Laurie

Biomedical research is a dif cult 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 rst 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.

Helen

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 suf cient accuracy.

I’d love to hear a proposal for methods to realistically replace animal models that ‘eliminate the risk of species di erences’, but currently none exist, and developing them is still well within the realm of science ction – Laurie

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,

LAURIE PYCROFT is one of the founders of Pro-Test, a British group that supported continuing animal testing in scientific research. Pro-Test wound up its operations in February 2011, but a related organization, Speaking of Research, is active in the US.

pro-test.org.uk

Pro-Test march in Oxford, UK.

NO

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

The human body is extremely complex. This is why animals are not good models for human medicine. Humans di er from other animals anatomically, genetically and metabolically – Helen

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 bene ts will result by pure chance.’ Such logic does not constitute good science. Good science, relevant and, importantly, ef cient science is what we must strive for.

Laurie

It’s undeniable that there are signi cant 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 bene ts, 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 ction. 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

Argument

insufcient 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 con rmed the results, leading to these tests becoming standard for pre-clinical drug testing.

Helen

Even when genetically modi ed, 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 scienti c (not ction) technologies such as micro uidic 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 speci c 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.

Laurie

Claiming that micro uidics and microdosing

can analyze drug effects on a full living system is absurd. How can a uid-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 ef cacy 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.

Helen

Without emotion, we can say that no model
is perfect, but a battery of human-speci c methodologies in pre-clinical testing is far more predictive than depending on data from another species. Even the US Federal Drug Administration con rms that nine out of ten drugs ‘proven’ successful in animal tests fail
in human trials. This not only questions the ef cacy 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 scienti c 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. ■