“Penicillin is toxic in guinea pigs but not to humans”

““Had they chosen to test penicillin on hamsters or guinea pigs, it is likely that it would have been discarded”

Taken on face value the statements above are true – penicillin is toxic to guinea pigs (1). The trouble comes when this is used as evidence that humans and animals do not have the same reactions to medicines

The short answer is that penicillin reacts similarly in humans as it does in almost every mammal – it fights bacterial infection inside the body. This is why penicillin is widely used in veterinary medicine. Indeed the discovery of the medical uses of penicillin depended on research on mice. Guinea pigs are one of the few species which have a significant adverse reaction to the drug, and activists have picked on it to suggest that animal research doesn’t work. This is wrong. Our understanding of animals helps us both understand why penicillin is dangerous to guinea pigs, and why we would not test penicillin on them to assess human safety.

The reasons why guinea pigs differ in their reactions from most other mammalian species are very specific. Unlike most other mammals (including humans), the intestinal flora of Guinea Pigs consists of mostly gram-positive bacteria. Overgrowth of Gram-negative bacteria such as coliforms and Gram-positive clostridial organisms such as C. difficile can result in diarrhoea and death (2). Antibiotics which strongly affect Gram-positive bacteria, such as penicillin, are therefore toxic to guinea pigs (3). Further studies have shown a number of antibiotics which, while relatively non-toxic in humans, mice, rats, rabbits and other laboratory animals, remain highly toxic for guinea pigs and hamsters, both of which have predominantly gram-positive intestinal flora bacteria (4).

It is important to note that while humans are less sensitive to antibiotic toxicity than guinea-pigs, C. difficile associated colitis following antibiotic treatment is a serious problem in clinical practice that hospitals need to be aware of and take measures to prevent.

The fundamental point is that toxicity test subjects are not randomly selected. Our understanding of guinea pigs (developed through prior animal research) means we know that they make a bad test subject for antibiotics. Species selection is important in toxicology – pharmaceuticals have no interest trying to move “bad” drugs into clinical trials as it is dangerous and costly to do so. They pick the animal models which will be expected to replicate human reactions most closely for any given chemical. It is also standard practise to test in multiple species to improve the accuracy of predicting human toxicity from animal models.

In reality, Penicillin is a good example of showing the similarity of humans and most animals. Penicillin is given to a wide range of animal species including cats, dogs, horses, poultry, sheep, cattle, pigs, and many more. Indeed, mice were key to the discovery of penicillin. After Fleming’s discovery of penicillin in 1928, the compound was not used as scientists were not aware of its potential to fight infection inside the body. The effectiveness of penicillin was found by Florey and Chain (who shared the Nobel Prize with Fleming) from a simple mouse safety test:

By 25 May 1940, the team had reached a point where they could carry out a new experiment that would test whether penicillin could be an important antibacterial drug. Eight mice were given lethal doses of streptococci. Four of the mice were then given injections of penicillin. By the next morning all the untreated mice were dead while those that had received penicillin survived for days to weeks.

With this result, Florey realised that he needed to expand production – an effective treatment for infection could be a valuable contribution to Britain’s war effort.

To return to the original question – penicillin may be toxic to guinea pigs and beneficial to humans, but scientists would not test penicillin in a guinea pig because they could predict beforehand that it would not be an accurate animal model to use. Moreover, penicillin has the same beneficial effect in most mammals as it does in humans, reinforcing the biological similarities across species that make animal research an important part of medical science.

Speaking of Research

(1) Hauduroy, P., and Rosset, W.. Ann Int Pasteur., 75, 67 (1948)

(2) Heidi Hoefer DVM, ABVP, Common Problems in Guinea Pigs (Atlantic Coast Veterinary Conference 2001)

(3) Farrar, E., Kent, T., and Elliott, V., Lethal Gram-Negative Bacterial Superinfection in Guinea Pigs given Bacitracin in Journal of Bacteriology, 92 (2), 1996

(4) Green, R., The Association of Viral Activation with Penicillin Toxicity in Guinea Pigs and Hamsters, in Yale Journal of Biology and Medicine, 3 166-181, 1974

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