Elephant Dose: When Drug Scaling Defies Intuition

Elephant Dose: When Drug Scaling Defies Intuition

If you’ve ever assumed that drug dosages scale proportionally with body mass, you’re not alone. I thought so, too — until I read Scale by Geoffrey West. The book includes the tragic story of an elephant named Tusko, illustrating how wrong this assumption can be.

Here is what happened. In the 1960s, researchers from the University of Oklahoma studied aggressive behavior in Asian elephants. They believed that this aggression might be linked to LSD naturally produced in the elephant’s brain. To test their theory, they selected an elephant named Tusko from the Oklahoma City Zoo and injected him with a hefty dose of LSD.

The experiment went tragically wrong. Shortly after the injection, Tusko collapsed, became epileptic, and died 1.5 hours later.

I’ll leave aside the ethical implications of this experiment. Instead, let’s focus on why the dose was miscalculated.

At the time, it was known that the typical dose for a cat (were there any animals they didn’t try?) was 0.1 milligrams per kilogram of body mass. Thus, for a cat weighing 4 kilograms, the dosage would be 4 times 0.1 = 0.4 milligrams. Based on this, scientists concluded that an elephant with a mass of 3000 kg could be given 3000 times 0.1 = 300 milligrams of LSD. This conclusion initially sounded reasonable to me — however, 300 mg killed Tusko.

It turns out that drug scaling is a very complex problem. In general, there is no linear relationship between dose and body mass. Instead, the appropriate dose depends on many factors, such as metabolism and which systems are involved in drug absorption. For instance, if specific cell membranes are responsible for drug absorption, the dosage should be proportional to the area of the membranes, not the body mass. In other words, the systems involved in drug absorption, unlike body mass, don’t scale with the volume of our bodies.

Whether Tusko died directly from the LSD or something else in the mix remains unclear source. This tragic example illustrates how non-intuitive scaling might be, especially in drug scaling. For example, this paper discusses that paracetamol dosage should be adjusted for obese children, as it might lead to a relative overdose.