Many helminths (parasitic worms) of clinical and commercial importance are nematodes (roundworms). They parasitize humans and other mammals, so it is hardly surprising that candidate anthelmintic drugs are usually tested in small laboratory mammals.
Scientists at the Janssen company in Belgium, however, “screened” compounds for their potential anthelmintic activity against worms in chickens (Raeymaekers et al. 1966). They found a chemical compound (thiazothienol) that was active against the worms, but when they put it into worm-infected rats and mice, it was inactive.
Because roundworms of mammals were the primary target, the investigators might have been expected to ignore this lead. Instead, they performed experiments that showed that the feces of the treated chickens contained a substance that was active against worms in rats and mice.
Interestingly, it was not the original substance but was instead its metabolic product! That excreted substance (thiazothielite) was chemically modified to improve its efficacy and was developed as the veterinary drug tetramisole. The levo-isomer of tetramisole, named levamisole, was later found to have an improved safety margin, and was developed into an enormously successful anthelmintic agent for use in livestock and, to a lesser extent, in humans.
Here we have the “happy accident” so characteristic of serendipity. The compound that led to the discovery of levamisole was not synthesized by the scientists; it was synthesized by the chickens! That result was totally unexpected.
It was the scientists, however, who had the insight to recognize, from the “failed” rodent tests, that the secret to the previously observed anthelmintic efficacy lay not in what went into the chickens but in what came out! From this insight, an important drug was developed.
Obviously, the lesson to be drawn from this episode is not that we should deliberately select the wrong animal model. If there is a lesson to be learned, surely it is two-fold: we should be ever alert to the unexpected, and there is no such thing as a “failed” experiment.
Scientists at the Janssen company in Belgium, however, “screened” compounds for their potential anthelmintic activity against worms in chickens (Raeymaekers et al. 1966). They found a chemical compound (thiazothienol) that was active against the worms, but when they put it into worm-infected rats and mice, it was inactive.
Because roundworms of mammals were the primary target, the investigators might have been expected to ignore this lead. Instead, they performed experiments that showed that the feces of the treated chickens contained a substance that was active against worms in rats and mice.
Interestingly, it was not the original substance but was instead its metabolic product! That excreted substance (thiazothielite) was chemically modified to improve its efficacy and was developed as the veterinary drug tetramisole. The levo-isomer of tetramisole, named levamisole, was later found to have an improved safety margin, and was developed into an enormously successful anthelmintic agent for use in livestock and, to a lesser extent, in humans.
Here we have the “happy accident” so characteristic of serendipity. The compound that led to the discovery of levamisole was not synthesized by the scientists; it was synthesized by the chickens! That result was totally unexpected.
It was the scientists, however, who had the insight to recognize, from the “failed” rodent tests, that the secret to the previously observed anthelmintic efficacy lay not in what went into the chickens but in what came out! From this insight, an important drug was developed.
Obviously, the lesson to be drawn from this episode is not that we should deliberately select the wrong animal model. If there is a lesson to be learned, surely it is two-fold: we should be ever alert to the unexpected, and there is no such thing as a “failed” experiment.
Posts
