EXAMPLE: Prior to the Serotonin-Selective-Reuptake-Inhibitors, used to treat mental disorders, all psychotropic medications were the result of chance observation in the clinic. Lithium came from studies looking for psychomimetic substances excreted in the urine of psychotic patients. The phenothiazines came from a search for better preanesthetic agents. The TCAs were the result of an unsuccessful attempt to improve on the antipsychotic effectiveness of phenothiazines. The monoamine oxidase inhibitors (MAOIs) came from a failed attempt to develop effective antitubercular medications. The first studies of benzodiazepines (anti-anxiety drugs) were unsuccessful attempts to treat patients with schizophrenia.

Other drugs called Zimelidine, the first SSRI-type antidepressant causing paralysis was withdrawn and delayed the release of Prozac in 1973, which itself is associated with severe side effects.PROZAC has an interesting story.

Many drug formulations are washed off due to animal experimentation and testing, the FDA selected the formulation that it judged safe because the difference between the pharmacological dose and the toxic dose was large enough to risk the drug on the market.

Based on experience, the correlation of animal data with human data is generally poor and cannot be predicted precisely. According to Dr Ralph Heywood, as one Scientific Executive of Huntingdon life Sciences, one of the largest laboratories engaged in animal drug testing, he estimated that:

Pharmacological and toxicological data vary among species. Animal-based studies will only prove that some drugs are toxic or not in the species tested. If the pharmacological dose to the toxic dose ratio is low, then the benefit to risk ratio is supposed to be low. In this case, regulators conclude that the drugs are likely to harm humans although only clinical trials will confirm or invalidate this assumption as evidenced by the list of drugs that did not pass the animal tests and gave false positive. Such drugs are or were valuable indeed, they are still used or not (corticosteroids, Depo-Provera, furosemide, isoniazid, penicillin, chloroform, digitalis, morphine, and so on).

Even though the pharmacological dose to the toxic dose ratio is high, the same variability applies among species but the drug industry and regulators will feel more confident though. However, the drug is still potentially toxic or of no use, neutral, as evidenced by the list of drugs that pass the animal tests but fail clinical trials or were recalled later on (thalidomide, diethylstilbestrol, suprofen, eraldin, chloramphenicol, phenylpropanolamine, this one by the way, in the U.S. 500 women under 50 were estimated to be suffering strokes as a result of PPA, some in their 20s. This is not a low number, not to mention the cases that were not reported and the cases that were wrongly diagnosed. What did the FDA wait for? More cases? There is no animal model, which could predict the toxicity, and PPA was tested extensively.

A very small percentage of all the research carried out on laboratory animals in industry, universities, medical schools and biomedical institutes worldwide, result in some useful applications. The rest produces a volume of data, published or not, that nobody really knows what to do with it. Some of the principles and drugs, proven safe and efficacious in animals, will then be tested during clinical trials (research involving human subjects) with a 80% chance of being uninformative.

At least, 80% of these clinical trials fail and 20% of drugs and medical devices are assessed by regulatory bodies but at the end of the process only 5% (of the 20%) go to the market. For instance, of 1000 drugs that were tested on animals, one will make it to the market with a 50% chance to be recalled or relabeled, given the FDA figures between 1975-85. Finding drugs cost tens of millions of dollars and takes an average of 7 years.