A former Director of the Wellcome Research Laboratories has stated that "the unsatisfactoriness of predicting adverse effects in humans from animal experiments has been known for a long time"(29) while the Lancet medical journal acknowledges that "animal tests are very imperfect indicators of human toxicity."(30) Most drug side-effects occurring in people undergoing treatment cannot be correctly predicted by animal experiments so it is not surprising that the great majority of drugs found safe and effective on the basis of animal tests fail during clinical trials with volunteers and patients.(31) While such trials are the most reliable test of a new medicine, some preliminary testing is essential to identify and reject the most toxic substances. It is here that in vitro studies with human cell promise better protection than experiments on animals.
The idea that a combination of in vitro tests would allow the general toxicity of chemicals to be correctly predicted, is a basic assumption behind a multicenter trial initiated during 1987 by the Scandinavian Society for Cell Toxicology.(32) The research aims to find exactly which combination of in vitro cell systems best predicts lethal doses of chemicals in human beings. Although many of the cell systems derive from animals, a human-oriented approach is possible. Indeed, while introducing a workshop on the application of tissue culture in toxicology, Dr. Zucco of Italy's National Council of Research explained how the problem of extrapolating data from animals to people could be bypassed with the use of human cell cultures, in effect allowing us "to carry out studies on our species directly."(60) For instance, in tests carried out at Denmark's Roskilde University Center, the lethal concentration of chemicals to cultures of human blood Iymphocytes showed "very good correlation" with their reported lethal doses in people.(33) The Iymphocytes were obtained from a volunteer's blood sample.
Such in vitro studies are valuable in assessing overall toxicity but a more sophisticated approach would be to carry out additional tests with tissues from organs most commonly damaged during drug treatment, such as the liver, kidney, blood and skin. For instance, some drugs damage the bone marrow producing fatal blood diseases; but scientists at Britain's Lister Hospital in Hertfordshire have recommended the use of human bone marrow cultures to detect hazardous products before they reach clinical trials. (34) They conclude that,
"any in vitro method using human tissue gives a degree of reassurance not provided ... by animal experiments".
The technique can detect chloramphenicol, an antibiotic known from clinical experience to cause the fatal blood disorder aplastic anaemia. Chloramphenicol was thought tc be safe after experiments on animals.(35)
In another example, researchers have proposed the use of human kidney tissue to study the damaging effects of aminoglycoside antibiotics.(36) These drugs are known to cause kidney problems in a substantial number of patients and tests with human tissue correctly identified the antibiotics that were most toxic in clinical practice. The results give confidence that human kidney tissue could accurately predict the harmful effects of entirely new drugs Other scientists have suggested human cell tests to identify drugs which damage the fetus,(37) while human blood Iymphocytes have been recommended as one way of detecting mutagens and cancer-causing chemicals.(38)
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