad Cow disease came about from feeding large quantities of ground up cow offal from abattoirs mixed up with grains to make 'tasty' feed pellets .. eventually a cow prion disease 'perfected' itself and went on to occassionally(?) affect humans - more common in cows than humans, etc.
With human cannabilism, we know about Kuru from the Fore people in PNG who, like many other groups in the highlands, practiced cannabilism as a mortuary ritual, a funeral practice to retain the essence of someone respected. Kuru was a specific human to human variation that evolved to become more common and overcome the defences against human -> human prion defence I mentioned earlier.
We have other reasons to suspect cannibalism was common elsewhere .. such as the documented European practice of medicinal cannibalism and the fashion of consumming bitumised mummies.
https://www.smithsonianmag.com/history/the-gruesome-history-...
https://www.mentalfloss.com/posts/eating-mummies-as-medicine
But, ahh, yeah - these days genetics is the thing, markers for defences against human prion diseases are a thing talked about in a group of papers post Kuru.
Like most other diseases species -> same species is an easier vector than species -> different species.
"Microscopic" is also a mischaracterization. Apparently, just a few _hundred_ atoms can act as a seed. This is a "nanoscopic" quantity.
> I would never have thought that such trace amounts of… everything one has ever shared a room with, essentially follow them everywhere dispersing as they go.
Everywhere you drive, you leave behind microplastics as particulate. These are washed into waterways and end up in aquatic ecosystems, including the seafood you eat. There's also some small enough to be airborne, thus prone to inhalation by humans and other animals.[1] Particulate production from road wear increases with the fourth power of the weight of the vehicle.[2] One has to assume by Newton's third law that the same is true of tires. Tires and roads are made of petroleum-based materials, i.e., they produce microplastics. This means a car twice as heavy (e.g. EVs vs ICE cars in the same form factor) produces sixteen times as much particulate matter. This also means that typical cars emit a minimum of four million times as much particulate as bicycles. E-bikes emit 10 times as much particulate as bicycles.
Microplastics cling to everything, that's just the nature of particulate. So they follow you everywhere.
[1] https://www.wbcsd.org/Sector-Projects/Tire-Industry-Project/...
The whole intro to this article really undersold to me how significant a phenomenon this is describing. My jaw dropped when I got into the Case Studies section. Apparently there are certain drugs which are nigh impossible to make today because a more stable (but medically ineffective (or still patented)) version of the crystal was once created and now contaminates the atmosphere in microscopic quantities.
> It is hypothesized that "unintentional seeding" may also be responsible for the phenomenon in which it often becomes easier to crystallize synthetic compounds over time.
(Well, to be fair, the only thing that's reversed is the human value judgement. The proposed mechanism is the same.)
The ultimate solution was hot extrusion: molten ritonavir is dispersed in an inert carrier, and then left to cool. The carrier insulates the droplets from outside contact, so it can't get contaminated with the more stable polymorph.
This idea itself is completely obvious. But like pretty much everything in engineering, it took a decade to perfect the process.
If you have a misfortune to get prescribed Paxlovid for COVID, break a tablet and look at it in a microscope. You'll clearly see the ritonavir droplets embedded inside the carrier material. It's super-cool.
(Ritonavir is used in Paxlovid not because of its antiviral properties, but because it inhibits some liver enzymes, thus slowing down the metabolism of the active ingredient)
I can imagine how this could present an issue for hardware manufacturing, but are there examples of this occurring in that industry?
I’m just an armchair observer though, and I’m sure something like this has cropped up in some unpublished paper.
At least I think that's what it says, I'm definitely not a chemist!
https://chemrxiv.org/engage/chemrxiv/article-details/645112f...
Nobody else's bullshit alarm is going off here? Just mine?
Seriously?
1) I can readily imagine the _labs_ being contaminated by the reference samples.
2) If the compound is stable, not clumping and not hygroscopic - yes, certainly. “Microscopic” doesn’t do it justice, as there doesn’t seem to be any limit to how small the seed crystals can get.
Since we’re manufacturing literally tons of pharmaceuticals, and carefully manually spreading them over the Earth surface to the pharmacies, so for stable substances it doesn’t seem such an exaggregation to me.
In section 3.3 it says that GSK argued their patent on the new form was being infringed because "there were batches of anhydrate that converted almost entirely into hemihydrate when stored at 40 °C and 75 % humidity within one month."
So "if you keep it wet and warm it will partially convert over the course of a month", and as far as I can tell the "seeding" aspect was not clarified, at least not in the article.
Also it bugs me that the Wikipedia author decided to call the loss for GSK a "technicality". It was decided that it was not relevant that microscopic quantities of the new form were created by accident, I think that is the correct decision and not a technicality.
My thought was more: would it not be possible to counter-sue and get damages from them in court. For after all, they "polluted" your lab / plot with something that you never asked for, and that is now causing damages / lost earnings.
Except this almost never happens. But if it does, Monsanto (now Bayer) will reimburse you the cost of contaminated crops.
Other than that, yeah, I guess it's exactly the same.