See also our followup blog post from animal testing expert Andrew Knight.
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Edmond Terakopian / PA Archive / Press Association
Biomedical research is a difficult process, to say the least. The human body is the most complex machine yet encountered, consisting of trillions of cells, each containing billions of molecules, many of which are composed of tens of thousands of atoms. These molecular machines perform their designated tasks with incredible precision, working within a stunningly interdependent environment, from the level of molecules communicating with each other over minute distances right up to entire organ systems interacting with one another. Biomedical researchers need tools capable of mimicking this level of complexity. The past century or so has seen an explosion in the availability of investigative tools – cell cultures, non-invasive imaging, computer models – these are all powerful techniques in humanity’s arsenal in the war against disease and ignorance, but none of them fully replicates the intricacy of a living organism.
Without the ability to use animals in their research, scientists’ efforts would be massively hampered, not only in the direct development of new treatments, but also in the fundamental research which underpins all biomedical knowledge. For example, it was Alan Lloyd Hodgkin and Andrew Huxley’s work on the nerves of squid that elucidated the basis of nervous transmission; and it was John C Eccles’ work on cats’ spinal cords that first incontrovertibly demonstrated the nature of the synapse, earning him a share of the 1963 Nobel in Physiology, along with Hodgkin and Huxley. Without their work on animals, we would know far less about the workings of our own nervous systems and how to treat them.
Lai Seng Sin / AP / Press Association Images
Absolutely! The human body – indeed most living systems – is extremely complex. This
complexity and intricacy is precisely why animals are not good models for human medicine.
Humans differ from other animals anatomically, genetically and metabolically, meaning data derived from animals cannot be extrapolated to humans with sufficient accuracy.
Understandably, when a drug or other medical treatment is developed, it must be tested in an entire living system. Using another species is using the wrong system. Considering the differences that occur on the metabolic, genetic and molecular levels, when applied to an entire biological system those intricate differences become exponential. Pre-clinical testing needs to be conducted in such a way that eliminates the risk of species differences and is instead directly applicable to humans.
Medical advances should be weighed up against the delays and tragedies caused by reliance on animal experiments – the thalidomide disaster whereby tens of thousands of children were born with severe deformities not predicted in animal tests, to name one of the most famous, but there are many others. While some discoveries have been attributed to animal use, it does not necessarily mean that they could not have been made through other means. Dr John McArdle said: ‘Historically, vivisection has been much like a slot machine. If researchers pull the experimentation lever often enough, eventually some benefits will result by pure chance.’ Such logic does not constitute good science. Good science, relevant and, importantly, efficient science is what we must strive for.
It’s undeniable that there are significant variations between species, but part of research is taking these differences into account and selecting appropriate model organisms to replicate the system one is testing. Fortunately, researchers have devised many routes of minimizing inter-species variation, such as the use of transgenic animals – genetically altered to replicate human physiology more closely. This has additional benefits, including shorter generation-span, allowing scientists to perform experiments which simply would not be possible using humans (even ignoring ethical concerns).
I’d love to hear a proposal for methods to realistically replace these animal models that ‘eliminate the risk of species differences’, but currently none exist, and developing these methods is still well within the realm of science fiction. To suggest otherwise is highly misleading. One can claim that medical discoveries can be made using exclusively non-animal methods, but unless one can suggest realistic replacements, these claims are hollow.
The thalidomide tragedy in fact resulted from insufficient animal testing. At the time it was not standard procedure to give pregnant animals drugs before clinical use. Once investigators became aware of thalidomide’s mutating effects, experiments using pregnant animals confirmed the results, leading to these tests becoming standard for pre-clinical drug testing.
Even when genetically modified, there is no single animal model that can accurately mimic the complex human situation. There are far too many unknown variables that cannot all be accounted for. Instead, we now have scientific (not fiction) technologies such as microfluidic chips and microdosing. Not only do these techniques analyse the effects of drugs on an entire living system, they analyze a human living system, eliminating error caused by species differences and resulting in data that is relevant to humans.
Systematic reviews conducted in the areas of toxicity testing and biomedical research have shown that alternatives are far more predictive of human outcomes than data obtained from animals.
The results obtained from testing thalidomide (post-disaster) on pregnant animals only resulted in defects when given to white New Zealand rabbits – at doses between 25 to 300 times that given to humans, and certain species of monkeys – at ten times the dose. Even if the drug had been tested on those specific species (by chance) thalidomide would still have gone to market since the vast majority of species showed no defects, and of those that did, only at much higher doses than given to humans.
Claiming that microfluidics and microdosing can analyze drug effects on a full living system is absurd. How can a fluid-based chip replicate the most basic heart, let alone a human one? Microdosing can be useful for studying uptake mechanisms of a drug, but gives extremely limited information on its efficacy at treating a condition. ‘Alternatives’ are already widely used in research, but expecting them to replace animal tests in the near future is hugely naïve. It’s true that thalidomide doesn’t affect all species, which is part of the basis for drugs being tested on a variety of carefully selected species. These models will never be perfect but, as any scientist will tell you, no test is. We must use the best available model, and some of the time this means using animals.
More importantly, you continue to ignore the most important use of animals in science – basic research. Without access to live organisms, we would know far less about the function of the cardiovascular system, how digestion works, hormonal interactions, and a vast array of other data which none of your proposed ‘alternatives’ could even hope to elucidate. Thus, if we value progression of medical knowledge, animal research is a necessity.
Without emotion, we can say that no model is perfect, but a battery of human-specific methodologies in pre-clinical testing is far more predictive than depending on data from another species. Even the US Federal Drug Administration confirms that nine out of ten drugs ‘proven’ successful in animal tests fail in human trials. This not only questions the efficacy and the fundamental argument for using animals, but critically raises the question about all the drugs that failed in animals which might have worked in humans. How many discarded cures for cancer?
In the past, much research has been based on animals because we didn’t know any better. Today we are far more aware of the dangers of extrapolating from one species to another and we have scientific research methods – mass spectrometry, genome mapping, innovative imaging techniques and highly developed computer models capable of simulating parts of the human body as mathematical equations and three-dimensional graphical models, just to name a few more.
Terminally ill patients don’t care whether a cancer drug works on a mouse, or that some disease can be cured in another species. Such claims only taunt them with false hope. These people need real cures based on real science – not misleading and antiquated animal experiments.