Ricin

Ricin is one of the most deadly toxins known to man. So toxic, in fact, that a single molecule is sufficient to kill a cell and 8 castor beans, which produce the toxin, can prove fatal to an adult if ingested. Amazingly, the production of these beans aren’t tightly controlled and they can be found in gardens and overgrown areas. Indeed, in some areas the growth of the castor plant is encouraged, as the oil is used in the production of soaps, lubricants and dyes.

Rarely does one plant have such contrasting uses. While its oil is used in simple manufacturing, the toxin contained within the beans has been classified by the Centres for Disease Control (CDC) as a serious threat for use in bioterrorism; such is the level of its toxicity. The CDC is certainly right to be worried; ricin has already been used for nefarious purposes that sound like they could have come straight out of a spy thriller. On September 7, 1978, the Bulgarian dissident Georgi Markov was jabbed in the leg in public on Waterloo Bridge in the middle of London by a man using a weapon built into an umbrella. The weapon embedded a small pellet containing ricin into Markov’s leg. Markov died four days later. Ricin powder has also been discovered in letters sent to United States senators.

161-Ricin_2aaiSo why is Ricin so dangerous? The toxin is made up of two chains – a targeting chain (the ‘B’ chain, shown in blue), which binds to the carbohydrates on the surface of the target cell, and an ‘A’ chain (shown in red), which is the toxic portion. When a person is poisoned, millions of ricin molecules bind to the surface of the host cells and the B chains form secondary structures, which chaperone the A chain inside the cell. Though not all the A chains will make it to the cytoplasm, this does not stop the toxin having its effect as just one molecule is enough to kill off a cell.

The A chain works by inactivating ribosomes, the machines that facilitate protein synthesis. Ricin is so potent that it can inactive 1,500 ribosomes every minute, ultimately bringing synthesis of all proteins grinding to a halt and killing the cell. Specifically, Ricin attacks a loop of the ribosome that is key to the attraction and action of the elongation factors that control the initiation of translation. Ricin does very little to this loop to inactivate the ribosome – all it needs to do is clip off an adenine residue. This is the secret behind its toxicity, since it can hop from ribosome to ribosome, inactivating each one until there are none left in the cell.

However, as is often the way with toxic compounds, we have found a way to use Ricin to our advantage. When combined with an antibody, it can form an immunotoxin, a new form of therapy specifically used against cancer cells. These molecules combine the specific targeting ability of antibodies with the extreme toxicity of Ricin. The antibody is chosen to bind specifically to molecules decorated on the outside of cancer cells, delivering the toxin directly to the pathological cells that we want to destroy.

‘Til next time…

Joe

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