In March 2006 there was wide publicity about extreme medical reactions to a new drug being tested by Parexel in Northwick Park Hospital, London. A medical trial was conducted for the German biotechnology firm TeGenero using eight healthy male paid volunteers who each received two thousand pounds. Two of the participants were injected with the placebo while the remaining six received various concentrations of the experimental leukaemia drug, designed to provoke an immune response. The infusions were supposed to be delivered over two hours, but the hospital staff cut corners and gave the infusions every two minutes. Soon the volunteers were burning up with fevers and screaming in pain, begging for pain relief. The indifferent staff merely gave them a mild painkiller while the male subjects pleaded for medical help. Eventually the seriousness of their plight was realised and they were put into a medically induced coma after several hours of agony. They were by then suffering from a cytokine storm of T cells and imminent organ failure and one man was dubbed the “elephant man” as his head ballooned in size. It was later deduced that the preceding animal trials which had cleared the drug for human use were of no use. This was due to the fact that sterile laboratory animals had been used that had an atypical immune system with no memory of previous infections. Unlike animals in the wild they had never encountered a disease or infection and therefore had an aberrant immune system that did not react to the monoclonal antibody drug TGN1412. On the basis of this flawed trial the experimental drug was cleared for the human phase of the trials. The ensuing catastrophe demonstrated the danger of casual extrapolation from sterile laboratory animals to humans. Since such atypical animals are still used in animal laboratories one may question the safety of such animal research. Animals such as monkeys are routinely used to test drugs with the assumption that they are our nearest relatives in the animal kingdom .Extrapolations are freely made from the apes to human beings. There are also the ethical problems to consider. Chimpanzees and other apes have been shown to be extremely intelligent by numerous studies. Apes have managed to complete mathematical tasks involving perfect memory recall in a shorter time than human volunteers. They are loveable creatures and their mistreatment has given rise to protest movements such as “SPEAK”. It is possible that in the future scientists will use artificial “virtual humans” to test the pharmaceutical products. A virtual human is a computer programme that may be used to simulate the hypothetical effects of drugs. The pros and cons of virtual humans have been debated widely. It seems that the animal laboratory technicians are winning as there are still numerous laboratories throughout the U.K. Some of these such as Huntingdon Life Sciences in Cambridge have been the scenes of severe protests by militant organisations such as the Animal Liberation Front (ALF).Occasionally such protesters go a bit too far and commit illegal acts of trespass and vandalism which do nothing to aid their cause. One member of the ALF even dug up a corpse of a family member connected with an animal testing facility. This ghoulish act received widespread censure and condemnation. The fundamental premise that animals should be treated humanely is undoubtedly a decent ideal. Various politicians have fought hard to establish a more principled set of guidelines to protect the rights of dumb animals who cannot speak. MEP` s have campaigned long and hard in the European Parliament to ensure that Laboratory animals are treated humanely. Such animals are now given sedatives and put to sleep without pain, although there are still breaches of Home Office guidelines that occasionally come to light.
The dangers of extrapolation from these caged animals are dramatically highlighted by the TeGenero disaster. These hapless volunteers have now been left with permanent damage to their immune systems and one of them is showing signs of cancer. Many experts such as Dr. M. Ehrenstein of University College London felt that this was an inherently dangerous drug since it over- ruled the natural immune system`s T cells (Rosenthal 2006). The victims have not even received proper compensation as the biotechnology firm TeGenero became bankrupt following the disaster. This incident demonstrates how patient safety is often compromised in the lucrative rush to get products onto the marketplace. The drug testing company Parexel was severely criticised by the MHRA for the way it had conducted the trial.
This incident should set a red flag waving about the use of laboratory animals. The dose given to the male volunteers was five hundred times less diluted than that given to the monkeys who had not suffered any obvious side effects. Clearly this terrible case should cause a review of testing procedures. It also indicates the dangers of extrapolation from animal studies to human patients.
Laboratory animals raised in a sterile environment have completely different immune systems that lack memory immune cells.
A drug that was approved by testing on laboratory animals for Parkinsons Disease has been discovered to have a bizarre side effect. Pramipexole has sent users to the gambling casinos. The drug causes a gambling compulsion in humans that would not have been indicated in a laboratory kept animal. There are no Las Vegas style casinos in the humble sterile animal laboratory!! The drug given to sufferers of Parkinsons disease has been shown to cause compulsive gambling and some users have lost a fortune at the casinos where previously they never gambled. The dopamine agonist also caused an obsession with sex. These behaviours are clearly mediated by the brain`s dopamine reward neurotransmitter system. Dopamine has been posited as being a reward and pleasure facilitating neurotransmitter. All symptoms ceased when the drug was withdrawn. Several lawsuits have been filed against the manufacturers of Pramipexole (Health News 2010). Some of the unfortunate patients taking the drug lost a fortune at the roulette tables before the problem was identified. A corollary of this interesting side-effect may be the insights gained into compulsive gambling. It seems reasonable to deduce that the dopamine reward system must be heavily implicated in such behaviour.
No comments:
Post a Comment