The Curious Case of the Disappearing Polymorph

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[andersjjensen]

I came for semi conductor tech but stayed for the well researched and delivered multitude of topics.... So the silicon bule analogy was welcome.

[samcavanagh]

This is a very similar concept to "prions" which are more stable forms of proteins which can spontaneously change other proteins to the new form. This can be very dangerous, as evident by the mad cow disease outbreaks caused by prions. Additionally, prions are extremely hard to sterilize against, and can last in the environment for decades.

[OldFArt-gxfh]

I worked at Abbott’s Australian affiliate and can confirm this story. This was in the late 90s - the stock of Norvir ran out and I was told that some strange things were happening to the capsules, nobody could explain it and it was almost like out of a sci-fi movie. Liquid norvir apparently had a terrible metallic taste. Thank you for clarifying this 25 years later.

[aonomus]

This video brings up some mild lab trauma for me - half a year in the lab focused on fine tuning a process to ensure the correct polymorph would form, sending it to the plant after 'bulletproofing' it in the lab (many hands, highly reproducible) only for the entire batch to come out as the wrong form - the ring of solids that built up in a reactor was the wrong form. Fortunately we had an 'out' with an engineered polymorph setting step which reconverted everything to the right form, albiet at a yield loss.

[pavloz]

*"Vladimir Renin, seizing the means of blood pressure"*
ehhh Ok

[weedmanwestvancouverbc]

And this is one of the things in computational chemistry that can help prevent things like this. You can go through with the molecular formulation and run it through simulations to see if there's any preferred thermodynamic polymorphs that the material will try to change into to reduce its energy to its lowest state

[Namelis]

Absoletly outstanding episode. Like. Holy crap. How did you even find this story. A pharma production line gets ice-nined. That's literally, actually science fiction. Outstanding work, Captain Asianometry.

[KarlBunker]

The medication for a contagious disease caught a contagious disease. Weird.

[hinkelstein]

Did not expect to get a video about this phenomenon here - for interested people, there are review articles: Accounts of Chemical Research 1995, 28, 193; Angewandte Chemie intern. Ed. 2015, 54, 6972

[tomsawyer]

"Aids, a generally unwanted condition". 😅😅😅 I'm dead

[JesseDunnack]

Loving all the bio-related content lately! Leaves me wanting more! Hate to be nitpicky but "protease" is usually pronounced more like "pro - tea - ace", and "renin" likely more like "ree - nin". Biology nomenclature is kinda jarring at first, but after encountering enough weird names, it'll become second nature lol

[Muonium]

Did you see that excellent space reentry video from Varda Space's tiny capsule maybe half a year or so ago that went a little viral (heh) on here? The one that was stuck in space for almost a year because they launched without a permit from the FAA for a reentry and the FAA wanted to make an example out of them for trying to just launch and get the permit later? This is what it was doing, converting and recrystallizing the form 2 of ritonavir into the stable form 3 in zero gravity. The paper that came out of it is "Return of the Ritonavir: A Study on the Stability of Pharmaceuticals Processed in Orbit".

[cva]

This sounds similar in spirit to a prion - a misfolded protein that spreads its misfolding to other copies of the protein, which leads to cell death in prion diseases (like Creutzfeld-Jakob).

Although it's actually, I guess, the same as the issue of chocolate tempering. Chocolate crystalizes in a lot of different forms and if you're not careful when you work with chocolate you'll get the wrong one.

Prion on the one hand, chocolate on the other. I'll go with the chocolate.

[bastiangugu]

'Vladimir Renin, seizing the means of blood pressure' made me chuckle quite a bit. Nice play on words.
Very interesting topic, by the way, and great video as always. Thank you.

[bobthecomputerguy]

I honestly thought this was going to be about object oriented programming. Glad it wasn't, as this is a really interesting phenomenon I've never heard of before.

[catcatcatcatcatcatcatcatcatca]

What a great explanation of a fascinating story older than I am. I had little to no interest in the topic but it was captivating.

My surface level understanding of chemistry was blown away by the idea of cycle of crystal forms. Different crystal structures depending on simple conditions like temperature, pressure and catalyst I knew about. But a form that acts like a pandemic was so outlandish I can understand why we weren’t taught this about in school.

[DavidA-]

Isn't Ice-9 a bar drink? Also
Cat's Cradle was published in 1963. Curious how the idea of unexpected polymorphism has been around for a while.

[r__and__r]

One of the antagonists in Red Dwarf is The Polymorph. I was half expecting a cameo from it.

[ChesturElegante]

This might be one of my favorite of your videos. I've never heard of this process of spontaneously occurring polymorphs. Although I have read cat's cradle. What a wild story.

[fabianmok]

It’s frightening how relevant this is to me. Been watching your channel for a few years now and I am doing my Masters thesis in Computational Chemistry for protease inhibitors