LSD and the Elephant

Humans are wonderful research subjects. They can think pretty well, and they can speak, too. Our ability to communicate clearly is probably our most prized asset in research, as it is the only way scientists can find out directly how their research participants are feeling.  For all the good that humans provide in research, however, researchers can only do so much. It would be unreasonably risky or unethical to perform certain experiments on our fellow humans. This is where animals come in.

In fact, animals are critical to many fields of scientific research.  Without animals, immunologists would not have been able to generate our flu vaccines, chemists would not be able to test any medications, surgeons would not know how to transplant or repair organs, and neurologists would be completely unaware of how to treat Parkinson’s disease.

Animal research has come under a lot of scrutiny over the years, especially in regard to how animals are presumed to be treated by scientists. But fortunately, through time and practice, scientists have embraced rules and regulations that aim to prevent unnecessary harm to animals. The animal experiment that I will describe below is shocking, but it demonstrates how an unethical (and to be frank, completely off-the-wall) animal experiment eventually led to a positive and permanent change in how animal research is conducted.

LSD and the Elephant: A True Story

Some animals, including elephants, exhibit a unique behavior during their mating season called “musth” (pronounced “must.”) Animal biologists characterize musth as a seemingly random episode of wild and erratic, rageful, and destructive behavior. Back in the 60s, a group of scientists wanted to investigate musth to determine how to stop it in captive Indian elephants. They argued that this behavior makes it hard to care for and conserve the species. This behavior, however, is unique to a certain set of animals, and there doesn’t seem to be a corresponding behavior in humans. So, humans were not the best model for studying it.  

To be able to study musth closely, they brought an elephant to their facility. They wanted to recreate the behavior in a controlled setting, on their own terms.  

As their research subject, they decided to use Tusko, a 14-year-old Indian elephant who lived at the Lincoln Park Zoo in Oklahoma City. In an attempt to induce a musth-like state in the elephant, the researchers chose to inject it with LSD. They hypothesized that LSD, because of its “well-known personality-disrupting” effects (as the paper described them), would be a great tool for inducing this wild, inexplicable behavior in Tusko.

When performing experiments with drugs in a new species, scientists find it very difficult to determine what dose to use. Different animals are of different sizes, weights, and densities; have different sized organs; and metabolize drugs at different rates. Therefore, scientists struggle to compare doses between species. Since elephants were not (and still are not) used for drug research, the researchers had no example to work off of. Consequently, they were left with only their best-educated guess.

These researchers knew they were entering risky territory because they understood that LSD is one of the most potent drugs known to exist.

In humans, 20-30 micrograms of LSD is enough to induce hallucinations. That’s only .02 – .03 milligrams or about .004 milligrams per kilogram of body weight).

Compare that to the 1000 milligrams, or 6 milligrams per kilogram, of aspirin you take to treat a headache.

About .1 – .2 milligrams or about .02 mg/kg) is enough to produce major mental disturbances that resemble psychosis and delirium in people. The authors argued animals require an even higher dose to induce similar disturbances in an elephant, so they chose to inject Tusko with 297 mg of LSD, or .1 mg/kg.

To summarize, this dose per kilogram is 25 times the dose needed to induce hallucinations in humans and five to ten times the dose needed to induce psychosis. In their paper, the researchers even acknowledged that this concentration of LSD in the human body would definitely cause an overdose. But based on previous research with other animals, they hypothesized that the elephant would be less sensitive to the drug.

As you may have guessed, shortly after they injected the elephant, it keeled over and started seizing.  As any scientist in their right mind would predict, Tusko had overdosed on LSD.

In an attempt to counteract the overdose, the researchers quickly injected the animal with promazine, an antipsychotic drug. This stopped the seizures. But Tusko wasn’t recovering, so they injected him with pentobarbital, a common, short-acting barbiturate that’s used today to execute prisoners.

Sadly, despite their efforts to revive Tusko, the animal died.

Because Tusko was taken from a zoo, his death was noticed and reported widely in the news. Understandably, and rightly so, his death left many questions unanswered and ignited a debate that still rages on today about the ethical treatment of animals.

For instance, many argue that the researcher’s methods were not scientifically sound.

This experiment was fraught with unjustified protocols and major assumptions that would not pass muster today. First, the researchers should never have started with such a high dose of LSD. Today, when researchers are testing a new drug in a new species, they start with a low dose and work their way up. They monitor the animals closely until they either induce the effects they are looking for or until they find that they are causing undue harm. This minimizes the risk of accidental overdose. In contrast, by starting with a dose that would cause an overdose in a human, the researchers running the LSD experiment were taking a major, unnecessary risk with Tusko.

Next, these scientists may have not taken the best approach to treating the overdose. It’s hard to know for sure because the researchers did not explain their protocol all that well. The researchers did not explain why they used promazine, an experimental antipsychotic drug, and they did not even specify what dose of pentobarbital they used. When scientists are running experiments, they are supposed to write down everything they do so that future scientist not only can replicate their experiments but also so that if something goes wrong, they can avoid making the same mistake again.

Some observers had problems with Dr. Louis West, the leader of the project, and his resume.  A former employee of the Central Intelligence Agency, he was heavily involved in the highly controversial and illegal MK Ultra program during the Cold War, which tested whether LSD could be used for mind control. Given his lax attitude towards the drug, some question whether Dr. West should have even been allowed to conduct research with LSD at all.

Overall, this study was, at the very least, poorly executed. Some might argue that it should not have been performed at all. The scientists who ran this study committed grave ethical errors, including subjecting an animal to undue risk, not keeping comprehensive records, and performing the experiment despite a potential conflict of interest.

When this experiment was performed, LSD was not yet an extremely popular recreational drug — Timothy Leary would not have started promoting the use of LSD for another few years. At the time, LSD was used primarily to treat psychiatric disorders, and as a result, it was widely available to researchers.

However, after this experiment, and after the uprising of LSD culture in the late sixties, the United States government banned LSD and related drugs. They not only made it illegal to use the drug recreationally, but they also stopped scientists from researching these drugs. Between the 1960s and 2000s, absolutely no research on the use of psychedelic drugs was conducted in the United States.

Efforts to monitor and regulate animal research were just beginning around the time this experiment was performed.  But in 1963, a year after this experiment was run, a group of veterinarians published The Guide for the Care and Use of Laboratory Animals, which, now in its 8th edition, still guides all animal research in the US today. In addition, throughout the 60s and 70s, a series of news reports describing the maltreatment of animals by scientists led to the formation of Institutional Animal Care and Use Committees (IACUCs) in 1986. Today, there is an IACUC at every federally funded research institution in the United States, and each one keeps a close watch on the animal research that is happening at their institution. By rule, all IACUCs are composed of a combination of veterinarians, animal researchers, and community members. Care is taken to ensure that the members of the committee have no relationship with each other outside of the committee or any mutual research interests that could influence their decisions about what studies to approve.   

IACUCs take every action possible to minimize discomfort, pain, and stress in research animals. Additionally, scientists must justify to the IACUC the type and number of animals used for each study. If an experimental protocol does not meet the IACUC’s requirements for the safe and ethical treatment of animals, it will not take place at a research institution that receives public funding (which is most of them).

If IACUCs existed 1962, they likely would not have allowed Dr. West to perform his experiment the way he did because of the obvious risk this protocol would place on the animal’s health. The death of Tusko the elephant, along with his fellow animal subjects, left a permanent scar on the animal research world and continues to influence IACUCs’ decisions today.

You can read the original, fascinating article describing the LSD experiment here (starting on the bottom half of the second page).