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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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In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

In the Pipeline

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December 15, 2004

Die-oxin?

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Posted by Derek

I've been meaning to get around to the Ukrainian dioxin-poisoning story, and now's the time. Dioxin is, as most everyone should know by know, seriously overrated as a human poison. It's had a reputation as a scary supertoxin, though, and that's my answer to why it seems to have been used in this case: because someone was an idiot. As a tool for assassination, dioxin is the sort of thing that Wile E. Coyote would have used on the Roadrunner.

Which means the Russian KGB probably wasn't involved, because those guys know about toxins. Whatever else you can say about them, they're professionals. Trying to kill someone with dioxin is silly on several levels - for one thing, it's not very acutely toxic at all. What risks it poses are for chloracne (as we've seen) and some increase in long-term cancer rates. It's also very easy to detect analytically, if you think to look for it. Chlorinated aromatic compounds have a long lifetime in the body and a very distinct signature in a mass spectrometer.

Much of what's known about high dioxin exposure in humans comes from the 1976 chemical plant explosion in Seveso, Italy, which exposed thousands of people. While there were hundreds of cases of chloracne, there were no fatalities and no apparent birth defects in pregnant women. The compound's overall risk to human health is still being debated, mainly because the long-term data are so close to the noise level. For some details on dioxin's toxicity (from a scathingly sceptical perspective) see JunkScience's take here. For livelier, not to say near-hysterical takes on the subject, just Google the word "dioxin" and brace yourself for a flood of invective from various environmental sites

For more on the Ukrainian angle, I'd suggest reading Blogs for Industry - they've got several long posts, and a good perspective on some of the other commentary floating around.

Comments (17) + TrackBacks (0) | Category: Toxicology


COMMENTS

1. steve on December 16, 2004 12:17 AM writes...

If I remember correctly, Junkscience.com considers evolution to be junk science. Which is to say, they are total morons.

Unless I'm mistaken, and it was some other site. But I think it was them.

Permalink to Comment

2. Derek Lowe on December 16, 2004 9:19 AM writes...

Hmmm. . .I just dug around over there, searching for "darwin", "evolution" and such. I found a couple of old reprints of deistic Wall St. Journal op-eds, but not much more.

For the most part, the JunkScience people seem to be more in the debunker's corner, roughly in Julian Simon / Elizabeth Whelan / Michael Fumento country, with a particularly revved-up attitude about environmentalism. I doubt if I'd subscribe to every position they endorse, but on the balance, I think they do more good than harm.



If anyone has more information, though, I'd be glad to revise my opinion. I agree with Steve: any outfit that trashes evolutionary theory won't be getting an endorsement from me. (While we're at it, the same goes for thermodynamics, relativity, and other well-established theories with or without religious implications.) If you try to ditch those, the replacement on offer had better be impressive, and I haven't seen anything remotely close from the anti-evolution people.

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3. Feelin' Snarky on December 16, 2004 11:50 AM writes...

While we're at it, the same goes for thermodynamics, relativity,[...]

WARNING: This book explores the theory of thermodynamics. Readers are cautioned that this is only a theory, and that competing theories exist. If this book is in Texas, readers are further cautioned that God Will Strike You Dead if you don't dispute the theory.

Permalink to Comment

4. Mike on December 16, 2004 12:30 PM writes...

How about the possibility that the poisoning was not an assassination attempt, but rather an attempt to intimidate or terrorize? Dioxin may be an ideal tool for this effect. It disfigures, but doesn't kill. And it's a common enough chemical that the chance of the poison being traced to a specific source is unlikely. Perhaps the KGB knows this, and got the result they were after.

Demonstrating to someone that you could kill them at any time can be more useful than actually killing them.

Permalink to Comment

5. CatCube on December 16, 2004 2:06 PM writes...

Demonstrating to someone that you could kill them at any time can be more useful than actually killing them.

Except that now his security will be on the alert for it, meaning that the KGB (assuming that it is them) will have a much harder job trying to "kill [him] at any time"

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6. Puff on December 16, 2004 4:02 PM writes...

I don't think killing or even poisoning per se were the desired results. Most likely reduction of charisma, interuption of campain, intimidation, and provoking a paranoid seeming outburst were the targets. And if the election wasn't being re-run who would actually care, no blood no foul and all that? So IMNSHO it did work, but they got called on it and now there is lots of blowback, same as with the intimidation at the polls.

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7. steve on December 17, 2004 1:54 AM writes...

And don't let anyone think I meant that Derek was endorsing anti-evolutionists, I didn't. The 'junk science' critics range from sensible skeptics to petro-shills, it's very hard to keep up with who's legit.

Snarky: very funny.

mike, etc: yeah, but a visible assassination attempt would probably turn public opinion against you, and public opinion propels revolutions.

Permalink to Comment

8. nguyenngocduc on December 17, 2004 10:50 AM writes...

hi ! i can help you?

Permalink to Comment

9. Sam Jaffe on December 17, 2004 10:53 AM writes...

Any thoughts on the recent AP story that the type of dioxin used was tetrachlorodibenzoparadioxin, or TCDD? And why didn't Yuschenko taste it in his soup?

The idea that this was an intimidation tactic just doesn't make sense. The Ukrainian regime is extremely clever and brutal--they don't think twice about political assassination. If they wanted to reduce the guy's charisma, they sure are political lightweights. What could be more charismatic than a formerly beautiful person reduced to scabs by an evil dictator. Karl Rove couldn't have thought of a better way to get Ukrainians on Yuschenko's side.

I actually think that a self-poisoning might be more plausible (although still wildly speculative and improbable) than a "charisma-hit". Yuschenko is an extremely ambitious and fatalistic man. If his advisors gave him a toxin that would scarrify him and maybe cause cancer twenty years from now, but would ensure his election, I think he would take it.

One final question: is there any possible chance that this was accidental? Does this chemical sit in some sort of product that might have been mislabeled?

Permalink to Comment

10. Derek Lowe on December 17, 2004 1:03 PM writes...

No, I think we can rule out mislabeling. It's not all that easy to buy any of the dioxins in anything greater than mass-spec-standard size vials. They're not useful intermediates for anything else, being chemically quite unreactive. I'm sure that there are quantities sitting around in Superfund limbo, but none of them are articles of commerce. I have to admit that I haven't sourced any Russian or Ukrainian suppliers yet, though. . .

Permalink to Comment

11. D Rogers on December 17, 2004 2:52 PM writes...

While it may be a poor assasination device, in my judgement most of the environmental panic is spot-on: here on the Left Coast, eagles on Catalina island still can't reproduce without human help due to thin egg-shells from dioxin dumped into the ocean in the 1950's. Long-lasting, fat-soluble, unreactive, makes it a pretty nasty pest if it gets loose.

(For the same reason, I bet you'll be hearing a lot more on the PFOA issue in years to come.)

Permalink to Comment

12. Derek Lowe on December 17, 2004 4:05 PM writes...

It's quite true that you're better off not dumping the stuff into the environment. Like a lot of the chlorinated aromatics, dioxins are quite persistent and can accumulate to dangerous effect. Unlike the case of DDT, though, where you can argue that human health (via malaria prevention) has suffered from avoiding the compound, there's no argument to be made for dioxin.



That must have been quite a pile of it around Catalina Island, though. According to the ecological literature, bald eagles aren't all that sensitive to dioxin. (See here as well.)

Permalink to Comment

13. Mike on December 17, 2004 4:43 PM writes...

D Rogers, Derek,

The likely culprit in the decline of the bald eagle population on Catalina Island is in fact DDT, not dioxin.

Permalink to Comment

14. Tree on December 17, 2004 8:16 PM writes...

You are 100% right. Please also remeber what happened in Taiwan President election. Two things are similar.

Permalink to Comment

15. Jason McCullough on December 20, 2004 3:49 PM writes...

As accurate as I think your dioxion analysis is, the junk science guy is basically a paid industry plant.

Permalink to Comment

16. per on December 21, 2004 12:52 AM writes...

not sure about this at all.
Total absorbed dose of TCDD will have been 2-3 milligrammes, or a couple of grains of TCDD. Cyanide isn't that toxic

It took three months to get a diagnosis on this, because there is quite a bit of individual variation in susceptibility to chloracne, and the chloracne takes time to develop. It is entirely possible that vast amounts of TCDD were in Yuschenko's food, and that only a small amount was absorbed. What we do know is that he was very ill, initially with liver, pancreas and gut problems. If he had died at this stage, no-one would have suspected dioxin, since there was no chloracne.

And one last thing. TCDD is actually very difficult to detect, even at the ng/kg levels here. What you need is specialised extraction methods, and big GC/MS/MS analytical suites. A typical dioxin assay will cost you 1000-1500 dollars. It is only "easy to detect" if you know what you are looking for.

yours
per

Permalink to Comment

17. Open Mind on December 21, 2004 6:36 PM writes...

Let the witch hunts begin. Start a rumor that junkscience.com questioned evolution and the wackos come out in force here, stamping their little feet and name-calling. Try thinking for yourself- it's an amazing experience. Requires you to do some work, though.

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