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

“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.

Guinea Pig in Laboratory

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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4 responses to “Myth Busting: “Penicillin is toxic in guinea pigs but not to humans”

  1. Just because penicillin was tested on mice does not mean that without testing on mice its efficacy would not have been known. The researchers at the time could have given the penicillin to any human or animal that just happened to have a streptococci infection. As the same knowledge would been produced, so testing on mice was not necessary.

    • Well Penicillin was discovered in 1928 (by Fleming; no animals involved). It then remained almost completely unused (a handful of examples of it used externally to treat eye infections). It wasn’t for a whole decade, until animal tests were run on it, that it was refined and came into proper use.

      You will note that we don’t give random substances to people to see what effects it has.

  2. The Speaking of Research “Animal Rights Myths” page has some additional information that addresses some of the other claims that animal rights activists make about penicillin.

    https://speakingofresearch.com/extremism-undone/bad-science/#1
    The various claims made about penicillin are a good illustration of favorite AR tactics, the half truth and misrepresentation. One claim made by Ray Greek in his book Specious Science is that Alexander Fleming, who discovered Penicillin in 1928, was dissuaded from following up on his discovery because of misleading results from tests in mice and rabbits which convinced him that the antibiotic was too unstable to be used internally.

    The Animal Research Info website has an explanation of the role of animal testing in the discovery of penicillin that sheds some light on this claim:

    “The story of Sir Alexander Fleming’s discovery of penicillin is well known. In 1929 he discovered a mould growing on a glass dish in his laboratory which appeared to kill the bacteria he was cultivating. In his follow-up studies, the crude penicillin broth that he had extracted from the mould was non-toxic to rabbits and mice.1 But it rapidly disappeared from their blood, and it seemed to work very slowly in the test tube.

    These results led Fleming to believe that penicillin would only be useful as an antiseptic for surface infections rather than as a powerful antibiotic for general infections. After this, little came of his discovery, although a few patients with eye infections were successfully treated by the application of impure extracts of penicillin broth in the 1930s.

    The enormous death toll from septic infections led to a great interest in developing antibiotics at the beginning of the 1940s. One of the substances tested by researchers was Fleming’s crude penicillin broth.

    Howard Florey and Ernst Chain, searching for potential antibiotics at Oxford University in 1940, used the mouse protection test. This animal test was first described in 1911 and was in routine use from 1927. In the test, Florey and Chain injected eight mice with a lethal suspension of bacteria, and four of these were also given penicillin.2 The four mice which received penicillin lived and all the rest died, giving definite proof that penicillin worked as an antibiotic against serious bacterial infections. It was this test which set Florey, Chain, Heatley and others on the long road to purifying and mass producing penicillin.

    In 1945, Alexander Fleming, Ernst Chain and Howard Florey received the Nobel Prize for the discovery and development of penicillin.

    References

    1. Fleming A (1929) Brit J Exper Path 10, 226

    2. Florey H (1953) Conquest 41, 4”

    The truth is that while the early forms of Penicillin were unstable in mice and rabbits they were also very unstable in humans, and Fleming was unable to produce enough Penicillin to overcome this instability and achieve a high enough concentration of the antibiotic in the blood of animals to evaluate its ability to prevent or cure infection. The instability of Penicillin was itself a major block to its production in useful quantities as most was lost during isolation procedures.

    The genius of Howard Florey, Ernst Chain and Norman Heatley was in their successful development of culture and purification techniques that allowed them to produce enough penicillin to conduct the protection tests in mice, and when these were successful to refine their production further in order to produce the larger amounts required for human trials. Even then the instability of Penicillin proved a problem, their first patient died when the antibiotic ran out before the infection was cured. It was not until after WWII that more stable verisons of Penicillin were developed, such as Penicillin G that is administered by injection when high doses are required, and Penicillin V which can be taken orally.

    You can find out much more about the work leading to the introduction of Penicillin at the Nobel Foundation.

    Another story repeated by anti-vivisectionists including Ray Greek is that of Florey’s cat. In 1942 during the early trails of penicillin friend of Fleming was dying of streptococcal meningitis and Fleming wished to treat her by spinal injection of penicillin, so he asked Florey about it. Florey injected a cat via the spinal canal with Penicillin and the cat died, whereas Fleming’s friend made a complete recovery after the same treatment.

    What this story misses out is the bigger picture. Penicillin is a neurotoxin, and is never administered directly by spinal injection because of the risk of serious damage to the nervous system (1). Even very high doses administered intravenously can cause damage to the brain and nervous system (2). In short Fleming’s friend was very, very lucky to both recover from her infection and avoid serious brain damage.

    The fact is that Penicillin is used to treat cats by veterinarians. See more: http://www.petmd.com/pet-medication/penicillin#.UbWrRZyeYcs

    1) Walker AE, Johnson HC, Kollros JJ “Penicillin convulsions: The convulsive effects of penicillin applied to the cerebral cortex of monkey and man” (1945) Surg Gynec Obstet 81:692-701.

    2) Raichle ME, Kutt H, Louis S, McDowell F. “Neurotoxicity of intravenously administered Penicillin G”(1971) Arch Neurol, 25:232-239

  3. Guinea Pigs and Vitamin C research is something to look into.