Continuing the Tweetorial theme of hematology terms with little-known connections to the wider world: let’s talk about the Congo Red stain. Where did it come from, and does it have a connection to the African Congo? I thank amyloidosis guru @MorieGertz @MayoClinic for this image: 
Congo Red didn’t start its life as a histological stain nor was it initially named “Congo”. Like Prussian Blue, it was developed to dye clothes. In 1857, William H. Perkin in the UK created the first synthetic aniline dye, a purple color he called mauvine, later known as "mauve".
Until that time, mostly natural dyes had been used to dye fabrics. After Perkin's discovery, there was a race to create synthetic colors – mostly in Germany, mostly aniline dyes. This is the chemical structure of Congo Red; aniline is a phenyl group attached to an amino group.
A major problem with older fabric dyes is that they wash out easily. To stop fading, another chemical, a mordant, is needed. Companies in the late 19th century were keen to find dyes that didn’t require a mordant, to save time and money. (A company in Connecticut sells this one)
In 1883, a young German chemist, Paul Böttinger created a new bright-red dye that stained fibres without needing a mordant. He brought it to the attention of his bosses at The Friedrich Bayer Company but they weren’t interested. Reportedly they were looking for a purple, not red
So Böttinger left Bayer and patented the chemical on his own. He offered it to several other companies, but they weren’t interested. Finally, a small Berlin-based dye manufacturing company called Agfa (Aktiengesellschaft für Anilinfabrikation), founded in 1867, bought it.
(An aside: My grandmother grew up in Hoboken, NJ and worked for Agfa in New York City for years in various secretarial roles. In the 1930s, when she was just starting out at age 15, she used to eat her lunch while admiring a nearby new art deco skyscraper: the Chrysler Building.)
Congo Red was a huge commercial success for Agfa – so much so that many other aniline dye companies went out of business. Bayer, the company that rejected Böttinger, only survived by creating their own Congo Red... Agfa then sued them. (Clever sticker is from a Medium blogpost.)
It became a classic case in patent law. The “non-obvious” clause in patent world comes from Congo Red. Agfa and Bayer decided the lawsuit was becoming too expensive so they settled, agreed to co-market Congo Red & share the profits. (This image is from chm.bris.ac.uk/motm/congo-red…)
The lawsuits & lost sales had almost bankrupted Bayer. But now, with money from Congo red sales, Bayer was able to hire new chemists. In 1898 Bayer marketed heroin (!), and in 1899 they marketed a new drug you’ve probably heard of: aspirin. Heroin and aspirin saved the company.
In 1925 Bayer and Agfa and four other chemical companies merged to form IG Farben (Farben = colors/dyes in German). IG Farben made helpful chemicals like dyes and medicines, but also some terrible chemicals, like the infamous Zyklon B. As a result, they were dissolved after WW2.
The month Congo Red was patented in 1885, there was a big event going on in Berlin: the Berlin West Africa Conference. In simple terms, the European powers were dividing colonial Africa. Otto von Bismarck, chancellor of the newly unified Germany, presided over the conference.
Britain & France already had established colonies; Italy controlled parts of East Africa, Portugal controlled Mozambique & Angola. The Congo basin was a sticking point everyone was talking about. Some "genius" marketer @Bayer thought: what better name to give our new vivid dye?
Other dyes created at about the same time were Sudan Black, Sudan Red, Coomassie Blue, and Bismarck Brown - notice a theme? Africa = exotic and colorful in the late 19th c. European mind. Incidentally, Sudan Black is also still used for histology, and Coomassie Blue in SDS-PAGE.
The real-world Congo was in the end given to the Belgian king, Leopold, as his private fiefdom. It became the site of some of the worst atrocities in human history, immortalized in Joseph Conrad’s book “Heart of Darkness”.
(I can also highly recommend @AdamHochschild’s 1998 book “King Leopold's Ghost: A Story of Greed, Terror and Heroism in Colonial Africa”, about how the Congo atrocities were remembered - or not, as it turned out - in Belgium at the time he wrote the book.)
Anyway - Congo Red, like many other aniline dyes, immediately started being used for histology. But it wasn't particularly useful until on 1922 a young German pathologist, Hans Herman Bennhold, discovered it binds to amyloid. His granddaughter wrote this: nytimes.com/2016/12/24/wor…
In 1929, Paul Divry, a Belgian neuropathologist studying degenerative changes in aging brains, first noted the characteristic green birefringence of amyloid substance when stained with Congo red and viewed under polarized light. (This image is from Lai et al 2007 Kidney Int'l.)
Curiously, Congo Red (CR) was also a procedure for a while. The patient with suspected amyloid would be injected with CR intravenously, and then after a period of time a CR level was drawn. If there was a lot of amyloid in the body for CR to bind to, blood levels might be low!
The preferred way to confirm what type of amyloid is present is now mass spectrometry. My late lab office-mate @MayoClinic Steve Zeldenrust was developing such protocols when he developed sarcoma. (An aside: a moving video that Steve made for his church vimeo.com/301694461)
The term “amyloid” was coined by German botanist Matthias Schleiden (1804 - 1881) to denote starchy stuff in plants that stained blue with iodine. In 1854, the great Rudolf Virchow described deposits in the nervous system that demonstrated the same iodine color reaction.
19th c. French & British pathologists used terms "waxy" or "lardaceous" to describe tissue changes of amyloid. The classic "sago spleen" is named after a tapioca-like palm starch. (What is it with pathologists and food metaphors?!) This yummy image is from Webpathology.com
I can't imagine anyone would want to read more about the history of Congo Red, but just in case, here is a link to an article I wrote in 2001 about this history based in part on too much time spent trawling through old German industrial archives: archivesofpathology.org/doi/10.1043/00…
(That image with its shiny white is a sago spleen.) Amylum in Latin = αμυλον in Greek = starch/carbohydrate, so amyloid = starch-ish. Schleiden didn’t quite know what he was dealing with. It is the same Schleiden who later came up with “cell theory” together with Theodor Schwann.
