From the October issue of my magazine:
The Monkeys (Don’t) Pause
The last two October From the Editor pages have been dominated by my 9.11 musings. I spent this year’s anniversary at home rather than the city, basically meditating and tending to my yard (puts me in mind of Candide, a little). While I believe it’s important that we hold onto the memory of that day, and try to keep snapshots of each of our worlds as they existed before and after, I understand that there’s also a strong impulse to move on to normalcy. That’s why I’d like to use this month’s column to write about another subject that’s important to me: monkeys on speed.
Researchers at Johns Hopkins recently had to retract the results of their hastily published experiments involving the effects of methylenedioxymethamphetamine (MDMA, a.k.a. ecstasy) on monkeys and baboons. The researchers found evidence of massive dopamine-linked neuron damage, leading to death or Parkinson’s syndrome-like symptoms in many of the subjects. Making a big splash in the War On Drugs, the lab published its results in Science magazine. Many teeth were gnashed as the media latched onto the story of how ecstasy use was going to leave our youth brain damaged, shaking with Parkinsonian tremors.
After all, the experiment–intended to measure the results of three “modest” doses of the drug–led to two of the 10 monkeys dying shortly after their second or third dose of the drug, and two others growing too sick to take the third dose. Six weeks later, dopamine levels in the surviving animals were still down 65%. The subjects, in short, were wrecked.
Faced with such chilling results, ecstasy advocates and some scientists pondered how the results could possibly mesh with real-world experience, given that we’ve yet to see an epidemic of this syndrome among hardcore ravers, casual users, or at my alma mater (see my Jan/Feb 2002 From the Editor column).
And that’s when the scientific method came into play. It turns out the researchers were unable to replicate their results in two subsequent experiments (oral dosage and IV), throwing their findings into question. An investigation revealed that the MDMA sample was mislabeled. Rather than injecting the monkeys with ecstasy, the scientists injected them with methamphetamine (a.k.a. speed). “Oops,” is right. The dosages employed, coupled with intravenous delivery, made the results a lot more explicable.
To its credit, the research team published a retraction of its findings. Still, the swiftness with which they reported their initial results has triggered a mini-firestorm about the political implications of the study (and, of course, its government financing). Why the results of the experiments were published before they could be replicated is certainly something to ponder. In fact, it all feels like a postscript (or prescript, given the location in the magazine) to this month’s Issue by Issue column by contributing editor Wayne Koberstein (Pharma Science Feels Outside Forces, pp. 32-36). Were the researchers more interested in science or anti-drug propaganda? It’s an issue that I fear we’re going to face more frequently in the future.
Another contributing editor, Derek Lowe, wondered about the practical aspects of this drug study on his blog:
I’m really taken aback to learn that they hadn’t looked at the original monkeys for MDMA levels before now. Getting blood samples from monkeys is no easy task, but why wait until there’s a problem to do the post-mortem brain levels? Those numbers really would have helped to shore up the original results–and would have immediately shown that there was a problem, long before the paper was even published. I don’t like to sound this way, but it’s true: in the drug industry, we consider pharmacokinetic data like this to be essential when interpreting an animal study.
My own objections to the results may be more observationally based. Now, perhaps these researchers didn’t have too much experience around recreational drug users, but it would seem to me that you could tell pretty easily whether a creature that so closely parallels human behavior was on ecstasy or on speed. It would probably be as easy as seeing if the monkeys were all touchy-feely or if they were jabbering around a mile-a-minute about their theory on how to square the circle.
Gil Roth
Editor