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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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« And Another Thing. . . | Main | The Library of Babel »

January 7, 2003

Ricin

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Posted by Derek

There's a report today that British authorities have rounded up several terrorist suspects in London - and that they had small quantities of ricin. So, what is the stuff, how bad is it, where did they get it, and what did they plan to do with it?

Ricin's a protein from castor beans - yep, the same ones used to prepare castor oil. The parent plant is sometimes used as a warm-weather ornamental, and used to be an industrial crop. The leaves aren't a problem, but the beans contain up to 5% ricin, which is a rather high yield for a natural product. It's quite toxic, although there are certainly worse things out there. Botulinum toxin, for example, is a thousand times more potent, but you can't grow anerobic bacteria very well in your back yard.

The purification methods for ricin are in the open literature, and aren't particularly challenging. It's probably one of the easiest toxins to isolate. For that matter, you can order various forms of it from biochemical supply houses. I looked at a few catalogs today, and it's quite cheap, by the standards of peptidic natural products (which are usually priced rather steeply.)

And what does the stuff do? Briefly, it's a very potent inhibitor of protein synthesis, which it accomplishes by attacking one subunit of the ribosome (the central RNA-to-protein machinery of the cell.) Rather than just binding to ribosomes and gumming them up, ricin is actually an enzyme all by itself. It tears up a specific adenine base in the ribosomal RNA, which disables the whole thing, and then it moves on to the next ribosome. One ricin molecule can turn over thousands of times, and needless to say, a cell can't lose thousands of ribosomes and expect to survive.

Ricin's a reasonably large protein, and it suffers from the defects of large proteins. The least dangerous way to be exposed to it is by eating it, since most of it gets digested, and much of the rest has trouble crossing from the gut into the bloodstream. In rodents, oral dosing is about 4000 times less potent than inhalation, which is the worst way to be exposed. The assumption is that if ricin were weaponized, it would be treated like anthrax spores and dispersed for maximum effect. The US and Britain carried out research that led to a prototype of a ricin bomb during World War II, just another one of many nasty weapons that actually didn't get used in that conflict.

Needless to say, there's not a whole lot of public data on just how toxic ricin might be in that form, and it would certainly depend on particle size, static charge, and all the other variables we learned about during the anthrax scare. We have a single public data point about injected ricin, though: Georgi Markov, a Bulgarian exile who worked for Radio Free Europe. One day in 1978, he felt a sharp pain as a stranger poked him with the tip of an umbrella. He began to feel ill within a few hours, and three days later, he was dead. A small pellet containing ricin had been injected into the muscle of his leg, as it turns out, in one of the more exotic assassinations known to have been carried out by the KGB. The best guess is that at most half a milligram proved lethal.

Which sounds pretty bad - but consider that terrorists are unlikely to be able to give masses of people intramuscular injections. And if they want to use inhalation, which is certainly the way to cause real damage with the stuff, they're faced with manufacturing problems similar to the use of anthrax spores.

It's not particularly water-soluble, so dumping it into a reservoir would be a waste of time. And adulterating food would be almost useless, although I've seen mentions of this possibility since the news story broke today. It takes a good handful of the beans themselves to kill an adult (and they have to be crunched up, too, because whole beans tend to pass unchanged through the digestive tract.) A back-of-the-envelope calculation for the pure toxin suggests that it would take a gram or two to reliably kill someone by ingestion. That adds up to a few hundred casualties per pound of ricin, but only if you can get all your victims to eat enough of it.

How worrisome is the news from London? It depends on how much ricin these people had, and what form it was in. I'm betting that it was straight precipitate from the beans, and not something ready to disperse for inhalation. In which case, the suspects were set up to commit retail murder. And not wholesale, fortunately.

(For as much detail as anyone could want, see this PDF, a book chapter written by two colonels from the Army's Medical Research Institute at Fort Detrick.)

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