Humans are wonderful research subjects. They can think pretty well, and they can speak, too. Our ability to speak is probably our most prized asset in research, as it is the only way researchers can find out directly how their research subjects are feeling. However, for all the good that humans provide in research, researchers can only do so much with their brethren, as it would be unreasonably risky or unethical to perform certain experiments on their fellow humans. This is where animals come in.
In fact, animals are critical to many fields of scientific research. Without animals, immunologists would not been able to generate our flu vaccines, chemists would not be able to design any medications, surgeons would not know how to transplant 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 over how animals are thought to be treated by scientists. However, through time and practice, scientists have embraced rules and regulations that aim to prevent 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 mating season called “musth” (pronounced “must”). Musth is characterized by a seemingly random episode of wild and erratic, rageful and destructive behavior. Musth is unique to a certain set of animals, and there doesn’t seem to be a corresponding behavior in humans. 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 therefore conserve, the species.
To study musth more closely, they wanted to recreate it in a controlled setting, on their own terms.
They used Tusko, a 14 year old Indian elephant who lived at the Lincoln Park Zoo in Oklahoma City as their subject. 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, would be a great tool for inducing this wild, inexplicable behavior in Tusko.
When performing experiments with drugs in a new species, it is very difficult to determine what dose to use. Different animals are different sizes, weights, and densities, have different sized organs, and metabolize drugs at different rates. Therefore, it is not easy to compare doses between species. Since elephants were not (and still are not) used for drug research, the authors had no example to work off of. Therefore, they were left with only their best educated guess to rely on.
LSD is one of the most potent drugs known to exist. In humans, 20-30 micrograms (.02 – .3 milligrams or about .004 milligrams per kilogram of body weight) of LSD is enough to induce hallucinations. About 100-200 micrograms (.1 – .2 milligrams or about .02 mg/kg) is enough to produce major mental disturbances that resemble psychosis and delirium. The authors argued animals require an even higher dose to induce similar disturbances, so they chose to inject Tusko with 297 mg of LSD, or .1 mg/kg. To summarize, this dose per kilogram is 50 times the dose needed to induce mental disturbances in humans. The authors 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. Tusko had overdosed on LSD.
In 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.
Despite these efforts, sadly, Tusko died.
Since Tusko was taken from a zoo, his death was noticed and reported widely in the news (you can read one of the original articles here). 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. 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 until they either induce the effects they are looking for or until they find that they are causing undue harm to the animal. This minimizes the risk of accidental overdose. By starting with a dose that would cause an overdose in a humans, the researchers were taking a major risk with Tusko.
Next, these scientists may have not taken the best approach to treating the overdose, although it is difficult to assess the validity of their protocol, because they did not explain it all that well.
This brings up another important point: the need to record every detail of an experiment. These scientists 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 figure out exactly what went wrong.
Others 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 with the highly controversial and illegal studies conducted during the Cold War that tested whether LSD could be used for mind control. Given his controversial 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, and at most, should not have been performed. 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, not only for recreational use, but from research as well. Between the 1960s and 2000s, absolutely no LSD research was conducted in the United States.
This story of Tusko the elephant is extremely upsetting, but at least we can rest assured that this study would never be performed today.
Efforts to monitor and regulate animal research were just beginning around the time this experiment was performed, and Dr. West was virtually free to perform any experiments that he wanted to. In 1963, a year after this experiment was done, a group of veterinarians published The Guide for the Care and Use of Laboratory Animals, which, now in its 8th edition, is still followed 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 used for each study. If an experimental protocol does not meet the IACUC’s requirements for the safe and ethical treatment of animals, it is not happen. Period.
If an IACUC was around in 1962, they would not have allowed Dr. West to inject Tusko with LSD because of the imminent harm in which he placed the animal. 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 about the LSD experiment here: http://www.psych.ufl.edu/~steh/PSB3002/LSDelephant.pdf
Ben Marcus is a recent graduate of the University of Chicago, where he received his Ph.D. in neurobiology. He is a co-editor of the ISC blog and a moderator of Ask A Scientist. You can follow Ben on Twitter @bmarcus128.