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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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February 1, 2004

Ricin Redux

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Posted by Derek

Now that the suspected ricin in the Senate (and White House?) has been confirmed, I thought I'd repost a version of something I wrote about a year ago on my previous site, Lagniappe. (This was written after British authorities had rounded up several suspects in London who had some ricin of their own.) So what is the stuff, and what kind of threat is 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 (and they're not very ornamental, either.)


The purification methods for ricin are in the open literature, and aren't particularly challenging. I'm not going to go over them, though, in the interest of not making its isolation any easier than it already is - it's already probably one of the easiest toxins to isolate. For that matter, you can order various forms of it from biochemical supply houses. It's quite cheap, by the standards of protein 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 that reaction 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 as a weapon 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, the worst way to be exposed is by inhalation. Oral dosing is about 4000 times less potent. 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. (It's hard to imagine the second World War being even worse than it was, but it had the potential.)


Needless to say, there's not a whole lot of public data on just how toxic ricin might be in that aerosol form, and its effects would certainly depend on particle size, static charge, and all the other variables we learned about during the anthrax scare. We sp 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 about a half a milligram proved lethal.


Well, that 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 wouldn't be easy, fortunately.


Ricin's not particularly water-soluble, so dumping it into a reservoir would be a waste of time. And adulterating food would be almost useless. 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, well, pretty much 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. (And I've no idea how stable the protein is in hot food, but I'd have to think that it would be inactivated pretty quickly._


The key to this latest ricin incident will be whether the stuff had been processed to the level of the anthrax attack material. If so, we have a potentially serious problem, but so far I don't see any sign that this is the case. Otherwise, this could well be the work of some disgruntled and/or deranged amateur. Those types I think we can deal with.

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