Answers in humans

We will find the answers in humans

 

The question is not whether treating humans must always trump animal interests; most people would like to see safe & effective new treatments for the terrible diseases which continue to afflict us (despite decades of research on irrelevant species).  The question is whether the use of non-human animals is, today, the most accurate means of identifying molecular targets for diseases which are uniquely human, or which manifest quite differently in other species, and then
for ascertaining whether drugs (particularly the latest biological drugs) will cause more harm than good.

Dr John Xuereb, director of the Cambridge Brain Bank: "Alzheimer's, Parkinson's and other neurodegenerative diseases occur in humans and it is in human tissue that we will find the answers to these diseases."

The failure of genetically modified knock-out animals, even where the disease in question is known to be caused by a single defective gene, to fully replicate the clinical symptoms experienced by people, is cautionary. The cystic fibrosis mouse is a good example of this and illustrates the importance of the differences in genetic background which invariably dog even the most well-thought out models.

The artificial induction of a disease or condition which mimics, to the best of our limited knowledge, what is seen in people is not the same as studying the disease either in the clinic, in 'waste' surgical tissues or in post-mortem samples.

The dramatic failure of cynomolgus monkey tests, even using 500 times the human dose, to predict the acute organ failure suffered by 6 young men in the Northwick Park trial of 2006 clearly showed that when it comes to predicting safety in people, 'close' is not close enough; the species in question must be human. In the wake of this most well-known failure, tests using human cells have been developed to replicate the effects suffered by the volunteers, something which has proven impossible in animal tests.

Moreover, in a 2007 report by the US National Research Council & commissioned by the US Environmental Protection Agency, Toxicity Testing in the 21st Century, it was recommended that time-consuming, expensive and doubtfully-relevant tests be replaced with more modern technologies, such as have been developed for medical research. 92% of
all potential new drugs fail in clinical trials, despite passing all the animal-based tests demanded by regulators (US Food & Drug Administration White Paper: Innovation or Stagnation, 2004).

Meanwhile, techniques rooted firmly in the biology of the target animal, humans, limp through decade-long validation processes that animal tests have never been required to pass.

Surely it is time to compare the human and animal data already available for failed drugs, with the results obtained from putting a number of those drugs through a battery of the latest technologies. A multi-agency collaboration in the US is already doing something similar for certain types of new technology. For more information on a UK initiative, please see www.safermedicines.org

Dr Margaret Clotworthy, Science Director, Safer Medicines Trust