Replacing animal experiments

Nick Anthis at the Scientific Activist finds another article about the evils of animal research published in Bioessays. Gill Langley from the "Dr Hadwen Trust for Humane Research" gets some real scientists in on the act:

"Universities are failing to take up the challenge of replacing their animal experiments with non-animal techniques, whilst industry has made significant strides forward, says an article to be published in the September issue of the international peer-reviewed journal BioEssays. Animal experiments conducted by industry in Britain have fallen significantly over several years, but those carried out by universities and medical schools have risen by 52% in the last decade.

The article is authored by eminent professors engaged in academic research in immunology, infection and pain, as well as the Dr Hadwen Trust’s Dr Gill Langley, one of the world’s leading authorities on non-animal replacement techniques...Replacing animal experiments is a well-established concept in industry, especially in the pharmaceutical, chemical and cosmetics sectors. By contrast, in academia, animal use continues to rise and efforts to replace animal experiments are all too often poorly prioritised or focused. In areas where researchers have pioneered replacement efforts, some animal experiments have been successfully replaced, such as in neurological, reproductive and dentistry research. But elsewhere in the university sector progress has been unnecessarily slow.
...
“In recent years industry has started to respond actively to the replacement challenge in a way that we have yet to see within academia. In safety testing, particularly within the cosmetics, chemical and pharmaceutical sectors, non-animal techniques are recognised as advanced methods that are more ethical and also more relevant to humans, as well as being quicker and cheaper solutions. There is a growing acknowledgement of the need to develop non-animal methods, with legislative reform and consumer pressure for cruelty-free choices both playing a key role in speeding up the pace of change. However, universities tend to be less accountable and more isolated from these external factors and as a consequence their animal use has continued to increase unabated.”"

So says the Dr Hadwen Trust about its own article. Not sure why they think that industry large scale toxicity testing has any repercussions for basic scientific research, but what do I know?

The article starts by making the perfectly valid observation that industry has reduced the number of animals used, whilst academia has increased the numbers (likely due in part to increased use of transgenics as Nick points out) and then highlights a couple of examples of where replacement has taken place (toxicity testing, computer models of placental physiology and orthodontics, and transcranial magnetic stimulation in brain research) and then goes on to suggests how replacement may help in other fields, for example in sepsis:

"Animal models have provided a large body of evidence to establish the major pathophysiological mechanisms that operate during sepsis, and as a springboard in the development of new therapies. However, they are imperfect models...The in vitro tools of molecular and cellular biology will still provide much important information in the future...Newer methods of cell culture using three-dimensional supports hold promise as better models of tissue function...and advances in stem cell biology may well allow quite complex tissues to be constructed entirely in vitro. Similarly, progress being made in computer modelling of sepsis may also allow modelling of septic processes without the use of animals...A greater use of human subjects and material in sepsis research could contribute to the reduction of animal experimentation, while providing mechanistic insights into this serious medical problem."

or respiratory disease:

In the case of COPD, epithelial cells at baseline and following exposure to tobacco smoke extract also exhibit markers of injury and repair that occur in vitro in the airway cells of patients, but not in those from normal volunteers...Building upon the in vitro monolayer system, it has been possible to produce a fully differentiated airway epithelium...they can be used to look for novel molecular targets using genomic and proteomic platforms. They can also be used as test systems for novel therapeutics...Computer simulations have also been used to explore mechanisms of asthma pathology and predict the efficacy of potential treatments"

and pain:

"Animal models have provided us with key information about the detailed anatomical connections of nociceptive pathways...and potential physiological mechanisms of pain perception...To achieve a more physiological approach to pain classification, it will be necessary to identify the normal physiological...and pathophysiological mechanisms of pain perception...For example, PET studies have shown a selective reduction in receptors for natural opiates in the brains of patients with severe pain due to stroke...Following identification of mechanisms in humans, targeted drug development should be narrowly based on modulation of those mechanisms. Having identified and measured the pathophysiological mechanisms, proof-of-concept trials will be much more cost-effective. Preferably no drug should be developed without establishing that it reaches the target organ in humans, prior to clinical trials. In many cases, this can be achieved using molecular imaging e.g. PET. In summary, techniques exist to begin to reclassify human pain physiologically and to identify candidate pathophysiological mechanisms in volunteers. By working back from these mechanisms to drug development, some animal experiments maybe replaced."

They go on to conclude that:

"In academia, with an emphasis more on fundamental medical research, change has been slower. There are several reasons: (1) open-ended research questions are perceived as being more difficult to pursue without animal experiments, (2) there are few avenues for consumer pressure to be exerted, and (3) academic research is less shaped by legislative and regulatory initiatives. However, recent systematic reviews of the translation of animal research into clinical benefit may well signal a change."

I'm sure this article will be jumped on by the anti-vivisection crowd but when you analyse it this is all so much smoke and mirrors. To a naive reader this looks like what the anti-vivs have to say is true, that there are all these alternatives to animal research out there and the evil scientists are ignoring them.

It is worth noting that they explicitly don't say that animals are so different to humans that all research on them is meaningless, and that is a rather popular trope among the anti-viv crowd, so it is interesting that they couldn't get the scientists to say that here. If you read the sections written by the scientists they explicitly say that animal research has contributed much knowledge (and notice the caveats about what non-animal methods may add), but what they don't say, and this goes to the heart of it, is that all scientists are well aware of these other techniques and they are already very widely used because they are complementary to other research (they are also relatively, last 20 years say, new, and could never have contributed to biological knowledge in the past because they simply didn't exist).

I mean, seriously, for fuck's sake, what working medical scientist isn't either aware of, or actively involved in in vitro molecular and cellular work? And how do we think these computer models and other assays were developed, how do we know they are accurate reflections of the biology? Oh yes, the animals. And that is not even to think about where half the reagents and tissue comes from (I'll give you a clue, they're fluffy).

When a working scientist reads this they are bemused, 'what is this article trying to tell us?', it simply mentions a few techniques which are already widely known and widely employed, they represent the state of play in a field of research, they are not replacements because they are doing different things. Sure, new techniques might give us new knowledge, quelle fucking surprise! This paper has absolutely nothing to add to the vivisection debate.

For instance, much of the rise in animal research has been in transgenics, animals with genetic manipulations. Let us take an example of a disease Huntington's disease, a neurodegenerative condition where mutations in the Huntingtin gene have been implicated. Now where do we go from here? We might wonder whether we can reverse the effects of this mutation with treatment or is the damage done too early for us to do anything about it? Luckily enough we can engineer an animal model with mutant Huntingtin, and interestingly it turns out that we can't reverse the neuronal damage and behavioural deterioration when it manifests, but we can arrest it by turning off the gene - making gene silencing therapies a promising avenue of research. But this was animal research precipitated by non-animal 'alternatives', oh no - it is like the alternatives aren't alternatives after all, but different modalities for research, complementary but not necessarily replacing animal experiments.

These genetic animal models, in, for example, Alzheimer's are loads better than the models we had before the genetic knowledge was there (for example, anticholinesterase treatment was inspired by previous models based on the degeneration of cholinergic cells in Alzheimer's, but this is merely a downstream consequence of the pathology, so the treatments cannot be curative only relieve symptoms).

This kind of stuff just seriously pisses me off - it isn't that offensive in and of itself, but it is just meaningless platitudinous drivel in pursuit of a wider agenda. It looks all reasonable until you see that it is attempting to provide intellectual cover for the anti-vivs through confusing non-scientists into thinking that there are somehow these magic replacements for animal research.

What they try and imply is that there are all these new techniques that don't (necessarily) require animal vivisection (true), and that animal research in academia has been rising in recent years (also true), but the link is not that scientists are therefore ignoring non-animal techniques because they are stupid, or not subject to 'consumer pressure', but quite possibly because new knowledge spurs on further research, some of which has to be done with animals.

Rant over!


Bizarrely one of the authors has this to say in spiked:

"I should teach the world that higher animals, and specifically humans, function
as complex systems, where the individual inputs produce effects greater than
their sum parts. While reductionist science can help in identifying the parts,
the real difficulty for medical science is how the parts interact in the intact
organism, and how the intact organism is ordered. This must be the challenge of
medical science for the current millennium."