Retrospectacle: A Neuroscience Blog

[I'm starting a new series here at Retrospectacle, called 'Science Vault,' of which this post is the first. Pretty much I'm just going to dig back into the forgotten and moldering annuls of scientific publications to find weird and interesting papers that very likely would never be published today (and perhaps never should have.) I'll probably try to do it once a week (and if you have suggestions, please do email me with them.)]

i-b48f6e3f64d96d02defff9c5374e10c4-lsd_death_elephant1_sm.jpg Most of you read the title and thought I was kidding, right? I mean, who in their right mind would give a huge dose of a psychotropic substance to an elephant, just to see what happened? Well, the year was 1962, and someone did just that. And, as icing on the cake, they got a Science paper out of it.

The history of LSD is a fascinating one, but rather lengthy so I’ll just brush over a few points for context. Before the 1960s, lysergic acid diethylamide (LSD) was seen as a compound which had promise as a therapeutic agent, specifically in psychiatric therapy. Until 1966, the lab which originally invented LSD (Sandoz Labs) provided LSD for free to interested researchers. The US military became quite interested in LSD during the Cold War as an aid in interrogation, and the CIA conducted many tests with LSD (now destroyed) before moving on to other drugs. Widespread abuse of LSD eventually led to the US government to ban it for recreational and medical uses in 1967, despite very positive results from ‘LSD psychotherapy.’

However, when this paper was published in 1963, the LSD still flowed to researchers. The three authors were from the University of Oklahoma, one of which (Louis West) was a CIA collaborator. The proposed point of the experiment was to determine whether an injection of LSD would induce “musth,” a mysterious pachydermian state where elephants become violent which lasts about 2 weeks. Elephants have been known to kill their handlers when in “musth.”

(Continued below the fold…..)

The authors saw this unique temporary madness as an opportunity for research. During musth, elephants release a sticky brown substance from a gland near their temples. No one really knew what it was, and whether there was an internal correlate which triggered musth somehow. The authors wanted to try to induce musth artificially, and theorized that the mystery musth-substance may be chemically similar to LSD. Specifically they decided to introduce to an elephant (not in musth) a “behavioral aberration that might resemble the phenomenon of going on musth.” That ‘aberration’ would be a huge dose of acid. They would then observe if the temporal glands began producing the brown substance, and collect it.

Now, to me, this seems a stretch to connect the dots “LSD produces changes in psychological state in humans” and “LSD induces violent and uncontrollable behavioral state in elephants.” But, I mean, it seems silly to pick out one incongruity in a paper full of them, so on we march.

The Experiment

The subject was a 14-year-old male Indian elephant named Tusko being housed at the Lincoln Park Zoo. As previous research had suggested that high doses to LSD were needed to get perceivable effects in “lower animals,” they decided to start with a 0.1 mg/kg dose of LSD for Tusko. That came to about 297 milligrams (in 5 mL of water, injected intramuscularly) of LSD for 7000 pound Tusko. The injection was delivered via a pressurized CO2 dart gun. For comparison, the threshold dosage for an effect in people is around 20-30 micrograms and a recreational 3+ hour dose would be around 100-200 micrograms.

After injection:

“Tusko began trumpeting and rushing around the pen, a reaction not unlike the one he had shown the day before (during the placebo shot). However, this time his restlessness appeared to increase for 3 minutes after the injection; then he stopped running and showed signs of marked incoordination. He began to sway, his hindquarters buckled, and it became increasingly difficult for him to maintain himself upright. Five minutes after the injection he trumpeted, collapsed, fell heavily on his right side, defecated, and went into status epilepticus.”

The researchers were understandable quite surprised and distressed by the elephants seriously bad reaction to the LSD (they theorized that elephants were actually quite resistant to psychotropic substances). They tried to alleviate the seizures by administering promazine hydrochloride (Thorazine, 2800 mg!), which had a modest effect in reducing the spasms but did nothing for Tusko’s overall state. A last ditch effort to save the animal by injection of pentobarbitol sodium was also unsuccessful, and Tusko died 1 hour and 40 minutes after the LSD dose.

Necropsy illuminated the cause of death as strangulation secondary to laryngeal spasms. The authors were really just grasping at straws as to *why* the elephant died, and so quickly, and tossed out theories from “autosensitization” (because Tusko had been in musth before, and if LSD was similar to whatever made the elephants go crazy…..) to accidental intravenous injection (unlikely in a muscle). They also deigned it appropriate to wax moral and suggest what to do in a human overdose:

“Despite efforts by its manufacturer to prevent misuse of the drug, LSD has been increasingly and sometimes irresponsibly administered to humans as a putative adjunct to psychotherapy. The possibility of suicide or even homicide by LSD cannot be ignored. Treatment of an individual in extremis from LSD poisoning would be symptomatic but a possible emergency requirement for anticonvulsant medication, and for a muscle relaxant such as succinylcholine, is suggested from the results of this single experiment.”

The Controversy

Well, it doesn’t seem reasonable to me to extrapolate anything about human reactions to LSD (or really, anything of scientific merit) from this ‘experiment.’ Unsurprisingly, a controversy appeared shortly after the paper was published, questioning whether it was actually the LSD that was lethal, rather than the high doses of Thorazine and pentobarbitol. Also, why would the researchers attempt to give the elephant so high a dose of a substance that they had no idea what effect it would have? Wouldn’t the prudent thing to do be to give a small dose, and give more later, if necessary? As Erowid points out:

If a human model had been used to determine the dose of LSD for the elephant, the dose would be in the neighborhood of 0.003 mg/kg. For a 60 – 100kg human, doses of .2mg (200 micrograms) is enough to cause substantial clinical effects. Based on this, the calculated dose for an elephant of Tusko’s size (3000 kg) would be about 9mg of LSD. West et al.’s choice to inject Tusko with 297mg was more than 30 times the effective oral dose for a human of Tusko’s weight. If the dosage had been chosen by metabolic rate, the amount would have been around 3.9mg and if based on brain size (elephants have brains about 3 times the size of human brains) only .64 mg. (Schmidt-Nielsen, 1972) Interspecies scaling of dosages can be extremely complicated and variations in enzymes and metabolism can completely invalidate any type of calculated scaling.

Another strange detail is the use of a valuable zoo animal (which had a mate who was in the pen at the time) for a dangerous chemical experiment–an animal which the authors themselves tout as intelligent and social. This certainly makes me quite glad to be in science during a time where much, much more care and justification is required to undertake risky (or even not risky) animal experimentation.

Reference:
West LJ, Pierce CM, Thomas WD. (1962). Lysergic acid diethylamide: Its effects on a male Asiatic elephant. Science, 138, 1100-1102. PDF

Comments

#1 coturnix
May 30, 2007

Wow! Just wow! No comment. I guess they were high on something themselves and tried to put it in decent English later to get a pub out of their crazy adventure.
#2 Dunc
May 30, 2007

Jesus! As someone with some familiarity with the effects of LSD, the idea of giving that big a dose to an elephant strikes me as (a) unbelievably stupid, and (b) plain cruel.

I’m guessing that none of the researchers involved had ever taken LSD themselves. Although if they had, and designed this “experiment” whilst under the influence, that might explain a thing or two…
#3 vika
May 30, 2007

Fascinating and fun stuff, thanks for this article. One thing I have to ask, though. You write:

Widespread abuse of LSD eventually led to the US government to ban it for recreational and medical uses

Could you provide a reference or two regarding this widespread abuse? Everything I know about the war on drugs is politically motivated, from banning opium and marijuana earlier in the 20th century to LSD in the 1960s. I was under the impression that LSD was restricted and then banned because of counterculture’s clashes with the US government, personified (sort of) in Timothy Leary’s clashes with Harvard University, where he worked.

More on the elephant can be found at Erowid.
#4 vika
May 30, 2007

Whoops, I totally missed your Erowid link. Apologies.
#5 Boosterz
May 30, 2007

Here’s a vid of the british trying LSD out on their soldiers
http://youtube.com/watch?v=61Vo46zlc0U
#6 Thony C.
May 30, 2007

This is just so fucking stupid as to be completely and utterly unbelievable and as Dunc says extremely cruel. The people who did this just give science a bad name.

Vika widespread abuse simple means that a hell of a lot of LSD found its way out of Sandoz and into the hands of experimental friendly freaks such as Ken Kesey and Robert Hunter just to name two of many and the government of the good old USA was not at all amused at what they did with their new found sweeties!
#7 vika
May 30, 2007

Thony, I know the general definition of abuse, and there’s gotta be more to it than fall into the hands of artists. Kesey participated in a CIA-funded study of many drugs, which served as inspiration for One Flew over the Cuckoo’s Nest. His arrests seem (according to wikipedia) to only be related to marijuana possession, nothing about LSD.

Hunter was another subject in the same CIA-sponsored study, along with Kesey, and his experimentation resulted in music. I can’t find any information involving Hunter and LSD and evil afoot in the world.

I ask again: where’s the substantiation for this widespread abuse? What, in the eyes of the federal government, qualified as sufficient abuse to outlaw a substance?
#8 Shelley
May 30, 2007

Well, my expertise is in science not drug policy. That said, the abuse I was referring to wasn’t just ‘recreational’ (obviously that continued after the ban, see here http://en.wikipedia.org/wiki/Lsd#_note-36). The US government (and others, apparently England was one) was performing human studies, often without informed consent. There was also some concern about its use in psychotherapy, although that was probably unwarranted. But yes, I agree that the ban on lsd was probably more political than scientific. Although thats a bit off topic.
#9 Harry
May 30, 2007

After taking LSD and getting high, the scientists got the idea to share the joy they got and give it to one of mother nature’s creatures.
#10 Crudely Wrott
May 30, 2007

Yeah, what Dunc said. This cruelty is the result of ignorance. Obviously the experimenters had no knowledge of either the effects of LSD or a reasonably clinical protocol for giving large animals drugs that were prima facie mysterious and poorly understood.

Vika, I would suggest that the free availability of such a substance was the cause of “widespread abuse” which might be roughly defined as “what happens when a sufficiently large number of knuckleheads start screwing around with stuff they know next to nothing about”. That is, they start to attract attention.

For a while there in mid-twentieth-century anyone who had an interest in the workings of the brain or mind wase fascinated by the idea of a drug that, uh, that is, of a miracle potion that could unleash . . . you know the Cosmic Consciousness and all; that is, um, it’s remarkable ability to lay bare the innermost and fundamental elements of perception, and um, and to force a new paradigm that touches the deepest . . . Ahh, shit. See what I mean?

No one understood it. Even those who chose it as their breakfast of champions. No one could define the affects of this molecule but that didn’t stop anyone from trying.

Given the lack of regulation, free, or nearly free, availability and the state of neurology and the model of the brain then extant, anybody and their brothers could, and did, conduct experiments at all levels of sophistication and/or legitimacy. Results ranged from funny and fascinating to foolish and frightening. I leave it to you to imagine what kind of results got air time on the evening news.

In the interest of full disclosure the only two times I ever took a known hallucinogen was the first time and the last time. Those times in between must have been someone else’s hullabalution.
#11 Alex Boese
May 30, 2007

I saw this article linked to on Reddit, so I thought I should take the opportunity to shamelessly plug my book, Elephants on Acid: And Other Bizarre Experiments, which will be coming out this November. The title refers to the 1962 experiment.

Some other interesting details about the experiment:

Newspaper accounts of the experiment published the day after it quoted the experimenters as saying that they themselves had taken LSD the day before they gave it to the elephant. So the elephant may not have been the only one on acid.

There was a rock band called Tusko Fatale, which named itself after the experiment.

The experiment was probably dreamed up by Warren Thomas, director of the Oklahoma City Zoo. In his experience working with elephants in Africa, he had found them to be highly resistant to the effects of drugs, which is why the researchers decided to give such a high dose of LSD.

Thomas later proposed using LSD as a way to cull the elephant population in Africa.

In 1982 Ronald Siegel of UCLA gave elephants LSD without killing them, proving that LSD at lesser doses is not toxic to elephants.
#12 Thony C.
May 30, 2007

Vika wrote:

What, in the eyes of the federal government, qualified as sufficient abuse to outlaw a substance?

People having fun! People having uncontrolled fun!
#13 yessir
May 30, 2007

You are beautiful!
#14 Ed Yong
May 30, 2007

After reading the headline, I was going to make a pink elephant joke, but there’s really nothing funny about this.

On the positive side, I love this idea for a series. Sort of a retro IgNobel awards. Nice one.
#15 thaumaturge
May 31, 2007

Neat. Terrible experimental design, though, and completely uninformative results. Too bad they wasted a perfectly good elephant.
#16 Nadia
May 31, 2007

“They tried to alleviate the seizures by administering promazine hydrochloride (Thorazine, 2800 mg!), which had a modest effect in reducing the spasms but did nothing for Tusko’s overall state. A last ditch effort to save the animal by injection of pentobarbitol sodium was also unsuccessful, and Tusko died 1 hour and 40 minutes after the LSD dose.”

Could be that he died not because of LSD but because of other stuff they injected.
#17 Ron Roizen
June 13, 2007

L.J. “Jolly” West also examined Jack Ruby, Lee Harvey Oswald’s killer, and testified on behalf of Patty Hearst (see http://www.icsahome.com/infoserv_profile/west_louis.asp). He also was one of three co-authors of a bitter attack on Mark and Linda Sobell’s research on behaviorist approaches to alcoholism treatment (see my http://www.roizen.com/ron/cont-dri.htm). He didn’t mind packing LSD into a pachyderm but objected vigorously to the notion that alcoholics should be exposed to alcohol.

Ron Roizen
Wallace, Idaho
#18 Chris
July 1, 2007

Wow, that was pretty stupid. At least people aren’t splicing human and primate testicles… oh wait…
#19 Cowicide
July 10, 2007

FYI, You are only a few clicks away from a Boingboing.net post here:
http://www.boingboing.net/2007/07/10/alpha_the_robot_meet.html

Which will take you here:
http://www.ectomo.com/?p=193

Then scroll down that article and the elephant link will take you here:
http://www.ectomo.com/?p=122

…and waa-la, your link is there… stank on ya…
#20 biased
August 20, 2007

What was the brown stuff coming from his the elephant?
#21 Connie
August 25, 2007

wow thats incredibly sad. its unfortunate that they didnt have their facts straight. i mean they killed an animal for an experiment. thats just horrible. its makes me even more sad that his mate was in the same area when he was meeting his end.
#22 Carlos
October 10, 2007

I ask again: where’s the substantiation for this widespread abuse? What, in the eyes of the federal government, qualified as sufficient abuse to outlaw a substance?

You may never find it. Sometimes humans will, given, say a rash of dumb kids ODing on street versions of this shit and ending up in hospitals, just get to a phone and convince someone upstairs to ban it before somebody dies.

That may rub many people the wrong way who feel the need to create fun out of interfering with their neurotransmitters. Fortunately, we don’t usually make policy by asking such types what we should do (but then the downside is then usually we have to spend endless hours slowly and patiently explaining our actions to them)

Out of 15 people I knew who took LSD, one committed suicide, another died in prison. None did particularly well with their lives. I won’t argue statistical significance from so small a sample, but I sure wish my friends were still alive.
#23 Sven DiMilo
October 12, 2007

Ah, the Tale of Tusko. Many learned of this from a classic gem of comparative physiology, Knut Schmidt-Nielsen’s How Animals Work, which uses it as a cautionary tale about the complications of scaling by body mass (i.e. the “elephantine fallacy” of the dosage calculations, originally pointed out in a follow-up letter to Science. (Publishing in Science was kind of diferent back then!))
As for the senior author, “Jolly” West, a very interesting and controversial character, he went on to become the founding Director of UCLA’s Neuropsychiatric Institute. Their main lecture hall is named for him.
#24 herbert browne
October 17, 2007

Yo, Carlos: it may be more than simply “having fun” that moves people to pursue the only available “Last Frontier”- ie the place inside our minds- by various means; and, of the dozens of dozens of people that were taking acid in the edgy 60s in my neighborhood, there were no suicides that were traceable to an LSD-induced experience [although, with most suicides (& I speak from conjecture, here) there's most likely a cumulative cause to the action].
I took 17 “street hits” once (250 mikes)- plus whatever I ingested incidental to capping up 300 hits from 75 mg of liquid (hard to say). My friend & I were putting up #1 caps with milk sugar (1966), and got the bright idea that such a tiny amount of liquid might be absorbed by the capsule, itself. (This wasn’t nice, blue pharma acid- it was made by a young chemist in Palm Desert, who was Not Owsley Stanley.) We made up about 30-some of these when we noticed that the very first ones were slowly shriveling up & turning a rusty color… not particularly salable, like that. So at the end of the session we split them up- and I took all mine at once (see… I was already “feeling it”)- and drove home, across the Bay Bridge. Other than having that venerable structure turn into an iron dragon which breathed me into downtown SF in a ball of varicolored fire, my Hillman Minx & I made it back to my apartment and I was just ripped for… I don’t know- the next 6 or 7 years… ^..^
#25 Brian
January 2, 2008

Other than having that venerable structure turn into an iron dragon which breathed me into downtown SF in a ball of varicolored fire,

I don’t know why, but I absolutely love this turn of phrase.
#26 Carol
January 2, 2008

Every time I read about something on par with this, I feel propelled to advocate for the rights of animals. I had a sick feeling about this before I started, and, yup, I do now feel like I ran up to look at somebody else’s destruction.
#27 syma
January 5, 2008

Thanks…
#28 muhabbet
February 23, 2008

On the positive side, I love this idea for a series. Sort of a retro IgNobel awards. Nice one.
#29 symonds
July 21, 2008

Very nice to read to this blog. I gathered lot of information. Save elephant.

———
symonds

Addiction Recovery Oklahoma
#30 film izle
September 25, 2008

What was the brown stuff coming from his the elephant?
#31 Buster Love
February 21, 2012

I think that the idea of giving that big a dose to an elephant strikes me as (a) unbelievably stupid, and (b) plain cruel.

I’m guessing that none of the researchers involved had ever taken LSD themselves. Although if they had, and designed this “experiment” whilst under the influence, that might explain a thing or two…