Like any drug, before Viagra was approved it underwent testing in animals. It was found to constipate mice and caused the livers of rats to swell. These problems were judged not to be severe enough to preclude human testing, and indeed it turned out that these side effects were not seen in men who took the drug. These are not unusual cases. A survey of some 150 compounds that were produced by various pharmaceutical companies as prospective drugs, but were never marketed because of some sort of toxic effect in people, revealed that only 43% of these drugs caused similar problems in rodents, and only 63% did so in other animals. The scientific literature is also full of examples of promising findings in laboratory animals that have not translated into effective treatments in humans. For example, tramiprostate (Alzhemed) was very effective in reducing the accumulation of amyloid protein in the brains of mice, a hallmark of Alzheimer’s disease. Yet it failed in human clinical trials. So did statins, which showed promise in mice but have turned out to be ineffective in treating Alzheimer’s patients.
Even closely related animal species do not necessarily respond the same way to chemicals. Take dioxins, for example. These are commonly described as the most toxic substances ever created. And they may well be. If you are a guinea pig. But the lethal dose for a hamster is one thousand times greater than that for a guinea pig. And we just don’t know where humans fit into the scheme of things. Victor Yuschenko, the Ukrainian President, was poisoned by a large amount of dioxin that somehow had been introduced into his food. Based on animal data, he should have died, but the only acute symptoms he suffered were inflammation of the liver and pancreas, along with facial palsy and a flare-up of a herpes infection. These quickly subsided, but the chloracne, characteristic of dioxin poisoning did disfigure his face. There is also the possibility, based on animal data, that he is at risk for a type of cancer known as soft tissue carcinoma. Certainly it will be interesting for scientists to follow his progress.
Obviously better models of testing are needed. And eventually this could come from testing chemicals on human cells in the laboratory. Of course cells don’t represent the whole organism, so there are still many issues here, but there is optimism. Techniques are being developed whereby liver or skin cells can be placed in thousands of tiny wells on a single dish, and different doses of chemicals can be systematically applied and the effects on the cells noted. Researchers are working on correlating results from such experiments with animal and human data, and within a few years we may in fact be able to test those thousands of chemicals to which we are exposed in a more reliable fashion. The next canary in a coal mine may very well be an isolated liver cell in a laboratory dish.