Arguments against experimenting on dogs
For years the scientific community has been talking about the uselessness of experimenting on dogs. According to most scientists and companies that produce pharmaceuticals, dogs have no role to play in proving any drug for humans.
Thirty years ago I had created the CPCSEA in the Environment Ministry. This was supposed to be the apex centre of deciding which experiments and which animals were to be used in India. It was supposed to bring in new ideas and promote safe animal alternatives. Unfortunately, instead of putting first class scientists on it, it was soon overrun by low level ministry directors and it degenerated into a dull and senseless office, which simply holds meeting every now and then to rubber stamp useless and repetitive experiments that lead nowhere and push up the prices and delay the issuance of vital drugs.
In October 2017, the first ever conference on the use of dogs in testing and research was held in Hyderabad, India. The event was organized by People For Animals India, partnered by Cruelty Free International a London-based scientific research agency, to bring attention to the practical and ethical problems associated with the laboratory testing of dogs. It was attended by government people and by the 16 Indian companies that test on dogs.
Every year, over 2 lakh dogs are used for testing worldwide to evaluate the safety of new chemicals and drugs. Most regulatory agencies around the world require a non-rodent species (usually dogs) to be used in pre-clinical trials to test the effect (toxicity and pharmacokinetics, pharmacokinetics which means the study of the movement of drugs in the body, including the processes of absorption, distribution, localization) of new chemicals before the tests are conducted on humans. This includes testing of pharmaceuticals, agrochemicals, pesticides etc.
Beagles are the most commonly used breed of dogs for animal testing, owing to their passive nature and small size. These dogs are kept in cages for years until the study is complete, and undergo very invasive and painful procedures during this time. Their vocal cords are sometimes cut so they cannot bark when hurt. These dogs rarely have access to veterinarians and are often not even given painkillers. When rescued, test dogs have been seen to have enlarged hearts and various diseases due to their high stress environments. They are also very anxious and scared of humans. It is a difficult task to rehabilitate even those dogs that manage to make it out of laboratories.
The practice of using dogs has become a part of most regulatory protocols over the decades, despite it lacking a scientific basis. The tests on dogs do not validate any drugs. The tests conducted on dogs have no added value and usually do not provide any new useful data which an original test on rodents cannot. It continues to be practiced despite immense public opposition and clear scientific and ethical arguments against it. In fact, tests done on dogs in the '50s delayed penicillin coming into the market, as dogs were found allergic to it and they died. When they were bypassed and humans were administered the test, it turned out to be a lifesaver.
For years, scientists believed that the central physiological functions of circulation, respiration, and nervous system were common to all mammals. However, no species of animal has been identified which has the same absorption, distribution, metabolism, and excretion processes of drugs as humans. It is unlikely that such an animal species will ever be found. Despite this, there is a persisting opinion that animal research has made a significant contribution to the treatment of human diseases. This is not based on fact, as most of the research using animals is known to be wasted.
The primary objection to the specific use of dogs in testing is thus simple – the data derived from dogs is not predictive enough to be applied to the case of humans. Any conclusions that come out of this forced extrapolation (an act of inferring an unknown from something that is known) between two such different species is largely unreliable. And the scientists know that. So, instead of paying attention to, or taking any interest in, the results of tests on dogs, it becomes simply one more step to fulfil on paper for bureaucrats, before they can get down to the real testing on human beings – which is the only test that matters.
For example, if a new drug is already known to have a 70% chance of not being toxic for humans, a negative test conducted on dogs will increase this probability to just 72%. The dog test thus does not provide significantly new or supporting evidence. It does, however, have a huge financial and ethical cost.
Dogs have always been found to be inconsistent predictors of toxic responses in humans. A study conducted, at the School of Pharmacy, University of Connecticut, as early as 1982 found that most derivatives of the drug benzodiazepine, used in many common medicines, have a much smaller half-life in dogs as compared to humans. As these drugs are processed and metabolized much faster in dogs, results of tests conducted on dogs become irrelevant to predict the side effects or toxicology on humans.
A study by Nerviano Medical Sciences, Italy found that the CYP3A enzyme – which is present in all animals and used to study drug toxicity – is extremely specific to the species being tested. The extrapolation of such data to human subjects is a risky exercise. Dogs are not a good metabolic model for humans due to major differences in their cytochrome P450 enzymes (CYPs), which are the key enzymes involved in the metabolism of over 90% drugs. Other research has also proven that the results obtained by studying drug metabolizing enzymes in animals could not be extrapolated for humans due to the molecular differences among different species.
The Department of Pharmaceutics and Pharmacodynamics at the University of Illinois conducted a study where 43 drugs were administered to dogs and humans. The overall correlation with regard to drug absorption and efficacy was relatively poor (r2 = 0.5123) in comparison to an earlier rat vs. human study on 64 drugs (r2 = 0.975). In fact, even poorer than rats which are tested on to begin with simply as a basic exercise. The data could not be used to build a better understanding of the effects on humans.
Further studies, including one conducted by AstraZeneca, a pharmaceutical company, have shown that several drugs when tested are observed to be free in the plasma of animals, meaning that they do not bind to proteins as they might do in humans and are thus irrelevant for human comparison.
Despite the consistently proven lack of scientific value, tests on dogs continue to be demanded by government regulatory bodies. This can have adverse repercussions on humans. Like penicillin, there could be a number of drugs/chemicals which have an unfavourable reaction on dogs, but may not have such a reaction on humans. There is a risk that a number of potentially useful compounds will be discarded at an early stage due to these early negative results.
On the other hand, there are high chances of drugs passing the tests on dogs but reacting unfavourably on humans. Many toxic compounds can wrongly reach the stage of human testing, and can harm humans in clinical trials. Few people know that 92-94% of all drugs which pass preclinical tests fail in clinical trials on humans – this fact has been revealed by Cruelty Free International after examining hundreds of thousands of studies. This happens largely due to unforeseen toxicities which did not show up in animal tests. Even worse, half of the drugs that get past human trials have been subsequently withdrawn, or re-labelled due to adverse drug reactions which were not detected in animal tests.
The advances in neuroscience and related technology make the practical need and ethics for conducting tests on dogs increasingly questionable. The advent of new technology provides a number of alternatives. Computer simulation programs have been developed, which can simulate cell models to help study effects of drugs at the molecular and cellular level. Such in-silico studies have a better scope at providing important results than studies on animals, as there is better control over the experiment parameters.
Another new method of testing is in-vitro testing, or the Tox21 method, which employs cells obtained from live humans. For example, anti-cancer studies are conducted on human cancer cells taken during surgeries by biopsy. This type of testing also gives researchers a more controlled environment, making the results more reliable and reproducible.
These, and other new methods, have a number of benefits over testing on animals, particularly dogs – they save huge amounts of time and money, they provide more reliable results, the ethical concerns are minimal and the financial and practical implications of rearing animals etc. are much lower. There is benefit for all involved, if a move is made away from animal testing, particularly laboratory testing of dogs.
My teams rescue the beagles that are still alive after the experiments have been done on them for years. If you were to see their state, and realise that all this suffering was for nothing, you would be appalled. The first step has been taken by holding the conference. The pharmaceutical industry says it would prefer not to use them. Now the bureaucrats and government scientists need to change the protocols that are using our tax money to inflict so much unnecessary harm.
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