Interview: Andre Menache, BSc(Hons) BVSc MRCVS     Bron 

Veterinarian Dr Andre Menache, BSc(Hons) BVSc MRCVSVeterinarian Dr Andre Menache has held various posts, including that of president of Doctors and Lawyers for Responsible Medicine ( UK ) and general manager of the Federation of Animal Protection Societies in Israel . Today he provides scientific support to several grass roots organisations, in addition to his official position as director of Antidote Europe, based in France .

Andre, you have campaigned against animal experiments for around thirty years now. What initially was your primary objection to using animals in medical research?

It was by chance during my veterinary studies that I came across a magazine of the South African Association Against Painful Experiment on Animals. This subject immediately got my attention. Like most people, my initial objection was on moral grounds. However, I soon discovered that the moral argument was inadequate in debates with animal researchers, who would resort to statements like “it’s either your dog or your child”. Statements like these persuaded me that I would need to find scientific arguments to explain why animal experiments are not only cruel but also represent bad science.

Can you explain briefly why animals are not good models on which to measure toxicity?

The simplest way to explain why animals are not good models in which to measure human toxicity is to look at species differences with respect to liver function. The human liver can metabolise paracetamol while the cat liver cannot. Conversely, there are drugs that appear safe in animals that turn out to be dangerous in humans. That would help to explain why the number one reason for the withdrawal of prescription drugs is liver toxicity in humans (despite animal testing). Fortunately, the pharmaceutical industry and the regulatory authorities are coming round to the fact that cultured human liver cells and donated human liver slices are a much better way of predicting human toxicity than relying on animals.  

Whilst non animal methods exist, researchers argue that drugs/chemicals need to be tested on an entire living system. How would you respond to this?
If we rely on animals to predict human response, we will get the right answer 33% of the time. This figure is based on the correlation between preclinical toxicity seen in animals and adverse drug effects seen in people. The general public expects 95% - 100% accuracy when lives are at stake, not 33%. It should be obvious that any method yielding less than 50% (equivalent to tossing a coin) is unacceptable. Human-based methods, such as cell culture, “lab-on-a-chip” combined with microfluidics and population based pharmacokinetic modelling and simulation (see for examplehttp://www.simcyp.com/) are in the range 70% - 100% predictive for humans. The choice is therefore between incomplete human data that is relevant, or complete animal data that is largely irrelevant, for humans. Based on species differences animal tests will always be less reliable than a coin toss, whereas modern science has the means to improve on current human based methods and approach the 100% mark.

Why then do animals continue to be used for this purpose? Is it a legal requirement?

In the context of pharmaceutical drug testing, animal tests are conducted more for legal reasons than scientific ones. These regulatory requirements were written more than 50 years ago. Science, however, has moved forward by 50 years but the laws have not kept up with the science. For things to improve, we need to update our laws. Sadly, most regulators prefer to hold on to what they are familiar with, even if it is outdated science. One way out of this impasse is for scientists familiar with modern toxicological methods (without animals), to educate politicians on this subject. Once politicians realise that animal studies are not predictive for humans they will hopefully push for changes in regulatory requirements and replace animal tests with modern science.

See http://antidote-europe.org/campaigns/people-are-not-70kg-rats.

During your time campaigning against animal experimentation, what do you consider to be the most significant development with regards to a shift towards using non animal methods?

The scientific world underwent a paradigm shift in 2000 with the discovery of the human genome. This discovery paves the way forward for personalised medicine, where every person is regarded as a unique individual, even to the point where identical twins may require different treatments for the same medical condition, based on tiny differences in their DNA. Science has identified the function of virtually all of the 24 000 genes in the human genome. This knowledge is already being applied to drug development and drug testing (pharmacogenomics), which represents a win-win situation for the pharmaceutical industry and the consumer alike: safer drugs means fewer side effects in people and fewer law suits against the drug manufacturer.     

And finally, what do you see as being the biggest hurdle faced by those of us who oppose animal experiments?

Ignorance. The public and our politicians are largely unaware of what has been said above. The scientific evidence to show that animal models are not predictive for humans is rock solid (see for example http://www.peh-med.com/content/4/1/2). The challenge is therefore to communicate this information to the general public and to our decision-makers as effectively as possible. In the case of our decision makers, there is no substitute for one-on-one meetings between modern scientists and politicians. In addition, a public awareness campaign would be effective if funds were available to pay for TV and newspaper ads and billboards for an extended period of time. The message would be simple: Why test drugs on animals? Humans are not 70kg rats.

RfDs zijn meestal afgeleid van dierlijke studies. Dieren (meestal ratten) zijn gedoseerd met wisselende hoeveelheden van de stof in kwestie, en de grootste dosis waartegen geen effecten worden waargenomen wordt geïdentificeerd. Deze dosis wordt genoemd de "geen waarneembare effect level," of NOEL. Verantwoordelijk voor het feit dat mensen meer of minder gevoelig dan het proefdier kunnen zijn, wordt een tienvoudige onzekerheidsfactor meestal toegepast op de NOEL. Deze onzekerheidsfactor heet de "interspecies onzekerheidsfactor" of Ufinter. Een extra tienvoudige onzekerheidsfactor, de "intraspecies onzekerheidsfactor" of Ufintra, wordt meestal toegepast op-account voor het feit dat sommige mensen aanzienlijk meer gevoelig voor de effecten van stoffen dan anderen wellicht. Extra onzekerheidsfactoren kunnen ook worden toegepast. In het algemeen.